Covalent immobilization of luminescent oxygen indicators reduces cytotoxicity

Luminescence-based oxygen sensing is a widely used tool in cell culture applications. In a typical configuration, the luminescent oxygen indicators are embedded in a solid, oxygen-permeable matrix in contact with the culture medium. However, in sensitive cell cultures even minimal leaching of the potentially cytotoxic indicators can become an issue. One way to prevent the leaching is to immobilize the indicators covalently into the supporting matrix. In this paper, we report on a method where platinum(II)-5,10,15,20-tetrakis-(2,3,4,5,6-pentafluorphenyl)-porphyrin (PtTFPP) oxygen indicators are covalently immobilized into a polymer matrix consisting of polystyrene and poly(pentafluorostyrene). We study how the covalent immobilization influences the sensing material’s cytotoxicity to human induced pluripotent stem cell-derived (hiPSC-derived) neurons and cardiomyocytes (CMs) through 7–13 days culturing experiments and various viability analyses. Furthermore, we study the effect of the covalent immobilization on the indicator leaching and the oxygen sensing properties of the material. In addition, we demonstrate the use of the covalently linked oxygen sensing material in real time oxygen tension monitoring in functional hypoxia studies of the hiPSC-derived CMs. The results show that the covalently immobilized indicators substantially reduce indicator leaching and the cytotoxicity of the oxygen sensing material, while the influence on the oxygen sensing properties remains small or nonexistent.

General information

Publication status: Published
MoE publication type: A1 Journal article-refereed
Organisations: BioMediTech, Tampere University
Contributors: Välimäki, H., Hyvärinen, T., Leivo, J., Iftikhar, H., Pekkanen-Mattila, M., Rajan, D. K., Verho, J., Kreutzer, J., Ryynänen, T., Pirhonen, J., Aalto-Setälä, K., Kallio, P., Narkilahti, S., Lekkala, J.
Publication date: 1 Jun 2020
Peer-reviewed: Yes

Publication information

Journal: BIOMEDICAL MICRODEVICES
Volume: 22
Issue number: 2
Article number: 41
ISSN (Print): 1387-2176
Original language: English
ASJC Scopus subject areas: Biomedical Engineering, Molecular Biology
Keywords: Covalently immobilized indicators, hiPSC-derived neurons and cardiomyocytes, Human induced pluripotent stem cell-derived cells, Luminescent-based oxygen sensing, PtTFPP cytotoxicity
Source: Scopus
Source ID: 85085923111

Research output: Contribution to journalArticleScientificpeer-review

Paclitaxel, carboplatin and 1,25-D3 inhibit proliferation of ovarian cancer cells in vitro

Background/Aim: The combination of paclitaxel and carboplatin is the standard chemotherapy for ovarian cancer. Previous studies have implied that vitamin D (1,25-D3) may have growth inhibitory effects in ovarian cancer. This study aimed to investigate the effect of paclitaxel, carboplatin and 1,25-D3 on the growth of ovarian cancer cells in vitro, based on the hypothesis that 1,25-D3 might potentiate the effect of paclitaxel and/or carboplatin. Materials and Methods: Three non-commercial ovarian carcinoma cell lines UT-OV-1(mucinous), UT-OV-3B (serous) and UT-OV-4 (endometrioid) were exposed to different concentrations of 1,25-D3, paclitaxel and carboplatin, respectively. The cell viability was measured using a Crystal violet assay kit. The cellular vitamin D receptor (VDR) mRNA levels were measured by qRT-PCR using the LightCycler equipment. Results: The growth-inhibitory effect of the combination of paclitaxel and carboplatin was 56% in UT-OV-1, 33% in UT-OV-3B and 47% in UT-OV-4 cells. Single 1,25-D3 (10 μM) inhibited the growth of UT-OV-3B and UT-OV-4 by 23% and 28%, respectively, whereas no effect was seen in UT-OV-1 cells. These results are in line with the finding that the expression of VDR was high in UT-OV-3B and UT-OV-4, but very low in UT-OV-1. The combination of 1,25-D3, paclitaxel and carboplatin resulted in 61%, 46% and 58% growth reduction in UT-OV-1, UT-OV-3B and UT-OV-4 cells, respectively. The additive effect of 1,25-D3 was 21% in UT-OV-4, 20% in UT-OV-3B and 12% in UT-OV-1 cell line. Conclusion: The results imply that combining 1,25-D3 with paclitaxel and carboplatin may potentiate their growth inhibitory effect on ovarian cancer cells with high VDR expression.

General information

Publication status: Published
MoE publication type: A1 Journal article-refereed
Organisations: BioMediTech, Tampere University Hospital, Tampere University, Turku University Hospital, Turun Yliopisto/Turun Biomateriaalikeskus
Contributors: Kuittinen, T., Rovio, P., Luukkaala, T., Laurila, M., Grénman, S., Kallioniemi, A., Mäenpää, J.
Number of pages: 10
Pages: 3129-3138
Publication date: 1 Jun 2020
Peer-reviewed: Yes

Publication information

Journal: Anticancer Research
Volume: 40
Issue number: 6
ISSN (Print): 0250-7005
Original language: English
ASJC Scopus subject areas: Oncology, Cancer Research
Keywords: 1,25-D3, Carboplatin, Growth inhibition, In vitro, Ovarian cancer, Paclitaxel, VDR, Vitamin D
Source: Scopus
Source ID: 85085970756

Research output: Contribution to journalArticleScientificpeer-review

All-Optical Electrophysiology Refines Populations of In Silico Human iPSC-CMs for Drug Evaluation

High-throughput in vitro drug assays have been impacted by recent advances in human induced pluripotent stem cell-derived cardiomyocyte (hiPSC-CM) technology and by contact-free all-optical systems simultaneously measuring action potentials (APs) and Ca2+ transients (CaTrs). Parallel computational advances have shown that in silico simulations can predict drug effects with high accuracy. We combine these in vitro and in silico technologies and demonstrate the utility of high-throughput experimental data to refine in silico hiPSC-CM populations and to predict and explain drug action mechanisms. Optically obtained hiPSC-CM APs and CaTrs were used from spontaneous activity and under optical pacing in control and drug conditions at multiple doses. An updated version of the Paci2018 model was developed to refine the description of hiPSC-CM spontaneous electrical activity; a population of in silico hiPSC-CMs was constructed and calibrated using simultaneously recorded APs and CaTrs. We tested in silico five drugs (astemizole, dofetilide, ibutilide, bepridil, and diltiazem) and compared the outcomes to in vitro optical recordings. Our simulations showed that physiologically accurate population of models can be obtained by integrating AP and CaTr control records. Thus, constructed population of models correctly predicted the drug effects and occurrence of adverse episodes, even though the population was optimized only based on control data and in vitro drug testing data were not deployed during its calibration. Furthermore, the in silico investigation yielded mechanistic insights; e.g., through simulations, bepridil's more proarrhythmic action in adult cardiomyocytes compared to hiPSC-CMs could be traced to the different expression of ion currents in the two. Therefore, our work 1) supports the utility of all-optical electrophysiology in providing high-content data to refine experimentally calibrated populations of in silico hiPSC-CMs, 2) offers insights into certain limitations when translating results obtained in hiPSC-CMs to humans, and 3) shows the strength of combining high-throughput in vitro and population in silico approaches.

General information

Publication status: Published
MoE publication type: A1 Journal article-refereed
Organisations: BioMediTech, University of Oxford, Carnegie Mellon University, University of Bologna, George Washington University
Contributors: Paci, M., Passini, E., Klimas, A., Severi, S., Hyttinen, J., Rodriguez, B., Entcheva, E.
Number of pages: 16
Pages: 2596-2611
Publication date: 19 May 2020
Peer-reviewed: Yes

Publication information

Journal: Biophysical Journal
Volume: 118
Issue number: 10
ISSN (Print): 0006-3495
Original language: English
ASJC Scopus subject areas: Biophysics
Electronic versions: 
Source: Scopus
Source ID: 85083303522

Research output: Contribution to journalArticleScientificpeer-review

Dissecting the in vivo dynamics of transcription locking due to positive supercoiling buildup

Positive supercoiling buildup (PSB) is a pervasive phenomenon in the transcriptional programs of Escherichia coli. After finding a range of Gyrase concentrations where the inverse of the transcription rate of a chromosome-integrated gene changes linearly with the inverse of Gyrase concentration, we apply a LineWeaver-Burk plot to dissect the expected in vivo transcription rate in absence of PSB. We validate the estimation by time-lapse microscopy of single-RNA production kinetics of the same gene when single-copy plasmid-borne, shown to be impervious to Gyrase inhibition. Next, we estimate the fraction of time in locked states and number of transcription events prior to locking, which we validate by measurements under Gyrase inhibition. Replacing the gene of interest by one with slower transcription rate decreases the fraction of time in locked states due to PSB. Finally, we combine data from both constructs to infer a range of possible transcription initiation locking kinetics in a chromosomal location, obtainable by tuning the transcription rate. We validate with measurements of transcription activity at different induction levels. This strategy for dissecting transcription initiation locking kinetics due to PSB can contribute to resolve the transcriptional programs of E. coli and in the engineering of synthetic genetic circuits.

General information

Publication status: Published
MoE publication type: A1 Journal article-refereed
Organisations: Research group: Laboratory of Biosystem Dynamics-LBD, Faculty of Biomedical Sciences and Engineering, BioMediTech, Tampere University
Contributors: Palma, C. S., Kandavalli, V., Bahrudeen, M. N., Minoia, M., Chauhan, V., Dash, S., Ribeiro, A. S.
Publication date: 1 May 2020
Peer-reviewed: Yes

Publication information

Journal: Biochimica et Biophysica Acta - Gene Regulatory Mechanisms
Volume: 1863
Issue number: 5
Article number: 194515
ISSN (Print): 1874-9399
Original language: English
ASJC Scopus subject areas: Biophysics, Structural Biology, Biochemistry, Molecular Biology, Genetics
Keywords: LineWeaver-Burk plots, Positive supercoiling buildup, Single-RNA production dynamics, Transcription locking kinetics

Bibliographical note

jufoid=52526006

Source: Scopus
Source ID: 85080975088

Research output: Contribution to journalArticleScientificpeer-review

High-content imaging and structure-based predictions reveal functional differences between Niemann-Pick C1 variants

The human Niemann-Pick C1 (NPC1) gene encoding a 1278 amino acid protein is very heterogeneous. While some variants represent benign polymorphisms, NPC disease carriers and patients may possess rare variants, whose functional importance remains unknown. An NPC1 cDNA construct known as NPC1 wild-type variant (WT-V), distributed between laboratories and used as a WT control in several studies, also contains changes regarding specific amino acids compared to the NPC1 Genbank reference sequence. To improve the dissection of subtle functional differences, we generated human cells stably expressing NPC1 variants from the AAVS1 safe-harbor locus on an NPC1-null background engineered by CRISPR/Cas9 editing. We then employed high-content imaging with automated image analysis to quantitatively assess LDL-induced, time-dependent changes in lysosomal cholesterol content and lipid droplet formation. Our results indicate that the L472P change present in NPC1 WT-V compromises NPC1 functionality in lysosomal cholesterol export. All-atom molecular dynamics simulations suggest that the L472P change alters the relative position of the NPC1 middle and the C-terminal luminal domains, disrupting the recently characterized cholesterol efflux tunnel. These results reveal functional defects in NPC1 WT-V and highlight the strength of simulations and quantitative imaging upon stable protein expression in elucidating subtle differences in protein function.

General information

Publication status: Published
MoE publication type: A1 Journal article-refereed
Organisations: Physics, University of Helsinki, Minerva Foundation Institute for Medical Research Helsinki, Computational Physics Laboratory
Contributors: Vanharanta, L., Peränen, J., Pfisterer, S. G., Enkavi, G., Vattulainen, I., Ikonen, E.
Number of pages: 12
Pages: 386-397
Publication date: 1 May 2020
Peer-reviewed: Yes

Publication information

Journal: Traffic
Volume: 21
Issue number: 5
ISSN (Print): 1398-9219
Original language: English
ASJC Scopus subject areas: Structural Biology, Biochemistry, Molecular Biology, Genetics, Cell Biology
Keywords: cholesterol transport, gene variants, late endosomes, lipid droplets, lysosomal storage diseases, Niemann-Pick C1
Source: Scopus
Source ID: 85083734743

Research output: Contribution to journalArticleScientificpeer-review

Salivary cortisol reactivity to psychological stressors in infancy: A meta-analysis

Measurement of salivary cortisol is a practical and non-invasive tool for studying stress reactivity to various types of stressors even in young infants. Whereas studies using physical stressors during the first months of life have found robust cortisol responses to painful stimuli, research with older infants using psychological stressors (e.g., parental separation) has produced mixed findings, limiting our understanding of potential developmental changes in cortisol reactivity across infancy. In the present study, we used meta-analysis to systematically investigate whether psychological stressor paradigms are associated with measurable cortisol responses in infants under 18 months of age and whether the magnitude of the responses is moderated by the type of psychological stressor (i.e., separation, frustration, novelty, or disruption of parental interaction), infant age, and other potential moderators. Across 47 studies (N = 4095, age range: 3–18 months), we found that commonly used psychological stressor paradigms are associated with a small (Hedges’ g = .11) increase in salivary cortisol levels in typically developing infants. Stressor type moderated the effect sizes, and when effect sizes in each category were analyzed separately, only the separation studies were associated with a consistent increase in cortisol following the stressor. Age did not moderate the effect sizes either in the full set of studies or within the separate stressor types. These meta-analytic results indicate that the normative cortisol response to psychological stressors across infancy is small and emphasize the need for standardized stressor paradigms to assess cortisol responses systematically across infancy.

General information

Publication status: Published
MoE publication type: A2 Review article in a scientific journal
Organisations: Education, Human Information Processing Laboratory
Contributors: Puhakka, I. J., Peltola, M. J.
Publication date: 1 May 2020
Peer-reviewed: Yes

Publication information

Journal: PSYCHONEUROENDOCRINOLOGY
Volume: 115
Article number: 104603
ISSN (Print): 0306-4530
Original language: English
ASJC Scopus subject areas: Endocrinology, Diabetes and Metabolism, Endocrinology, Endocrine and Autonomic Systems, Psychiatry and Mental health, Biological Psychiatry
Keywords: Cortisol, Infant, Meta-Analysis, Saliva, Stressor
Source: Scopus
Source ID: 85081216139

Research output: Contribution to journalReview ArticleScientificpeer-review

Utilizing Gelatinized Starchy Waste from Rice Noodle Factory as Substrate for L(+)-Lactic Acid Production by Amylolytic Lactic Acid Bacterium Enterococcus faecium K-1

To valorize starchy waste from rice noodle factory, bioconversion of gelatinized starchy waste (GSW) to value-added product as L(+)-lactic acid, the monomer for polylactate synthesis, was investigated using amylolytic lactic acid bacterium, Enterococcus faecium K-1. Screening for appropriate nitrogen source to replace expensive organic nitrogen sources revealed that corn steep liquor (CSL) was the most suitable regarding high efficacy for L(+)-LA achievement and low-cost property. The successful applying statistic experimental design, Plackett-Burman design incorporated with central composite design (CCD), predicted the maximum L(+)-LA of 93.07 g/L from the optimized medium (OM) containing 125.7 g/L GSW and 207.3 g/L CSL supplemented with CH3COONa, MgSO4, MnSO4, K2HPO4, CaCl2, (NH4)2HC6H5O7, and Tween80. Minimizing the medium cost by removal of all inorganic salts and Tween80 from OM was not an effect on L(+)-LA yield. Fermentation using the optimized medium without minerals (OM-Mi) containing only GSW (125.7 g/L) and CSL (207.3 g/L) in a 10-L fermenter was also successful. Thinning GSW with α-amylase from Lactobacillus plantarum S21 increased L(+)-LA productivity in the early stage of 24-h fermentation. Not only showing the feasible bioconversion process for GSW utilizing as a substrate for L(+)-LA production, this research also demonstrated the efficient model for industrial starchy waste valorization.

General information

Publication status: Published
MoE publication type: A1 Journal article-refereed
Organisations: Materials Science and Environmental Engineering, Chiang Mai University, North Dakota State University
Contributors: Unban, K., Khanongnuch, R., Kanpiengjai, A., Shetty, K., Khanongnuch, C.
Publication date: May 2020
Peer-reviewed: Yes

Publication information

Journal: Applied Biochemistry and Biotechnology
ISSN (Print): 0273-2289
Original language: English
ASJC Scopus subject areas: Biotechnology, Bioengineering, Biochemistry, Applied Microbiology and Biotechnology, Molecular Biology
Keywords: ALAB, Enterococcus faecium, L-lactic acid, Low-cost medium, Starchy waste
Source: Scopus
Source ID: 85084316077

Research output: Contribution to journalArticleScientificpeer-review

Evaluation of scaffold microstructure and comparison of cell seeding methods using micro-computed tomography-based tools

Micro-computed tomography (micro-CT) provides a means to analyse and model three-dimensional (3D) tissue engineering scaffolds. This study proposes a set of micro-CT-based tools firstly for evaluating the microstructure of scaffolds and secondly for comparing different cell seeding methods. The pore size, porosity and pore interconnectivity of supercritical CO2 processed poly(l-lactide-co-ɛ-caprolactone) (PLCL) and PLCL/β-tricalcium phosphate scaffolds were analysed using computational micro-CT models. The models were supplemented with an experimental method, where iron-labelled microspheres were seeded into the scaffolds and micro-CT imaged to assess their infiltration into the scaffolds. After examining the scaffold architecture, human adipose-derived stem cells (hASCs) were seeded into the scaffolds using five different cell seeding methods. Cell viability, number and 3D distribution were evaluated. The distribution of the cells was analysed using micro-CT by labelling the hASCs with ultrasmall paramagnetic iron oxide nanoparticles. Among the tested seeding methods, a forced fluid flow-based technique resulted in an enhanced cell infiltration throughout the scaffolds compared with static seeding. The current study provides an excellent set of tools for the development of scaffolds and for the design of 3D cell culture experiments.

General information

Publication status: Published
MoE publication type: A1 Journal article-refereed
Organisations: BioMediTech, Research group: Biomaterials and Tissue Engineering Group, Research group: Computational Biophysics and Imaging Group, Orton Orthopaedic Hospital, Tampere University Hospital
Contributors: Palmroth, A., Pitkänen, S., Hannula, M., Paakinaho, K., Hyttinen, J., Miettinen, S., Kellomäki, M.
Number of pages: 12
Publication date: 1 Apr 2020
Peer-reviewed: Yes

Publication information

Journal: Journal of the Royal Society. Interface
Volume: 17
Issue number: 165
Article number: 20200102
ISSN (Print): 1742-5689
Original language: English
ASJC Scopus subject areas: Biotechnology, Biophysics, Bioengineering, Biomaterials, Biochemistry, Biomedical Engineering
Keywords: cell seeding, micro-CT, microsphere, supercritical CO2 processing, tissue engineering, USPIO

Bibliographical note

INT=bmte,"Miettinen, Susanna"

Research output: Contribution to journalArticleScientificpeer-review

Mixed carbon substrates: a necessary nuisance or a missed opportunity?

Although fermentation with single carbon sources is the preferred mode of operation in current industrial biotechnology, the use of multiple substrates has been continuously investigated throughout the years. Generally, microbial metabolism varies significantly when cells are presented with mixed carbon substrates compared to a single carbon-energy source, as different nutrients interact in complex ways within the metabolic network. By exploiting these distinct modes of interaction, researchers have identified unique opportunities to optimize metabolism using mixed carbon sources. Here we review situations where process yield and productivity are markedly improved through the judicious introduction of substrate mixtures. Our goal is to illustrate that with proper design of the choice of substrates and the way they are introduced to cultures, metabolic optimization with mixed substrates can be a unique strategy that complements genetic engineering techniques to enhance cell performance beyond what is accomplished in single substrate fermentations.

General information

Publication status: Published
MoE publication type: A2 Review article in a scientific journal
Organisations: Materials Science and Environmental Engineering, Massachusetts Institute of Technology, Department of Chemical Engineering
Contributors: Liu, N., Santala, S., Stephanopoulos, G.
Number of pages: 7
Pages: 15-21
Publication date: 1 Apr 2020
Peer-reviewed: Yes

Publication information

Journal: CURRENT OPINION IN BIOTECHNOLOGY
Volume: 62
ISSN (Print): 0958-1669
Original language: English
ASJC Scopus subject areas: Biotechnology, Bioengineering, Biomedical Engineering
Source: Scopus
Source ID: 85071874245

Research output: Contribution to journalReview ArticleScientificpeer-review

The effect of start-up on energy recovery and compositional changes in brewery wastewater in bioelectrochemical systems

Start-up of bioelectrochemical systems (BESs) fed with brewery wastewater was compared at different adjusted anode potentials (−200 and 0 mV vs. Ag/AgCl) and external resistances (50 and 1000 Ω). Current generation stabilized faster with the external resistances (9 ± 3 and 1.70 ± 0.04 A/m3 with 50 and 1000 Ω, respectively), whilst significantly higher current densities of 76 ± 39 and 44 ± 9 A/m3 were obtained with the adjusted anode potentials of −200 and 0 mV vs. Ag/AgCl, respectively. After start-up, when operated using 47 Ω external resistance, the current densities and Coulombic efficiencies of all BESs stabilized to 9.5 ± 2.9 A/m3 and 12 ± 2%, respectively, demonstrating that the start-up protocols were not critical for long-term BES operation in microbial fuel cell mode. With adjusted anode potentials, two times more biofilm biomass (measured as protein) was formed by the end of the experiment as compared to start-up with the fixed external resistances. After start-up, the organics in the brewery wastewater, mainly sugars and alcohols, were transformed to acetate (1360 ± 250 mg/L) and propionate (610 ± 190 mg/L). Optimized start-up is required for prompt BES recovery, for example, after process disturbances. Based on the results of this study, adjustment of anode potential to −200 mV vs. Ag/AgCl is recommended for fast BES start-up.

General information

Publication status: Published
MoE publication type: A1 Journal article-refereed
Organisations: Materials Science and Environmental Engineering, Research group: Bio- and Circular Economy
Contributors: Haavisto, J. M., Kokko, M. E., Lakaniemi, A. M., Sulonen, M. L., Puhakka, J. A.
Number of pages: 8
Publication date: 1 Apr 2020
Peer-reviewed: Yes
Early online date: 2019

Publication information

Journal: BIOELECTROCHEMISTRY
Volume: 132
Article number: 107402
ISSN (Print): 1567-5394
Original language: English
ASJC Scopus subject areas: Biophysics, Physical and Theoretical Chemistry, Electrochemistry
Keywords: Adjusted anode potential, Brewery wastewater, External resistance, Microbial fuel cell, Process recovery, Start-up protocol
Source: Scopus
Source ID: 85075970236

Research output: Contribution to journalArticleScientificpeer-review

Utilizing Neurons for Digital Logic Circuits: A Molecular Communications Analysis

With the advancement of synthetic biology, several new tools have been conceptualized over the years as alternative treatments for current medical procedures. As part of this work, we investigate how synthetically engineered neurons can operate as digital logic gates that can be used towards bio-computing inside the brain and its impact on epileptic seizure-like behaviour. We quantify the accuracy of logic gates under high firing rates amid a network of neurons and by how much it can smooth out uncontrolled neuronal firings. To test the efficacy of our method, simulations composed of computational models of neurons connected in a structure that represents a logic gate are performed. Our simulations demonstrate the accuracy of performing the correct logic operation, and how specific properties such as the firing rate can play an important role in the accuracy. As part of the analysis, the mean squared error is used to quantify the quality of our proposed model and predict the accurate operation of a gate based on different sampling frequencies. As an application, the logic gates were used to smooth out epileptic seizure-like activity in a biological neuronal network, where the results demonstrated the effectiveness of reducing its mean firing rate. Our proposed system has the potential to be used in future approaches to treating neurological conditions in the brain.

General information

Publication status: Published
MoE publication type: A1 Journal article-refereed
Organisations: Electrical Engineering, Waterford Institute of Technology, Tampere University, Telecommunications Software and Systems Group (TSSG)
Contributors: Adonias, G. L., Yastrebova, A., Barros, M. T., Koucheryavy, Y., Cleary, F., Balasubramaniam, S.
Number of pages: 13
Pages: 224-236
Publication date: 1 Apr 2020
Peer-reviewed: Yes

Publication information

Journal: IEEE Transactions on Nanobioscience
Volume: 19
Issue number: 2
ISSN (Print): 1536-1241
Original language: English
ASJC Scopus subject areas: Biotechnology, Bioengineering, Medicine (miscellaneous), Biomedical Engineering, Pharmaceutical Science, Computer Science Applications, Electrical and Electronic Engineering
Keywords: Boolean algebra, Logic gates, nano communications, nanonetworks, synthetic biology

Bibliographical note

EXT="Balasubramaniam, Sasitharan"

Source: Scopus
Source ID: 85083430394

Research output: Contribution to journalArticleScientificpeer-review

Sequential Collinear Photofragmentation and Atomic Absorption Spectroscopy for Online Laser Monitoring of Triatomic Metal Species

Industrial chemical processes are struggling with adverse effects, such as corrosion and deposition, caused by gaseous alkali and heavy metal species. Mitigation of these problems requires novel monitoring concepts that provide information on gas-phase chemistry. However, selective optical online monitoring of the most problematic diatomic and triatomic species is challenging due to overlapping spectral features. In this work, a selective, all-optical, in situ gas-phase monitoring technique for triatomic molecules containing metallic atoms was developed and demonstrated with detection of PbCl2. Sequential collinear photofragmentation and atomic absorption spectroscopy (CPFAAS) enables determination of the triatomic PbCl2 concentration through detection of released Pb atoms after two consecutive photofragmentation processes. Absorption cross-sections of PbCl2, PbCl, and Pb were determined experimentally in a laboratory-scale reactor to enable calibration-free quantitative determination of the precursor molecule concentration in an arbitrary environment. Limit of detection for PbCl2 in the laboratory reactor was determined to be 0.25 ppm. Furthermore, the method was introduced for in situ monitoring of PbCl2 concentration in a 120 MWth power plant using demolition wood as its main fuel. In addition to industrial applications, the method can provide information on chemical reaction kinetics of the intermediate species that can be utilized in reaction simulations.

General information

Publication status: Published
MoE publication type: A1 Journal article-refereed
Organisations: Physics, Research group: Applied Optics, Tampere University, University Central Hospital Kuopio, Valmet Automation Oy, Universidad Nacional Autónoma de México
Contributors: Viljanen, J., Kalmankoski, K., Contreras, V., Sarin, J. K., Sorvajärvi, T., Kinnunen, H., Enestam, S., Toivonen, J.
Number of pages: 14
Publication date: 18 Jan 2020
Peer-reviewed: Yes

Publication information

Journal: Sensors (Basel, Switzerland)
Volume: 20
Issue number: 2
Article number: 533
ISSN (Print): 1424-8220
Original language: English
ASJC Scopus subject areas: Analytical Chemistry, Biochemistry, Atomic and Molecular Physics, and Optics, Instrumentation, Electrical and Electronic Engineering
Keywords: absorption, combustion, kinetics, lead, photofragmentation

Bibliographical note

INT=phys,"Kalmankoski, Kim"
INT=phys,"Sarin, Jaakko K."

Source: Scopus
Source ID: 85078213348

Research output: Contribution to journalArticleScientificpeer-review

A concise synthesis of carbasugars isolated from Streptomyces lincolnensis

(−)-Quinic acid was used as a starting material in the hemisynthesis of two epimeric carbasugars isolated from Streptomyces lincolnensis. Previous 10–12 steps syntheses for the carbasugars have been herein shortened to 4–6 steps by using quinic acid as a chiron, based on a regioselective reduction step, with stereoinversion of a tertiary center. Both C-5 epimers of (1R, 2R, 3R)-5-(hydroxymethyl)cyclohexane-1,2,3-triol were obtained in up to 76% overall yield.

General information

Publication status: E-pub ahead of print
MoE publication type: A1 Journal article-refereed
Organisations: Materials Science and Environmental Engineering, Universidade de Aveiro
Contributors: Holmstedt, S., Candeias, N. R.
Publication date: 2020
Peer-reviewed: Yes

Publication information

Journal: Tetrahedron
Article number: 131346
ISSN (Print): 0040-4020
Original language: English
ASJC Scopus subject areas: Biochemistry, Drug Discovery, Organic Chemistry
Keywords: Carbasugar, Chiron, Cyclitol, Hemisynthesis, Quinic acid
Source: Scopus
Source ID: 85086914275

Research output: Contribution to journalArticleScientificpeer-review

Co-culture of human induced pluripotent stem cell-derived retinal pigment epithelial cells and endothelial cells on double collagen-coated honeycomb films

In vitro cell culture models representing the physiological and pathological features of the outer retina are urgently needed. Artificial tissue replacements for patients suffering from degenerative retinal diseases are similarly in great demand. Here, we developed a co-culture system based solely on the use of human induced pluripotent stem cell (hiPSC)-derived cells. For the first time, hiPSC-derived retinal pigment epithelium (RPE) and endothelial cells (EC) were cultured on opposite sides of porous polylactide substrates prepared by breath figures (BF), where both surfaces had been collagen-coated by Langmuir–Schaefer (LS) technology. Small modifications of casting conditions during material preparation allowed the production of free-standing materials with distinct porosity, wettability and ion diffusion capacity. Complete pore coverage was achieved by the collagen coating procedure, resulting in a detectable nanoscale topography. Primary retinal endothelial cells (ACBRI181) and umbilical cord vein endothelial cells (hUVEC) were utilised as EC references. Mono-cultures of all ECs were prepared for comparison. All tested materials supported cell attachment and growth. In mono-culture, properties of the materials had a major effect on the growth of all ECs. In co-culture, the presence of hiPSC-RPE affected the primary ECs more significantly than hiPSC-EC. In consistency, hiPSC-RPE were also less affected by hiPSC-EC than by the primary ECs. Finally, our results show that the modulation of the porosity of the materials can promote or prevent EC migration. In short, we showed that the behaviour of the cells is highly dependent on the three main variables of the study: the presence of a second cell type in co-culture, the source of endothelial cells and the biomaterial properties. The combination of BF and LS methodologies is a powerful strategy to develop thin but stable materials enabling cell growth and modulation of cell-cell contact. Statement of significance: Artificial blood-retinal barriers (BRB), mimicking the interface at the back of the eye, are urgently needed as physiological and disease models, and for tissue transplantation targeting patients suffering from degenerative retinal diseases. Here, we developed a new co-culture model based on thin, biodegradable porous films, coated on both sides with collagen, one of the main components of the natural BRB, and cultivated endothelial and retinal pigment epithelial cells on opposite sides of the films, forming a three-layer structure. Importantly, our hiPSC-EC and hiPSC-RPE co-culture model is the first to exclusively use human induced pluripotent stem cells as cell source, which have been widely regarded as an practical candidate for therapeutic applications in regenerative medicine.

General information

Publication status: Published
MoE publication type: A1 Journal article-refereed
Organisations: BioMediTech, Research group: Biomaterials and Tissue Engineering Group, Materials Science and Environmental Engineering, Research group: Chemistry & Advanced Materials, Research group: Micro and Nanosystems Research Group, Heart Group, BioMediTech Institute and Faculty of Medicine and Life Science, University of Tampere, The Heart Center, Tampere University Hospital , Univ Tampere, University of Tampere, BioMediTech, BMT FM5, BioMediTech, Tampere University, Tampere University Hospital, Tampere University, University of Tampere, Adult Stem Cell Research Group
Contributors: Rebelo Calejo, T., Vuorenpää, H., Vuorimaa-Laukkanen, E., Kallio, P., Aalto-Setälä, K., Miettinen, S., Skottman, H., Kellomäki, M., Juuti-Uusitalo, K.
Number of pages: 17
Pages: 327-343
Publication date: 2020
Peer-reviewed: Yes
Early online date: 2019

Publication information

Journal: Acta Biomaterialia
Volume: 101
ISSN (Print): 1742-7061
Original language: English
ASJC Scopus subject areas: Biotechnology, Biomaterials, Biochemistry, Biomedical Engineering, Molecular Biology
Keywords: Breath figures, Co-culture, hiPSC-endothelial cells, hiPSC-RPE, Polylactide
Electronic versions: 

Bibliographical note

INT=BMTE,"Saari, Jaakko"
INT=BMTE,"Vuorenpää, Hanna"
INT=BMTE,"Aalto-Setälä, Katriina"
INT=BMTE,"Miettinen, Susanna"
INT=BMTE,"Skottman, Heli"
INT=BMTE,"Juuti-Uusitalo, Kati"

Source: Scopus
Source ID: 85075520020

Research output: Contribution to journalArticleScientificpeer-review

Membrane-Dependent Binding and Entry Mechanism of Dopamine into Its Receptor

Synaptic neurotransmission has recently been proposed to function via either a membrane-independent or a membrane-dependent mechanism, depending on the neurotransmitter type. In the membrane-dependent mechanism, amphipathic neurotransmitters first partition to the lipid headgroup region and then diffuse along the membrane plane to their membrane-buried receptors. However, to date, this mechanism has not been demonstrated for any neurotransmitter-receptor complex. Here, we combined isothermal calorimetry measurements with a diverse set of molecular dynamics simulation methods to investigate the partitioning of an amphipathic neurotransmitter (dopamine) and the mechanism of its entry into the ligand-binding site. Our results show that the binding of dopamine to its receptor is consistent with the membrane-dependent binding and entry mechanism. Both experimental and simulation results showed that dopamine favors binding to lipid membranes especially in the headgroup region. Moreover, our simulations revealed a ligand-entry pathway from the membrane to the binding site. This pathway passes through a lateral gate between transmembrane alpha-helices 5 and 6 on the membrane-facing side of the protein. All in all, our results demonstrate that dopamine binds to its receptor by a membrane-dependent mechanism, and this is complemented by the more traditional binding mechanism directly through the aqueous phase. The results suggest that the membrane-dependent mechanism is common in other synaptic receptors, too.

General information

Publication status: E-pub ahead of print
MoE publication type: A1 Journal article-refereed
Organisations: Physics, Department of Physics, Physics, University of Helsinki, Biochemistry Center, Universitat Heidelberg, Computational Physics Laboratory, Uniwersytet Jagiellonski w Krakowie, Institute of Biomedicine, Turun Yliopisto/Turun Biomateriaalikeskus, University of Eastern Finland, Turku University Hospital, Center for Biomembrane Physics, MEMPHYS
Contributors: Lolicato, F., Juhola, H., Zak, A., Postila, P. A., Saukko, A., Rissanen, S., Enkavi, G., Vattulainen, I., Kepczynski, M., Róg, T.
Publication date: 2020
Peer-reviewed: Yes

Publication information

Journal: ACS Chemical Neuroscience
ISSN (Print): 1948-7193
Original language: English
ASJC Scopus subject areas: Biochemistry, Physiology, Cognitive Neuroscience, Cell Biology
Keywords: ligand entry pathway prediction, lipid membrane, molecular dynamics, random acceleration molecular dynamics, synaptic neurotransmission, umbrella sampling
Source: Scopus
Source ID: 85087135930

Research output: Contribution to journalArticleScientificpeer-review

Multiphoton microscopy of the dermoepidermal junction and automated identification of dysplastic tissues with deep learning

Histopathological image analysis performed by a trained expert is currently regarded as the gold-standard for the diagnostics of many pathologies, including cancers. However, such approaches are laborious, time consuming and contain a risk for bias or human error. There is thus a clear need for faster, less intrusive and more accurate diagnostic solutions, requiring also minimal human intervention. Multiphoton microscopy (MPM) can alleviate some of the drawbacks specific to traditional histopathology by exploiting various endogenous optical signals to provide virtual biopsies that reflect the architecture and composition of tissues, both in-vivo or ex-vivo. Here we show that MPM imaging of the dermoepidermal junction (DEJ) in unstained fixed tissues provides useful cues for a histopathologist to identify the onset of non-melanoma skin cancers. Furthermore, we show that MPM images collected on the DEJ, besides being easy to interpret by a trained specialist, can be automatically classified into healthy and dysplastic classes with high precision using a Deep Learning method and existing pre-trained convolutional neural networks. Our results suggest that deep learning enhanced MPM for in-vivo skin cancer screening could facilitate timely diagnosis and intervention, enabling thus more optimal therapeutic approaches.

General information

Publication status: Published
MoE publication type: A1 Journal article-refereed
Organisations: Physics, Research group: Nonlinear Optics, University Politehnica of Bucharest, Carol Davila University of Medicine and Pharmacy
Contributors: Huttunen, M. J., Hristu, R., Dumitru, A., Floroiu, I., Costache, M., Stanciu, S. G.
Number of pages: 14
Pages: 186-199
Publication date: 2020
Peer-reviewed: Yes

Publication information

Journal: Biomedical Optics Express
Volume: 11
Issue number: 1
ISSN (Print): 2156-7085
Original language: English
ASJC Scopus subject areas: Biotechnology, Atomic and Molecular Physics, and Optics
Source: Scopus
Source ID: 85078941474

Research output: Contribution to journalArticleScientificpeer-review

Pulmonary Surfactant Lipid Reorganization Induced by the Adsorption of the Oligomeric Surfactant Protein B Complex

Surfactant protein B (SP-B) is essential in transferring surface-active phospholipids from membrane-based surfactant complexes into the alveolar air–liquid interface. This allows maintaining the mechanical stability of the surfactant film under high pressure at the end of expiration; therefore, SP-B is crucial in lung function. Despite its necessity, the structure and the mechanism of lipid transfer by SP-B have remained poorly characterized. Earlier, we proposed higher-order oligomerization of SP-B into ring-like supramolecular assemblies. In the present work, we used coarse-grained molecular dynamics simulations to elucidate how the ring-like oligomeric structure of SP-B determines its membrane binding and lipid transfer. In particular, we explored how SP-B interacts with specific surfactant lipids, and how consequently SP-B reorganizes its lipid environment to modulate the pulmonary surfactant structure and function. Based on these studies, there are specific lipid–protein interactions leading to perturbation and reorganization of pulmonary surfactant layers. Especially, we found compelling evidence that anionic phospholipids and cholesterol are needed or even crucial in the membrane binding and lipid transfer function of SP-B. Also, on the basis of the simulations, larger oligomers of SP-B catalyze lipid transfer between adjacent surfactant layers. Better understanding of the molecular mechanism of SP-B will help in the design of therapeutic SP-B-based preparations and novel treatments for fatal respiratory complications, such as the acute respiratory distress syndrome.

General information

Publication status: Published
MoE publication type: A1 Journal article-refereed
Organisations: Physics, Research group: Biological Physics and Soft Matter, University of Helsinki, Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Universidad Complutense de Madrid, Research Institut “Hospital 2 de Octubre (imas12)”, MEMPHYS
Contributors: Liekkinen, J., Enkavi, G., Javanainen, M., Olmeda, B., Pérez-Gil, J., Vattulainen, I.
Number of pages: 18
Pages: 3251-3268
Publication date: 2020
Peer-reviewed: Yes

Publication information

Journal: JOURNAL OF MOLECULAR BIOLOGY
Volume: 432
Issue number: 10
ISSN (Print): 0022-2836
Original language: English
ASJC Scopus subject areas: Structural Biology, Molecular Biology
Keywords: molecular dynamics simulation, protein–lipid interactions, pulmonary surfactant, SP-B

Bibliographical note

EXT="Enkavi, Giray"

Source: Scopus
Source ID: 85082856561

Research output: Contribution to journalArticleScientificpeer-review

Surface Stabilization and Dissolution Rate Improvement of Amorphous Compacts with Thin Polymer Coatings: Can We Have It All?

The distinction between surface and bulk crystallization of amorphous pharmaceuticals, as well as the importance of surface crystallization for pharmaceutical performance, is becoming increasingly evident. An emerging strategy in stabilizing the amorphous drug form is to utilize thin coatings at the surface. While the physical stability of systems coated with pharmaceutical polymers has recently been studied, the effect on dissolution performance as a function of storage time, as a further necessary step toward the success of these formulations, has not been previously studied. Furthermore, the effect of coating thickness has not been elucidated. This study investigated the effect of these polymer-coating parameters on the interplay between amorphous surface crystallization and drug dissolution for the first time. The study utilized simple tablet-like coated dosage forms, comprising a continuous amorphous drug core and thin polymer coating (hundreds of nanometers to a micrometer thick). Monitoring included analysis of both the solid-state of the model drug (with SEM, XRD, and ATR FTIR spectroscopy) and dissolution performance (and associated morphology and solid-state changes) after different storage times. Stabilization of the amorphous form (dependent on the coating thickness) and maintenance of early-stage intrinsic dissolution rates characteristic for the unaged amorphous drug were achieved. However, dissolution in the latter stages was likely inhibited by the presence of a polymer at the surface. Overall, this study introduced a versatile coated system for studying the dissolution of thin-coated amorphous dosage forms suitable for different drugs and coating agents. It demonstrated the importance of multiple factors that need to be taken into consideration when aiming to achieve both physical stability and improved release during the shelf life of amorphous formulations.

General information

Publication status: Published
MoE publication type: A1 Journal article-refereed
Organisations: Materials Science and Environmental Engineering, Research group: Chemistry & Advanced Materials, University of Helsinki, University of Otago, Danmarks Tekniske Universitet, DTU Informatik
Contributors: Novakovic, D., Peltonen, L., Isomäki, A., Fraser-Miller, S. J., Nielsen, L. H., Laaksonen, T., Strachan, C. J.
Number of pages: 13
Pages: 1248-1260
Publication date: 2020
Peer-reviewed: Yes

Publication information

Journal: Molecular Pharmaceutics
Volume: 17
Issue number: 4
ISSN (Print): 1543-8384
Original language: English
ASJC Scopus subject areas: Molecular Medicine, Pharmaceutical Science, Drug Discovery
Keywords: amorphous, dissolution, indomethacin, polymer coating, surface crystallization
Source: Scopus
Source ID: 85080145435

Research output: Contribution to journalArticleScientificpeer-review

The Na,K-ATPase acts upstream of phosphoinositide PI(4,5)P2 facilitating unconventional secretion of Fibroblast Growth Factor 2

FGF2 is a tumor cell survival factor that is exported from cells by an ER/Golgi-independent secretory pathway. This unconventional mechanism of protein secretion is based on direct translocation of FGF2 across the plasma membrane. The Na,K-ATPase has previously been shown to play a role in this process, however, the underlying mechanism has remained elusive. Here, we define structural elements that are critical for a direct physical interaction between FGF2 and the α1 subunit of the Na,K-ATPase. In intact cells, corresponding FGF2 mutant forms were impaired regarding both recruitment at the inner plasma membrane leaflet and secretion. Ouabain, a drug that inhibits both the Na,K-ATPase and FGF2 secretion, was found to impair the interaction of FGF2 with the Na,K-ATPase in cells. Our findings reveal the Na,K-ATPase as the initial recruitment factor for FGF2 at the inner plasma membrane leaflet being required for efficient membrane translocation of FGF2 to cell surfaces.

General information

Publication status: Published
MoE publication type: A1 Journal article-refereed
Organisations: Research group: Biological Physics and Soft Matter, Physics, Universitat Heidelberg, Freie Universität Berlin, University of Helsinki
Contributors: Legrand, C., Saleppico, R., Sticht, J., Lolicato, F., Müller, H. M., Wegehingel, S., Dimou, E., Steringer, J. P., Ewers, H., Vattulainen, I., Freund, C., Nickel, W.
Number of pages: 16
Publication date: 2020
Peer-reviewed: Yes

Publication information

Journal: Communications biology
Volume: 3
Issue number: 1
Article number: 141
ISSN (Print): 2399-3642
Original language: English
ASJC Scopus subject areas: Biochemistry, Genetics and Molecular Biology(all), Agricultural and Biological Sciences(all), Medicine (miscellaneous)
Source: Scopus
Source ID: 85082407227

Research output: Contribution to journalArticleScientificpeer-review

Tidal breathing flow profiles during sleep in wheezing children measured by impedance pneumography

For the first time, impedance pneumography (IP) enables a continuous analysis of the tidal breathing flow volume (TBFV), overnight. We studied how corticosteroid inhalation treatments, sleep stage, and time from sleep onset modify the nocturnal TBFV profiles of children. Seventy children, 1–5 years old and with recurrent wheezing, underwent three, full-night TBFVs recordings at home, using IP. The first recorded one week before ending a 3-months inhaled corticosteroids treatment, and remaining two, 2 and 4 weeks after treatment. TBFV profiles were grouped by hour from sleep onset and estimated sleep stage. Compared with on-medication, the off-medication profiles showed lower volume at exhalation peak flow, earlier interruption of expiration, and less convex middle expiration. The differences in the first two features were significant during non-rapid eye movement (NREM), and the differences in the third were more prominent during REM after 4 h of sleep. These combinations of TBFV features, sleep phase, and sleep time potentially indicate airflow limitation in young children.

General information

Publication status: Published
MoE publication type: A1 Journal article-refereed
Organisations: Research group: Physiological Measurement Systems and Methods Group, BioMediTech, Revenio Research Ltd., Tampere University Hospital
Contributors: Gracia-Tabuenca, J., Seppä, V., Jauhiainen, M., Paassilta, M., Viik, J., Karjalainen, J.
Publication date: 2020
Peer-reviewed: Yes
Early online date: 1 Oct 2019

Publication information

Journal: Respiratory Physiology and Neurobiology
Volume: 271
Article number: 103312
ISSN (Print): 1569-9048
Original language: English
ASJC Scopus subject areas: Neuroscience(all), Physiology, Pulmonary and Respiratory Medicine
Keywords: Impedance pneumography, Lung function, Tidal breathing, Wheezing children

Bibliographical note

EXT="Seppä, Ville-Pekka"
dupl=51710383

Source: Scopus
Source ID: 85073034217

Research output: Contribution to journalArticleScientificpeer-review

Toward Rigorous Materials Production: New Approach Methodologies Have Extensive Potential to Improve Current Safety Assessment Practices

Advanced material development, including at the nanoscale, comprises costly and complex challenges coupled to ensuring human and environmental safety. Governmental agencies regulating safety have announced interest toward acceptance of safety data generated under the collective term New Approach Methodologies (NAMs), as such technologies/approaches offer marked potential to progress the integration of safety testing measures during innovation from idea to product launch of nanomaterials. Divided in overall eight main categories, searchable databases for grouping and read across purposes, exposure assessment and modeling, in silico modeling of physicochemical structure and hazard data, in vitro high-throughput and high-content screening assays, dose-response assessments and modeling, analyses of biological processes and toxicity pathways, kinetics and dose extrapolation, consideration of relevant exposure levels and biomarker endpoints typify such useful NAMs. Their application generally agrees with articulated stakeholder needs for improvement of safety testing procedures. They further fit for inclusion and add value in nanomaterials risk assessment tools. Overall 37 of 50 evaluated NAMs and tiered workflows applying NAMs are recommended for considering safer-by-design innovation, including guidance to the selection of specific NAMs in the eight categories. An innovation funnel enriched with safety methods is ultimately proposed under the central aim of promoting rigorous nanomaterials innovation.

General information

Publication status: Published
MoE publication type: A2 Review article in a scientific journal
Organisations: Physics, Research group: The Instrumentation, Emissions, and Atmospheric Aerosols Group, Karolinska Institutet, Misvik Biology, National Institute for Public Health and the Environment, TNO, STL Group, Gaiker, University of Helsinki Institute of Biotechnology, National Institute for Occupational Health, University of Witwatersrand, National Research Center for the Work Environment, Health Canada, Tampere University
Contributors: Nymark, P., Bakker, M., Dekkers, S., Franken, R., Fransman, W., García-Bilbao, A., Greco, D., Gulumian, M., Hadrup, N., Halappanavar, S., Hongisto, V., Hougaard, K. S., Jensen, K. A., Kohonen, P., Koivisto, A. J., Dal Maso, M., Oosterwijk, T., Poikkimäki, M., Rodriguez-Llopis, I., Stierum, R., Sørli, J. B., Grafström, R.
Number of pages: 13
Publication date: 2020
Peer-reviewed: Yes

Publication information

Journal: Small
Volume: 16
Issue number: 6
Article number: 1904749
ISSN (Print): 1613-6810
Original language: English
ASJC Scopus subject areas: Biotechnology, Biomaterials, Chemistry(all), Materials Science(all)
Keywords: human risk assessment tools, nanomaterials, new approach methodologies, safer by design, Stage-Gate innovation funnel

Bibliographical note

INT=bmte, "Greco, Dario"
dupl=51711359

Source: Scopus
Source ID: 85077876153

Research output: Contribution to journalReview ArticleScientificpeer-review

Enhanced Population Control in a Synthetic Bacterial Consortium by Interconnected Carbon Cross-Feeding

Engineered microbial consortia can provide several advantages over monocultures in terms of utilization of mixed substrates, resistance to perturbations, and division of labor in complex tasks. However, maintaining stability, reproducibility, and control over population levels in variable conditions can be challenging in multispecies cultures. In our study, we modeled and constructed a synthetic symbiotic consortium with a genetically encoded carbon cross-feeding system. The system is based on strains of Escherichia coli and Acinetobacter baylyi ADP1, both engineered to be incapable of growing on glucose on their own. In a culture supplemented with glucose as the sole carbon source, growth of the two strains is afforded by the exchange of gluconate and acetate, resulting in inherent control over carbon availability and population balance. We investigated the system robustness in terms of stability and population control under different inoculation ratios, substrate concentrations, and cultivation scales, both experimentally and by modeling. To illustrate how the system might facilitate division of genetic circuits among synthetic microbial consortia, a green fluorescent protein sensitive to pH and a slowly maturing red fluorescent protein were expressed in the consortium as measures of a circuit's susceptibility to external and internal variability, respectively. The symbiotic consortium maintained stable and linear growth and circuit performance regardless of the initial substrate concentration or inoculation ratio. The developed cross-feeding system provides simple and reliable means for population control without expression of non-native elements or external inducer addition, being potentially exploitable in consortia applications involving precisely defined cell tasks or division of labor.

General information

Publication status: Published
MoE publication type: A1 Journal article-refereed
Organisations: Materials Science and Environmental Engineering, Research group: Bio- and Circular Economy
Contributors: Losoi, P. S., Santala, V. P., Santala, S. M.
Number of pages: 9
Pages: 2642-2650
Publication date: 20 Dec 2019
Peer-reviewed: Yes

Publication information

Journal: ACS Synthetic Biology
Volume: 8
Issue number: 12
ISSN (Print): 2161-5063
Ratings: 
  • Scopus rating (2019): CiteScore 7.7 SJR 2.029 SNIP 0.989
Original language: English
ASJC Scopus subject areas: Biomedical Engineering, Biochemistry, Genetics and Molecular Biology (miscellaneous)
Keywords: consortium modeling, cross-feeding, population control, synthetic consortium
Source: Scopus
Source ID: 85075600278

Research output: Contribution to journalArticleScientificpeer-review

Data-driven multiscale modeling reveals the role of metabolic coupling for the spatio-temporal growth dynamics of yeast colonies

Background: Multicellular entities like mammalian tissues or microbial biofilms typically exhibit complex spatial arrangements that are adapted to their specific functions or environments. These structures result from intercellular signaling as well as from the interaction with the environment that allow cells of the same genotype to differentiate into well-organized communities of diversified cells. Despite its importance, our understanding how this cell-cell and metabolic coupling lead to functionally optimized structures is still limited. Results: Here, we present a data-driven spatial framework to computationally investigate the development of yeast colonies as such a multicellular structure in dependence on metabolic capacity. For this purpose, we first developed and parameterized a dynamic cell state and growth model for yeast based on on experimental data from homogeneous liquid media conditions. The inferred model is subsequently used in a spatially coarse-grained model for colony development to investigate the effect of metabolic coupling by calibrating spatial parameters from experimental time-course data of colony growth using state-of-the-art statistical techniques for model uncertainty and parameter estimations. The model is finally validated by independent experimental data of an alternative yeast strain with distinct metabolic characteristics and illustrates the impact of metabolic coupling for structure formation. Conclusions: We introduce a novel model for yeast colony formation, present a statistical methodology for model calibration in a data-driven manner, and demonstrate how the established model can be used to generate predictions across scales by validation against independent measurements of genetically distinct yeast strains.

General information

Publication status: Published
MoE publication type: A1 Journal article-refereed
Organisations: BioMediTech, Research group: Computational Systems Biology, Aalto University, University of Washington Seattle, Utah State University, Institute for Systems Biology, Seattle, Washington, USA, University of Luxembourg, University of California San Diego, Pacific Northwest Research Institute
Contributors: Intosalmi, J., Scott, A. C., Hays, M., Flann, N., Yli-Harja, O., Lähdesmäki, H., Dudley, A. M., Skupin, A.
Number of pages: 13
Publication date: 19 Dec 2019
Peer-reviewed: Yes

Publication information

Journal: BMC Molecular and Cell Biology
Volume: 20
Issue number: 1
Article number: 59
ISSN (Print): 2661-8850
Ratings: 
  • Scopus rating (2019): CiteScore 0.1
Original language: English
ASJC Scopus subject areas: Molecular Biology, Cell Biology
Keywords: Bayesian optimization, Diauxic shift, Markov chain Monte Carlo, Metabolic coupling, Multicellular systems, Multiscale modeling, Yeast colony
Electronic versions: 

Bibliographical note

EXT="Intosalmi, Jukka"
EXT="Lähdesmäki, Harri"

Source: Scopus
Source ID: 85076968105

Research output: Contribution to journalArticleScientificpeer-review

Ensuring Quality Standards and Reproducible Research for Data Analysis Services in Oncology: A Cooperative Service Model

Modern molecular high-throughput devices, e.g., next-generation sequencing, have transformed medical research. Resulting data sets are usually high-dimensional on a genomic-scale providing multi-factorial information from intertwined molecular and cellular activities of genes and their products. This genomics-revolution installed precision medicine offering breathtaking opportunities for patient's diagnosis and treatment. However, due to the speed of these developments the quality standards of the involved data analyses are lacking behind, as exemplified by the infamous Duke Saga. In this paper, we argue in favor of a two-stage cooperative serve model that couples data generation and data analysis in the most beneficial way from the perspective of a patient to ensure data analysis quality standards including reproducible research.

General information

Publication status: Published
MoE publication type: A1 Journal article-refereed
Organisations: Research group: Predictive Society and Data Analytics (PSDA), Computing Sciences, BioMediTech, University of Applied Sciences Upper Austria, School of Management, Nankai University, Institute for Systems Biology, Seattle, Washington, USA
Contributors: Emmert-Streib, F., Dehmer, M., Yli-Harja, O.
Publication date: 17 Dec 2019
Peer-reviewed: Yes

Publication information

Journal: Frontiers in cell and developmental biology
Volume: 7
Article number: 349
ISSN (Print): 2296-634X
Ratings: 
  • Scopus rating (2019): CiteScore 5.8 SJR 2.572 SNIP 1.288
Original language: English
ASJC Scopus subject areas: Developmental Biology, Cell Biology
Keywords: biostatistics, computational biology, data science, genomics, oncology, precision medicine, reproducible research
Electronic versions: 
Source: Scopus
Source ID: 85077340569

Research output: Contribution to journalArticleScientificpeer-review

Environmental monitoring with distributed mesh networks: An overview and practical implementation perspective for urban scenario

Almost inevitable climate change and increasing pollution levels around the world are the most significant drivers for the environmental monitoring evolution. Recent activities in the field of wireless sensor networks have made tremendous progress concerning conventional centralized sensor networks known for decades. However, most systems developed today still face challenges while estimating the trade-off between their flexibility and security. In this work, we provide an overview of the environmental monitoring strategies and applications. We conclude that wireless sensor networks of tomorrow would mostly have a distributed nature. Furthermore, we present the results of the developed secure distributed monitoring framework from both hardware and software perspectives. The developed mechanisms provide an ability for sensors to communicate in both infrastructure and mesh modes. The system allows each sensor node to act as a relay, which increases the system failure resistance and improves the scalability. Moreover, we employ an authentication mechanism to ensure the transparent migration of the nodes between different network segments while maintaining a high level of system security. Finally, we report on the real-life deployment results.

General information

Publication status: Published
MoE publication type: A1 Journal article-refereed
Organisations: Electrical Engineering, Research group: Emerging Technologies for Nano-Bio-Info-Cogno, St. Petersburg State University of Aerospace Instrumentation, ITMO University, Brno University of Technology, National Research University Higher School of Economics
Contributors: Ometov, A., Bezzateev, S., Voloshina, N., Masek, P., Komarov, M.
Number of pages: 19
Publication date: 2 Dec 2019
Peer-reviewed: Yes

Publication information

Journal: Sensors (Switzerland)
Volume: 19
Issue number: 24
Article number: 5548
ISSN (Print): 1424-8220
Ratings: 
  • Scopus rating (2019): CiteScore 5 SJR 0.653 SNIP 1.586
Original language: English
ASJC Scopus subject areas: Analytical Chemistry, Biochemistry, Atomic and Molecular Physics, and Optics, Instrumentation, Electrical and Electronic Engineering
Keywords: Authentication mechanism, Distributed systems, Environmental monitoring, Security, Wireless sensor network
Electronic versions: 

Bibliographical note

EXT="Komarov, Mikhail"

Source: Scopus
Source ID: 85076920114

Research output: Contribution to journalArticleScientificpeer-review

Key drivers of cloud response to surface-active organics

Aerosol-cloud interactions constitute the largest source of uncertainty in global radiative forcing estimates, hampering our understanding of climate evolution. Recent empirical evidence suggests surface tension depression by organic aerosol to significantly influence the formation of cloud droplets, and hence cloud optical properties. In climate models, however, surface tension of water is generally assumed when predicting cloud droplet concentrations. Here we show that the sensitivity of cloud microphysics, optical properties and shortwave radiative effects to the surface phase are dictated by an interplay between the aerosol particle size distribution, composition, water availability and atmospheric dynamics. We demonstrate that accounting for the surface phase becomes essential in clean environments in which ultrafine particle sources are present. Through detailed sensitivity analysis, quantitative constraints on the key drivers – aerosol particle number concentrations, organic fraction and fixed updraft velocity – are derived for instances of significant cloud microphysical susceptibilities to the surface phase.

General information

Publication status: Published
MoE publication type: A1 Journal article-refereed
Organisations: Stockholm University, University of Exeter, University of California, Riverside, Lawrence Berkeley National Laboratory, University of Manchester
Contributors: Lowe, S. J., Partridge, D. G., Davies, J. F., Wilson, K. R., Topping, D., Riipinen, I.
Number of pages: 12
Publication date: 1 Dec 2019
Peer-reviewed: Yes

Publication information

Journal: Nature Communications
Volume: 10
Issue number: 1
Article number: 5214
ISSN (Print): 2041-1723
Ratings: 
  • Scopus rating (2019): SJR 5.569 SNIP 2.847
Original language: English
ASJC Scopus subject areas: Chemistry(all), Biochemistry, Genetics and Molecular Biology(all), Physics and Astronomy(all)
Electronic versions: 

Bibliographical note

INT=phys,"Riipinen, I."

Source: Scopus
Source ID: 85075163902

Research output: Contribution to journalArticleScientificpeer-review

Programmable responsive hydrogels inspired by classical conditioning algorithm

Living systems have inspired research on non-biological dynamic materials and systems chemistry to mimic specific complex biological functions. Upon pursuing ever more complex life-inspired non-biological systems, mimicking even the most elementary aspects of learning is a grand challenge. We demonstrate a programmable hydrogel-based model system, whose behaviour is inspired by associative learning, i.e., conditioning, which is among the simplest forms of learning. Algorithmically, associative learning minimally requires responsivity to two different stimuli and a memory element. Herein, nanoparticles form the memory element, where a photoacid-driven pH-change leads to their chain-like assembly with a modified spectral behaviour. On associating selected light irradiation with heating, the gel starts to melt upon the irradiation, originally a neutral stimulus. A logic diagram describes such an evolution of the material response. Coupled chemical reactions drive the system out-of-equilibrium, allowing forgetting and memory recovery. The findings encourage to search non-biological materials towards associative and dynamic properties.

General information

Publication status: Published
MoE publication type: A1 Journal article-refereed
Organisations: Materials Science and Environmental Engineering, Research group: Chemistry & Advanced Materials, Aalto University
Contributors: Zhang, H., Zeng, H., Priimägi, A., Ikkala, O.
Publication date: 1 Dec 2019
Peer-reviewed: Yes

Publication information

Journal: Nature Communications
Volume: 10
Issue number: 1
Article number: 3267
ISSN (Print): 2041-1723
Ratings: 
  • Scopus rating (2019): SJR 5.569 SNIP 2.847
Original language: English
ASJC Scopus subject areas: Chemistry(all), Biochemistry, Genetics and Molecular Biology(all), Physics and Astronomy(all)
Electronic versions: 
Source: Scopus
Source ID: 85070331406

Research output: Contribution to journalArticleScientificpeer-review

The role of highly oxygenated organic molecules in the Boreal aerosol-cloud-climate system

Over Boreal regions, monoterpenes emitted from the forest are the main precursors for secondary organic aerosol (SOA) formation and the primary driver of the growth of new aerosol particles to climatically important cloud condensation nuclei (CCN). Autoxidation of monoterpenes leads to rapid formation of Highly Oxygenated organic Molecules (HOM). We have developed the first model with near-explicit representation of atmospheric new particle formation (NPF) and HOM formation. The model can reproduce the observed NPF, HOM gas-phase composition and SOA formation over the Boreal forest. During the spring, HOM SOA formation increases the CCN concentration by ~10 % and causes a direct aerosol radiative forcing of −0.10 W/m2. In contrast, NPF reduces the number of CCN at updraft velocities < 0.2 m/s, and causes a direct aerosol radiative forcing of +0.15 W/m2. Hence, while HOM SOA contributes to climate cooling, NPF can result in climate warming over the Boreal forest.

General information

Publication status: Published
MoE publication type: A1 Journal article-refereed
Organisations: Lunds Universitet / Lunds Tekniska Högskola, University of Helsinki, Stockholm University, Aarhus Universitet, Ita-Suomen yliopisto, University of Oulu, Aerodyne Research Inc., University of Salzburg
Contributors: Roldin, P., Ehn, M., Kurtén, T., Olenius, T., Rissanen, M. P., Sarnela, N., Elm, J., Rantala, P., Hao, L., Hyttinen, N., Heikkinen, L., Worsnop, D. R., Pichelstorfer, L., Xavier, C., Clusius, P., Öström, E., Petäjä, T., Kulmala, M., Vehkamäki, H., Virtanen, A., Riipinen, I., Boy, M.
Publication date: 1 Dec 2019
Peer-reviewed: Yes

Publication information

Journal: Nature Communications
Volume: 10
Issue number: 1
Article number: 4370
ISSN (Print): 2041-1723
Ratings: 
  • Scopus rating (2019): SJR 5.569 SNIP 2.847
Original language: English
ASJC Scopus subject areas: Chemistry(all), Biochemistry, Genetics and Molecular Biology(all), Physics and Astronomy(all)
Source: Scopus
Source ID: 85072652175

Research output: Contribution to journalArticleScientificpeer-review

Transcription closed and open complex formation coordinate expression of genes with a shared promoter region

Many genes are spaced closely, allowing coordination without explicit control through shared regulatory elements and molecular interactions. We study the dynamics of a stochastic model of a gene-pair in a head-to-head configuration, sharing promoter elements, which accounts for the rate-limiting steps in transcription initiation. We find that only in specific regions of the parameter space of the rate-limiting steps is orderly coexpression exhibited, suggesting that successful cooperation between closely spaced genes requires the coevolution of compatible rate-limiting step configuration. The model predictions are validated using in vivo single-cell, single-RNA measurements of the dynamics of pairs of genes sharing promoter elements. Our results suggest that, in E. coli, the kinetics of the rate-limiting steps in active transcription can play a central role in shaping the dynamics of gene-pairs sharing promoter elements.

General information

Publication status: Published
MoE publication type: A1 Journal article-refereed
Organisations: BioMediTech, Research group: Laboratory of Biosystem Dynamics-LBD
Contributors: Häkkinen, A., Oliveira, S. M., Neeli-Venkata, R., Ribeiro, A. S.
Number of pages: 11
Publication date: 1 Dec 2019
Peer-reviewed: Yes

Publication information

Journal: Journal of the Royal Society Interface
Volume: 16
Issue number: 161
Article number: 20190507
ISSN (Print): 1742-5689
Ratings: 
  • Scopus rating (2019): SJR 1.694 SNIP 1.411
Original language: English
ASJC Scopus subject areas: Biotechnology, Biophysics, Bioengineering, Biomaterials, Biochemistry, Biomedical Engineering
Keywords: Bidirectional promoter, Gene expression noise, Transcription
Source: Scopus
Source ID: 85076351347

Research output: Contribution to journalArticleScientificpeer-review

Spectral object recognition in hyperspectral holography with complex-domain denoising

In this paper, we have applied a recently developed complex-domain hyperspectral denoiser for the object recognition task, which is performed by the correlation analysis of investigated objects’ spectra with the fingerprint spectra from the same object. Extensive experiments carried out on noisy data from digital hyperspectral holography demonstrate a significant enhancement of the recognition accuracy of signals masked by noise, when the advanced noise suppression is applied.

General information

Publication status: Published
MoE publication type: A1 Journal article-refereed
Organisations: Computing Sciences, Research group: Computational Imaging-CI, ITMO University, University of Ulm Medical Center, University of Stuttgart
Contributors: Shevkunov, I., Katkovnik, V., Claus, D., Pedrini, G., Petrov, N. V., Egiazarian, K.
Number of pages: 10
Publication date: 26 Nov 2019
Peer-reviewed: Yes

Publication information

Journal: Sensors (Switzerland)
Volume: 19
Issue number: 23
Article number: 5188
ISSN (Print): 1424-8220
Ratings: 
  • Scopus rating (2019): CiteScore 5 SJR 0.653 SNIP 1.586
Original language: English
ASJC Scopus subject areas: Analytical Chemistry, Biochemistry, Atomic and Molecular Physics, and Optics, Instrumentation, Electrical and Electronic Engineering
Keywords: Hyperspectral imaging, Noise filtering, Noise in imaging systems, Singular value decomposition, Sparse representation
Electronic versions: 
Source: Scopus
Source ID: 85075511855

Research output: Contribution to journalArticleScientificpeer-review

Phosphorylation of NFATC1 at PIM1 target sites is essential for its ability to promote prostate cancer cell migration and invasion

Background: Progression of prostate cancer from benign local tumors to metastatic carcinomas is a multistep process. Here we have investigated the signaling pathways that support migration and invasion of prostate cancer cells, focusing on the role of the NFATC1 transcription factor and its post-translational modifications. We have previously identified NFATC1 as a substrate for the PIM1 kinase and shown that PIM1-dependent phosphorylation increases NFATC1 activity without affecting its subcellular localization. Both PIM kinases and NFATC1 have been reported to promote cancer cell migration, invasion and angiogenesis, but it has remained unclear whether the effects of NFATC1 are phosphorylation-dependent and which downstream targets are involved. Methods: We used mass spectrometry to identify PIM1 phosphorylation target sites in NFATC1, and analysed their functional roles in three prostate cancer cell lines by comparing phosphodeficient mutants to wild-type NFATC1. We used luciferase assays to determine effects of phosphorylation on NFAT-dependent transcriptional activity, and migration and invasion assays to evaluate effects on cell motility. We also performed a microarray analysis to identify novel PIM1/NFATC1 targets, and validated one of them with both cellular expression analyses and in silico in clinical prostate cancer data sets. Results: Here we have identified ten PIM1 target sites in NFATC1 and found that prevention of their phosphorylation significantly decreases the transcriptional activity as well as the pro-migratory and pro-invasive effects of NFATC1 in prostate cancer cells. We observed that also PIM2 and PIM3 can phosphorylate NFATC1, and identified several novel putative PIM1/NFATC1 target genes. These include the ITGA5 integrin, which is differentially expressed in the presence of wild-type versus phosphorylation-deficient NFATC1, and which is coexpressed with PIM1 and NFATC1 in clinical prostate cancer specimens. Conclusions: Based on our data, phosphorylation of PIM1 target sites stimulates NFATC1 activity and enhances its ability to promote prostate cancer cell migration and invasion. Therefore, inhibition of the interplay between PIM kinases and NFATC1 may have therapeutic implications for patients with metastatic forms of cancer.

General information

Publication status: Published
MoE publication type: A1 Journal article-refereed
Organisations: BioMediTech, Turun yliopisto, Tampere University, University of Eastern Finland, Helsinki University, Fimlab Laboratories
Contributors: Eerola, S. K., Santio, N. M., Rinne, S., Kouvonen, P., Corthals, G. L., Scaravilli, M., Scala, G., Serra, A., Greco, D., Ruusuvuori, P., Latonen, L., Rainio, E. M., Visakorpi, T., Koskinen, P. J.
Publication date: 15 Nov 2019
Peer-reviewed: Yes

Publication information

Journal: CELL COMMUNICATION AND SIGNALING
Volume: 17
Issue number: 1
Article number: 148
ISSN (Print): 1478-811X
Ratings: 
  • Scopus rating (2019): CiteScore 4.6 SJR 1.762 SNIP 1.1
Original language: English
ASJC Scopus subject areas: Biochemistry, Molecular Biology, Cell Biology
Keywords: Cell motility, Metastatic carcinoma, NFATC1, PIM kinases, Prostate cancer
Electronic versions: 
Source: Scopus
Source ID: 85075057648

Research output: Contribution to journalArticleScientificpeer-review

Statistical evaluation of barkhausen noise testing (BNT) for ground samples

Barkhausen noise testing (BNT) is a nondestructive method for investigating many properties of ferromagnetic materials. The most common application is the monitoring of grinding burns caused by introducing locally high temperatures while grinding. Other features, such as microstructure, residual stress changes, hardening depth, and so forth, can be monitored as well. Nevertheless, because BNT is a method based on a complex magnetoelectric phenomenon, it is not yet standardized. Therefore, there is a need to study the traceability and stability of the measurement method. This study aimed to carry out a statistical analysis of ferromagnetic samples after grinding processes by the use of BNT. The first part of the experiment was to grind samples in different facilities (Sweden and Finland) with similar grinding parameters, different grinding wheels, and different hardness values. The second part was to evaluate measured BNT parameters to determine significant factors affecting BNT signal value. The measurement data from the samples were divided into two different batches according to where they were manufactured. Both grinding batches contained measurement data from three different participants. The main feature for calculation was the root-mean-square (RMS) value. The first processing step was to normalize the RMS values for all the measurements. A standard analysis of variance (ANOVA) was applied for the normalized dataset. The ANOVA showed that the grinding parameters had a significant impact on the BNT signal value, while the other investigated factors (e.g., participant) were negligible. The reasons for this are discussed at the end of the paper.

General information

Publication status: Published
MoE publication type: A1 Journal article-refereed
Organisations: Materials Science and Environmental Engineering, Univ of Oulu, Schlumpf Scandinavia AB, Kungliga Tekniska Högskolan KTH
Contributors: Tomkowski, R., Sorsa, A., Santa-Aho, S., Lundin, P., Vippola, M.
Publication date: 1 Nov 2019
Peer-reviewed: Yes

Publication information

Journal: Sensors (Switzerland)
Volume: 19
Issue number: 21
Article number: 4716
ISSN (Print): 1424-8220
Ratings: 
  • Scopus rating (2019): CiteScore 5 SJR 0.653 SNIP 1.586
Original language: English
ASJC Scopus subject areas: Analytical Chemistry, Biochemistry, Atomic and Molecular Physics, and Optics, Instrumentation, Electrical and Electronic Engineering
Keywords: ANOVA, Barkhausen noise testing (BNT), Proficiency test, Uncertainty
Electronic versions: 
Source: Scopus
Source ID: 85074321480

Research output: Contribution to journalArticleScientificpeer-review

Estimating RNA numbers in single cells by RNA fluorescent tagging and flow cytometry

Estimating the statistics of single-cell RNA numbers has become a key source of information on gene expression dynamics. One of the most informative methods of in vivo single-RNA detection is MS2d-GFP tagging. So far, it requires microscopy and laborious semi-manual image analysis, which hampers the amount of collectable data. To overcome this limitation, we present a new methodology for quantifying the mean, standard deviation, and skewness of single-cell distributions of RNA numbers, from flow cytometry data on cells expressing RNA tagged with MS2d-GFP. The quantification method, based on scaling flow-cytometry data from microscopy single-cell data on integer-valued RNA numbers, is shown to readily produce precise, big data on in vivo single-cell distributions of RNA numbers and, thus, can assist in studies of transcription dynamics.

General information

Publication status: Published
MoE publication type: A1 Journal article-refereed
Organisations: Research group: Laboratory of Biosystem Dynamics-LBD, BioMediTech, Boston University
Contributors: Bahrudeen, M. N., Chauhan, V., Palma, C. S., Oliveira, S. M., Kandavalli, V. K., Ribeiro, A. S.
Publication date: 22 Oct 2019
Peer-reviewed: Yes

Publication information

Journal: Journal of Microbiological Methods
Volume: 166
Article number: 105745
ISSN (Print): 0167-7012
Ratings: 
  • Scopus rating (2019): CiteScore 3.2 SJR 0.636 SNIP 0.695
Original language: English
ASJC Scopus subject areas: Microbiology, Molecular Biology, Microbiology (medical)
Keywords: Flow cytometry, MS2d-GFP RNA tagging, Single-cell RNA numbers, Time-lapse microscopy
Electronic versions: 

Bibliographical note

DUPL=50893300

Source: Scopus
Source ID: 85073824125

Research output: Contribution to journalArticleScientificpeer-review

Improved water services cooperation through clarification of rules and roles

Water services face global challenges, many of which are institutional by nature. While technical solutions may suit several situations, institutional frameworks are likely to vary more. On the basis of constructive research approach and new institutional economics we analyze and illustrate water services and the roles of various water sector actors in Finnish water utility setting using the "soccer analogy" by the Nobel Laureate D.C. North: Institutions are the "formal and informal rules of the game" while organizations are the "players". Additionally, we assess the Finnish water governance system and discuss issues of scale and fragmentation and distinguish terms water provision and production. Finally, we elaborate the limitations of the soccer analogy to water services through ownership of the systems. According to the soccer analogy, inclusive institutional development requires skillful players (competent staff), team play (collaboration), proper coaching (education), supporters (citizens, media), managers (policymakers), and referees (authorities). We argue that institutional diversity and player/stakeholder collaboration are the foundation for enhancing good multi-level water governance, and that water management, although fragmented, should be seen as a connector of different sectors. For successful outcomes, scientific results should be communicated to public in more common language.

General information

Publication status: Published
MoE publication type: A1 Journal article-refereed
Organisations: Civil Engineering, Research group: Capacity Development of Water and Environmental Services CADWES
Contributors: Inha, L. M., Katko, T. S., Rajala, R. P.
Publication date: 19 Oct 2019
Peer-reviewed: Yes

Publication information

Journal: Water (Switzerland)
Volume: 11
Issue number: 10
Article number: 2172
ISSN (Print): 2073-4441
Ratings: 
  • Scopus rating (2019): SJR 0.657 SNIP 1.074
Original language: English
ASJC Scopus subject areas: Biochemistry, Geography, Planning and Development, Aquatic Science, Water Science and Technology
Keywords: Good governance, Institutional diversity, Institutions, Rules and roles, Soccer analogy, Stakeholder collaboration
Electronic versions: 
Source: Scopus
Source ID: 85074329077

Research output: Contribution to journalArticleScientificpeer-review

Effects of elevated pressures on the activity of acidophilic bioleaching microorganisms

This study reports effects of elevated pressures on the oxidation of a soluble ferrous iron and low-grade sulphidic ore as little is known about biological iron and sulphur oxidation under these conditions. Pressure effects were studied in a pressurised batch-operated stirred tank reactor using acidophilic enrichment cultures. The oxidation of soluble Fe2+ by enrichment culture dominated by Leptospirillum ferriphilum, Sulfobacillus sp. and Ferrimicrobium acidiphilum increased with increasing pressure induced by technical air to up to +3 bar (0.63 bar PO2) and was inhibited at +7 bar (1.47 bar PO2). Elevated pressures induced by nitrogen (low oxygen partial pressure) were tolerated up to +40 bar. Another enrichment culture dominated by Acidithiobacillus ferrivorans, Sulfobacillus sp. and F. acidiphilum partially oxidised the ore at pressures up to +20 bar induced with air (4.2 bar PO2). This is the first study reporting activity of acidophiles under pressurised conditions in a stirred tank reactor.

General information

Publication status: Published
MoE publication type: A1 Journal article-refereed
Organisations: Materials Science and Environmental Engineering
Contributors: Hajdu-Rahkama, R., Ahoranta, S., Lakaniemi, A., Puhakka, J. A.
Publication date: 15 Oct 2019
Peer-reviewed: Yes

Publication information

Journal: Biochemical Engineering Journal
Volume: 150
Article number: 107286
ISSN (Print): 1369-703X
Ratings: 
  • Scopus rating (2019): CiteScore 6.3 SJR 0.879 SNIP 1.18
Original language: English
ASJC Scopus subject areas: Biotechnology, Bioengineering, Environmental Engineering, Biomedical Engineering
Keywords: Acidophiles, Biooxidation, Iron oxidation, Pressure tolerance, Pressurised stirred tank reactor
Source: Scopus
Source ID: 85070494949

Research output: Contribution to journalArticleScientificpeer-review

Controlled Orientations of Neighboring Tetracene Units by Mixed Self-Assembled Monolayers on Gold Nanoclusters for High-Yield and Long-Lived Triplet Excited States through Singlet Fission

Although tetracene (Tc) is well-known as a good candidate for singlet fission (SF), the number of high-yield and long-lived triplet excited states through SF is extremely limited because of the relative acceleration of the reverse triplet-triplet annihilation (TTA) considering the energy matching between a singlet and two triplet states. Systematic control of electronic interactions between two neighboring units using conventional covalent linkages and molecular assembly methods to optimize these kinetic processes is quite difficult because of the complicated synthesis and random orientations. In this study, we propose a novel supramolecular strategy utilizing mixed self-assembled monolayers (SAMs) with two different chain lengths. Specifically, mixed Tc-SAMs on gold nanoclusters, which are prepared using Tc-modified heterodisulfides with two different chain lengths, attain high-yield SF (ΦSF ≈ 90%) and individual triplet yields (ΦΤ ≈ 160%). The obtained ΦSF is the highest value among Tc derivatives in homogeneous solution to the best of our knowledge.

General information

Publication status: Published
MoE publication type: A1 Journal article-refereed
Organisations: Materials Science and Environmental Engineering, Research group: Chemistry & Advanced Materials, Keio University, Kobe University
Contributors: Saegusa, T., Sakai, H., Nagashima, H., Kobori, Y., Tkachenko, N. V., Hasobe, T.
Number of pages: 8
Pages: 14720-14727
Publication date: 18 Sep 2019
Peer-reviewed: Yes

Publication information

Journal: Journal of the American Chemical Society
Volume: 141
Issue number: 37
ISSN (Print): 0002-7863
Ratings: 
  • Scopus rating (2019): CiteScore 24.8 SJR 6.976 SNIP 2.682
Original language: English
ASJC Scopus subject areas: Catalysis, Chemistry(all), Biochemistry, Colloid and Surface Chemistry
Source: Scopus
Source ID: 85072270985

Research output: Contribution to journalArticleScientificpeer-review

Effects of nanofibrillated cellulose hydrogels on adipose tissue extract and hepatocellular carcinoma cell spheroids in freeze-drying

The aim of this study was to evaluate the effects of two nanofibrillated cellulose (NFC) hydrogels on two human derivatives during freeze-drying. Native NFC hydrogel is a suitable platform to culture 3D cell spheroids and a hydrogel processed further, called anionic NFC (ANFC) hydrogel, is an excellent platform for controlled release of proteins. Moreover, it has been shown to be compatible with freeze-drying when correct lyoprotectants are implemented. Freeze-drying is a method, where substance is first frozen, and then vacuum dried trough sublimation of water in order to achieve dry matter without the loss of the original three-dimensional structures. The first chosen human derivative was adipose tissue extract (ATE) which is a cell-free growth factor-rich preparation capable of promoting growth of regenerative cells. The release of growth factors from the freeze-dried mixture of ATE and ANFC was compared to that of non-freeze-dried control mixtures. The release profiles remained at the same level after freeze-drying. The second derivative was hepatocellular carcinoma (HepG2) cell spheroids which were evaluated before and after freeze-drying. The 3D structure of the HepG2 cell spheroids was preserved and the spheroids retained 18% of their metabolic activity after rehydration. However, the freeze-dried and rehydrated HepG2 cell spheroids did not proliferate and the cell membrane was damaged by fusion and formation of crystals.

General information

Publication status: E-pub ahead of print
MoE publication type: A1 Journal article-refereed
Organisations: Materials Science and Environmental Engineering, Research group: Chemistry & Advanced Materials, University of Helsinki, Tampere University, Universita degli Studi di Padova, Italy
Contributors: Auvinen, V., Merivaara, A., Kiiskinen, J., Paukkonen, H., Laurén, P., Hakkarainen, T., Koivuniemi, R., Sarkanen, R., Ylikomi, T., Laaksonen, T., Yliperttula, M.
Publication date: 15 Sep 2019
Peer-reviewed: Yes

Publication information

Journal: Cryobiology
ISSN (Print): 0011-2240
Ratings: 
  • Scopus rating (2019): SJR 0.696 SNIP 1.073
Original language: English
ASJC Scopus subject areas: Biochemistry, Genetics and Molecular Biology(all), Agricultural and Biological Sciences(all)
Keywords: 3D cell culture, Adipose tissue extract, Cell spheroids, Freeze-drying, Nanofibrillated cellulose

Bibliographical note

dupl=50229030

Source: Scopus
Source ID: 85072559849

Research output: Contribution to journalArticleScientificpeer-review

An efficient auxin-inducible degron system with low basal degradation in human cells

Auxin-inducible degron technology allows rapid and controlled protein depletion. However, basal degradation without auxin and inefficient auxin-inducible depletion have limited its utility. We have identified a potent auxin-inducible degron system composed of auxin receptor F-box protein AtAFB2 and short degron miniIAA7. The system showed minimal basal degradation and enabled rapid auxin-inducible depletion of endogenous human transmembrane, cytoplasmic and nuclear proteins in 1 h with robust functional phenotypes.

General information

Publication status: Published
MoE publication type: A1 Journal article-refereed
Organisations: Physics, University of Helsinki Faculty of Medicine, Minerva Foundation Institute for Medical Research Helsinki, University of Helsinki, Computational Physics Laboratory
Contributors: Li, S., Prasanna, X., Salo, V. T., Vattulainen, I., Ikonen, E.
Number of pages: 4
Pages: 866-869
Publication date: 1 Sep 2019
Peer-reviewed: Yes

Publication information

Journal: Nature Methods
Volume: 16
Issue number: 9
ISSN (Print): 1548-7091
Ratings: 
  • Scopus rating (2019): CiteScore 31.3 SJR 20.148 SNIP 6.018
Original language: English
ASJC Scopus subject areas: Biotechnology, Biochemistry, Molecular Biology, Cell Biology
Source: Scopus
Source ID: 85071234380

Research output: Contribution to journalArticleScientificpeer-review

Behavior of the DPH fluorescence probe in membranes perturbed by drugs

1,6-Diphenyl-1,3,5-hexatriene (DPH) is one of the most commonly used fluorescent probes to study dynamical and structural properties of lipid bilayers and cellular membranes via measuring steady-state or time-resolved fluorescence anisotropy. In this study, we present a limitation in the use of DPH to predict the order of lipid acyl chains when the lipid bilayer is doped with itraconazole (ITZ), an antifungal drug. Our steady-state fluorescence anisotropy measurements showed a significant decrease in fluorescence anisotropy of DPH embedded in the ITZ-containing membrane, suggesting a substantial increase in membrane fluidity, which indirectly indicates a decrease in the order of the hydrocarbon chains. This result or its interpretation is in disagreement with the fluorescence recovery after photobleaching measurements and molecular dynamics (MD) simulation data. The results of these experiments and calculations indicate an increase in the hydrocarbon chain order. The MD simulations of the bilayer containing both ITZ and DPH provide explanations for these observations. Apparently, in the presence of the drug, the DPH molecules are pushed deeper into the hydrophobic membrane core below the lipid double bonds, and the probe predominately adopts the orientation of the ITZ molecules that is parallel to the membrane surface, instead of orienting parallel to the lipid acyl chains. For this reason, DPH anisotropy provides information related to the less ordered central region of the membrane rather than reporting the properties of the upper segments of the lipid acyl chains.

General information

Publication status: Published
MoE publication type: A1 Journal article-refereed
Organisations: Physics, Research group: Biological Physics and Soft Matter, Research area: Computational Physics, Uniwersytet Jagiellonski w Krakowie, Max Planck Institute of Colloids and Interfaces, J. Heyrovský Institute of Physical Chemistry
Contributors: Poojari, C., Wilkosz, N., Lira, R. B., Dimova, R., Jurkiewicz, P., Petka, R., Kepczynski, M., Róg, T.
Publication date: 1 Sep 2019
Peer-reviewed: Yes

Publication information

Journal: Chemistry and Physics of Lipids
Volume: 223
Article number: 104784
ISSN (Print): 0009-3084
Ratings: 
  • Scopus rating (2019): CiteScore 4.4 SJR 0.712 SNIP 0.814
Original language: English
ASJC Scopus subject areas: Biochemistry, Molecular Biology, Organic Chemistry, Cell Biology
Keywords: 1,6-diphenyl-1,3,5-hexatriene, Fluorescence anisotropy, Lipid bilayers, Molecular dynamics simulations
Electronic versions: 
Source: Scopus
Source ID: 85067516562

Research output: Contribution to journalArticleScientificpeer-review

Pneumatic unidirectional cell stretching device for mechanobiological studies of cardiomyocytes

In this paper, we present a transparent mechanical stimulation device capable of uniaxial stimulation, which is compatible with standard bioanalytical methods used in cellular mechanobiology. We validate the functionality of the uniaxial stimulation system using human-induced pluripotent stem cells-derived cardiomyocytes (hiPSC-CMs). The pneumatically controlled device is fabricated from polydimethylsiloxane (PDMS) and provides uniaxial strain and superior optical performance compatible with standard inverted microscopy techniques used for bioanalytics (e.g., fluorescence microscopy and calcium imaging). Therefore, it allows for a continuous investigation of the cell state during stretching experiments. The paper introduces design and fabrication of the device, characterizes the mechanical performance of the device and demonstrates the compatibility with standard bioanalytical analysis tools. Imaging modalities, such as high-resolution live cell phase contrast imaging and video recordings, fluorescent imaging and calcium imaging are possible to perform in the device. Utilizing the different imaging modalities and proposed stretching device, we demonstrate the capability of the device for extensive further studies of hiPSC-CMs. We also demonstrate that sarcomere structures of hiPSC-CMs organize and orient perpendicular to uniaxial strain axis and thus express more maturated nature of cardiomyocytes.

General information

Publication status: E-pub ahead of print
MoE publication type: A1 Journal article-refereed
Organisations: Research group: Micro and Nanosystems Research Group, BioMediTech, Risø Campus, Tampere University of Applied Sciences, Eindhoven University of Technology, Tampere University Hospital
Contributors: Kreutzer, J., Viehrig, M., Pölönen, R. P., Zhao, F., Ojala, M., Aalto-Setälä, K., Kallio, P.
Publication date: 23 Aug 2019
Peer-reviewed: Yes

Publication information

Journal: BIOMECHANICS AND MODELING IN MECHANOBIOLOGY
ISSN (Print): 1617-7959
Ratings: 
  • Scopus rating (2019): CiteScore 5.2 SJR 0.85 SNIP 1.159
Original language: English
ASJC Scopus subject areas: Biotechnology, Modelling and Simulation, Mechanical Engineering
Keywords: Cardiomyocytes, hiPSC, Mechanical stimulation, PDMS

Bibliographical note

EXT="Zhao, Feihu"

Source: Scopus
Source ID: 85070939275

Research output: Contribution to journalArticleScientificpeer-review

Influence of ions to modulate hydrazone and oxime reaction kinetics to obtain dynamically cross-linked hyaluronic acid hydrogels

Dynamic covalent chemistry forming hydrazone and oxime linkages is attractive due to its simplicity, selectivity and compatibility under aqueous conditions. However, the low reaction rate at physiological pH hampers its use in biomedical applications. Herein, we present different monovalent and bivalent aqueous salt solutions as bio-friendly, non-toxic catalysts which can drive the hydrazone and oxime reactions with excellent efficacy at physiological pH. Direct comparison of hydrazone and oxime reactions using a small molecule model, without any salt catalysis, indicated that oxime formation is 6-times faster than hydrazone formation. Addition of different salts (NaCl, NaBr, KCl, LiCl, LiClO4, Na2SO4, MgCl2 and CaCl2) accelerated the pseudo-first-order reaction kinetics by ∼1.2-4.9-fold for acylhydrazone formation and by ∼1.5-6.9-fold for oxime formation, in a concentration-dependent manner. We further explored the potential of such catalysts to develop acylhydrazone and oxime cross-linked hyaluronic acid (HA) hydrogels with different physicochemical properties without changing the degree of chemical modification. Analogous to the small molecule model system, the addition of monovalent and divalent salts as catalysts significantly reduced the gelling time. The gelling time for the acylhydrazone cross-linked HA-hydrogel (1.6 wt%) could be reduced from 300 min to 1.2 min by adding 100 mM CaCl2, while that for the oxime cross-linked HA-hydrogel (1.2 wt%) could be reduced from 68 min to 1.1 min by adding 50 mM CaCl2. This difference in the gelling time also resulted in hydrogels with differential swelling properties as measured after 24 h. Our results are the first to demonstrate the use of salts, for catalyzing hydrogel formation under physiologically relevant conditions.

General information

Publication status: Published
MoE publication type: A1 Journal article-refereed
Organisations: BioMediTech, Research group: Biomaterials and Tissue Engineering Group, University of Montreal, Uppsala University
Contributors: Wang, S., Nawale, G. N., Oommen, O. P., Hilborn, J., Varghese, O. P.
Number of pages: 6
Pages: 4322-4327
Publication date: 21 Aug 2019
Peer-reviewed: Yes

Publication information

Journal: Polymer Chemistry
Volume: 10
Issue number: 31
ISSN (Print): 1759-9954
Ratings: 
  • Scopus rating (2019): CiteScore 9 SJR 1.459 SNIP 1.057
Original language: English
ASJC Scopus subject areas: Bioengineering, Biochemistry, Polymers and Plastics, Organic Chemistry
Electronic versions: 
Source: Scopus
Source ID: 85070404630

Research output: Contribution to journalArticleScientificpeer-review

Sodium channels enable fast electrical signaling and regulate phagocytosis in the retinal pigment epithelium

Background: Voltage-gated sodium (Nav) channels have traditionally been considered a trademark of excitable cells. However, recent studies have shown the presence of Nav channels in several non-excitable cells, such as astrocytes and macrophages, demonstrating that the roles of these channels are more diverse than was previously thought. Despite the earlier discoveries, the presence of Nav channel-mediated currents in the cells of retinal pigment epithelium (RPE) has been dismissed as a cell culture artifact. We challenge this notion by investigating the presence and possible role of Nav channels in RPE both ex vivo and in vitro. Results: Our work demonstrates that several subtypes of Nav channels are found in human embryonic stem cell (hESC)-derived and mouse RPE, most prominently subtypes Nav1.4, Nav1.6, and Nav1.8. Whole cell patch clamp recordings from the hESC-derived RPE monolayers showed that the current was inhibited by TTX and QX-314 and was sensitive to the selective blockers of the main Nav subtypes. Importantly, we show that the Nav channels are involved in photoreceptor outer segment phagocytosis since blocking their activity significantly reduces the efficiency of particle internalization. Consistent with this role, our electron microscopy results and immunocytochemical analysis show that Nav1.4 and Nav1.8 accumulate on phagosomes and that pharmacological inhibition of Nav channels as well as silencing the expression of Nav1.4 with shRNA impairs the phagocytosis process. Conclusions: Taken together, our study shows that Nav channels are present in RPE, giving this tissue the capacity of fast electrical signaling. The channels are critical for the physiology of RPE with an important role in photoreceptor outer segment phagocytosis.

General information

Publication status: Published
MoE publication type: A1 Journal article-refereed
Organisations: BioMediTech, Tampere University, University of Jyvaskyla, Tampere University Hospital
Contributors: Johansson, J. K., Karema-Jokinen, V. I., Hakanen, S., Jylhä, A., Uusitalo, H., Vihinen-Ranta, M., Skottman, H., Ihalainen, T. O., Nymark, S.
Publication date: 15 Aug 2019
Peer-reviewed: Yes

Publication information

Journal: BMC BIOLOGY
Volume: 17
Issue number: 1
Article number: 63
ISSN (Print): 1741-7007
Ratings: 
  • Scopus rating (2019): CiteScore 9.5 SJR 3.698 SNIP 1.604
Original language: English
ASJC Scopus subject areas: Biotechnology, Structural Biology, Ecology, Evolution, Behavior and Systematics, Physiology, Biochemistry, Genetics and Molecular Biology(all), Agricultural and Biological Sciences(all), Plant Science, Developmental Biology, Cell Biology
Keywords: Ion channels, Na, Patch clamp, Phagocytosis, Photoreceptors, Retina, RPE
Electronic versions: 
Source: Scopus
Source ID: 85071165212

Research output: Contribution to journalArticleScientificpeer-review

Characterisation and in vitro and in vivo evaluation of supercritical-CO2-foamed β-TCP/PLCL composites for bone applications

Most synthetic bone grafts are either hard and brittle ceramics or paste-like materials that differ in applicability from the gold standard autologous bone graft, which restricts their widespread use. Therefore, the aim of the study was to develop an elastic, highly porous and biodegradable β-tricalciumphosphate/poly(L-lactide-co-ε-caprolactone) (β-TCP/PLCL) composite for bone applications using supercritical CO2 foaming. Ability to support osteogenic differentiation was tested in human adipose stem cell (hASC) culture for 21 d. Biocompatibility was evaluated for 24 weeks in a rabbit femur-defect model. Foamed composites had a high ceramic content (50 wt%) and porosity (65-67 %). After 50 % compression, in an aqueous environment at 37 °C, tested samples returned to 95 % of their original height. Hydrolytic degradation of β-TCP/PLCL composite, during the 24-week follow-up, was very similar to that of porous PLCL scaffold both in vitro and in vivo. Osteogenic differentiation of hASCs was demonstrated by alkaline phosphatase activity analysis, alizarin red staining, soluble collagen analysis, immunocytochemical staining and qRT-PCR. In vitro, hASCs formed a pronounced mineralised collagen matrix. A rabbit femur defect model confirmed biocompatibility of the composite. According to histological Masson-Goldner's trichrome staining and micro-computed tomography, β-TCP/PLCL composite did not elicit infection, formation of fibrous capsule or cysts. Finally, native bone tissue at 4 weeks was already able to grow on and in the β-TCP/PLCL composite. The elastic and highly porous β-TCP/PLCL composite is a promising bone substitute because it is osteoconductive and easy-to-use and mould intraoperatively.

General information

Publication status: Published
MoE publication type: A1 Journal article-refereed
Organisations: BioMediTech
Contributors: Pitkänen, S., Paakinaho, K., Pihlman, H., Ahola, N., Hannula, M., Asikainen, S., Manninen, M., Morelius, M., Keränen, P., Hyttinen, J., Kellomäki, M., Laitinen-Vapaavuori, O., Miettinen, S.
Number of pages: 16
Pages: 35-50
Publication date: 5 Aug 2019
Peer-reviewed: Yes

Publication information

Journal: European cells & materials
Volume: 38
ISSN (Print): 1473-2262
Ratings: 
  • Scopus rating (2019): CiteScore 6 SJR 1.141 SNIP 1.069
Original language: English
ASJC Scopus subject areas: Bioengineering, Biochemistry, Biomaterials, Biomedical Engineering, Cell Biology
Electronic versions: 
Source: Scopus
Source ID: 85071152630

Research output: Contribution to journalArticleScientificpeer-review

Alkane and wax ester production from lignin-related aromatic compounds

Lignin has potential as a sustainable feedstock for microbial production of industrially relevant molecules. However, the required lignin depolymerization yields a heterogenic mixture of aromatic monomers that are challenging substrates for the microorganisms commonly used in the industry. Here, we investigated the properties of lignin-related aromatic compounds (LRAs), namely coumarate, ferulate, and caffeate, in the synthesis of biomass and products in an LRA-utilizing bacterial host Acinetobacter baylyi ADP1. The biosynthesis products, wax esters, and alkanes are relevant compounds for the chemical and fuel industries. Here, wax esters were produced by a native pathway of ADP1, whereas alkanes were produced by a synthetic pathway introduced to the host. Using individual LRAs as substrates, the growth and product formation were monitored with internal biosensors and off-line analytics. Of the tested LRAs, coumarate was the most propitious in terms of product synthesis. Wax esters were produced from coumarate with yield and titer of 37 mg/gcoumarate and 202 mg/L, whereas alkanes were produced with a yield of 62.3 µg /gcoumarate and titer of 152 µg/L. This study demonstrates the microbial preference for certain LRAs and highlights the potential of A. baylyi ADP1 as a host for LRA upgrading to value-added products.

General information

Publication status: Published
MoE publication type: A1 Journal article-refereed
Organisations: Materials Science and Environmental Engineering, Research group: Bio- and Circular Economy
Contributors: Salmela, M., Lehtinen, T., Efimova, E., Santala, S., Santala, V.
Number of pages: 12
Pages: 1934-1945
Publication date: 1 Aug 2019
Peer-reviewed: Yes

Publication information

Journal: Biotechnology and Bioengineering
Volume: 116
Issue number: 8
ISSN (Print): 0006-3592
Ratings: 
  • Scopus rating (2019): CiteScore 7.1 SJR 1.191 SNIP 1.139
Original language: English
ASJC Scopus subject areas: Biotechnology, Bioengineering, Applied Microbiology and Biotechnology
Keywords: Acinetobacter baylyi ADP1, alkane, lignin, wax ester
Source: Scopus
Source ID: 85070728183

Research output: Contribution to journalArticleScientificpeer-review

Comparing deep belief networks with support vector machines for classifying gene expression data from complex disorders

Genomics data provide great opportunities for translational research and the clinical practice, for example, for predicting disease stages. However, the classification of such data is a challenging task due to their high dimensionality, noise, and heterogeneity. In recent years, deep learning classifiers generated much interest, but due to their complexity, so far, little is known about the utility of this method for genomics. In this paper, we address this problem by studying a computational diagnostics task by classification of breast cancer and inflammatory bowel disease patients based on high-dimensional gene expression data. We provide a comprehensive analysis of the classification performance of deep belief networks (DBNs) in dependence on its multiple model parameters and in comparison with support vector machines (SVMs). Furthermore, we investigate combined classifiers that integrate DBNs with SVMs. Such a classifier utilizes a DBN as representation learner forming the input for a SVM. Overall, our results provide guidelines for the complex usage of DBN for classifying gene expression data from complex diseases.

General information

Publication status: Published
MoE publication type: A1 Journal article-refereed
Organisations: Computing Sciences, Research group: Predictive Society and Data Analytics (PSDA), Tampere University, University of Turku, University of Applied Sciences Upper Austria, School of Management, Hall in Tyrol, Nankai University
Contributors: Smolander, J., Dehmer, M., Emmert-Streib, F.
Number of pages: 17
Pages: 1232-1248
Publication date: 1 Jul 2019
Peer-reviewed: Yes

Publication information

Journal: FEBS Open Bio
Volume: 9
Issue number: 7
ISSN (Print): 2211-5463
Ratings: 
  • Scopus rating (2019): CiteScore 3 SJR 0.74 SNIP 0.615
Original language: English
ASJC Scopus subject areas: Biochemistry, Genetics and Molecular Biology(all)
Keywords: artificial intelligence, deep belief network, deep learning, genomics, neural networks, support vector machine

Bibliographical note

int=comp,"Smolander, Johannes"

Source: Scopus
Source ID: 85068440161

Research output: Contribution to journalArticleScientificpeer-review

An architectural understanding of natural sway frequencies in trees

The relationship between form and function in trees is the subject of a longstanding debate in forest ecology and provides the basis for theories concerning forest ecosystem structure and metabolism. Trees interact with the wind in a dynamic manner and exhibit natural sway frequencies and damping processes that are important in understanding wind damage. Tree-wind dynamics are related to tree architecture, but this relationship is not well understood. We present a comprehensive view of natural sway frequencies in trees by compiling a dataset of field measurement spanning conifers and broadleaves, tropical and temperate forests. The field data show that a cantilever beam approximation adequately predicts the fundamental frequency of conifers, but not that of broadleaf trees. We also use structurally detailed tree dynamics simulations to test fundamental assumptions underpinning models of natural frequencies in trees. We model the dynamic properties of greater than 1000 trees using a finite-element approach based on accurate three-dimensional model trees derived from terrestrial laser scanning data. We show that (1) residual variation, the variation not explained by the cantilever beam approximation, in fundamental frequencies of broadleaf trees is driven by their architecture; (2) slender trees behave like a simple pendulum, with a single natural frequency dominating their motion, which makes them vulnerable to wind damage and (3) the presence of leaves decreases both the fundamental frequency and the damping ratio. These findings demonstrate the value of new three-dimensional measurements for understanding wind impacts on trees and suggest new directions for improving our understanding of tree dynamics from conifer plantations to natural forests.

General information

Publication status: Published
MoE publication type: A1 Journal article-refereed
Organisations: Computing Sciences, University of Oxford, SCION, University of Connecticut, Delft University of Technology, Wageningen University and Research Centre, University of Massachusetts Amherst, National Parks Board, University of Melbourne, Oregon State University, Universiteit Gent, National Physical Laboratory, University College London, NERC National Centre for Earth Observation (NCEO), 16 Center for International Forestry Research (CIFOR), Swedish University of Agricultural Sciences, INRA
Contributors: Jackson, T., Shenkin, A., Moore, J., Bunce, A., van Emmerik, T., Kane, B., Burcham, D., James, K., Selker, J., Calders, K., Origo, N., Disney, M., Burt, A., Wilkes, P., Raumonen, P., Gonzalez de Tanago Menaca, J., Lau, A., Herold, M., Goodman, R. C., Fourcaud, T., Malhi, Y.
Number of pages: 1
Publication date: 28 Jun 2019
Peer-reviewed: Yes

Publication information

Journal: Journal of the Royal Society. Interface
Volume: 16
Issue number: 155
ISSN (Print): 1742-5689
Ratings: 
  • Scopus rating (2019): SJR 1.694 SNIP 1.411
Original language: English
ASJC Scopus subject areas: Biotechnology, Biophysics, Bioengineering, Biomaterials, Biochemistry, Biomedical Engineering
Keywords: finite-element analysis, fundamental frequency, natural frequencies, terrestrial laser scanning, tree architecture, wind damage
Source: Scopus
Source ID: 85067464325

Research output: Contribution to journalArticleScientificpeer-review

Synthetic Design of Asymmetric miRNA with an Engineered 3′ Overhang to Improve Strand Selection

We developed a novel miRNA design that significantly improves strand selection within the RISC complex by engineering the 3′ end by adding extra nucleotides. Addition of seven nucleotides at the 3′ ends of the miR or miR* strand resulted in a thermodynamic asymmetry at either of the two ends, which resulted in selective RISC recruitment, as demonstrated by a stem-loop PCR experiment. Such selective recruitment was also corroborated at the protein level by western blot analysis. To investigate the functional effect because of selective recruitment, we performed apoptosis and metastasis studies using human colon carcinoma cells (HCT116)and human osteosarcoma cells (MG63). These experiments indicated that recruitment of the miR strand is responsible for inducing apoptosis and inhibiting the invasiveness of cancer cells. Recruitment of the miR* strand, on the other hand, had the opposite effect. To the best of our knowledge, our strand engineering strategy is the first report of improved strand selection of a desired miRNA strand by RISC without using any chemical modifications or mismatches. We believe that such structural modifications of miR34a could mitigate some of the off-target effects of miRNA therapy and would also allow a better understanding of sequence-specific gene regulation. Such a design could also be adapted to other miRNAs to enhance their therapeutic potential.

General information

Publication status: Published
MoE publication type: A1 Journal article-refereed
Organisations: BioMediTech, Uppsala University
Contributors: Kadekar, S., Nawale, G. N., Karlsson, K., Ålander, C., Oommen, O. P., Varghese, O. P.
Number of pages: 8
Pages: 597-604
Publication date: 7 Jun 2019
Peer-reviewed: Yes

Publication information

Journal: Molecular Therapy - Nucleic Acids
Volume: 16
ISSN (Print): 2162-2531
Ratings: 
  • Scopus rating (2019): SJR 2.089 SNIP 1.199
Original language: English
ASJC Scopus subject areas: Molecular Medicine, Drug Discovery
Keywords: anticancer therapy, miR34a, miRNA, RNAi, strand selection
Electronic versions: 
Source: Scopus
Source ID: 85065418583

Research output: Contribution to journalArticleScientificpeer-review

The Role of Temperature and Lipid Charge on Intake/Uptake of Cationic Gold Nanoparticles into Lipid Bilayers

Understanding the molecular mechanisms governing nanoparticle–membrane interactions is of prime importance for drug delivery and biomedical applications. Neutron reflectometry (NR) experiments are combined with atomistic and coarse-grained molecular dynamics (MD) simulations to study the interaction between cationic gold nanoparticles (AuNPs) and model lipid membranes composed of a mixture of zwitterionic di-stearoyl-phosphatidylcholine (DSPC) and anionic di-stearoyl-phosphatidylglycerol (DSPG). MD simulations show that the interaction between AuNPs and a pure DSPC lipid bilayer is modulated by a free energy barrier. This can be overcome by increasing temperature, which promotes an irreversible AuNP incorporation into the lipid bilayer. NR experiments confirm the encapsulation of the AuNPs within the lipid bilayer at temperatures around 55 °C. In contrast, the AuNP adsorption is weak and impaired by heating for a DSPC–DSPG (3:1) lipid bilayer. These results demonstrate that both the lipid charge and the temperature play pivotal roles in AuNP–membrane interactions. Furthermore, NR experiments indicate that the (negative) DSPG lipids are associated with lipid extraction upon AuNP adsorption, which is confirmed by coarse-grained MD simulations as a lipid-crawling effect driving further AuNP aggregation. Overall, the obtained detailed molecular view of the interaction mechanisms sheds light on AuNP incorporation and membrane destabilization.

General information

Publication status: Published
MoE publication type: A1 Journal article-refereed
Organisations: Research group: Biological Physics and Soft Matter, Research area: Computational Physics, Physics, Computational Physics Laboratory, University of Helsinki, Politecnico di Milano, Institut Laue-Langevin, Max Planck Institute of Colloids and Interfaces, MEMPHYS−Center for Biomembrane Physics, Norwegian Univ. of Sci. and Technol., G2Elab/Institut Néel
Contributors: Lolicato, F., Joly, L., Martinez-Seara, H., Fragneto, G., Scoppola, E., Baldelli Bombelli, F., Vattulainen, I., Akola, J., Maccarini, M.
Publication date: 7 Jun 2019
Peer-reviewed: Yes

Publication information

Journal: Small
Volume: 15
Issue number: 23
Article number: 1805046
ISSN (Print): 1613-6810
Ratings: 
  • Scopus rating (2019): CiteScore 15.7 SJR 3.717 SNIP 1.695
Original language: English
ASJC Scopus subject areas: Biotechnology, Biomaterials, Chemistry(all), Materials Science(all)
Keywords: gold nanoparticles, lipid membranes, molecular dynamics simulations, nanotoxicity, neutron reflectometry
Electronic versions: 

Bibliographical note

EXT="Martinez-Seara, Hector"

Source: Scopus
Source ID: 85064688737

Research output: Contribution to journalArticleScientificpeer-review

Methods for simultaneous robot-world-hand–eye calibration: A comparative study

In this paper, we propose two novel methods for robot-world-hand-eye calibration and provide a comparative analysis against six state-of-the-art methods. We examine the calibration problem from two alternative geometrical interpretations, called 'hand-eye' and 'robot-world-hand-eye', respectively. The study analyses the effects of specifying the objective function as pose error or reprojection error minimization problem. We provide three real and three simulated datasets with rendered images as part of the study. In addition, we propose a robotic arm error modeling approach to be used along with the simulated datasets for generating a realistic response. The tests on simulated data are performed in both ideal cases and with pseudo-realistic robotic arm pose and visual noise. Our methods show significant improvement and robustness on many metrics in various scenarios compared to state-of-the-art methods.

General information

Publication status: Published
MoE publication type: A1 Journal article-refereed
Organisations: Computing Sciences, Remote Handling Project Team
Contributors: Ali, I., Suominen, O., Gotchev, A., Morales, E. R.
Publication date: 2 Jun 2019
Peer-reviewed: Yes

Publication information

Journal: Sensors (Switzerland)
Volume: 19
Issue number: 12
Article number: 2837
ISSN (Print): 1424-8220
Ratings: 
  • Scopus rating (2019): CiteScore 5 SJR 0.653 SNIP 1.586
Original language: English
ASJC Scopus subject areas: Analytical Chemistry, Atomic and Molecular Physics, and Optics, Biochemistry, Instrumentation, Electrical and Electronic Engineering
Keywords: Hand-eye calibration, Optimization, Robot-world-hand-eye calibration
Electronic versions: 
Source: Scopus
Source ID: 85068904338

Research output: Contribution to journalArticleScientificpeer-review

Technical Note: Noise models for virtual clinical trials of digital breast tomosynthesis

Purpose: To investigate the use of an affine-variance noise model, with correlated quantum noise and spatially dependent quantum gain, for the simulation of noise in virtual clinical trials (VCT) of digital breast tomosynthesis (DBT). Methods: Two distinct technologies were considered: an amorphous-selenium (a-Se) detector with direct conversion and a thallium-doped cesium iodide (CsI(Tl)) detector with indirect conversion. A VCT framework was used to generate noise-free projections of a uniform three-dimensional simulated phantom, whose geometry and absorption match those of a polymethyl methacrylate (PMMA) uniform physical phantom. The noise model was then used to generate noisy observations from the simulated noise-free data, while two clinically available DBT units were used to acquire projections of the PMMA physical phantom. Real and simulated projections were then compared using the signal-to-noise ratio (SNR) and normalized noise power spectrum (NNPS). Results: Simulated images reported errors smaller than 4.4% and 7.0% in terms of SNR and NNPS, respectively. These errors are within the expected variation between two clinical units of the same model. The errors increase to 65.8% if uncorrelated models are adopted for the simulation of systems featuring indirect detection. The assumption of spatially independent quantum gain generates errors of 11.2%. Conclusions: The investigated noise model can be used to accurately reproduce the noise found in clinical DBT. The assumption of uncorrelated noise may be adopted if the system features a direct detector with minimal pixel crosstalk.

General information

Publication status: Published
MoE publication type: A1 Journal article-refereed
Organisations: Computing Sciences, University of São Paulo, University of Pennsylvania, Pio XII Foundation
Contributors: Borges, L. R., Barufaldi, B., Caron, R. F., Bakic, P. R., Foi, A., Maidment, A. D., Vieira, M. A.
Number of pages: 7
Pages: 2683-2689
Publication date: 1 Jun 2019
Peer-reviewed: Yes

Publication information

Journal: Medical Physics
Volume: 46
Issue number: 6
ISSN (Print): 0094-2405
Ratings: 
  • Scopus rating (2019): SJR 1.275 SNIP 1.497
Original language: English
ASJC Scopus subject areas: Biophysics, Radiology Nuclear Medicine and imaging
Keywords: digital breast tomosynthesis, electronic noise, noise simulation, quantum noise, virtual clinical trials
Electronic versions: 
URLs: 
Source: Scopus
Source ID: 85065342539

Research output: Contribution to journalArticleScientificpeer-review

Connection of Collimation, Asymmetric Beaming, and Independent Transmission-Reflection Processes in Concentric-Groove Gratings Supporting Spoof Surface Plasmons

Transmission through subwavelength apertures enables separation of the incidence half-space and the exit half-space, which leads to that the spatial distribution of the field in the latter is not affected by the distribution in the former. The distribution in the exit half-space is mainly determined by the properties of surface plasmons (SPs) at the exit-side interface. In this paper, for the microwave structures with one-side concentric corrugations around a single annular hole, we demonstrate the possible connections between asymmetric transmission in the beaming regime and collimation of the waves incident at different angles, which can be considered as two sides of the same phenomenon occurring due to the common effect of such a separation and the radiation shaping effect being possible due to the spoof SPs at the corrugated exit interface. Collimation manifests itself in that the waves incident at different angles from a wide range contribute to the single outgoing beam so that a far-zone observer cannot distinguish between the contributions of different angles of arrival. Asymmetry in transmission manifests itself in that the spatial shaping of radiation (beaming) in the exit half-space appears only for one of the two opposite incidence directions. Moreover, even in the structures with the same corrugations on both sides, i.e., without asymmetric transmission, spatial separation of two wave processes, e.g., two symmetric or asymmetric collimation processes, can be obtained for a wide range of nonzero angles of incidence.

General information

Publication status: Published
MoE publication type: A1 Journal article-refereed
Organisations: Photonics, Bilkent University, KU Leuven, Adam Mickiewicz University
Contributors: Habib, M., Serebryannikov, A. E., Caglayan, H., Vandenbosch, G. A., Ozbay, E.
Number of pages: 9
Pages: 721-729
Publication date: Jun 2019
Peer-reviewed: Yes
Early online date: 2018

Publication information

Journal: Plasmonics
Volume: 14
Issue number: 3
ISSN (Print): 1557-1955
Ratings: 
  • Scopus rating (2019): SJR 0.648 SNIP 0.778
Original language: English
ASJC Scopus subject areas: Biotechnology, Biophysics, Biochemistry
Keywords: Asymmetric transmission, Beaming, Collimation, Spoof plasmon
Source: Scopus
Source ID: 85053476979

Research output: Contribution to journalArticleScientificpeer-review

Bioimpedance Sensor Array for Long-Term Monitoring of Wound Healing from Beneath the Primary Dressings and Controlled Formation of H2O2 Using Low-Intensity Direct Current

Chronic wounds impose a significant financial burden for the healthcare system. Currently, assessment and monitoring of hard-to-heal wounds are often based on visual means and measuring the size of the wound. The primary wound dressings must be removed before assessment can be done. We have developed a quasi-monopolar bioimpedance-measurement-based method and a measurement system to determine the status of wound healing. The objective of this study was to demonstrate that with an appropriate setup, long-term monitoring of wound healing from beneath the primary dressings is feasible. The developed multielectrode sensor array was applied on the wound area and left under the primary dressings for 142 h. The impedance of the wounds and the surrounding intact skin area was measured regularly during the study at 150 Hz, 300 Hz, 1 kHz, and 5 kHz frequencies. At the end of the follow-up period, the wound impedance had reached the impedance of the intact skin at the higher frequencies and increased significantly at the lowest frequencies. The measurement frequency affected the measurement sensitivity in wound monitoring. The skin impedance remained stable over the measurement period. The sensor array also enabled the administration of periodical low-intensity direct current (LIDC) stimulation in order to create an antimicrobial environment across the wound area via the controlled formation of hydrogen peroxide (H2O2).

General information

Publication status: Published
MoE publication type: A1 Journal article-refereed
Organisations: BioMediTech, Turku University Hospital, Kaarinantie 700, Åbo Akademi University
Contributors: Kekonen, A., Bergelin, M., Johansson, M., Kumar Joon, N., Bobacka, J., Viik, J.
Publication date: 31 May 2019
Peer-reviewed: Yes

Publication information

Journal: Sensors
Volume: 19
Issue number: 11
ISSN (Print): 1424-8220
Ratings: 
  • Scopus rating (2019): CiteScore 5 SJR 0.653 SNIP 1.586
Original language: English
ASJC Scopus subject areas: Analytical Chemistry, Atomic and Molecular Physics, and Optics, Biochemistry, Instrumentation, Electrical and Electronic Engineering
Keywords: beneath the dressings, bioimpedance, hydrogen peroxide, long-term monitoring, low-intensity direct current, multielectrode, quasi-monopolar, sensor array, wound dressing, wound monitoring, wound stimulation
Electronic versions: 
Source: Scopus
Source ID: 85067176313

Research output: Contribution to journalArticleScientificpeer-review

Understanding the Role of Lipids in Signaling Through Atomistic and Multiscale Simulations of Cell Membranes

Cell signaling controls essentially all cellular processes. While it is often assumed that proteins are the key architects coordinating cell signaling, recent studies have shown more and more clearly that lipids are also involved in signaling processes in a number of ways. Lipids do, for instance, act as messengers, modulate membrane receptor conformation and dynamics, and control membrane receptor partitioning. Further, through structural modifications such as oxidation, the functions of lipids as part of signaling processes can be modified. In this context, in this article we discuss the understanding recently revealed by atomistic and coarse-grained computer simulations of nanoscale processes and underlying physicochemical principles related to lipidsrsquo functions in cellular signaling.

General information

Publication status: Published
MoE publication type: A2 Review article in a scientific journal
Organisations: Research group: Biological Physics and Soft Matter, Research area: Computational Physics, Physics, Indian Institute of Science Education and Research Bhopal, Helsinki University
Contributors: Manna, M., Nieminen, T., Vattulainen, I.
Number of pages: 19
Pages: 421-439
Publication date: 6 May 2019
Peer-reviewed: Yes

Publication information

Journal: ANNUAL REVIEW OF BIOPHYSICS
Volume: 48
ISSN (Print): 1936-122X
Ratings: 
  • Scopus rating (2019): CiteScore 18.3 SJR 7.456 SNIP 2.86
Original language: English
ASJC Scopus subject areas: Biophysics, Structural Biology, Bioengineering, Biochemistry, Cell Biology
Keywords: computer simulations, lipids, molecular dynamics, multiscale simulations, signaling

Bibliographical note

EXT="Manna, Moutusi"

Source: Scopus
Source ID: 85065827906

Research output: Contribution to journalReview ArticleScientificpeer-review

Reduced level of docosahexaenoic acid shifts GPCR neuroreceptors to less ordered membrane regions

G protein-coupled receptors (GPCRs) control cellular signaling and responses. Many of these GPCRs are modulated by cholesterol and polyunsaturated fatty acids (PUFAs) which have been shown to co-exist with saturated lipids in ordered membrane domains. However, the lipid compositions of such domains extracted from the brain cortex tissue of individuals suffering from GPCR-associated neurological disorders show drastically lowered levels of PUFAs. Here, using free energy techniques and multiscale simulations of numerous membrane proteins, we show that the presence of the PUFA DHA helps helical multi-pass proteins such as GPCRs partition into ordered membrane domains. The mechanism is based on hybrid lipids, whose PUFA chains coat the rough protein surface, while the saturated chains face the raft environment, thus minimizing perturbations therein. Our findings suggest that the reduction of GPCR partitioning to their native ordered environments due to PUFA depletion might affect the function of these receptors in numerous neurodegenerative diseases, where the membrane PUFA levels in the brain are decreased. We hope that this work inspires experimental studies on the connection between membrane PUFA levels and GPCR signaling.

General information

Publication status: Published
MoE publication type: A1 Journal article-refereed
Organisations: Physics, University of Helsinki, Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Universitat Autònoma de Barcelona, University of Texas Health Science Center at Houston, MEMPHYS
Contributors: Javanainen, M., Enkavi, G., Guixà-Gonzaléz, R., Kulig, W., Martinez-Seara, H., Levental, I., Vattulainen, I.
Publication date: 1 May 2019
Peer-reviewed: Yes

Publication information

Journal: PLoS Computational Biology
Volume: 15
Issue number: 5
Article number: e1007033
ISSN (Print): 1553-734X
Ratings: 
  • Scopus rating (2019): SJR 2.91 SNIP 1.537
Original language: English
ASJC Scopus subject areas: Ecology, Evolution, Behavior and Systematics, Modelling and Simulation, Ecology, Molecular Biology, Genetics, Cellular and Molecular Neuroscience, Computational Theory and Mathematics
Electronic versions: 

Bibliographical note

EXT="Martinez-Seara, Hector"

Source: Scopus
Source ID: 85066964975

Research output: Contribution to journalArticleScientificpeer-review

Effects of percutaneous transluminal angioplasty of superficial femoral artery on photoplethysmographic pulse transit times

We analyze the changes in upper and lower limb pulse transit times (PTT) caused by peripheral artery disease (PAD) and its treatment with percutaneous transluminal angioplasty (PTA) of the superficial femoral artery. PTTs were extracted from the photoplethysmograms (PPG) recorded from an index finger and 2nd toes. PTTs were defined between the R-peaks of the ECG and different reference points of the (PPG): foot and peak points, maxima of 1st and 2nd derivative, and by means of intersecting tangents method. Also the PTTs between the toe and finger pulses were analyzed. Our sample consists of 24 subjects examined before and after the PTA and in 1-month follow-up visit. Also 28 older than 65 years controls having normal ankle-to-brachial pressure index (ABI) and no history in cardiovascular diseases as well as 21 younger subjects were examined. The differences between the groups and pre- and post-treatment phases were analyzed by means of non-parametric statistical tests. The changes in the PTTs of upper limb and non-treated lower limb were negligible. The agreement with the reference values, ABI and toe pressures, was studied by kappa-analysis, resulting in kappa-values of 0.33<formula><tex>$\times$</tex></formula>0.91. Differences in PTTs were found between pre-treatment state of the treated limb, post-treatment state and the follow-up visit, as well as between the pre-treatment state and controls. If patients' age and systolic blood pressure were taken into consideration, the method of lower limb PTT calculation from the peak point turns out feasible in finding the markers of PAD and monitoring post- treatment vascular remodellation.

General information

Publication status: Published
MoE publication type: A1 Journal article-refereed
Organisations: Faculty of Biomedical Sciences and Engineering, Research group: Sensor Technology and Biomeasurements (STB), Division of Vascular Surgery, Division of Interventional Radiology, Oulu University Hospital, Tampere University Hospital
Contributors: Peltokangas, M., Suominen, V., Vakhitov, D., Korhonen, J., Verho, J., Mattila, V. M., Romsi, P., Lekkala, J., Vehkaoja, A., Oksala, N.
Pages: 1058-1065
Publication date: May 2019
Peer-reviewed: Yes
Early online date: 27 Jun 2018

Publication information

Journal: IEEE Journal of Biomedical and Health Informatics
Volume: 23
Issue number: 3
ISSN (Print): 2168-2194
Ratings: 
  • Scopus rating (2019): CiteScore 9.1 SJR 1.306 SNIP 2.522
Original language: English
ASJC Scopus subject areas: Biotechnology, Computer Science Applications, Electrical and Electronic Engineering, Health Information Management
Keywords: Atherosclerosis, Peripheral artery disease, Photoplethysmography, Pulse wave measurements
Additional files: 
Source: Scopus
Source ID: 85049142393

Research output: Contribution to journalArticleScientificpeer-review

Alpha radiation-induced luminescence by am-241 in aqueous nitric acid solution

When exposed to air, alpha particles cause the production of light by exciting the molecules surrounding them. This light, the radioluminescence, is indicative of the presence of alpha radiation, thus allowing for the optical sensing of alpha radiation from distances larger than the few centimeters an alpha particle can travel in air. While the mechanics of radioluminescence in air and other gas compositions is relatively well understood, the same cannot be said about the radioluminescence properties of liquids. Better understanding of the radioluminescence properties of liquids is essential to design methods for the detection of radioactively contaminated liquids by optical means. In this article, we provide radioluminescence images of Am-241 dissolved in aqueous nitric acid (HNO 3 ) solution and present the recorded radioluminescence spectrum with a maximum between and, and a steep decrease at the short wavelength side of the maximum. The shape of the spectrum resembles a luminescence process rather than Cerenkov light, bremsstrahlung, or other mechanisms with broadband emission. We show that the amount of light produced is about 150 times smaller compared to that of the same amount of Am-241 in air. The light production in the liquid is evenly distributed throughout the sample volume with a slight increase on the surface of the liquid. The radioluminescence intensity is shown to scale linearly with the Am-241 concentration and not be affected by the HNO 3 concentration.

General information

Publication status: Published
MoE publication type: A1 Journal article-refereed
Organisations: Physics, University of Helsinki, European Commission Joint Research Centre
Contributors: Kerst, T., Malmbeck, R., lal Banik, N. L., Toivonen, J.
Publication date: 1 Apr 2019
Peer-reviewed: Yes

Publication information

Journal: Sensors (Switzerland)
Volume: 19
Issue number: 7
Article number: 1602
ISSN (Print): 1424-8220
Ratings: 
  • Scopus rating (2019): CiteScore 5 SJR 0.653 SNIP 1.586
Original language: English
ASJC Scopus subject areas: Analytical Chemistry, Atomic and Molecular Physics, and Optics, Biochemistry, Instrumentation, Electrical and Electronic Engineering
Keywords: Alpha radiation, Americium, Liquid phase luminescence, Radioluminescence
Electronic versions: 
Source: Scopus
Source ID: 85064822061

Research output: Contribution to journalArticleScientificpeer-review

Positioning information privacy in intelligent transportation systems: An overview and future perspective

Today, the Intelligent Transportation Systems (ITS) are already in deep integration phase all over the world. One of the most significant enablers for ITS are vehicle positioning and tracking techniques. Worldwide integration of ITS employing Dedicated Short Range Communications (DSRC) and European standard for vehicular communication, known as ETSI ITS-G5, brings a variety of options to improve the positioning in areas where GPS connectivity is lacking precision. Utilization of the ready infrastructure, next-generation cellular 5G networks, and surrounding electronic devices together with conventional positioning techniques could become the solution to improve the overall ITS operation in vehicle-to-everything (V2X) communication scenario. Nonetheless, effective and secure communication protocols between the vehicle and roadside units should be both analyzed and improved in terms of potential attacks on the transmitted positioning-related data. In particular, said information might be misused or stolen at the infrastructure side conventionally assumed to be trusted. In this paper, we first survey different methods of vehicle positioning, which is followed by an overview of potential attacks on ITS systems. Next, we propose potential improvements allowing mutual authentication between the vehicle and infrastructure aiming at improving positioning data privacy. Finally, we propose a vision on the development and standardization aspects of such systems.

General information

Publication status: Published
MoE publication type: A1 Journal article-refereed
Organisations: Electrical Engineering, St. Petersburg State University of Aerospace Instrumentation, ITMO University, Brno University of Technology
Contributors: Ometov, A., Bezzateev, S., Davydov, V., Shchesniak, A., Masek, P., Lohan, E. S., Koucheryavy, Y.
Publication date: 1 Apr 2019
Peer-reviewed: Yes

Publication information

Journal: Sensors
Volume: 19
Issue number: 7
Article number: 1603
ISSN (Print): 1424-8220
Ratings: 
  • Scopus rating (2019): CiteScore 5 SJR 0.653 SNIP 1.586
Original language: English
ASJC Scopus subject areas: Analytical Chemistry, Atomic and Molecular Physics, and Optics, Biochemistry, Instrumentation, Electrical and Electronic Engineering
Keywords: Authentication, Data privacy, GDPR, Intelligent transportation systems, Positioning
Electronic versions: 
Source: Scopus
Source ID: 85064829981

Research output: Contribution to journalArticleScientificpeer-review

Deep Learning in Image Cytometry: A Review

Artificial intelligence, deep convolutional neural networks, and deep learning are all niche terms that are increasingly appearing in scientific presentations as well as in the general media. In this review, we focus on deep learning and how it is applied to microscopy image data of cells and tissue samples. Starting with an analogy to neuroscience, we aim to give the reader an overview of the key concepts of neural networks, and an understanding of how deep learning differs from more classical approaches for extracting information from image data. We aim to increase the understanding of these methods, while highlighting considerations regarding input data requirements, computational resources, challenges, and limitations. We do not provide a full manual for applying these methods to your own data, but rather review previously published articles on deep learning in image cytometry, and guide the readers toward further reading on specific networks and methods, including new methods not yet applied to cytometry data.

General information

Publication status: Published
MoE publication type: A2 Review article in a scientific journal
Organisations: Faculty of Biomedical Sciences and Engineering, Uppsala University, BioImage Informatics Facility of SciLifeLab
Contributors: Gupta, A., Harrison, P. J., Wieslander, H., Pielawski, N., Kartasalo, K., Partel, G., Solorzano, L., Suveer, A., Klemm, A. H., Spjuth, O., Sintorn, I. M., Wählby, C.
Pages: 366-380
Publication date: Apr 2019
Peer-reviewed: Yes
Early online date: 2018

Publication information

Journal: Cytometry Part A
Volume: 95
Issue number: 4
ISSN (Print): 1552-4922
Ratings: 
  • Scopus rating (2019): SJR 1.227 SNIP 1.002
Original language: English
ASJC Scopus subject areas: Pathology and Forensic Medicine, Histology, Cell Biology
Keywords: biomedical image analysis, cell analysis, convolutional neural networks, deep learning, image cytometry, machine learning, microscopy
Electronic versions: 
Source: Scopus
Source ID: 85058853028

Research output: Contribution to journalReview ArticleScientificpeer-review

Synthetic metabolic pathway for the production of 1-alkenes from lignin-derived molecules

Background: Integration of synthetic metabolic pathways to catabolically diverse chassis provides new opportunities for sustainable production. One attractive scenario is the use of abundant waste material to produce a readily collectable product, which can reduce the production costs. Towards that end, we established a cellular platform for the production of semivolatile medium-chain α-olefins from lignin-derived molecules: we constructed 1-undecene synthesis pathway in Acinetobacter baylyi ADP1 using ferulate, a lignin-derived model compound, as the sole carbon source for both cell growth and product synthesis. Results: In order to overcome the toxicity of ferulate, we first applied adaptive laboratory evolution to A. baylyi ADP1, resulting in a highly ferulate-tolerant strain. The adapted strain exhibited robust growth in 100 mM ferulate while the growth of the wild type strain was completely inhibited. Next, we expressed two heterologous enzymes in the wild type strain to confer 1-undecene production from glucose: a fatty acid decarboxylase UndA from Pseudomonas putida, and a thioesterase 'TesA from Escherichia coli. Finally, we constructed the 1-undecene synthesis pathway in the ferulate-tolerant strain. The engineered cells were able to produce biomass and 1-undecene solely from ferulate, and excreted the product directly to the culture headspace. Conclusions: In this study, we employed a bacterium Acinetobacter baylyi ADP1 to integrate a natural aromatics degrading pathway to a synthetic production route, allowing the upgradation of lignin derived molecules to value-added products. We developed a highly ferulate-tolerant strain and established the biosynthesis of an industrially relevant chemical, 1-undecene, solely from the lignin-derived model compound. This study reports the production of alkenes from lignin derived molecules for the first time and demonstrates the potential of lignin as a sustainable resource in the bio-based synthesis of valuable products.

General information

Publication status: Published
MoE publication type: A1 Journal article-refereed
Organisations: Materials Science and Environmental Engineering, Research group: Bio- and Circular Economy
Contributors: Luo, J., Lehtinen, T., Efimova, E., Santala, V., Santala, S.
Number of pages: 13
Publication date: 11 Mar 2019
Peer-reviewed: Yes

Publication information

Journal: Microbial Cell Factories
Volume: 18
Issue number: 1
Article number: 48
ISSN (Print): 1475-2859
Ratings: 
  • Scopus rating (2019): CiteScore 7.4 SJR 1.356 SNIP 1.308
Original language: English
ASJC Scopus subject areas: Biotechnology, Bioengineering, Applied Microbiology and Biotechnology
Keywords: 1-Alkenes, Acinetobacter baylyi, Adaptive laboratory evolution, Ferulate, Lignin
Source: Scopus
Source ID: 85062867820

Research output: Contribution to journalArticleScientificpeer-review

Vertical stratification of bacteria and archaea in sediments of a small boreal humic lake

Although sediments of small boreal humic lakes are important carbon stores and greenhouse gas sources, the composition and structuring mechanisms of their microbial communities have remained understudied. We analyzed the vertical profiles of microbial biomass indicators (PLFAs, DNA and RNA) and the bacterial and archaeal community composition (sequencing of 16S rRNA gene amplicons and qPCR of mcrA) in sediment cores collected from a typical small boreal lake. While microbial biomass decreased with sediment depth, viable microbes (RNA and PLFA) were present all through the profiles. The vertical stratification patterns of the bacterial and archaeal communities resembled those in marine sediments with well-characterized groups (e.g. Methanomicrobia, Proteobacteria, Cyanobacteria, Bacteroidetes) dominating in the surface sediment and being replaced by poorly-known groups (e.g. Bathyarchaeota, Aminicenantes and Caldiserica) in the deeper layers. The results also suggested that, similar to marine systems, the deep bacterial and archaeal communities were predominantly assembled by selective survival of taxa able to persist in the low energy conditions. Methanotrophs were rare, further corroborating the role of these methanogen-rich sediments as important methane emitters. Based on their taxonomy, the deep-dwelling groups were putatively organo-heterotrophic, organo-autotrophic and/or acetogenic and thus may contribute to changes in the lake sediment carbon storage.

General information

Publication status: Published
MoE publication type: A1 Journal article-refereed
Organisations: Materials Science and Environmental Engineering, Department of Biological and Environmental Science, Jyväskylän yliopisto, University of Eastern Finland
Contributors: Rissanen, A. J., Peura, S., Mpamah, P. A., Taipale, S., Tiirola, M., Biasi, C., Mäki, A., Nykänen, H.
Publication date: 1 Mar 2019
Peer-reviewed: Yes

Publication information

Journal: FEMS Microbiology Letters
Volume: 366
Issue number: 5
ISSN (Print): 0378-1097
Ratings: 
  • Scopus rating (2019): CiteScore 2.4 SJR 0.84 SNIP 0.518
Original language: English
ASJC Scopus subject areas: Microbiology, Molecular Biology, Genetics
Keywords: 16S rRNA, archaea, bacteria, biomass, lake, sediment
Electronic versions: 

Research output: Contribution to journalArticleScientificpeer-review

Metabolic syndrome is associated with decreased heart rate variability in a sex-dependent manner: a comparison between 252 men and 249 women

Impaired heart rate variability (HRV) is associated with increased risk of cardiovascular disease, but evidence regarding alterations of HRV in metabolic syndrome (MetS) remains elusive. In order to examine HRV in MetS, we subjected 501 volunteers without atherosclerosis, diabetes or antihypertensive medication, mean age 48 years, to passive head-up tilt. The subjects were divided to control men (n = 131), men with MetS (n = 121), control women (n = 191) and women with MetS (n = 58) according to the criteria by Alberti et al. (Circulation, 2009, 120, 1640). In unadjusted analyses (i) men and women with MetS had lower total power and high-frequency (HF) power of HRV than controls whether supine or upright (P<0·05 for all). (ii) Supine low-frequency (LF) power of HRV was lower in men (P = 0·012) but not in women (P = 0·064) with MetS than in controls, while men and women with MetS had lower upright LF power of HRV than controls (P <0·01 for both). (iii) The LF:HF ratio did not differ between subjects with and without MetS. After adjustment for age, smoking habits, alcohol intake, height, heart rate and breathing frequency, only the differences in upright total power and HF power of HRV between women with MetS and control women remained significant (P<0·05). In conclusion, reduced total and HF power of HRV in the upright position may partially explain why the relative increase in cardiovascular risk associated with MetS is greater in women than in men. Additionally, the present results emphasize that the confounding factors must be carefully taken into consideration when evaluating HRV.

General information

Publication status: Published
MoE publication type: A1 Journal article-refereed
Organisations: Faculty of Biomedical Sciences and Engineering, Research group: Physiological Measurement Systems and Methods Group, Tampere University Hospital, Central Hospital of Seinäjoki
Contributors: Kangas, P., Tikkakoski, A., Uitto, M., Viik, J., Bouquin, H., Niemelä, O., Mustonen, J., Pörsti, I.
Number of pages: 8
Pages: 160-167
Publication date: Mar 2019
Peer-reviewed: Yes
Early online date: 2018

Publication information

Journal: Clinical Physiology and Functional Imaging
Volume: 39
Issue number: 2
ISSN (Print): 1475-0961
Ratings: 
  • Scopus rating (2019): CiteScore 4.4 SJR 0.659 SNIP 0.866
Original language: English
ASJC Scopus subject areas: Physiology, Physiology (medical)
Keywords: cardiac autonomic tone, cardiovascular risk, head-up tilt, obesity, sex
Source: Scopus
Source ID: 85054818066

Research output: Contribution to journalArticleScientificpeer-review

Iterative unsupervised domain adaptation for generalized cell detection from brightfield z-stacks

Background: Cell counting from cell cultures is required in multiple biological and biomedical research applications. Especially, accurate brightfield-based cell counting methods are needed for cell growth analysis. With deep learning, cells can be detected with high accuracy, but manually annotated training data is required. We propose a method for cell detection that requires annotated training data for one cell line only, and generalizes to other, unseen cell lines. Results: Training a deep learning model with one cell line only can provide accurate detections for similar unseen cell lines (domains). However, if the new domain is very dissimilar from training domain, high precision but lower recall is achieved. Generalization capabilities of the model can be improved with training data transformations, but only to a certain degree. To further improve the detection accuracy of unseen domains, we propose iterative unsupervised domain adaptation method. Predictions of unseen cell lines with high precision enable automatic generation of training data, which is used to train the model together with parts of the previously used annotated training data. We used U-Net-based model, and three consecutive focal planes from brightfield image z-stacks. We trained the model initially with PC-3 cell line, and used LNCaP, BT-474 and 22Rv1 cell lines as target domains for domain adaptation. Highest improvement in accuracy was achieved for 22Rv1 cells. F 1 -score after supervised training was only 0.65, but after unsupervised domain adaptation we achieved a score of 0.84. Mean accuracy for target domains was 0.87, with mean improvement of 16 percent. Conclusions: With our method for generalized cell detection, we can train a model that accurately detects different cell lines from brightfield images. A new cell line can be introduced to the model without a single manual annotation, and after iterative domain adaptation the model is ready to detect these cells with high accuracy.

General information

Publication status: Published
MoE publication type: A1 Journal article-refereed
Organisations: BioMediTech, Tampere University of Applied Sciences, University of Eastern Finland
Contributors: Liimatainen, K., Kananen, L., Latonen, L., Ruusuvuori, P.
Publication date: 15 Feb 2019
Peer-reviewed: Yes

Publication information

Journal: BMC Bioinformatics
Volume: 20
Issue number: 1
Article number: 80
ISSN (Print): 1471-2105
Ratings: 
  • Scopus rating (2019): CiteScore 4.6 SJR 1.626 SNIP 1.156
Original language: English
ASJC Scopus subject areas: Structural Biology, Biochemistry, Molecular Biology, Computer Science Applications, Applied Mathematics
Keywords: Brightfield, Cell detection, Deep learning, Semi-supervised learning, Unsupervised domain adaptation
Electronic versions: 

Bibliographical note

DUPL=47150514

Source: Scopus
Source ID: 85061610929

Research output: Contribution to journalArticleScientificpeer-review

Regulation of asymmetries in the kinetics and protein numbers of bacterial gene expression

Genetic circuits change the status quo of cellular processes when their protein numbers cross thresholds. We investigate the regulation of RNA and protein threshold crossing propensities in Escherichia coli. From in vivo single RNA time-lapse microscopy data from multiple promoters, mutants, induction schemes and media, we study the asymmetry and tailedness (quantified by the skewness and kurtosis, respectively) of the distributions of time intervals between transcription events. We find that higher thresholds can be reached by increasing the skewness and kurtosis, which is shown to be achievable without affecting mean and coefficient of variation, by regulating the rate-limiting steps in transcription initiation. Also, they propagate to the skewness and kurtosis of the distributions of protein expression levels in cell populations. The results suggest that the asymmetry and tailedness of RNA and protein numbers in cell populations, by controlling the propensity for threshold crossing, and due to being sequence dependent and subject to regulation, may be key regulatory variables of decision-making processes in E. coli.

General information

Publication status: Published
MoE publication type: A1 Journal article-refereed
Organisations: Research group: Laboratory of Biosystem Dynamics-LBD, Faculty of Biomedical Sciences and Engineering, Signal Processing
Contributors: Startceva, S., Kandavalli, V. K., Visa, A., Ribeiro, A. S.
Number of pages: 10
Pages: 119-128
Publication date: 1 Feb 2019
Peer-reviewed: Yes
Early online date: 14 Dec 2018

Publication information

Journal: Biochimica et Biophysica Acta - Gene Regulatory Mechanisms
Volume: 1862
Issue number: 2
ISSN (Print): 1874-9399
Ratings: 
  • Scopus rating (2019): SJR 1.92 SNIP 1.066
Original language: English
ASJC Scopus subject areas: Biophysics, Structural Biology, Biochemistry, Molecular Biology, Genetics
Keywords: Asymmetry and tailedness, RNA and protein numbers, Single-cell time-lapse microscopy, Threshold crossing, Transcription initiation
Electronic versions: 
Source: Scopus
Source ID: 85058814221

Research output: Contribution to journalArticleScientificpeer-review

Detection of Pancreatic Cancer by Urine Volatile Organic Compound Analysis

BACKGROUND/AIM: Most pancreatic cancer patients are diagnosed at an advanced stage, since the diagnosis is demanding. Field asymmetric waveform ion mobility spectrometry (FAIMS) is a sensitive technique used for the detection of volatile organic compounds (VOC). We evaluated the ability of FAIMS to discriminate between pancreatic cancer and healthy controls from a urine sample. PATIENTS AND METHODS: For a proof-of-concept study in three Finnish hospitals, 68 patients with pancreatic cancer, 36 with acute pancreatitis, 18 with chronic pancreatitis, 8 with pancreatic pre-malign lesions and 52 healthy controls were prospectively recruited. Urine samples were collected at the time of diagnosis and stored at -70°C. The samples were subsequently measured with FAIMS. The data were processed with linear discriminant analysis and cross-validated with leave-one-out cross-validation. RESULTS: FAIMS distinguished pancreatic cancer from controls with a sensitivity of 79% and specificity of 79%. CONCLUSION: As a non-invasive and rapid urine test, FAIMS can discriminate patients with pancreatic cancer from healthy controls.

General information

Publication status: Published
MoE publication type: A1 Journal article-refereed
Organisations: Faculty of Biomedical Sciences and Engineering, University of Eastern Finland, University Central Hospital Kuopio, Hatanpää Hospital, Central Hospital of Seinäjoki, Tampere University Hospital, Fimlab Laboratories Ltd, Finnish Cardiovascular Research Center
Contributors: Nissinen, S. I., Roine, A., Hokkinen, L., Karjalainen, M., Venäläinen, M., Helminen, H., Niemi, R., Lehtimäki, T., Rantanen, T., Oksala, N.
Number of pages: 7
Pages: 73-79
Publication date: Jan 2019
Peer-reviewed: Yes
Early online date: 2018

Publication information

Journal: Anticancer Research
Volume: 39
Issue number: 1
ISSN (Print): 0250-7005
Ratings: 
  • Scopus rating (2019): CiteScore 3.3 SJR 0.716 SNIP 0.633
Original language: English
ASJC Scopus subject areas: Oncology, Cancer Research
Keywords: FAIMS, linear discriminant analysis, Pancreatic cancer, pre-malignant lesion, urine test, volatile organic compound
Source: Scopus
Source ID: 85059243029

Research output: Contribution to journalArticleScientificpeer-review

Advances in Human Stem Cell-Derived Neuronal Cell Culturing and Analysis

This chapter provides an overview of the current stage of human in vitro functional neuronal cultures, their biological application areas, and modalities to analyze their behavior. During the last 10 years, this research area has changed from being practically non-existent to one that is facing high expectations. Here, we present a case study as a comprehensive short history of this process based on extensive studies conducted at NeuroGroup (University of Tampere) and Computational Biophysics and Imaging Group (Tampere University of Technology), ranging from the differentiation and culturing of human pluripotent stem cell (hPSC)-derived neuronal networks to their electrophysiological analysis. After an introduction to neuronal differentiation in hPSCs, we review our work on their functionality and approaches for extending cultures from 2D to 3D systems. Thereafter, we discuss our target applications in neuronal developmental modeling, toxicology, drug screening, and disease modeling. The development of signal analysis methods was required due to the unique functional and developmental properties of hPSC-derived neuronal cells and networks, which separate them from their much-used rodent counterparts. Accordingly, a line of microelectrode array (MEA) signal analysis methods was developed. This work included the development of action potential spike detection methods, entropy-based methods and additional methods for burst detection and quantification, joint analysis of spikes and bursts to analyze the spike waveform compositions of bursts, assessment methods for network synchronization, and computational simulations of synapses and neuronal networks.

General information

Publication status: Published
MoE publication type: A3 Part of a book or another research book
Organisations: Research group: Computational Biophysics and Imaging Group, BioMediTech, NeuroGroup, Danish Research Institute of Translational Neuroscience - DANDRITE, Aarhus Universitet, Department of Biomedicine, Tampere University
Contributors: Ylä-Outinen, L., Tanskanen, J. M., Kapucu, F. E., Hyysalo, A., Hyttinen, J. A., Narkilahti, S.
Number of pages: 31
Pages: 299-329
Publication date: 2019

Host publication information

Title of host publication: In Vitro Neuronal Networks : From Culturing Methods to Neuro-Technological Applications
Publisher: Springer New York LLC
ISBN (Print): 978-3-030-11134-2
ISBN (Electronic): 978-3-030-11135-9

Publication series

Name: Advances in Neurobiology
Volume: 22
ISSN (Print): 2190-5215
ASJC Scopus subject areas: Biochemistry, Neurology, Developmental Neuroscience, Cellular and Molecular Neuroscience
Keywords: Human neurons, Human pluripotent stem cells, Microelectrode arrays, Signal analysis
URLs: 

Bibliographical note

EXT="Ylä-Outinen, Laura"
EXT="Kapucu, Fikret E."

Source: Scopus
Source ID: 85065845190

Research output: Chapter in Book/Report/Conference proceedingChapterScientificpeer-review

Bioactive glass-ceramics: From macro to nano

Bioactive glasses have opened the path to a new generation of biomaterials that are able to promote new bone formation by triggering bone cell signaling pathways. They can also promote angiogenesis, confer antimicrobial properties, and control the release of therapeutic ions as well as bond to soft tissue. The most used bioactive glasses belong to the silicate family. However, their low network connectivity generally leads to poor thermal processability, inhibiting proper sintering or fiber drawing. Their crystallization can decrease or even suppress the bioactivity. While crystallization of known bioactive glasses cannot be controlled, researchers have developed glass-ceramics. They showed that upon control of the crystalline phase, overall crystallinity, and crystal size the bioactivity could be maintained or improved, the mechanical property can be enhanced, and the dissolution profile controlled. Glass-ceramics have found space in dental and bone applications. Routes to nanostructure the glass-ceramics surface have led to unique biological properties.

General information

Publication status: Published
MoE publication type: A3 Part of a book or another research book
Organisations: BioMediTech
Contributors: Massera, J.
Number of pages: 18
Pages: 275-292
Publication date: 2019

Host publication information

Title of host publication: Nanostructured Biomaterials for Regenerative Medicine
Publisher: Woodhead Publishing
ISBN (Print): 9780081025956
ISBN (Electronic): 9780081025949
ASJC Scopus subject areas: Medicine(all), Biochemistry, Genetics and Molecular Biology(all)
Keywords: Bioactive glasses, Cells, Clinical applications, Crystallization, Glass-ceramics

Research output: Chapter in Book/Report/Conference proceedingChapterScientificpeer-review

Disease modeling of a mutation in α-actinin 2 guides clinical therapy in hypertrophic cardiomyopathy

Hypertrophic cardiomyopathy (HCM) is a cardiac genetic disease accompanied by structural and contractile alterations. We identified a rare c.740C>T (p.T247M) mutation in ACTN2, encoding α-actinin 2 in a HCM patient, who presented with left ventricular hypertrophy, outflow tract obstruction, and atrial fibrillation. We generated patient-derived human-induced pluripotent stem cells (hiPSCs) and show that hiPSC-derived cardiomyocytes and engineered heart tissues recapitulated several hallmarks of HCM, such as hypertrophy, myofibrillar disarray, hypercontractility, impaired relaxation, and higher myofilament Ca2+ sensitivity, and also prolonged action potential duration and enhanced L-type Ca2+ current. The L-type Ca2+ channel blocker diltiazem reduced force amplitude, relaxation, and action potential duration to a greater extent in HCM than in isogenic control. We translated our findings to patient care and showed that diltiazem application ameliorated the prolonged QTc interval in HCM-affected son and sister of the index patient. These data provide evidence for this ACTN2 mutation to be disease-causing in cardiomyocytes, guiding clinical therapy in this HCM family. This study may serve as a proof-of-principle for the use of hiPSC for personalized treatment of cardiomyopathies.

General information

Publication status: E-pub ahead of print
MoE publication type: A1 Journal article-refereed
Organisations: BioMediTech, Hamburg-Eppendorf, National Research Council, Humanitas Clinical and Research Center, University of Oxford, partner site Hamburg/Kiel/Lübeck
Contributors: Prondzynski, M., Lemoine, M. D., Zech, A. T., Horváth, A., Di Mauro, V., Koivumäki, J. T., Kresin, N., Busch, J., Krause, T., Krämer, E., Schlossarek, S., Spohn, M., Friedrich, F. W., Münch, J., Laufer, S. D., Redwood, C., Volk, A. E., Hansen, A., Mearini, G., Catalucci, D., Meyer, C., Christ, T., Patten, M., Eschenhagen, T., Carrier, L.
Publication date: 2019
Peer-reviewed: Yes

Publication information

Journal: EMBO Molecular Medicine
Article number: e11115
ISSN (Print): 1757-4676
Ratings: 
  • Scopus rating (2019): CiteScore 17.2 SJR 4.816 SNIP 2.057
Original language: English
ASJC Scopus subject areas: Molecular Medicine
Keywords: disease modeling, human-induced pluripotent stem cells, hypertrophic cardiomyopathy, long QT syndrome, precision medicine
Electronic versions: 
Source: Scopus
Source ID: 85074749509

Research output: Contribution to journalArticleScientificpeer-review

Do bone geometric properties of the proximal femoral diaphysis reflect loading history, muscle properties, or body dimensions?

Objectives: The aim of this study was to investigate activity-induced effects from bone geometric properties of the proximal femur in athletic vs nonathletic healthy females by statistically controlling for variation in body size, lower limb isometric, and dynamic muscle strength, and cross-sectional area of Musculus gluteus maximus. Methods: The material consists of hip and proximal thigh magnetic resonance images of Finnish female athletes (N = 91) engaged in either high jump, triple jump, soccer, squash, powerlifting, endurance running or swimming, and a group of physically active nonathletic women (N = 20). Cross-sectional bone geometric properties were calculated for the lesser trochanter, sub-trochanter, and mid-shaft of the femur regions. Bone geometric properties were analyzed using a general linear model that included body size, muscle size, and muscle strength as covariates. Results: Body size and isometric muscle strength were positively associated with bone geometric properties at all three cross-sectional levels of the femur, while muscle size was positively associated with bone properties only at the femur mid-shaft. When athletes were compared to nonathletic females, triple jump, soccer, and squash resulted in greater values in all studied cross-sections; high jump and endurance running resulted in greater values at the femoral mid-shaft cross-section; and swimming resulted in lower values at sub-trochanter and femur mid-shaft cross-sections. Conclusions: Activity effects from ground impact loading were associated with higher bone geometric values, especially at the femur mid-shaft, but also at lesser and sub-trochanter cross-sections. Bone geometric properties along the femur can be used to assess the mechanical stimuli experienced, where ground impact loading seems to be more important than muscle loading.

General information

Publication status: E-pub ahead of print
MoE publication type: A1 Journal article-refereed
Organisations: Computing Sciences, Civil Engineering, BioMediTech, Univ of Oulu, Natural Resources Institute Finland (Luke), Jyväskylän yliopisto, GeroCenter Foundation, Jyvaskyla Central Hospital, CNRS, Université de Bordeaux, ICMCB, UKK Institute Finland
Contributors: Niinimäki, S., Narra, N., Härkönen, L., Abe, S., Nikander, R., Hyttinen, J., Knüsel, C. J., Sievänen, H.
Publication date: 2019
Peer-reviewed: Yes

Publication information

Journal: American Journal of Human Biology
Article number: e23246
ISSN (Print): 1042-0533
Ratings: 
  • Scopus rating (2019): CiteScore 2.6 SJR 0.565 SNIP 0.734
Original language: English
ASJC Scopus subject areas: Anatomy, Ecology, Evolution, Behavior and Systematics, Anthropology, Genetics
Source: Scopus
Source ID: 85064702174

Research output: Contribution to journalArticleScientificpeer-review

L1000 viewer: A search engine and Web interface for the LINCS data repository

The LINCS L1000 data repository contains almost two million gene expression profiles for thousands of small molecules and drugs. However, due to the complexity and the size of the data repository and a lack of an interoperable interface, the creation of pharmacologically meaningful workflows utilizing these data is severely hampered. In order to overcome this limitation, we developed the L1000 Viewer, a search engine and graphical web interface for the LINCS data repository. The web interface serves as an interactive platform allowing the user to select different forms of perturbation profiles, e.g., for specific cell lines, drugs, dosages, time points and combinations thereof. At its core, our method has a database we created from inferring and utilizing the intricate dependency graph structure among the data files. The L1000 Viewer is accessible via http://L1000viewer.bio-complexity.com/.

General information

Publication status: Published
MoE publication type: A1 Journal article-refereed
Organisations: Computing Sciences, Research group: Predictive Society and Data Analytics (PSDA), University of Applied Sciences Upper Austria, School of Medical Engineering and Applied Social Sciences, Hall in Tyrol, Nankai University
Contributors: Musa, A., Tripathi, S., Dehmer, M., Emmert-Streib, F.
Publication date: 2019
Peer-reviewed: Yes

Publication information

Journal: Frontiers in Genetics
Volume: 10
Issue number: JUN
Article number: 557
ISSN (Print): 1664-8021
Ratings: 
  • Scopus rating (2019): SJR 1.469 SNIP 0.975
Original language: English
ASJC Scopus subject areas: Molecular Medicine, Genetics, Genetics(clinical)
Keywords: Big data, Data science, Gene expression, Pharmacogenomics, Visualization, Web application
Electronic versions: 
Source: Scopus
Source ID: 85068966589

Research output: Contribution to journalArticleScientificpeer-review

Mechanical impact stimulation platform tailored for high-resolution light microscopy

High frequency (HF) mechanical vibration has been used in vitro to study the cellular response to mechanical stimulation and induce stem cell differentiation. However, detailed understanding of the effect of the mechanical cues on cellular physiology is lacking. To meet this limitation, we have designed a system, which enables monitoring of living cells by high-resolution light microscopy during mechanical stimulation by HF vibration or mechanical impacts. The system consists of a commercial speaker, and a 3D printed sample vehicle and frame. The speaker moves the sample in the horizontal plane, allowing simultaneous microscopy. The HF vibration (30–200 Hz) performances of two vehicles made of polymer and aluminum were characterized with accelerometer. The mechanical impacts were characterized by measuring the acceleration of the aluminum vehicle and by time lapse imaging. The lighter polymer vehicle produced higher HF vibration magnitudes at 30–50 Hz frequencies than the aluminum vehicle. However, the aluminum vehicle performed better at higher frequencies (60–70 Hz, 90–100 Hz, 150 Hz). Compatibility of the system in live cell experiments was investigated with epithelial cells (MDCKII, expressing Emerald-Occludin) and HF (0.56 Gpeak, 30 Hz and 60 Hz) vibration. Our findings indicated that our system is compatible with high-resolution live cell microscopy. Furthermore, the epithelial cells were remarkable stable under mechanical vibration stimulation. To conclude, we have designed an inexpensive tool for the studies of cellular biophysics, which combines versatile in vivo like mechanical stimuli with live cell imaging, showing a great potential for several cellular applications.

General information

Publication status: E-pub ahead of print
MoE publication type: A1 Journal article-refereed
Organisations: BioMediTech, Research group: Computational Biophysics and Imaging Group
Contributors: Halonen, H. T., Hyttinen, J. A., Ihalainen, T. O.
Publication date: 2019
Peer-reviewed: Yes

Publication information

Journal: HEALTH AND TECHNOLOGY
ISSN (Print): 2190-7188
Ratings: 
  • Scopus rating (2019): SJR 0.246 SNIP 0.631
Original language: English
ASJC Scopus subject areas: Biotechnology, Bioengineering, Applied Microbiology and Biotechnology, Biomedical Engineering
Keywords: HF vibration, In vitro mechanical stimulation, Live cell imaging, Mechanical impacts, Mechanobiology, Real-time imaging
Source: Scopus
Source ID: 85074696220

Research output: Contribution to journalArticleScientificpeer-review

Metabolic profiling of water-soluble compounds from the extracts of dark septate endophytic fungi (DSE) isolated from scots pine (Pinus sylvestris L.) seedlings using UPLC–orbitrap–MS

Endophytes are microorganisms living inside plant hosts and are known to be beneficial for the host plant vitality. In this study, we isolated three endophytic fungus species from the roots of Scots pine seedlings growing on Finnish drained peatland setting. The isolated fungi belonged to dark septate endophytes (DSE). The metabolic profiles of the hot water extracts of the fungi were investigated using Ultrahigh Performance Liquid Chromatography with Diode Array Detection and Electron Spray Ionization source Mass Spectrometry with Orbitrap analyzer (UPLC–DAD–ESI–MS–Orbitrap). Out of 318 metabolites, we were able to identify 220, of which a majority was amino acids and peptides. Additionally, opine amino acids, amino acid quinones, Amadori compounds, cholines, nucleobases, nucleosides, nucleotides, siderophores, sugars, sugar alcohols and disaccharides were found, as well as other previously reported metabolites from plants or endophytes. Some differences of the metabolic profiles, regarding the amount and identity of the found metabolites, were observed even though the fungi were isolated from the same host. Many of the discovered metabolites have been described possessing biological activities and properties, which may make a favorable contribution to the host plant nutrient availability or abiotic and biotic stress tolerance.

General information

Publication status: Published
MoE publication type: A1 Journal article-refereed
Organisations: Materials Science and Environmental Engineering, Research group: Bio- and Circular Economy, Natural Resources Institute Finland (Luke), Turku University of Applied Science, University of Helsinki, School of Chemical Engineering, Aalto University
Contributors: Tienaho, J., Karonen, M., Muilu–Mäkelä, R., Wähälä, K., Denegri, E. L., Franzén, R., Karp, M., Santala, V., Sarjala, T.
Publication date: 2019
Peer-reviewed: Yes

Publication information

Journal: Molecules
Volume: 24
Issue number: 12
Article number: 2330
ISSN (Print): 1420-3049
Ratings: 
  • Scopus rating (2019): SJR 0.698 SNIP 1.15
Original language: English
ASJC Scopus subject areas: Analytical Chemistry, Chemistry (miscellaneous), Molecular Medicine, Pharmaceutical Science, Drug Discovery, Physical and Theoretical Chemistry, Organic Chemistry
Keywords: Acephala applanata, Coniochaeta mutabilis, Endophytes, Endophytic fungi, Humicolopsis cephalosporioides, Metabolites, Peptides, Phialocephala fortinii, Scots pine, UPLC–MS
Electronic versions: 

Bibliographical note

EXT="Franzén, Robert"

Source: Scopus
Source ID: 85068104207

Research output: Contribution to journalArticleScientificpeer-review

Optical wireless cochlear implants

In the present contribution, we introduce a wireless optical communication-based system architecture which is shown to significantly improve the reliability and the spectral and power efficiency of the transcutaneous link in cochlear implants (CIs). We refer to the proposed system as optical wireless cochlear implant (OWCI). In order to provide a quantified understanding of its design parameters, we establish a theoretical framework that takes into account the channel particularities, the integration area of the internal unit, the transceivers misalignment, and the characteristics of the optical units. To this end, we derive explicit expressions for the corresponding average signal-to-noise-ratio, outage probability, ergodic spectral efficiency and capacity of the transcutaneous optical link (TOL). These expressions are subsequently used to assess the dependence of the TOL’s communication quality on the transceivers design parameters and the corresponding channels characteristics. The offered analytic results are corroborated with respective results from Monte Carlo simulations. Our findings reveal that OWCI is a particularly promising architecture that drastically increases the reliability and effectiveness of the CI TOL, whilst it requires considerably lower transmit power compared to the corresponding widely-used radio frequency (RF) solution.

General information

Publication status: Published
MoE publication type: A1 Journal article-refereed
Organisations: Research group: Wireless Communications and Positioning, Electrical Engineering, Aristotle University of Thessaloniki, Khalifa University, University of Piraeus, Department of Electrical and Computer Engineering
Contributors: Trevlakis, S. E., Boulogeorgos, A. A. A., Sofotasios, P. C., Muhaidat, S., Karagiannidis, G. K.
Number of pages: 24
Pages: 707-730
Publication date: 2019
Peer-reviewed: Yes

Publication information

Journal: Biomedical Optics Express
Volume: 10
Issue number: 2
ISSN (Print): 2156-7085
Ratings: 
  • Scopus rating (2019): CiteScore 6.7 SJR 1.591 SNIP 1.796
Original language: English
ASJC Scopus subject areas: Biotechnology, Atomic and Molecular Physics, and Optics
Source: Scopus
Source ID: 85061526751

Research output: Contribution to journalArticleScientificpeer-review

O2-requiring molecular reporters of gene expression for anaerobic microorganisms

Many genetic reporter systems require molecular oxygen; therefore, the use of reporter genes to study molecular mechanisms in anaerobic microorganisms has been hampered by the lack of convenient reporting systems. We describe reporter gene whole cell-based biosensor systems based on luciferase genes and the associated oxygen-requiring enzymes. By using two different oxygen-dependent reporters, insect and bacterial luciferases, and two bacterial hosts, Gram (+) Bifidobacterium longum and Gram (-) Escherichia coli, we show that the enzymes can be used in gene expression studies of anaerobic bacteria. E. coli, a facultative anaerobe, was grown both in aerobic and anaerobic conditions with an arabinose-inducible expression system. We show that a short treatment time of few minutes in ambient atmosphere is sufficient to detect light emission from living cells that is directly proportional to the number of cells and to the inducer concentration. The induction levels were the same in both the aerobically and anaerobically cultured cells. Similar results were obtained in the case of B. longum cultured in anaerobic conditions.

General information

Publication status: Published
MoE publication type: A1 Journal article-refereed
Organisations: Chemistry and Bioengineering, Research group: Bio- and Circular Economy, Università degli Studi di Milano
Contributors: Guglielmetti, S., Santala, V., Mangayil, R., Ciranna, A., Karp, M. T.
Number of pages: 6
Pages: 1-6
Publication date: 2019
Peer-reviewed: Yes
Early online date: 20 Sep 2018

Publication information

Journal: Biosensors and Bioelectronics
Volume: 123
ISSN (Print): 0956-5663
Ratings: 
  • Scopus rating (2019): SJR 2.68 SNIP 1.888
Original language: English
ASJC Scopus subject areas: Biotechnology, Biophysics, Biomedical Engineering, Electrochemistry
Keywords: Bioluminescence, Gram (+), Gram (-), Luciferase, Arabinose induction
Electronic versions: 
Source: Scopus
Source ID: 85053858794

Research output: Contribution to journalArticleScientificpeer-review

Prostate cancer gene regulatory network inferred from RNA-seq data

Background: Cancer is a complex disease with a lucid etiology and in understanding the causation, we need to appreciate this complexity. Objective: Here we are aiming to gain insights into the genetic associations of prostate cancer through a network-based systems approach using the BC3Net algorithm. Methods: Specifically, we infer a prostate cancer Gene Regulatory Network (GRN) from a large-scale gene expression data set of 333 patient RNA-seq profiles obtained from The Cancer Genome Atlas (TCGA) database. Results: We analyze the functional components of the inferred network by extracting subnetworks based on biological process information and interpret the role of known cancer genes within each process. Furthermore, we investigate the local landscape of prostate cancer genes and discuss pathological associations that may be relevant in the development of new targeted cancer therapies. Conclusion: Our network-based analysis provides a practical systems biology approach to reveal the collective gene-interactions of prostate cancer. This allows a close interpretation of biological activity in terms of the hallmarks of cancer.

General information

Publication status: Published
MoE publication type: A1 Journal article-refereed
Organisations: Research group: Computational Medicine and Statistical Learning Laboratory (CMSL), Computing Sciences, Research group: Predictive Society and Data Analytics (PSDA), Queen's University, Belfast, Northern Ireland, Harvard Medical School, Hall in Tyrol, Nankai University, University of Applied Sciences Upper Austria, School of Management
Contributors: Moore, D., Simoes, R. D. M., Dehmer, M., Emmert-Streib, F.
Number of pages: 11
Pages: 38-48
Publication date: 2019
Peer-reviewed: Yes

Publication information

Journal: CURRENT GENOMICS
Volume: 20
Issue number: 1
ISSN (Print): 1389-2029
Ratings: 
  • Scopus rating (2019): SJR 0.766 SNIP 0.721
Original language: English
ASJC Scopus subject areas: Genetics, Genetics(clinical)
Keywords: Data science, Gene regulatory network, Genomics, Network inference, Precision medicine, Prostate cancer, Systems biology
Source: Scopus
Source ID: 85067620170

Research output: Contribution to journalArticleScientificpeer-review

Proteome-transcriptome alignment of molecular portraits achieved by self-contained gene set analysis: Consensus colon cancer subtypes case study

Gene set analysis (GSA) has become the common methodology for analyzing transcriptomics data. However, self-contained GSA techniques are rarely, if ever, used for proteomics data analysis. Here we present a self-contained proteome level GSA of four consensus molecular subtypes (CMSs) previously established by transcriptome dissection of colon carcinoma specimens. Despite notable difference in structure of proteomics and transcriptomics data, many pathway-wide characteristic features of CMSs found at the mRNA level were reproduced at the protein level. In particular, CMS1 features show heavy involvement of immune system as well as the pathways related to mismatch repair, DNA replication and functioning of proteasome, while CMS4 tumors upregulate complement pathway and proteins participating in epithelial-to-mesenchymal transition (EMT). In addition, protein level GSA yielded a set of novel observations visible at the proteome, but not at the transcriptome level, including possible involvement of major histocompatibility complex II (MHC-II) antigens in the known immunogenicity of CMS1 and a connection between cholesterol trafficking and the regulation of Integrin-linked kinase (ILK) in CMS3. Overall, this study proves utility of self-contained GSA approaches as a critical tool for analyzing proteomics data in general and dissecting protein-level molecular portraits of human tumors in particular.

General information

Publication status: Published
MoE publication type: A1 Journal article-refereed
Organisations: Research group: Computational Medicine and Statistical Learning Laboratory (CMSL), Computing Sciences, Research group: Predictive Society and Data Analytics (PSDA), University of Arkansas for Medical Sciences, George Mason University, Research Center for Medical Genetics
Contributors: Glazko, G., Zybailov, B., Emmert-Streib, F., Baranova, A., Rahmatallah, Y.
Publication date: 2019
Peer-reviewed: Yes

Publication information

Journal: PLoS ONE
Volume: 14
Issue number: 8
Article number: e0221444
ISSN (Print): 1932-6203
Ratings: 
  • Scopus rating (2019): CiteScore 5.2 SJR 1.023 SNIP 1.205
Original language: English
ASJC Scopus subject areas: Biochemistry, Genetics and Molecular Biology(all), Agricultural and Biological Sciences(all)
Electronic versions: 
Source: Scopus
Source ID: 85071115865

Research output: Contribution to journalArticleScientificpeer-review

Quality and Capacity Analysis of Molecular Communications in Bacterial Synthetic Logic Circuits

Synthetic logic circuits have been proposed as potential solutions for theranostics of biotechnological problems. One proposed model is the engineering of bacteria cells to create logic gates, and the communication between the bacteria populations will enable the circuit operation. In this paper, we analyse the quality of bacteria-based synthetic logic circuit through molecular communications that represent communication along a bus between three gates. In the bacteria-based synthetic logic circuit, the system receives environmental signals as molecular inputs and will process this information through a cascade of synthetic logic gates and free diffusion channels. We analyse the performance of this circuit by evaluating its quality and its relationship to the channel capacity of the molecular communications links that interconnect the bacteria populations. Our results show the effect of the molecular environmental delay and molecular amplitude differences over both the channel capacity and circuit quality. Furthermore, based on these metrics we also obtain an optimum region for the circuit operation resulting in an accuracy of 80&#x0025; for specific conditions. These results show that the performance of synthetic biology circuits can be evaluated through molecular communications, and lays the groundwork for combined systems that can contribute to future biomedical and biotechnology applications.

General information

Publication status: Accepted/In press
MoE publication type: A1 Journal article-refereed
Organisations: Electrical Engineering, Waterford Institute of Technology
Contributors: Martins, D. P., Barros, M. T., Balasubramaniam, S.
Publication date: 2019
Peer-reviewed: Yes

Publication information

Journal: IEEE Transactions on Nanobioscience
ISSN (Print): 1536-1241
Ratings: 
  • Scopus rating (2019): CiteScore 5.4 SJR 0.62 SNIP 1.01
Original language: English
ASJC Scopus subject areas: Biotechnology, Bioengineering, Medicine (miscellaneous), Biomedical Engineering, Pharmaceutical Science, Computer Science Applications, Electrical and Electronic Engineering
Keywords: Engineered bacteria, Logic circuits, Logic gates, Microorganisms, Molecular communication (telecommunication), Molecular communications, Sensors, Sociology, Statistics, Synthetic logic circuits
Source: Scopus
Source ID: 85070392121

Research output: Contribution to journalArticleScientificpeer-review

Recurrent moderate-risk mutations in Finnish breast and ovarian cancer patients

Mutations in BRCA1 and BRCA2 genes predispose to breast and ovarian cancer (BC/OC) with a high lifetime risk, whereas mutations in PALB2, CHEK2, ATM, FANCM, RAD51C and RAD51D genes cause a moderately elevated risk. In the Finnish population, recurrent mutations have been identified in all of these genes, the latest being CHEK2 c.319+2T>A and c.444+1G>A. By genotyping 3,156 cases and 2,089 controls, we estimated the frequencies of CHEK2 c.319+2T>A and c.444+1G>A in Finnish BC patients. CHEK2 c.319+2T>A was detected in 0.7% of the patients, and it was associated with a high risk of BC in the unselected patient group (OR = 5.40 [95% CI 1.58–18.45], p = 0.007) and similarly in the familial patient group. CHEK2 c.444+1G>A was identified in 0.1% of all patients. Additionally, we evaluated the combined prevalence of recurrent moderate-risk gene mutations in 2,487 BC patients, 556 OC patients and 261 BRCA1/2 carriers from 109 families. The overall frequency of the mutations was 13.3% in 1,141 BRCA1/2-negative familial BC patients, 7.5% in 1,727 unselected BC patients and 7.2% in 556 unselected OC patients. At least one moderate-risk gene mutation was found in 12.5% of BRCA1 families and 7.1% of BRCA1 index patients, as well as in 17.0% of BRCA2 families and 11.3% of BRCA2 index patients, and the mutations were associated with an additional risk in the BRCA1/2 index patients (OR = 2.63 [1.15–5.48], p = 0.011). These results support gene panel testing of even multiple members of BC families where several mutations may segregate in different individuals.

General information

Publication status: E-pub ahead of print
MoE publication type: A1 Journal article-refereed
Organisations: BioMediTech, Helsinki University Central Hospital, Turku University Hospital, University of Helsinki
Contributors: Nurmi, A., Muranen, T. A., Pelttari, L. M., Kiiski, J. I., Heikkinen, T., Lehto, S., Kallioniemi, A., Schleutker, J., Bützow, R., Blomqvist, C., Aittomäki, K., Nevanlinna, H.
Publication date: 2019
Peer-reviewed: Yes

Publication information

Journal: International Journal of Cancer
ISSN (Print): 0020-7136
Ratings: 
  • Scopus rating (2019): SJR 2.154 SNIP 1.559
Original language: English
ASJC Scopus subject areas: Oncology, Cancer Research
Keywords: breast cancer, CHEK2, double heterozygote, moderate-risk gene, ovarian cancer
Source: Scopus
Source ID: 85064913446

Research output: Contribution to journalArticleScientificpeer-review

Robocasting of Bioactive SiO2-P2O5-CaO-MgO-Na2O-K2O Glass Scaffolds

Bioactive silicate glass scaffolds were fabricated by a robocasting process in which all the movements of the printing head were programmed by compiling a script (text file). A printable ink made of glass powder and Pluronic F-127, acting as a binder, was extruded to obtain macroporous scaffolds with a grid-like three-dimensional structure. The scaffold architecture was investigated by scanning electron microscopy and microtomographic analysis, which allowed quantifying the microstructural parameters (pore size 150-180 μm and strut diameter 300 μm). In vitro tests in simulated body fluid (SBF) confirmed the apatite-forming ability (i.e., bioactivity) of the scaffolds. The compressive strength (around 10 MPa for as-produced scaffolds) progressively decreased during immersion in SBF (3.3 MPa after 4 weeks) but remains acceptable for bone repair applications. Taken together, these results (adequate porosity and mechanical strength as well as bioactivity) support the potential suitability of the prepared scaffolds for bone substitution.

General information

Publication status: Published
MoE publication type: A1 Journal article-refereed
Organisations: BioMediTech, Politecnico di Torino, Innovation Center Iceland (ICI)
Contributors: Baino, F., Barberi, J., Fiume, E., Orlygsson, G., Massera, J., Verné, E.
Publication date: 2019
Peer-reviewed: Yes

Publication information

Journal: Journal of Healthcare Engineering
Volume: 2019
Article number: 5153136
ISSN (Print): 2040-2295
Ratings: 
  • Scopus rating (2019): SJR 0.42 SNIP 1.052
Original language: English
ASJC Scopus subject areas: Biotechnology, Surgery, Biomedical Engineering, Health Informatics
Electronic versions: 
Source: Scopus
Source ID: 85065603850

Research output: Contribution to journalArticleScientificpeer-review

Synthesis of 6,12-disubstituted methanodibenzo[b,f ][1,5]dioxocins: Pyrrolidine catalyzed self-condensation of 2′-Hydroxyacetophenones

The preparation of unprecedented 6,12-disubstituted methanodibenzo[b,f ][1,5]dioxocins from pyrrolidine catalyzed self-condensation of 2′-hydroxyacetophenones is herein described. This method provides easy access to this highly bridged complex core, resulting in construction of two C-O and two C-C bonds, a methylene bridge and two quaternary centers in a single step. The intricate methanodibenzo[b,f ][1,5]dioxocin compounds were obtained in up to moderate yields after optimization of the reaction conditions concerning solvent, reaction times and the use of additives. Several halide substituted methanodibenzo[b,f ][1,5]dioxocins could be prepared from correspondent 2′-hydroxyacetophenones.

General information

Publication status: Published
MoE publication type: A1 Journal article-refereed
Organisations: Materials Science and Environmental Engineering, Faculdade de Farmacia da Universidade de Lisboa, University of Jyvaskyla
Contributors: Assoah, B., Riihonen, V., Vale, J. R., Valkonen, A., Candeias, N. R.
Publication date: 2019
Peer-reviewed: Yes

Publication information

Journal: Molecules
Volume: 24
Issue number: 13
Article number: 2405
ISSN (Print): 1420-3049
Ratings: 
  • Scopus rating (2019): SJR 0.698 SNIP 1.15
Original language: English
ASJC Scopus subject areas: Analytical Chemistry, Chemistry (miscellaneous), Molecular Medicine, Pharmaceutical Science, Drug Discovery, Physical and Theoretical Chemistry, Organic Chemistry
Keywords: 1,5-dioxocin, 20-hydroxyacetophenone, Enamine, Self-condensation
Electronic versions: 

Bibliographical note

EXT="Valkonen, Arto"
INT=msee,"Riihonen, Vesa"
INT=msee,"Vale, João R."

Source: Scopus
Source ID: 85068362408

Research output: Contribution to journalArticleScientificpeer-review

SCIP: a single-cell image processor toolbox

Summary: Each cell is a phenotypically unique individual that is influenced by internal and external processes, operating in parallel. To characterize the dynamics of cellular processes one needs to observe many individual cells from multiple points of view and over time, so as to identify commonalities and variability. With this aim, we engineered a software, 'SCIP', to analyze multi-modal, multi-process, time-lapse microscopy morphological and functional images. SCIP is capable of automatic and/or manually corrected segmentation of cells and lineages, automatic alignment of different microscopy channels, as well as detect, count and characterize fluorescent spots (such as RNA tagged by MS2-GFP), nucleoids, Z rings, Min system, inclusion bodies, undefined structures, etc. The results can be exported into *mat files and all results can be jointly analyzed, to allow studying not only each feature and process individually, but also find potential relationships. While we exemplify its use on Escherichia coli, many of its functionalities are expected to be of use in analyzing other prokaryotes and eukaryotic cells as well. We expect SCIP to facilitate the finding of relationships between cellular processes, from small-scale (e.g. gene expression) to large-scale (e.g. cell division), in single cells and cell lineages. Availability and implementation: http://www.ca3-uninova.org/project_scip. Supplementary information: Supplementary data are available at Bioinformatics online.

General information

Publication status: Published
MoE publication type: A1 Journal article-refereed
Organisations: Faculty of Biomedical Sciences and Engineering, Campus FCT-UNL
Contributors: Martins, L., Neeli-Venkata, R., Oliveira, S. M., Häkkinen, A., Ribeiro, A. S., Fonseca, J. M.
Number of pages: 3
Pages: 4318-4320
Publication date: 15 Dec 2018
Peer-reviewed: Yes

Publication information

Journal: Bioinformatics
Volume: 34
Issue number: 24
ISSN (Print): 1367-4803
Ratings: 
  • Scopus rating (2018): CiteScore 9.7 SJR 4.549 SNIP 1.908
Original language: English
ASJC Scopus subject areas: Statistics and Probability, Biochemistry, Molecular Biology, Computer Science Applications, Computational Theory and Mathematics, Computational Mathematics

Research output: Contribution to journalArticleScientificpeer-review

Beaming random lasers with soliton control

Random lasers are resonator-less light sources where feedback stems from recurrent scattering at the expense of spatial profile and directionality. Suitably-doped nematic liquid crystals can random lase when optically pumped near resonance(s); moreover, through molecular reorientation within the transparency region, they support self-guided optical spatial solitons, i.e., light-induced waveguides. Here, we synergistically combine solitons and collinear pumping in weakly scattering dye-doped nematic liquid crystals, whereby random lasing and self-confinement concur to beaming the emission, with several improved features: all-optical switching driven by a low-power input, laser directionality and smooth output profile with high-conversion efficiency, externally controlled angular steering. Such effects make soliton-assisted random lasers an outstanding route towards application-oriented random lasers.

General information

Publication status: Published
MoE publication type: A1 Journal article-refereed
Organisations: Photonics, Research group: Nonlinear Optics, University “Roma Tre”, University of Southampton, Case Western Reserve University, CNR-NANOTEC & University of Calabria, Institute for Complex Systems
Contributors: Perumbilavil, S., Piccardi, A., Barboza, R., Buchnev, O., Kauranen, M., Strangi, G., Assanto, G.
Number of pages: 7
Publication date: 1 Dec 2018
Peer-reviewed: Yes

Publication information

Journal: Nature Communications
Volume: 9
Issue number: 1
Article number: 3863
ISSN (Print): 2041-1723
Ratings: 
  • Scopus rating (2018): CiteScore 12.19 SJR 5.992 SNIP 2.86
Original language: English
ASJC Scopus subject areas: Chemistry(all), Biochemistry, Genetics and Molecular Biology(all), Physics and Astronomy(all)
Electronic versions: 
Source: Scopus
Source ID: 85053667214

Research output: Contribution to journalArticleScientificpeer-review

Dynamic decoupling of biomass and wax ester biosynthesis in Acinetobacter baylyi by an autonomously regulated switch

For improving the microbial production of fuels and chemicals, gene knock-outs and overexpression are routinely applied to intensify the carbon flow from substrate to product. However, their possibilities in dynamic control of the flux between the biomass and product synthesis are limited, whereas dynamic metabolic switches can be used for optimizing the distribution of carbon and resources. The production of single cell oils is especially challenging, as the synthesis is strictly regulated, competes directly with biomass, and requires defined conditions, such as nitrogen limitation. Here, we engineered a metabolic switch for redirecting carbon flow from biomass to wax ester production in Acinetobacter baylyi ADP1 using acetate as a carbon source. Isocitrate lyase, an essential enzyme for growth on acetate, was expressed under an arabinose inducible promoter. The autonomous downregulation of the expression is based on the gradual oxidation of the arabinose inducer by a glucose dehydrogenase gcd. The depletion of the inducer, occurring simultaneously to acetate consumption, switches the cells from a biomass mode to a lipid synthesis mode, enabling the efficient channelling of carbon to wax esters in a simple batch culture. In the engineered strain, the yield and titer of wax esters were improved by 3.8 and 3.1 folds, respectively, over the control strain. In addition, the engineered strain accumulated wax esters 19% of cell dry weight, being the highest reported among microbes. The study provides important insights into the dynamic engineering of the biomass-dependent synthesis pathways for the improved production of biocompounds from low-cost and sustainable substrates.

General information

Publication status: Published
MoE publication type: A1 Journal article-refereed
Organisations: Chemistry and Bioengineering, Research group: Bio- and Circular Economy
Contributors: Santala, S., Efimova, E., Santala, V.
Publication date: 1 Dec 2018
Peer-reviewed: Yes

Publication information

Journal: Metabolic Engineering Communications
Volume: 7
Article number: e00078
ISSN (Print): 2214-0301
Ratings: 
  • Scopus rating (2018): CiteScore 7.4 SJR 1.699 SNIP 1.112
Original language: English
ASJC Scopus subject areas: Biotechnology, Bioengineering
Keywords: Acetate, Autonomous circuit, Decoupling, Dynamic control, Lipid biosynthesis, Wax esters
Electronic versions: 
Source: Scopus
Source ID: 85053844687

Research output: Contribution to journalArticleScientificpeer-review

Machine learning plastic deformation of crystals

Plastic deformation of micron-scale crystalline solids exhibits stress-strain curves with significant sample-to-sample variations. It is a pertinent question if this variability is purely random or to some extent predictable. Here we show, by employing machine learning techniques such as regression neural networks and support vector machines that deformation predictability evolves with strain and crystal size. Using data from discrete dislocations dynamics simulations, the machine learning models are trained to infer the mapping from features of the pre-existing dislocation configuration to the stress-strain curves. The predictability vs strain relation is non-monotonic and exhibits a system size effect: larger systems are more predictable. Stochastic deformation avalanches give rise to fundamental limits of deformation predictability for intermediate strains. However, the large-strain deformation dynamics of the samples can be predicted surprisingly well.

General information

Publication status: Published
MoE publication type: A1 Journal article-refereed
Organisations: Physics, Aalto University, Department of Applied Physics
Contributors: Salmenjoki, H., Alava, M. J., Laurson, L.
Publication date: 1 Dec 2018
Peer-reviewed: Yes

Publication information

Journal: Nature Communications
Volume: 9
Issue number: 1
Article number: 5307
ISSN (Print): 2041-1723
Ratings: 
  • Scopus rating (2018): CiteScore 12.19 SJR 5.992 SNIP 2.86
Original language: English
ASJC Scopus subject areas: Chemistry(all), Biochemistry, Genetics and Molecular Biology(all), Physics and Astronomy(all)
Electronic versions: 
Source: Scopus
Source ID: 85058601336

Research output: Contribution to journalArticleScientificpeer-review

Normalization of force to muscle cross-sectional area: A helpful attempt to reduce data scattering in contractility studies?

General information

Publication status: Published
MoE publication type: A1 Journal article-refereed
Organisations: Faculty of Biomedical Sciences and Engineering, Hamburg-Eppendorf, University of Murcia, University of Freiburg
Contributors: Pecha, S., Koivumäki, J., Geelhoed, B., Kempe, R., Berk, E., Engel, A., Reichenspurner, H., Eschenhagen, T., Ravens, U., Kaumann, A., Christ, T.
Number of pages: 4
Publication date: 1 Dec 2018
Peer-reviewed: Yes

Publication information

Journal: Acta Physiologica
Volume: 224
Issue number: 4
Article number: e13202
ISSN (Print): 1748-1708
Ratings: 
  • Scopus rating (2018): CiteScore 3.4 SJR 1.751 SNIP 1.306
Original language: English
ASJC Scopus subject areas: Physiology
Source: Scopus
Source ID: 85056564696

Research output: Contribution to journalEditorialScientificpeer-review

Structural basis of actin monomer re-charging by cyclase-Associated protein

Actin polymerization powers key cellular processes, including motility, morphogenesis, and endocytosis. The actin turnover cycle depends critically on "re-charging" of ADP-Actin monomers with ATP, but whether this reaction requires dedicated proteins in cells, and the underlying mechanism, have remained elusive. Here we report that nucleotide exchange catalyzed by the ubiquitous cytoskeletal regulator cyclase-Associated protein (CAP) is critical for actin-based processes in vivo. We determine the structure of the CAP-Actin complex, which reveals that nucleotide exchange occurs in a compact, sandwich-like complex formed between the dimeric actin-binding domain of CAP and two ADP-Actin monomers. In the crystal structure, the C-Terminal tail of CAP associates with the nucleotide-sensing region of actin, and this interaction is required for rapid re-charging of actin by both yeast and mammalian CAPs. These data uncover the conserved structural basis and biological role of protein-catalyzed re-charging of actin monomers.

General information

Publication status: Published
MoE publication type: A1 Journal article-refereed
Organisations: Physics, University of Helsinki Institute of Biotechnology, Brandeis University
Contributors: Kotila, T., Kogan, K., Enkavi, G., Guo, S., Vattulainen, I., Goode, B. L., Lappalainen, P.
Publication date: 1 Dec 2018
Peer-reviewed: Yes

Publication information

Journal: Nature Communications
Volume: 9
Issue number: 1
Article number: 1892
ISSN (Print): 2041-1723
Ratings: 
  • Scopus rating (2018): CiteScore 12.19 SJR 5.992 SNIP 2.86
Original language: English
ASJC Scopus subject areas: Chemistry(all), Biochemistry, Genetics and Molecular Biology(all), Physics and Astronomy(all)
Electronic versions: 
Source: Scopus
Source ID: 85047005231

Research output: Contribution to journalArticleScientificpeer-review

Bi-directional cell-pericellular matrix interactions direct stem cell fate

Modifiable hydrogels have revealed tremendous insight into how physical characteristics of cells’ 3D environment drive stem cell lineage specification. However, in native tissues, cells do not passively receive signals from their niche. Instead they actively probe and modify their pericellular space to suit their needs, yet the dynamics of cells’ reciprocal interactions with their pericellular environment when encapsulated within hydrogels remains relatively unexplored. Here, we show that human bone marrow stromal cells (hMSC) encapsulated within hyaluronic acid-based hydrogels modify their surroundings by synthesizing, secreting and arranging proteins pericellularly or by degrading the hydrogel. hMSC’s interactions with this local environment have a role in regulating hMSC fate, with a secreted proteinaceous pericellular matrix associated with adipogenesis, and degradation with osteogenesis. Our observations suggest that hMSC participate in a bi-directional interplay between the properties of their 3D milieu and their own secreted pericellular matrix, and that this combination of interactions drives fate.

General information

Publication status: Published
MoE publication type: A1 Journal article-refereed
Organisations: Research group: Biomaterials and Tissue Engineering Group, Faculty of Biomedical Sciences and Engineering, King’s College London, The Francis Crick Institute, UCL Eastman Dental Institute, Imperial College, London, 24.8.2012, University College London, Uppsala University, University of Toronto, Canada
Contributors: Ferreira, S. A., Motwani, M. S., Faull, P. A., Seymour, A. J., Yu, T. T., Enayati, M., Taheem, D. K., Salzlechner, C., Haghighi, T., Kania, E. M., Oommen, O. P., Ahmed, T., Loaiza, S., Parzych, K., Dazzi, F., Varghese, O. P., Festy, F., Grigoriadis, A. E., Auner, H. W., Snijders, A. P., Bozec, L., Gentleman, E.
Number of pages: 12
Publication date: Dec 2018
Peer-reviewed: Yes

Publication information

Journal: Nature Communications
Volume: 9
Issue number: 1
Article number: 4049
ISSN (Print): 2041-1723
Ratings: 
  • Scopus rating (2018): CiteScore 12.19 SJR 5.992 SNIP 2.86
Original language: English
ASJC Scopus subject areas: Chemistry(all), Biochemistry, Genetics and Molecular Biology(all), Physics and Astronomy(all)
Electronic versions: 
Source: Scopus
Source ID: 85054315213

Research output: Contribution to journalArticleScientificpeer-review

The importance of controlled mismatch of biomechanical compliances of implantable scaffolds and native tissue for articular cartilage regeneration

Scaffolds for articular cartilage repair have to be optimally biodegradable with simultaneous promotion of hyaline cartilage formation under rather complex biomechanical and physiological conditions. It has been generally accepted that scaffold structure and composition would be the best when it mimics the structure of native cartilage. However, a reparative construct mimicking the mature native tissue in a healing tissue site presents a biological mismatch of reparative stimuli. In this work, we studied a new recombinant human type III collagen-polylactide (rhCol-PLA) scaffolds. The rhCol-PLA scaffolds were assessed for their relative performance in simulated synovial fluids of 1 and 4 mg/mL sodium hyaluronate with application of model-free analysis with Biomaterials Enhanced Simulation Test (BEST). Pure PLA scaffold was used as a control. The BEST results were compared to the results of a prior in vivo study with rhCol-PLA. Collectively the data indicated that a successful articular cartilage repair require lower stiffness of the scaffold compared to surrounding cartilage yet matching the strain compliance both in static and dynamic conditions. This ensures an optimal combination of load transfer and effective oscillatory nutrients supply to the cells. The results encourage further development of intelligent scaffold structures for optimal articular cartilage repair rather than simply trying to imitate the respective original tissue.

General information

Publication status: Published
MoE publication type: A1 Journal article-refereed
Organisations: Faculty of Biomedical Sciences and Engineering, Aalto University, Seqvera Ltd., University of Helsinki
Contributors: Gasik, M., Zühlke, A., Haaparanta, A., Muhonen, V., Laine, K., Bilotsky, Y., Kellomäki, M., Kiviranta, I.
Publication date: 30 Nov 2018
Peer-reviewed: Yes

Publication information

Journal: Frontiers in Bioengineering and Biotechnology
Volume: 6
Issue number: NOV
Article number: 187
ISSN (Print): 2296-4185
Ratings: 
  • Scopus rating (2018): CiteScore 4.04 SJR 1.248 SNIP 1.327
Original language: English
ASJC Scopus subject areas: Biotechnology, Bioengineering, Histology, Biomedical Engineering
Keywords: Articular cartilage, Biomechanics, Collagen, PLA, Scaffold, Synovial fluid, Testing
Electronic versions: 
Source: Scopus
Source ID: 85058709882

Research output: Contribution to journalArticleScientificpeer-review

Machine learning analysis of extreme events in optical fibre modulation instability

A central research area in nonlinear science is the study of instabilities that drive extreme events. Unfortunately, techniques for measuring such phenomena often provide only partial characterisation. For example, real-time studies of instabilities in nonlinear optics frequently use only spectral data, limiting knowledge of associated temporal properties. Here, we show how machine learning can overcome this restriction to study time-domain properties of optical fibre modulation instability based only on spectral intensity measurements. Specifically, a supervised neural network is trained to correlate the spectral and temporal properties of modulation instability using simulations, and then applied to analyse high dynamic range experimental spectra to yield the probability distribution for the highest temporal peaks in the instability field. We also use unsupervised learning to classify noisy modulation instability spectra into subsets associated with distinct temporal dynamic structures. These results open novel perspectives in all systems exhibiting instability where direct time-domain observations are difficult.

General information

Publication status: Published
MoE publication type: A1 Journal article-refereed
Organisations: Photonics, UMR 6174
Contributors: Närhi, M., Salmela, L., Toivonen, J., Billet, C., Dudley, J. M., Genty, G.
Number of pages: 1
Publication date: 22 Nov 2018
Peer-reviewed: Yes

Publication information

Journal: Nature Communications
Volume: 9
Issue number: 1
ISSN (Print): 2041-1723
Ratings: 
  • Scopus rating (2018): CiteScore 12.19 SJR 5.992 SNIP 2.86
Original language: English
ASJC Scopus subject areas: Chemistry(all), Biochemistry, Genetics and Molecular Biology(all), Physics and Astronomy(all)
Electronic versions: 
Source: Scopus
Source ID: 85057100886

Research output: Contribution to journalArticleScientificpeer-review

M2M Communication Assessment in Energy-Harvesting and Wake-Up Radio Assisted Scenarios Using Practical Components

Techniques for wireless energy harvesting (WEH) are emerging as a fascinating set of solutions to extend the lifetime of energy-constrained wireless networks, and are commonly regarded as a key functional technique for almost perpetual communications. For example, with WEH technology, wireless devices are able to harvest energy from different light sources or Radio Frequency (RF) signals broadcast by ambient or dedicated wireless transmitters to support their operation and communications capabilities. WEH technology will have increasingly wider range of use in upcoming applications such as wireless sensor networks, Machine-to-Machine (M2M) communications, and the Internet of Things. In this paper, the usability and fundamental limits of joint RF and solar cell or photovoltaic harvesting based M2M communication systems are studied and presented. The derived theoretical bounds are in essence based on the Shannon capacity theorem, combined with selected propagation loss models, assumed additional link nonidealities, diversity processing, as well as the given energy harvesting and storage capabilities. Fundamental performance limits and available capacity of the communicating link are derived and analyzed, together with extensive numerical results evaluated in different practical scenarios, including realistic implementation losses and state-of-the-art printed supercapacitor performance figures with voltage doubler-based voltage regulator. In particular, low power sensor type communication applications using passive and semi-passive wake-up radio (WuR) are addressed in the study. The presented analysis principles and results establish clear feasibility regions and performance bounds for wireless energy harvesting based low rate M2M communications in the future IoT networks.

General information

Publication status: Published
MoE publication type: A1 Journal article-refereed
Organisations: Electronics and Communications Engineering, Nano Communication Centre, Department of Electrical and Computer Engineering, Ohio State University
Contributors: Rinne, J., Keskinen, J., Berger, P. R., Lupo, D., Valkama, M.
Publication date: 16 Nov 2018
Peer-reviewed: Yes

Publication information

Journal: Sensors (Basel, Switzerland)
Volume: 18
Issue number: 11
ISSN (Print): 1424-8220
Ratings: 
  • Scopus rating (2018): CiteScore 4.3 SJR 0.592 SNIP 1.642
Original language: English
ASJC Scopus subject areas: Analytical Chemistry, Atomic and Molecular Physics, and Optics, Biochemistry, Instrumentation, Electrical and Electronic Engineering
Keywords: diversity system, M2M communications, perpetual communications, propagation loss, Shannon limit, supercapacitor, wake-up radio, wireless energy harvesting
Electronic versions: 
Source: Scopus
Source ID: 85056711381

Research output: Contribution to journalArticleScientificpeer-review

Molecular-Scale Ligand Effects in Small Gold-Thiolate Nanoclusters

Because of the small size and large surface area of thiolate-protected Au nanoclusters (NCs), the protecting ligands are expected to play a substantial role in modulating the structure and properties, particularly in the solution phase. However, little is known on how thiolate ligands explicitly modulate the structural properties of the NCs at atomic level, even though this information is critical for predicting the performance of Au NCs in application settings including as a catalyst interacting with small molecules and as a sensor interacting with biomolecular systems. Here, we report a combined experimental and theoretical study, using synchrotron X-ray spectroscopy and quantum mechanics/molecular mechanics simulations, that investigates how the protecting ligands impact the structure and properties of small Au18(SR)14 NCs. Two representative ligand types, smaller aliphatic cyclohexanethiolate and larger hydrophilic glutathione, are selected, and their structures are followed experimentally in both solid and solution phases. It was found that cyclohexanethiolate ligands are significantly perturbed by toluene solvent molecules, resulting in structural changes that cause disorder on the surface of Au18(SR)14 NCs. In particular, large surface cavities in the ligand shell are created by interactions between toluene and cyclohexanethiolate. The appearance of these small molecule-accessible sites on the NC surface demonstrates the ability of Au NCs to act as a catalyst for organic phase reactions. In contrast, glutathione ligands encapsulate the Au NC core via intermolecular interactions, minimizing structural changes caused by interactions with water molecules. The much better protection from glutathione ligands imparts a rigidified surface and ligand structure, making the NCs desirable for biomedical applications due to the high stability and also offering a structural-based explanation for the enhanced photoluminescence often reported for glutathione-protected Au NCs.

General information

Publication status: Published
MoE publication type: A1 Journal article-refereed
Organisations: Physics, Dalhousie University, Universitat Autonoma de Barcelona, Spain, Catalan Institute for Research and Advanced Studies (ICREA), Carnegie Mellon University, National University of Singapore, Norwegian Univ. of Sci. and Technol.
Contributors: Chevrier, D. M., Raich, L., Rovira, C., Das, A., Luo, Z., Yao, Q., Chatt, A., Xie, J., Jin, R., Akola, J., Zhang, P.
Number of pages: 7
Pages: 15430-15436
Publication date: 14 Nov 2018
Peer-reviewed: Yes

Publication information

Journal: Journal of the American Chemical Society
Volume: 140
Issue number: 45
ISSN (Print): 0002-7863
Ratings: 
  • Scopus rating (2018): CiteScore 24.4 SJR 7.468 SNIP 2.652
Original language: English
ASJC Scopus subject areas: Catalysis, Chemistry(all), Biochemistry, Colloid and Surface Chemistry
Source: Scopus
Source ID: 85056236370

Research output: Contribution to journalArticleScientificpeer-review

Understanding Dissolution and Crystallization with Imaging: A Surface Point of View

The tendency for crystallization during storage and administration is the most considerable hurdle for poorly water-soluble drugs formulated in the amorphous form. There is a need to better detect often subtle and complex surface crystallization phenomena and understand their influence on the critical quality attribute of dissolution. In this study, the interplay between surface crystallization of the amorphous form during storage and dissolution testing, and its influence on dissolution behavior, is analyzed for the first time with multimodal nonlinear optical imaging (coherent anti-Stokes Raman scattering (CARS) and sum frequency generation (SFG)). Complementary analyses are provided with scanning electron microscopy, X-ray diffraction and infrared and Raman spectroscopies. Amorphous indomethacin tablets were prepared and subjected to two different storage conditions (30 °C/23% RH and 30 °C/75% RH) for various durations and then dissolution testing using a channel flow-through device. Trace levels of surface crystallinity previously imaged with nonlinear optics after 1 or 2 days of storage did not significantly decrease dissolution and supersaturation compared to the freshly prepared amorphous tablets while more extensive crystallization after longer storage times did. Multimodal nonlinear optical imaging of the tablet surfaces after 15 min of dissolution revealed complex crystallization behavior that was affected by both storage condition and time, with up to four crystalline polymorphs simultaneously observed. In addition to the well-known α- and ?-forms, the less reported metastable ?- and ?-forms were also observed, with the ?-form being widely observed in samples that had retained significant surface amorphousness during storage. This form was also prepared in the pure form and further characterized. Overall, this study demonstrates the potential value of nonlinear optical imaging, together with more established solid-state analysis methods, to understand complex surface crystallization behavior and its influence on drug dissolution during the development of amorphous drugs and dosage forms.

General information

Publication status: Published
MoE publication type: A1 Journal article-refereed
Organisations: Chemistry and Bioengineering, Research group: Chemistry & Advanced Materials, University of Helsinki, University of Helsinki Faculty of Medicine, University of Otago
Contributors: Novakovic, D., Isomäki, A., Pleunis, B., Fraser-Miller, S. J., Peltonen, L., Laaksonen, T., Strachan, C. J.
Number of pages: 13
Pages: 5361-5373
Publication date: 5 Nov 2018
Peer-reviewed: Yes

Publication information

Journal: Molecular Pharmaceutics
Volume: 15
Issue number: 11
ISSN (Print): 1543-8384
Ratings: 
  • Scopus rating (2018): CiteScore 7.4 SJR 1.402 SNIP 1.182
Original language: English
ASJC Scopus subject areas: Molecular Medicine, Pharmaceutical Science, Drug Discovery
Keywords: amorphous, dissolution, indomethacin, nonlinear optics, polymorphism, surface crystallization
Electronic versions: 

Bibliographical note

EXT="Isomäki, Antti"

Source: Scopus
Source ID: 85054882971

Research output: Contribution to journalArticleScientificpeer-review

Super-resolution microscopy for biological specimens: Lensless phase retrieval in noisy conditions

The paper is devoted to a computational super-resolution microscopy. A complex-valued wavefront of a transparent biological cellular specimen is restored from multiple intensity diffraction patterns registered with noise. For this problem, the recently developed lensless super-resolution phase retrieval algorithm [Optica, 4(7), 786 (2017)] is modified and tuned. This algorithm is based on a random phase coding of the wavefront and on a sparse complex-domain approximation of the specimen. It is demonstrated in experiments, that the reliable phase and amplitude imaging of the specimen is achieved for the low signal-to-noise ratio provided a low dynamic range of observations. The filterings in the observation domain and specimen variables are specific features of the applied algorithm. If these filterings are omitted the algorithm becomes a super-resolution version of the standard iterative phase retrieval algorithms. In comparison with this simplified algorithm with no filterings, our algorithm shows a valuable improvement in imaging with much smaller number of observations and shorter exposure time. In this way, presented algorithm demonstrates ability to work in a low radiation photon-limited mode.

General information

Publication status: Published
MoE publication type: A1 Journal article-refereed
Organisations: Signal Processing, Research group: Computational Imaging-CI, ITMO University
Contributors: Shevkunov, I., Katkovnik, V., Petrov, N. V., Egiazarian, K.
Number of pages: 13
Pages: 5511-5523
Publication date: 1 Nov 2018
Peer-reviewed: Yes

Publication information

Journal: Biomedical Optics Express
Volume: 9
Issue number: 11
Article number: #340805
ISSN (Print): 2156-7085
Ratings: 
  • Scopus rating (2018): CiteScore 6.5 SJR 1.516 SNIP 1.604
Original language: English
ASJC Scopus subject areas: Biotechnology, Atomic and Molecular Physics, and Optics
Electronic versions: 
Source: Scopus
Source ID: 85056609807

Research output: Contribution to journalArticleScientificpeer-review

How to minimize dye-induced perturbations while studying biomembrane structure and dynamics: PEG linkers as a rational alternative

Organic dye-tagged lipid analogs are essential for many fluorescence-based investigations of complex membrane structures, especially when using advanced microscopy approaches. However, lipid analogs may interfere with membrane structure and dynamics, and it is not obvious that the properties of lipid analogs would match those of non-labeled host lipids. In this work, we bridged atomistic simulations with super-resolution imaging experiments and biomimetic membranes to assess the performance of commonly used sphingomyelin-based lipid analogs. The objective was to compare, on equal footing, the relative strengths and weaknesses of acyl chain labeling, headgroup labeling, and labeling based on poly-ethyl-glycol (PEG) linkers in determining biomembrane properties. We observed that the most appropriate strategy to minimize dye-induced membrane perturbations and to allow consideration of Brownian-like diffusion in liquid-ordered membrane environments is to decouple the dye from a membrane by a PEG linker attached to a lipid headgroup. Yet, while the use of PEG linkers may sound a rational and even an obvious approach to explore membrane dynamics, the results also suggest that the dyes exploiting PEG linkers interfere with molecular interactions and their dynamics. Overall, the results highlight the great care needed when using fluorescent lipid analogs, in particular accurate controls.

General information

Publication status: Published
MoE publication type: A1 Journal article-refereed
Organisations: Physics, University of Helsinki, Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Max Planck Institute of Molecular Cell Biology and Genetics, Weatherall Institute of Molecular Medicine, Friedrich-Schiller-University Jena, Leibniz Institute of Photonic Technology e.V., MEMPHYS - Center for Biomembrane Physics (www.memphys.dk), Laboratory of Physics
Contributors: Mobarak, E., Javanainen, M., Kulig, W., Honigmann, A., Sezgin, E., Aho, N., Eggeling, C., Rog, T., Vattulainen, I.
Pages: 2436-2445
Publication date: Nov 2018
Peer-reviewed: Yes
Early online date: 2018

Publication information

Journal: Biochimica et Biophysica Acta - Biomembranes
Volume: 1860
Issue number: 11
ISSN (Print): 0005-2736
Ratings: 
  • Scopus rating (2018): CiteScore 3.64 SJR 1.427 SNIP 1.108
Original language: English
ASJC Scopus subject areas: Biophysics, Biochemistry, Cell Biology
Keywords: Atomistic simulation, Fluorescent probe, Lipid membrane, Molecular dynamics simulation, PEG linker, Super-resolution microscopy
Electronic versions: 
Source: Scopus
Source ID: 85050121034

Research output: Contribution to journalArticleScientificpeer-review

Alzheimer's disease and alpha-synuclein pathology in the olfactory bulbs of infants, children, teens and adults ≤ 40 years in Metropolitan Mexico City. APOE4 carriers at higher risk of suicide accelerate their olfactory bulb pathology

There is growing evidence that air pollution is a risk factor for a number of neurodegenerative diseases, most notably Alzheimer's (AD) and Parkinson's (PD). It is generally assumed that the pathology of these diseases arises only later in life and commonly begins within olfactory eloquent pathways prior to the onset of the classical clinical symptoms. The present study demonstrates that chronic exposure to high levels of air pollution results in AD- and PD-related pathology within the olfactory bulbs of children and relatively young adults ages 11 months to 40 years. The olfactory bulbs (OBs) of 179 residents of highly polluted Metropolitan Mexico City (MMC) were evaluated for AD- and alpha-synuclein-related pathology. Even in toddlers, hyperphosphorylated tau (hTau) and Lewy neurites (LN) were identified in the OBs. By the second decade, 84% of the bulbs exhibited hTau (48/57), 68% LNs and vascular amyloid (39/57) and 36% (21/57) diffuse amyloid plaques. OB active endothelial phagocytosis of red blood cell fragments containing combustion-derived nanoparticles (CDNPs) and the neurovascular unit damage were associated with myelinated and unmyelinated axonal damage. OB hTau neurites were associated mostly with pretangle stages 1a and 1b in subjects ≤ 20 years of age, strongly suggesting olfactory deficits could potentially be an early guide of AD pretangle subcortical and cortical hTau. APOE4 versus APOE3 carriers were 6–13 times more likely to exhibit OB vascular amyloid, neuronal amyloid accumulation, alpha-synuclein aggregates, hTau neurofibrillary tangles, and neurites. Remarkably, APOE4 carriers were 4.57 times more likely than non-carriers to die by suicide. The present findings, along with previous data that over a third of clinically healthy MMC teens and young adults exhibit low scores on an odor identification test, support the concept that olfactory testing may aid in identifying young people at high risk for neurodegenerative diseases. Moreover, results strongly support early neuroprotective interventions in fine particulate matter (PM2.5) and CDNP's exposed individuals ≤ 20 years of age, and the critical need for air pollution control.

General information

Publication status: Published
MoE publication type: A1 Journal article-refereed
Organisations: Physics, The University of Montana, Universidad del Valle de México, Instituto Nacional de Pediatría, Lake Erie College of Osteopathic Medicine, Boise State University, Department of Electrical Engineering, University of Pennsylvania
Contributors: Calderón-Garcidueñas, L., González-Maciel, A., Reynoso-Robles, R., Kulesza, R. J., Mukherjee, P. S., Torres-Jardón, R., Rönkkö, T., Doty, R. L.
Number of pages: 15
Pages: 348-362
Publication date: 1 Oct 2018
Peer-reviewed: Yes

Publication information

Journal: Environmental Research
Volume: 166
ISSN (Print): 0013-9351
Ratings: 
  • Scopus rating (2018): CiteScore 8.3 SJR 1.567 SNIP 1.578
Original language: English
ASJC Scopus subject areas: Biochemistry, Environmental Science(all)
Keywords: Air pollution, Alpha synuclein, Alpha-synucleinopathies, Alzheimer, Amyloid plaques, APOE4, Children, Combustion-derived nanoparticles CDNPs, Corpora amylacea, Hyperphosphorylated tau, Mexico City, Nanocluster aerosol particles, Olfactory bulb, Parkinson, PM, Suicide, Tauopathies, Young adults
Source: Scopus
Source ID: 85048709486

Research output: Contribution to journalArticleScientificpeer-review

Novel osteoconductive β-tricalcium phosphate/poly(L-lactide-co-e-caprolactone) scaffold for bone regeneration: a study in a rabbit calvarial defect

The advantages of synthetic bone graft substitutes over autogenous bone grafts include abundant graft volume, lack of complications related to the graft harvesting, and shorter operation and recovery times for the patient. We studied a new synthetic supercritical CO2 –processed porous composite scaffold of β-tricalcium phosphate and poly(L-lactide-co-caprolactone) copolymer as a bone graft substitute in a rabbit calvarial defect. Bilateral 12 mm diameter critical size calvarial defects were successfully created in 18 rabbits. The right defect was filled with a scaffold moistened with bone marrow aspirate, and the other was an empty control. The material was assessed for applicability during surgery. The follow-up times were 4, 12, and 24 weeks. Radiographic and micro-CT studies and histopathological analysis were used to evaluate new bone formation, tissue ingrowth, and biocompatibility. The scaffold was easy to shape and handle during the surgery, and the bone-scaffold contact was tight when visually evaluated after the implantation. The material showed good biocompatibility and its porosity enabled rapid invasion of vasculature and full thickness mesenchymal tissue ingrowth already at four weeks. By 24 weeks, full thickness bone ingrowth within the scaffold and along the dura was generally seen. In contrast, the empty defect had only a thin layer of new bone at 24 weeks. The radiodensity of the material was similar to the density of the intact bone. In conclusion, the new porous scaffold material, composed of microgranular β-TCP bound into the polymer matrix, proved to be a promising osteoconductive bone graft substitute with excellent handling properties. [Figure not available: see fulltext.].

General information

Publication status: Published
MoE publication type: A1 Journal article-refereed
Organisations: Electronics and Communications Engineering, Faculty of Biomedical Sciences and Engineering, Research group: Computational Biophysics and Imaging Group, Faculty of Veterinary Medicine, University of Helsinki, Orton Orthopaedic Hospital, Muonio Health Center
Contributors: Pihlman, H., Keränen, P., Paakinaho, K., Linden, J., Hannula, M., Manninen, I. K., Hyttinen, J., Manninen, M., Laitinen-Vapaavuori, O.
Publication date: 1 Oct 2018
Peer-reviewed: Yes

Publication information

Journal: Journal of Materials Science: Materials in Medicine
Volume: 29
Issue number: 10
Article number: 156
ISSN (Print): 0957-4530
Ratings: 
  • Scopus rating (2018): CiteScore 4.7 SJR 0.612 SNIP 0.855
Original language: English
ASJC Scopus subject areas: Biophysics, Bioengineering, Biomaterials, Biomedical Engineering
Source: Scopus
Source ID: 85054473480

Research output: Contribution to journalArticleScientificpeer-review

Molecular Communications Pulse-based Jamming Model for Bacterial Biofilm Suppression

Studies have recently shown that the bacteria survivability within biofilms is responsible for the emergence of superbugs. The combat of bacterial infections, without enhancing its resistance to antibiotics, includes the use of nanoparticles to quench the quorum sensing of these biofilm-forming bacteria. Several sequential and parallel multi-stage communication processes are involved in the formation of biofilms. In this paper, we use proteomic data from a wet lab experiment to identify the communication channels that are vital to these processes.We also identified the main proteins from each channel and propose the use of jamming signals from synthetically engineered bacteria to suppress the production of those proteins. This biocompatible technique is based on synthetic biology and enables the inhibition of biofilm formation. We analyse the communications performance of the jamming process, by evaluating the path loss for a number of conditions that include different engineered bacterial population sizes, distances between the populations and molecular signal power. Our results show that sufficient molecular pulsebased jamming signals are able to prevent the biofilm formation by creating lossy communications channels (almost -3 dB for certain scenarios). From these results, we define the main design parameters to develop a fully operational bacteria-based jamming system.

General information

Publication status: Published
MoE publication type: A1 Journal article-refereed
Organisations: Electronics and Communications Engineering, Research group: Emerging Technologies for Nano-Bio-Info-Cogno, Waterford Institute of Technology, Kasetsart University
Contributors: Martins, D. P., Leetanasaksakul, K., Barros, M. T., Thamchaipenet, A., Donnelly, W., Balasubramaniam, S.
Number of pages: 12
Pages: 533-542
Publication date: Oct 2018
Peer-reviewed: Yes
Early online date: 19 Sep 2018

Publication information

Journal: IEEE Transactions on Nanobioscience
Volume: 17
Issue number: 4
ISSN (Print): 1536-1241
Ratings: 
  • Scopus rating (2018): CiteScore 5 SJR 0.541 SNIP 0.792
Original language: English
ASJC Scopus subject areas: Biotechnology, Bioengineering, Medicine (miscellaneous), Biomedical Engineering, Pharmaceutical Science, Computer Science Applications, Electrical and Electronic Engineering
Keywords: Biofilm suppression, Communications systems, Jamming, Synthetic logic circuits
Source: Scopus
Source ID: 85053611196

Research output: Contribution to journalArticleScientificpeer-review

Quantifying branch architecture of tropical trees using terrestrial LiDAR and 3D modelling

Key message: A method using terrestrial laser scanning and 3D quantitative structure models opens up new possibilities to reconstruct tree architecture from tropical rainforest trees. Abstract: Tree architecture is the three-dimensional arrangement of above ground parts of a tree. Ecologists hypothesize that the topology of tree branches represents optimized adaptations to tree’s environment. Thus, an accurate description of tree architecture leads to a better understanding of how form is driven by function. Terrestrial laser scanning (TLS) has demonstrated its potential to characterize woody tree structure. However, most current TLS methods do not describe tree architecture. Here, we examined nine trees from a Guyanese tropical rainforest to evaluate the utility of TLS for measuring tree architecture. First, we scanned the trees and extracted individual tree point clouds. TreeQSM was used to reconstruct woody structure through 3D quantitative structure models (QSMs). From these QSMs, we calculated: (1) length and diameter of branches > 10 cm diameter, (2) branching order and (3) tree volume. To validate our method, we destructively harvested the trees and manually measured all branches over 10 cm (279). TreeQSM found and reconstructed 95% of the branches thicker than 30 cm. Comparing field and QSM data, QSM overestimated branch lengths thicker than 50 cm by 1% and underestimated diameter of branches between 20 and 60 cm by 8%. TreeQSM assigned the correct branching order in 99% of all cases and reconstructed 87% of branch lengths and 97% of tree volume. Although these results are based on nine trees, they validate a method that is an important step forward towards using tree architectural traits based on TLS and open up new possibilities to use QSMs for tree architecture.

General information

Publication status: Published
MoE publication type: A1 Journal article-refereed
Organisations: Mathematics, Research group: Inverse Problems, Wageningen University and Research Centre, Center for International Forestry Research (CIFOR), Sonoma State University, University of Oxford
Contributors: Lau, A., Bentley, L. P., Martius, C., Shenkin, A., Bartholomeus, H., Raumonen, P., Malhi, Y., Jackson, T., Herold, M.
Number of pages: 13
Pages: 1219-1231
Publication date: Oct 2018
Peer-reviewed: Yes
Early online date: 25 May 2018

Publication information

Journal: Trees - Structure and Function
Volume: 32
Issue number: 5
ISSN (Print): 0931-1890
Ratings: 
  • Scopus rating (2018): CiteScore 2.04 SJR 0.702 SNIP 1.015
Original language: English
ASJC Scopus subject areas: Forestry, Physiology, Ecology, Plant Science
Keywords: Destructive harvesting, Quantitative structure models, Terrestrial LiDAR, Tree architecture, Tree metrics
Source: Scopus
Source ID: 85047390214

Research output: Contribution to journalArticleScientificpeer-review

Temperature control as key factor for optimal biohydrogen production from thermomechanical pulping wastewater

This study evaluates the use of non-pretreated thermo-mechanical pulping (TMP) wastewater as a potential substrate for hydrogen production by dark fermentation. Batch incubations were conducted in a temperature gradient incubator at temperatures ranging from 37 to 80 °C, using an inoculum from a thermophilic, xylose-fed, hydrogen-producing fluidised bed reactor. The aim was to assess the short-term response of the microbial communities to the different temperatures with respect to both hydrogen yield and composition of the active microbial community. High throughput sequencing (MiSeq) of the reversely transcribed 16S rRNA showed that Thermoanaerobacterium sp. dominated the active microbial community at 70 °C, resulting in the highest hydrogen yield of 3.6 (±0.1) mmol H2 g−1 CODtot supplied. Lower hydrogen yields were obtained at the temperature range from 37 to 65 °C, likely due to consumption of the produced hydrogen by homoacetogenesis. No hydrogen production was detected at temperatures above 70 °C. Thermomechanical pulping wastewaters are released at high temperatures (50–80 °C), and thus dark fermentation at 70 °C could be sustained using the heat produced by the pulp and paper plant itself without any requirement for external heating.

General information

Publication status: Published
MoE publication type: A1 Journal article-refereed
Organisations: Chemistry and Bioengineering, Research group: Bio- and Circular Economy, Research group: Industrial Bioengineering and Applied Organic Chemistry, Natl. University of Ireland, Galway, Institute for Water Education, UNESCO–IHE
Contributors: Dessì, P., Porca, E., Lakaniemi, A., Collins, G., Lens, P. N.
Number of pages: 8
Pages: 214-221
Publication date: 15 Sep 2018
Peer-reviewed: Yes

Publication information

Journal: Biochemical Engineering Journal
Volume: 137
ISSN (Print): 1369-703X
Ratings: 
  • Scopus rating (2018): CiteScore 6 SJR 0.904 SNIP 1.167
Original language: English
ASJC Scopus subject areas: Biotechnology, Bioengineering, Environmental Engineering, Biomedical Engineering
Keywords: Dark fermentation, MiSeq, Pulp and paper mill wastewater, Thermoanaerobacterium, Thermomechanical pulping, Thermophilic
Source: Scopus
Source ID: 85048157059

Research output: Contribution to journalArticleScientificpeer-review

Assessment of mutation probabilities of KRAS G12 missense mutants and their long-timescale dynamics by atomistic molecular simulations and Markov state modeling

A mutated KRAS protein is frequently observed in human cancers. Traditionally, the oncogenic properties of KRAS missense mutants at position 12 (G12X) have been considered as equal. Here, by assessing the probabilities of occurrence of all KRAS G12X mutations and KRAS dynamics we show that this assumption does not hold true. Instead, our findings revealed an outstanding mutational bias. We conducted a thorough mutational analysis of KRAS G12X mutations and assessed to what extent the observed mutation frequencies follow a random distribution. Unique tissue-specific frequencies are displayed with specific mutations, especially with G12R, which cannot be explained by random probabilities. To clarify the underlying causes for the nonrandom probabilities, we conducted extensive atomistic molecular dynamics simulations (170 μs) to study the differences of G12X mutations on a molecular level. The simulations revealed an allosteric hydrophobic signaling network in KRAS, and that protein dynamics is altered among the G12X mutants and as such differs from the wild-type and is mutation-specific. The shift in long-timescale conformational dynamics was confirmed with Markov state modeling. A G12X mutation was found to modify KRAS dynamics in an allosteric way, which is especially manifested in the switch regions that are responsible for the effector protein binding. The findings provide a basis to understand better the oncogenic properties of KRAS G12X mutants and the consequences of the observed nonrandom frequencies of specific G12X mutations.

General information

Publication status: Published
MoE publication type: A1 Journal article-refereed
Organisations: Physics, Research group: Biological Physics and Soft Matter, University of Eastern Finland, University Hospital Tuebingen, Eberhard-Karls University Tuebingen, University of Helsinki, MEMPHYS-Center for Biomembrane Physics
Contributors: Pantsar, T., Rissanen, S., Dauch, D., Laitinen, T., Vattulainen, I., Poso, A.
Publication date: 10 Sep 2018
Peer-reviewed: Yes

Publication information

Journal: PLoS Computational Biology
Volume: 14
Issue number: 9
Article number: e1006458
ISSN (Print): 1553-734X
Ratings: 
  • Scopus rating (2018): CiteScore 4.35 SJR 2.949 SNIP 1.408
Original language: English
ASJC Scopus subject areas: Ecology, Evolution, Behavior and Systematics, Modelling and Simulation, Ecology, Molecular Biology, Genetics, Cellular and Molecular Neuroscience, Computational Theory and Mathematics
Electronic versions: 
Source: Scopus
Source ID: 85054571349

Research output: Contribution to journalArticleScientificpeer-review

Computational modeling of electrophysiology and pharmacotherapy of atrial fibrillation: Recent advances and future challenges

The pathophysiology of atrial fibrillation (AF) is broad, with components related to the unique and diverse cellular electrophysiology of atrial myocytes, structural complexity, and heterogeneity of atrial tissue, and pronounced disease-associated remodeling of both cells and tissue. A major challenge for rational design of AF therapy, particularly pharmacotherapy, is integrating these multiscale characteristics to identify approaches that are both efficacious and independent of ventricular contraindications. Computational modeling has long been touted as a basis for achieving such integration in a rapid, economical, and scalable manner. However, computational pipelines for AF-specific drug screening are in their infancy, and while the field is progressing quite rapidly, major challenges remain before computational approaches can fill the role of workhorse in rational design of AF pharmacotherapies. In this review, we briefly detail the unique aspects of AF pathophysiology that determine requirements for compounds targeting AF rhythm control, with emphasis on delimiting mechanisms that promote AF triggers from those providing substrate or supporting reentry. We then describe modeling approaches that have been used to assess the outcomes of drugs acting on established AF targets, as well as on novel promising targets including the ultra-rapidly activating delayed rectifier potassium current, the acetylcholine-activated potassium current and the small conductance calcium-activated potassium channel. Finally, we describe how heterogeneity and variability are being incorporated into AF-specific models, and how these approaches are yielding novel insights into the basic physiology of disease, as well as aiding identification of the important molecular players in the complex AF etiology.

General information

Publication status: Published
MoE publication type: A2 Review article in a scientific journal
Organisations: Faculty of Biomedical Sciences and Engineering, Simula Research Laboratory, Centre for Molecular Medicine Norway, Nordic European Molecular Biology Laboratory Partnership, University of Oslo, Center for Cardiological Innovation, University of Eastern Finland
Contributors: Vagos, M. R., van Herck, I. G., Sundnes, J., Arevalo, H. J., Edwards, A. G., Koivumäki, J. T.
Publication date: 4 Sep 2018
Peer-reviewed: Yes

Publication information

Journal: Frontiers in Physiology
Volume: 9
Issue number: SEP
Article number: 1221
ISSN (Print): 1664-042X
Ratings: 
  • Scopus rating (2018): CiteScore 3.5 SJR 1.153 SNIP 1.056
Original language: English
ASJC Scopus subject areas: Physiology, Physiology (medical)
Keywords: Atrial fibrillation, Computational modeling, Drug therapies, In silico drug screening, Pathophysiology, Pharmacodynamics, Pharmacology
Electronic versions: 
Source: Scopus
Source ID: 85053074392

Research output: Contribution to journalReview ArticleScientificpeer-review

Comparative analysis of tissue reconstruction algorithms for 3D histology

Motivation: Digital pathology enables new approaches that expand beyond storage, visualization or analysis of histological samples in digital format. One novel opportunity is 3D histology, where a three-dimensional reconstruction of the sample is formed computationally based on serial tissue sections. This allows examining tissue architecture in 3D, for example, for diagnostic purposes. Importantly, 3D histology enables joint mapping of cellular morphology with spatially resolved omics data in the true 3D context of the tissue at microscopic resolution. Several algorithms have been proposed for the reconstruction task, but a quantitative comparison of their accuracy is lacking. Results: We developed a benchmarking framework to evaluate the accuracy of several free and commercial 3D reconstruction methods using two whole slide image datasets. The results provide a solid basis for further development and application of 3D histology algorithms and indicate that methods capable of compensating for local tissue deformation are superior to simpler approaches.

General information

Publication status: Published
MoE publication type: A1 Journal article-refereed
Organisations: Faculty of Biomedical Sciences and Engineering, Mechanical Engineering and Industrial Systems, Signal Processing, Research group: Data-analytics and Optimization, Tampere University Hospital, Faculty of Medicine and Life Sciences, BioMediTech, Fimlab Laboratories Ltd, BioMediTech Institute
Contributors: Kartasalo, K., Latonen, L., Vihinen, J., Visakorpi, T., Nykter, M., Ruusuvuori, P.
Number of pages: 9
Pages: 3013-3021
Publication date: 1 Sep 2018
Peer-reviewed: Yes

Publication information

Journal: Bioinformatics
Volume: 34
Issue number: 17
ISSN (Print): 1367-4803
Ratings: 
  • Scopus rating (2018): CiteScore 9.7 SJR 4.549 SNIP 1.908
Original language: English
ASJC Scopus subject areas: Statistics and Probability, Biochemistry, Molecular Biology, Computer Science Applications, Computational Theory and Mathematics, Computational Mathematics
Electronic versions: 
Source: Scopus
Source ID: 85055091427

Research output: Contribution to journalArticleScientificpeer-review

Nocturnal Heart Rate Variability Spectrum Characterization in Preschool Children with Asthmatic Symptoms

Asthma is a chronic lung disease that usually develops during chilhood. Despite that symptoms can almost be controlled with medication, early diagnosis is desirable in order to reduce permanent airway obstruction risk. It has been suggested that abnormal parasympathetic nervous system (PSNS) activity might be closely related with the pathogenesis of asthma, and that this PSNS activity could be reflected in cardiac vagal control. In this work, an index to measure the spectral regularity of the high frequency (HF) component of heart rate variability (HRV) spectrum, named peakness (P), is proposed. Three different implementations of P, based on electrocardiogram (ECG) recordings, impedance pneumography (IP) recordings and a combination of both, were employed in the characterization of a group of pre-school children classified attending to their risk of developing asthma. Peakier componentswere observed in the HF band of those children classified as high-risk (p &lt; 0.005), who also presented reduced sympathvoagal balance. Results suggest that high-risk of developing asthma might be related with a lack of adaptability of PSNS.

General information

Publication status: Published
MoE publication type: A1 Journal article-refereed
Organisations: Faculty of Biomedical Sciences and Engineering, Research group: Physiological Measurement Systems and Methods Group, University of Zaragoza, KU Leuven, University of Helsinki
Contributors: Milagro, J., Gil, E., Lazaro, J., Seppae, V. P., Malmberg, L. P., Pelkonen, A. S., Kotaniemi-Syrjanen, A., Makela, M., Viik, J., Bailon, R.
Pages: 1332-1340
Publication date: Sep 2018
Peer-reviewed: Yes
Early online date: 16 Nov 2017

Publication information

Journal: IEEE Journal of Biomedical and Health Informatics
Volume: 22
Issue number: 5
ISSN (Print): 2168-2194
Ratings: 
  • Scopus rating (2018): CiteScore 9.2 SJR 1.122 SNIP 2.524
Original language: English
ASJC Scopus subject areas: Biotechnology, Computer Science Applications, Electrical and Electronic Engineering, Health Information Management
Keywords: asthma, children, Electrocardiography, Heart rate variability, heart rate variability, Informatics, parasympathetic nervous system, peakness, Pediatrics, Pregnancy, Respiratory system, Signal to noise ratio
Source: Scopus
Source ID: 85035749268

Research output: Contribution to journalArticleScientificpeer-review

Physiologically-relevant levels of sphingomyelin, but not GM1, induces a β-sheet-rich structure in the amyloid-β(1-42) monomer

To resolve the contribution of ceramide-containing lipids to the aggregation of the amyloid-β protein into β-sheet rich toxic oligomers, we employed molecular dynamics simulations to study the effect of cholesterol-containing bilayers comprised of POPC (70% POPC, and 30% cholesterol) and physiologically relevant concentrations of sphingomyelin (SM) (30% SM, 40% POPC, and 30% cholesterol), and the GM1 ganglioside (5% GM1, 70% POPC, and 25% cholesterol). The increased bilayer rigidity provided by SM (and to a lesser degree, GM1) reduced the interactions between the SM-enriched bilayer and the N-terminus of Aβ42 (and also residues Ser26, Asn27, and Lys28), which facilitated the formation of a β-sheet in the normally disordered N-terminal region. Aβ42 remained anchored to the SM-enriched bilayer through hydrogen bonds with the side chain of Arg5. With β-sheets in the at the N and C termini, the structure of Aβ42 in the sphingomyelin-enriched bilayer most resembles β-sheet-rich structures found in higher-ordered Aβ fibrils. Conversely, when bound to a bilayer comprised of 5% GM1, the conformation remained similar to that observed in the absence of GM1, with Aβ42 only making contact with one or two GM1 molecules. This article is part of a Special Issue entitled: Protein Aggregation and Misfolding at the Cell Membrane Interface edited by Ayyalusamy Ramamoorthy.

General information

Publication status: Published
MoE publication type: A1 Journal article-refereed
Organisations: Physics, Forschungszentrum Jülich (FZJ), Masaryk University, Heinrich Heine University Düsseldorf
Contributors: Owen, M. C., Kulig, W., Poojari, C., Rog, T., Strodel, B.
Pages: 1709-1720
Publication date: Sep 2018
Peer-reviewed: Yes
Early online date: 1 Jan 2018

Publication information

Journal: Biochimica et Biophysica Acta - Biomembranes
Volume: 1860
Issue number: 9
ISSN (Print): 0005-2736
Ratings: 
  • Scopus rating (2018): CiteScore 3.64 SJR 1.427 SNIP 1.108
Original language: English
ASJC Scopus subject areas: Biophysics, Biochemistry, Cell Biology
Keywords: Amyloid-β peptide, Gangliosides, GM1, Lipid rafts, Membrane simulations, Molecular dynamics, Peptide-ganglioside interactions, Peptide-membrane interactions, Sphingomyelin
Source: Scopus
Source ID: 85045553236

Research output: Contribution to journalArticleScientificpeer-review

Comparison of food frequency questionnaire data and shopping records for the assessment of food intake

Questionnaires are typically used for collecting information
describing health behavior in areas such as diet, physical activity and sleep.
Utilization of the digital footprint, formed from an individual’s unique digital
activities, forms a potential new opportunity for describing lifestyle and
health-related behavior. We studied if passively collected shopping data
describes food intake when compared to food frequency questionnaire (FFQ)
data providing information on food and beverage consumption. For 4 out of 21
food groups the results were comparable. Shopping information from only one
department store chain gives only a partial picture of the food consumption and
differing family sizes add noise to the estimate. If the whole digital footprint
would be available, including detailed product-level shopping information from
all stores and restaurants, the food intake could probably be estimated more
accurately and applied e.g. in personalized coaching.

General information

Publication status: Published
MoE publication type: A4 Article in a conference publication
Organisations: Faculty of Biomedical Sciences and Engineering, Faculty of Biomedical Sciences and Engineering, Tampere University of Technology, Institute for Molecular Medicine, FIMM, HiLIFE, University of Helsinki
Contributors: Kallonen, A., Nieminen, H., Das, S., Sallinen, R.
Pages: 25-30
Publication date: 27 Aug 2018

Host publication information

Title of host publication: Proceedings of Seventh International Conference on Well-Being in the Information Society: Fighting Inequalities (WIS 2018)
ISBN (Electronic): 978-952-12-3727-0

Publication series

Name: TUCS Lecture Notes
Volume: 28
ISSN (Electronic): 1797-8831
ASJC Scopus subject areas: Molecular Medicine
Keywords: Food intake assessment, shopping data, food frequency questionnaire, digital footprint

Bibliographical note

INT=TUT-BMT,"Das, Soumya"

Research output: Chapter in Book/Report/Conference proceedingConference contributionScientificpeer-review

Production of alkanes from CO2 by engineered bacteria

Background: Microbial biosynthesis of alkanes is considered a promising method for the sustainable production of drop-in fuels and chemicals. Carbon dioxide would be an ideal carbon source for these production systems, but efficient production of long carbon chains from CO2 is difficult to achieve in a single organism. A potential solution is to employ acetogenic bacteria for the reduction of CO2 to acetate, and engineer a second organism to convert the acetate into long-chain hydrocarbons. Results: In this study, we demonstrate alkane production from CO2 by a system combining the acetogen Acetobacterium woodii and a non-native alkane producer Acinetobacter baylyi ADP1 engineered for alkane production. Nine synthetic two-step alkane biosynthesis pathways consisting of different aldehyde- and alkane-producing enzymes were combinatorically constructed and expressed in A. baylyi. The aldehyde-producing enzymes studied were AAR from Synechococcus elongatus, Acr1 from A. baylyi, and a putative dehydrogenase from Nevskia ramosa. The alkane-producing enzymes were ADOs from S. elongatus and Nostoc punctiforme, and CER1 from Arabidopsis thaliana. The performance of the pathways was evaluated with a twin-layer biosensor, which allowed the monitoring of both the intermediate (fatty aldehyde), and end product (alkane) formation. The highest alkane production, as indicated by the biosensor, was achieved with a pathway consisting of AAR and ADO from S. elongatus. The performance of this pathway was further improved by balancing the relative expression levels of the enzymes to limit the accumulation of the intermediate fatty aldehyde. Finally, the acetogen A. woodii was used to produce acetate from CO2 and H2, and the acetate was used for alkane production by the engineered A. baylyi, thereby leading to the net production of long-chain alkanes from CO2. Conclusions: A modular system for the production of drop-in liquid fuels from CO2 was demonstrated. Among the studied synthetic pathways, the combination of ADO and AAR from S. elongatus was found to be the most efficient in heterologous alkane production in A. baylyi. Furthermore, limiting the accumulation of the fatty aldehyde intermediate was found to be beneficial for the alkane production. Nevertheless, the alkane productivity of the system remained low, representing a major challenge for future research.

General information

Publication status: Published
MoE publication type: A1 Journal article-refereed
Organisations: Chemistry and Bioengineering, Research group: Bio- and Circular Economy
Contributors: Lehtinen, T., Virtanen, H., Santala, S., Santala, V.
Publication date: 21 Aug 2018
Peer-reviewed: Yes

Publication information

Journal: Biotechnology for Biofuels
Volume: 11
Article number: 228
ISSN (Print): 1754-6834
Ratings: 
  • Scopus rating (2018): CiteScore 8.4 SJR 1.762 SNIP 1.468
Original language: English
ASJC Scopus subject areas: Biotechnology, Applied Microbiology and Biotechnology, Renewable Energy, Sustainability and the Environment, Energy(all), Management, Monitoring, Policy and Law
Keywords: Acetate, Acetogen, Acinetobacter baylyi ADP1, Aldehyde, Alkane, Biofuel, Biosensor, Carbon dioxide, CO, Drop in

Bibliographical note

INT=keb,"Virtanen, Henri"

Source: Scopus
Source ID: 85052519319

Research output: Contribution to journalArticleScientificpeer-review

The effect of S53P4-based borosilicate glasses and glass dissolution products on the osteogenic commitment of human adipose stem cells

Despite the good performance of silicate bioactive glasses in bone regeneration, there is considerable potential to enhance their properties by chemical modifications. In this study, S53P4-based borosilicate glasses were synthesized and their dissolution profile was studied in simulated body fluid by assessing pH change, ion release and conversion to hydroxyapatite. The viability, proliferation, attachment, osteogenesis and endothelial marker expression of human adipose stem cells (hASCs) was evaluated upon direct culture on glass discs and in the extract medium. This is the first study evaluating cell behavior in response to borosilicate glasses based on S53P4 (commercially available as BonAlive®). Replacing silicate with borate in S53P4 increased the glass reactivity. Despite the good viability of hASCs under all conditions, direct culture of cells on borosilicate discs and in undiluted extract medium reduced cell proliferation. This was accompanied with changes in cell morphology. Regarding osteogenic commitment, alkaline phosphatase activity was significantly reduced by the borosilicate glass discs and extracts, whereas the expression of osteogenic markers RUNX2a, OSTERIX, DLX5 and OSTEOPONTIN was upregulated. There was also a borosilicate glass-induced increase in osteocalcin protein production. Moreover, osteogenic supplements containing borosilicate extracts significantly increased the mineral production in comparison to the osteogenic medium control. Interestingly, borosilicate glasses stimulated the expression of endothelial markers vWF and PECAM-1. To conclude, our results reveal that despite reducing hASC proliferation, S53P4-based borosilicate glasses and their dissolution products stimulate osteogenic commitment and upregulate endothelial markers, thus supporting their further evaluation for regenerative medicine.

General information

Publication status: Published
MoE publication type: A1 Journal article-refereed
Organisations: Faculty of Biomedical Sciences and Engineering, Research group: Biomaterials and Tissue Engineering Group, Faculty of Medicine and Life Sciences, National Center of Science and Technology, Ministry of Education and Science, Republic of Kazakhstan, Tampere University Hospital, Department of Biomedical Sciences and Engineering
Contributors: Ojansivu, M., Mishra, A., Vanhatupa, S., Juntunen, M., Larionova, A., Massera, J., Miettinen, S.
Publication date: 1 Aug 2018
Peer-reviewed: Yes

Publication information

Journal: PLoS ONE
Volume: 13
Issue number: 8
Article number: e0202740
ISSN (Print): 1932-6203
Ratings: 
  • Scopus rating (2018): CiteScore 5.4 SJR 1.1 SNIP 1.167
Original language: English
ASJC Scopus subject areas: Biochemistry, Genetics and Molecular Biology(all), Agricultural and Biological Sciences(all)
Electronic versions: 
Source: Scopus
Source ID: 85052558510

Research output: Contribution to journalArticleScientificpeer-review

Selenate removal in biofilm systems: Effect of nitrate and sulfate on selenium removal efficiency, biofilm structure and microbial community

BACKGROUND: Selenium (Se) discharged into natural waterbodies can accumulate over time and have negative impacts on the environment. Se-laden wastewater streams can be treated using biological processes. However, the presence of other electron acceptors in wastewater, such as nitrate (NO3 -) and sulfate (SO4 2-), can influence selenate (SeO4 2-) reduction and impact the efficiency of biological treatment systems. RESULTS: SeO4 2- removal by biofilms formed from an anaerobic sludge inoculum was investigated in the presence of NO3 - and SO4 2- using drip flow reactors operated continuously for 10days at pH7.0 and 30°C. The highest total Se (∼60%) and SeO4 2- (∼80%) removal efficiencies were observed when the artificial wastewater contained SO4 2-. A maximum amount of 68μmol Se cm-2 was recovered from the biofilm matrix in SO4 2-+SeO4 2- exposed biofilms and biofilm mass was 2.7-fold increased for biofilms grown in the presence of SO4 2-. When SeO4 2- was the only electron acceptor, biofilms were thin and compact. In the simultaneous presence of NO3 - or SO4 2-, biofilms were thicker (> 0.6mm), less compact and exhibited gas pockets. CONCLUSION: The presence of SO4 2- had a beneficial effect on biofilm growth and the SeO4 2- removal efficiency, while the presence of NO3 - did not have a significant effect on SeO4 2- removal by the biofilms.

General information

Publication status: Published
MoE publication type: A1 Journal article-refereed
Organisations: Chemistry and Bioengineering, Hydraulic and Environmental Engineering (IHE) Inst. for Water Education, Montana State University (MSU), Bhabha Atomic Research Centre, UPEM
Contributors: Tan, L. C., Espinosa-Ortiz, E. J., Nancharaiah, Y. V., van Hullebusch, E. D., Gerlach, R., Lens, P. N.
Pages: 2380-2389
Publication date: Aug 2018
Peer-reviewed: Yes
Early online date: 1 Jan 2018

Publication information

Journal: Journal of Chemical Technology and Biotechnology
Volume: 93
Issue number: 8
ISSN (Print): 0268-2575
Ratings: 
  • Scopus rating (2018): CiteScore 4.8 SJR 0.715 SNIP 0.891
Original language: English
ASJC Scopus subject areas: Biotechnology, Chemical Engineering(all), Renewable Energy, Sustainability and the Environment, Fuel Technology, Waste Management and Disposal, Pollution, Organic Chemistry, Inorganic Chemistry
Keywords: Biofilm, Biofilm characterization, Co-electron acceptors, Nitrate, Selenate, Selenium removal, Sulfate
Source: Scopus
Source ID: 85043713774

Research output: Contribution to journalArticleScientificpeer-review

Metabolic pairing of aerobic and anaerobic production in a one-pot batch cultivation

Background: The versatility of microbial metabolic pathways enables their utilization in vast number of applications. However, the electron and carbon recovery rates, essentially constrained by limitations of cell energetics, are often too low in terms of process feasibility. Cocultivation of divergent microbial species in a single process broadens the metabolic landscape, and thus, the possibilities for more complete carbon and energy utilization. Results: In this study, we integrated the metabolisms of two bacteria, an obligate anaerobe Clostridium butyricum and an obligate aerobe Acinetobacter baylyi ADP1. In the process, a glucose-negative mutant of A. baylyi ADP1 first deoxidized the culture allowing C. butyricum to grow and produce hydrogen from glucose. In the next phase, ADP1 produced long chain alkyl esters (wax esters) utilizing the by-products of C. butyricum, namely acetate and butyrate. The coculture produced 24.5 ± 0.8 mmol/l hydrogen (1.7 ± 0.1 mol/mol glucose) and 28 mg/l wax esters (10.8 mg/g glucose). Conclusions: The cocultivation of strictly anaerobic and aerobic bacteria allowed the production of both hydrogen gas and long-chain alkyl esters in a simple one-pot batch process. The study demonstrates the potential of 'metabolic pairing' using designed microbial consortia for more optimal electron and carbon recovery.

General information

Publication status: Published
MoE publication type: A1 Journal article-refereed
Organisations: Chemistry and Bioengineering
Contributors: Salmela, M., Lehtinen, T., Efimova, E., Santala, S., Mangayil, R.
Publication date: 3 Jul 2018
Peer-reviewed: Yes

Publication information

Journal: Biotechnology for Biofuels
Volume: 11
Issue number: 1
Article number: 187
ISSN (Print): 1754-6834
Ratings: 
  • Scopus rating (2018): CiteScore 8.4 SJR 1.762 SNIP 1.468
Original language: English
ASJC Scopus subject areas: Biotechnology, Applied Microbiology and Biotechnology, Renewable Energy, Sustainability and the Environment, Energy(all), Management, Monitoring, Policy and Law
Keywords: Hydrogen production, Integrated metabolism, Metabolic pairing, Synthetic microbial consortia, Wax esters
Electronic versions: 
Source: Scopus
Source ID: 85049884043

Research output: Contribution to journalArticleScientificpeer-review

Pectin and Mucin Enhance the Bioadhesion of Drug Loaded Nanofibrillated Cellulose Films

Purpose: Bioadhesion is an important property of biological membranes, that can be utilized in pharmaceutical and biomedical applications. In this study, we have fabricated mucoadhesive drug releasing films with bio-based, non-toxic and biodegradable polymers that do not require chemical modifications. Methods: Nanofibrillar cellulose and anionic type nanofibrillar cellulose were used as film forming materials with known mucoadhesive components mucin, pectin and chitosan as functional bioadhesion enhancers. Different polymer combinations were investigated to study the adhesiveness, solid state characteristics, film morphology, swelling, mechanical properties, drug release with the model compound metronidazole and in vitro cytotoxicity using TR146 cells to model buccal epithelium. Results: SEM revealed lamellar structures within the films, which had a thickness ranging 40–240 μm depending on the film polymer composition. All bioadhesive components were non-toxic and showed high adhesiveness. Rapid drug release was observed, as 60–80% of the total amount of metronidazole was released in 30 min depending on the film formulation. Conclusions: The liquid molding used was a straightforward and simple method to produce drug releasing highly mucoadhesive films, which could be utilized in treating local oral diseases, such as periodontitis. All materials used were natural biodegradable polymers from renewable sources, which are generally regarded as safe.

General information

Publication status: Published
MoE publication type: A1 Journal article-refereed
Organisations: Chemistry and Bioengineering, Research group: Chemistry & Advanced Materials, Aalto University, Universita degli Studi di Padova, Italy, University of Helsinki, University of Helsinki
Contributors: Laurén, P., Paukkonen, H., Lipiäinen, T., Dong, Y., Oksanen, T., Räikkönen, H., Ehlers, H., Laaksonen, P., Yliperttula, M., Laaksonen, T.
Publication date: 1 Jul 2018
Peer-reviewed: Yes

Publication information

Journal: Pharmaceutical Research
Volume: 35
Issue number: 7
Article number: 145
ISSN (Print): 0724-8741
Ratings: 
  • Scopus rating (2018): CiteScore 6.9 SJR 1.093 SNIP 1.131
Original language: English
ASJC Scopus subject areas: Biotechnology, Molecular Medicine, Pharmacology, Pharmaceutical Science, Organic Chemistry, Pharmacology (medical)
Keywords: bioadhesion, drug release, mucoadhesion, nanofibrillar cellulose, TR146
Electronic versions: 
URLs: 
Source: Scopus
Source ID: 85047448577

Research output: Contribution to journalArticleScientificpeer-review

Segmentation of vessel structures from photoacoustic images with reliability assessment

Photoacoustic imaging enables the imaging of soft biological tissue with combined optical contrast and ultrasound resolution. One of the targets of interest is tissue vasculature. However, the photoacoustic images may not directly provide the information on, for example, vasculature structure. Therefore, the images are improved by reducing noise and artefacts, and processed for better visualisation of the target of interest. In this work, we present a new segmentation method of photoacoustic images that also straightforwardly produces assessments of its reliability. The segmentation depends on parameters which have a natural tendency to increase the reliability as the parameter values monotonically change. The reliability is assessed by counting classifications of image voxels with different parameter values. The resulting segmentation with reliability offers new ways and tools to analyse photoacoustic images and new possibilities for utilising them as anatomical priors in further computations. Our MATLAB implementation of the method is available as an open-source software package [P. Raumonen, Matlab, 2018].

General information

Publication status: Published
MoE publication type: A1 Journal article-refereed
Organisations: Mathematics, University of Eastern Finland, University College London
Contributors: Raumonen, P., Tarvainen, T.
Number of pages: 18
Pages: 2887-2904
Publication date: 1 Jul 2018
Peer-reviewed: Yes

Publication information

Journal: Biomedical Optics Express
Volume: 9
Issue number: 7
ISSN (Print): 2156-7085
Ratings: 
  • Scopus rating (2018): CiteScore 6.5 SJR 1.516 SNIP 1.604
Original language: English
ASJC Scopus subject areas: Biotechnology, Atomic and Molecular Physics, and Optics
Source: Scopus
Source ID: 85049377889

Research output: Contribution to journalArticleScientificpeer-review

Automatic optimization of an in silico model of human iPSC derived cardiomyocytes recapitulating calcium handling abnormalities

The growing importance of human induced pluripotent stem cell-derived cardiomyoyctes (hiPSC-CMs), as patient-specific and disease-specific models for studying cellular cardiac electrophysiology or for preliminary cardiotoxicity tests, generated better understanding of hiPSC-CM biophysical mechanisms and great amount of action potential and calcium transient data. In this paper, we propose a new hiPSC-CM in silico model, with particular attention to Ca2+ handling. We used (i) the hiPSC-CM Paci2013 model as starting point, (ii) a new dataset of Ca2+ transient measurements to tune the parameters of the inward and outward Ca2+ fluxes of sarcoplasmic reticulum, and (iii) an automatic parameter optimization to fit action potentials and Ca2+ transients. The Paci2018 model simulates, together with the typical hiPSC-CM spontaneous action potentials, more refined Ca2+ transients and delayed afterdepolarizations-like abnormalities, which the old Paci2013 was not able to predict due to its mathematical formulation. The Paci2018 model was validated against (i) the same current blocking experiments used to validate the Paci2013 model, and (ii) recently published data about effects of different extracellular ionic concentrations. In conclusion, we present a new and more versatile in silico model, which will provide a platform for modeling the effects of drugs or mutations that affect Ca2+ handling in hiPSC-CMs.

General information

Publication status: Published
MoE publication type: A1 Journal article-refereed
Organisations: Faculty of Biomedical Sciences and Engineering, Research group: Computational Biophysics and Imaging Group, University of Bologna, Faculty of Medicine and Life Sciences, Tampere University Hospital
Contributors: Paci, M., Pölönen, R., Cori, D., Penttinen, K., Aalto-Setälä, K., Severi, S., Hyttinen, J.
Publication date: 26 Jun 2018
Peer-reviewed: Yes

Publication information

Journal: Frontiers in Physiology
Volume: 9
Issue number: JUN
Article number: 709
ISSN (Print): 1664-042X
Ratings: 
  • Scopus rating (2018): CiteScore 3.5 SJR 1.153 SNIP 1.056
Original language: English
ASJC Scopus subject areas: Physiology, Physiology (medical)
Keywords: Action potential, Calcium transient, Computer simulation, Human induced pluripotent stem cell-derived cardiomyocyte, In silico modeling
Electronic versions: 

Bibliographical note

EXT="Penttinen, Kirsi"

Source: Scopus
Source ID: 85049116471

Research output: Contribution to journalArticleScientificpeer-review

Monitoring of heart rate and inter-beat intervals with wrist plethysmography in patients with atrial fibrillation

Objective: Atrial fibrillation (AF) causes marked risk for patients, while silent fibrillation may remain unnoticed if not suspected and screened. Development of comfortable yet accurate beat-to-beat heart rate (HR) monitoring with good AF detection sensitivity would facilitate screening and improve treatment. The purpose of this study was to evaluate whether a wrist-worn photoplethysmography (PPG) device can be used to monitor beat-to-beat HR accurately during post-operative treatment in patients suffering from AF and whether wrist-PPG can be used to distinguish AF from sinus rhythm (SR). Approach: Twenty-nine patients (14 with AF, 15 with SR, mean age 71.5 years) with multiple comorbidities were monitored during routine post-operative treatment. The monitoring included standard ECG, finger PPG monitoring and a wrist-worn PPG monitor with green and infrared light sources. The HR from PPG sensors was compared against ECG-derived HR. Main results: The wrist PPG technology had very good HR and beat detection accuracy when using green light. For the SR group, the mean absolute error (MAE) for HR was 1.50 bpm, and for the inter-beat intervals (IBI), the MAE was 7.64 ms. For the AF group, the MAE for HR was 4.28 bpm and for IBI, the MAE was 14.67 ms. Accuracy for the infrared (IR) channel was worse. Finger PPG provided similar accuracy for HR and better accuracy for the IBI. AF detection sensitivity using green light was 99.0% and the specificity was 93.0%. Performance can be improved by discarding unreliable IBI periods. Significance: Results suggest that wrist PPG measurement allows accurate HR and beat-to-beat HR monitoring also in AF patients, and could be used for differentiating between SR and AF with very good sensitivity.

General information

Publication status: Published
MoE publication type: A1 Journal article-refereed
Organisations: Faculty of Biomedical Sciences and Engineering, Tampere University Hospital, PulseOn SA, Pulseon Oy, University of Tampere, Medical School
Contributors: Harju, J., Tarniceriu, A., Parak, J., Vehkaoja, A., Yli-Hankala, A., Korhonen, I.
Publication date: 26 Jun 2018
Peer-reviewed: Yes

Publication information

Journal: Physiological Measurement
Volume: 39
Issue number: 6
Article number: 065007
ISSN (Print): 0967-3334
Ratings: 
  • Scopus rating (2018): CiteScore 2.44 SJR 0.609 SNIP 1.279
Original language: English
ASJC Scopus subject areas: Biophysics, Physiology, Biomedical Engineering, Physiology (medical)
Keywords: atrial fibrillation, heart rate, perioperative monitoring, photoplethysmography, pulse rate
URLs: 
Source: Scopus
Source ID: 85049779555

Research output: Contribution to journalArticleScientificpeer-review

Structure and dynamics of a human myelin protein P2 portal region mutant indicate opening of the β barrel in fatty acid binding proteins

Background: Myelin is a multilayered proteolipid sheath wrapped around selected axons in the nervous system. Its constituent proteins play major roles in forming of the highly regular membrane structure. P2 is a myelin-specific protein of the fatty acid binding protein (FABP) superfamily, which is able to stack lipid bilayers together, and it is a target for mutations in the human inherited neuropathy Charcot-Marie-Tooth disease. A conserved residue that has been proposed to participate in membrane and fatty acid binding and conformational changes in FABPs is Phe57. This residue is thought to be a gatekeeper for the opening of the portal region upon ligand entry and egress. Results: We performed a structural characterization of the F57A mutant of human P2. The mutant protein was crystallized in three crystal forms, all of which showed changes in the portal region and helix α2. In addition, the behaviour of the mutant protein upon lipid bilayer binding suggested more unfolding than previously observed for wild-type P2. On the other hand, membrane binding rendered F57A heat-stable, similarly to wild-type P2. Atomistic molecular dynamics simulations showed opening of the side of the discontinuous β barrel, giving important indications on the mechanism of portal region opening and ligand entry into FABPs. The results suggest a central role for Phe57 in regulating the opening of the portal region in human P2 and other FABPs, and the F57A mutation disturbs dynamic cross-correlation networks in the portal region of P2. Conclusions: Overall, the F57A variant presents similar properties to the P2 patient mutations recently linked to Charcot-Marie-Tooth disease. Our results identify Phe57 as a residue regulating conformational changes that may accompany membrane surface binding and ligand exchange in P2 and other FABPs.

General information

Publication status: Published
MoE publication type: A1 Journal article-refereed
Organisations: Physics, University of Oulu, European Spallation Source (ESS), University of Bergen, Univ Lille Nord de France, University of Helsinki
Contributors: Laulumaa, S., Nieminen, T., Raasakka, A., Krokengen, O. C., Safaryan, A., Hallin, E. I., Brysbaert, G., Lensink, M. F., Ruskamo, S., Vattulainen, I., Kursula, P.
Publication date: 25 Jun 2018
Peer-reviewed: Yes

Publication information

Journal: BMC Structural Biology
Volume: 18
Issue number: 1
Article number: 8
ISSN (Print): 1472-6807
Ratings: 
  • Scopus rating (2018): CiteScore 2.2 SJR 0.546 SNIP 0.408
Original language: English
ASJC Scopus subject areas: Structural Biology
Keywords: Crystal structure, Fatty acid-binding protein, Membrane binding, Molecular dynamics, Mutation, Myelin, Protein stability
Electronic versions: 
Source: Scopus
Source ID: 85049186598

Research output: Contribution to journalArticleScientificpeer-review

Effect of surfactant type and sonication energy on the electrical conductivity properties of nanocellulose-CNT nanocomposite films

We present a detailed study on the influence of sonication energy and surfactant type on the electrical conductivity of nanocellulose-carbon nanotube (NFC-CNT) nanocomposite films. The study was made using a minimum amount of processing steps, chemicals and materials, to optimize the conductivity properties of free-standing flexible nanocomposite films. In general, the NFC-CNT film preparation process is sensitive concerning the dispersing phase of CNTs into a solution with NFC. In our study, we used sonication to carry out the dispersing phase of processing in the presence of surfactant. In the final phase, the films were prepared from the dispersion using centrifugal cast molding. The solid films were analyzed regarding their electrical conductivity using a four-probe measuring technique. We also characterized how conductivity properties were enhanced when surfactant was removed from nanocomposite films; to our knowledge this has not been reported previously. The results of our study indicated that the optimization of the surfactant type clearly affected the formation of freestanding films. The effect of sonication energy was significant in terms of conductivity. Using a relatively low 16 wt. % concentration of multiwall carbon nanotubes we achieved the highest conductivity value of 8.4 S/cm for nanocellulose-CNT films ever published in the current literature. This was achieved by optimizing the surfactant type and sonication energy per dry mass. Additionally, to further increase the conductivity, we defined a preparation step to remove the used surfactant from the final nanocomposite structure.

General information

Publication status: Published
MoE publication type: A1 Journal article-refereed
Organisations: Materials Science, Faculty of Biomedical Sciences and Engineering, VTT Technical Research Centre of Finland
Contributors: Siljander, S., Keinänen, P., Räty, A., Ramakrishnan, K. R., Tuukkanen, S., Kunnari, V., Harlin, A., Vuorinen, J., Kanerva, M.
Publication date: 20 Jun 2018
Peer-reviewed: Yes

Publication information

Journal: International Journal of Molecular Sciences
Volume: 19
Issue number: 6
Article number: 1819
ISSN (Print): 1661-6596
Ratings: 
  • Scopus rating (2018): CiteScore 5.2 SJR 1.312 SNIP 1.274
Original language: English
ASJC Scopus subject areas: Catalysis, Molecular Biology, Spectroscopy, Computer Science Applications, Physical and Theoretical Chemistry, Organic Chemistry, Inorganic Chemistry
Keywords: Carbon nanotubes, Conductivity, Nanocellulose, Nanocomposite, Surfactant
Electronic versions: 

Bibliographical note

INT=mol,"Räty, Anna"
EXT="Harlin, Ali"

Source: Scopus
Source ID: 85048936349

Research output: Contribution to journalArticleScientificpeer-review

Acquiring respiration rate from photoplethysmographic signal by recursive bayesian tracking of intrinsic modes in time-frequency spectra

Respiration rate (RR) provides useful information for assessing the status of a patient. We propose RR estimation based on photoplethysmography (PPG) because the blood perfusion dynamics are known to carry information on breathing, as respiration-induced modulations in the PPG signal. We studied the use of amplitude variability of transmittance mode finger PPG signal in RR estimation by comparing four time-frequency (TF) representation methods of the signal cascaded with a particle filter. The TF methods compared were short-time Fourier transform (STFT) and three types of synchrosqueezing methods. The public VORTAL database was used in this study. The results indicate that the advanced frequency reallocation methods based on synchrosqueezing approach may present improvement over linear methods, such as STFT. The best results were achieved using wavelet synchrosqueezing transform, having a mean absolute error and median error of 2.33 and 1.15 breaths per minute, respectively. Synchrosqueezing methods were generally more accurate than STFT on most of the subjects when particle filtering was applied. While TF analysis combined with particle filtering is a promising alternative for real-time estimation of RR, artefacts and non-respiration-related frequency components remain problematic and impose requirements for further studies in the areas of signal processing algorithms an PPG instrumentation.

General information

Publication status: Published
MoE publication type: A1 Journal article-refereed
Organisations: Faculty of Biomedical Sciences and Engineering, Research group: Sensor Technology and Biomeasurements (STB)
Contributors: Pirhonen, M., Peltokangas, M., Vehkaoja, A.
Publication date: 1 Jun 2018
Peer-reviewed: Yes

Publication information

Journal: Sensors
Volume: 18
Issue number: 6
Article number: 1693
ISSN (Print): 1424-8220
Ratings: 
  • Scopus rating (2018): CiteScore 4.3 SJR 0.592 SNIP 1.642
Original language: English
ASJC Scopus subject areas: Analytical Chemistry, Atomic and Molecular Physics, and Optics, Biochemistry, Instrumentation, Electrical and Electronic Engineering
Keywords: Particle filters, Photoplethysmography, Respiration, Synchrosqueezing, Time-frequency analysis
Electronic versions: 

Bibliographical note

int=TUT-BMT,"Pirhonen, Mikko"

Source: Scopus
Source ID: 85047608517

Research output: Contribution to journalArticleScientificpeer-review

Altered polyamine profiles in colorectal cancer

Background: The declining mortality rate of patients with colorectal cancer (CRC) can be explained, at least partially, with early diagnosis. Simple diagnostic methods are needed to achieve a maximal patient participation rate in screening. Materials and Methods: Liquid chromatography electrospray tandem mass spectrometry (LC-MS/MS) was used to determine urinary polyamine (PA) profiles. In a prospective setting, 116 patients were included in the study: 57 with CRC, 13 with inflammatory bowel disease (IBD), 12 with adenoma, and 34 controls. Results: N1,N12-diacetylspermine (DiAcSPM) level was significantly higher in patients with CRC than controls (sensitivity=78.0%, specificity=70.6%; p=0.00049). The level of diacetylated cadaverine (p=0.0068) was lower and that of diacetylated putrescine (p=0.0078) was higher in patients with CRC than in those with IBD. Cadaverine (p=0.00010) and spermine (p=0.042) levels were lower and that of DiAcSPM (p=0.018) higher in patients with CRC than in those with adenoma. Conclusion: The simultaneous determination of urinary PAs by means of LC-MS/MS can be used to discriminate CRC from controls and patients with benign colorectal diseases.

General information

Publication status: Published
MoE publication type: A1 Journal article-refereed
Organisations: Faculty of Biomedical Sciences and Engineering, Ita-Suomen yliopisto, University Central Hospital Kuopio, Hatanpää Hospital, Fimlab Laboratories Ltd, Tampere University Hospital, Central Hospital of Seinäjoki
Contributors: Venäläinen, M. K., Roine, A. N., Häkkinen, M. R., Vepsäläinen, J. J., Kumpulainen, P. S., Kiviniemi, M. S., Lehtimäki, T., Oksala, N. K., Rantanen, T. K.
Number of pages: 7
Pages: 3601-3607
Publication date: 1 Jun 2018
Peer-reviewed: Yes

Publication information

Journal: Anticancer Research
Volume: 38
Issue number: 6
ISSN (Print): 0250-7005
Ratings: 
  • Scopus rating (2018): CiteScore 3.2 SJR 0.722 SNIP 0.65
Original language: English
ASJC Scopus subject areas: Oncology, Cancer Research
Keywords: Colorectal cancer, Diagnostic methods, Inflammatory bowel disease, Polyamines
Source: Scopus
Source ID: 85048248512

Research output: Contribution to journalArticleScientificpeer-review

Enhancing the usability of low-cost eye trackers for rehabilitation applications

Eye tracking is one of the most widely used technique for assessment, screening and human-machine interaction related applications. There are certain issues which limit the usage of eye trackers in practical scenarios, viz., i) need to perform multiple calibrations and ii) presence of inherent noise in the recorded data. To address these issues, we have proposed a protocol for one-time calibration against the “regular” or the “multiple” calibration phases. It is seen that though it is always desirable to perform multiple calibration, the onetime calibration also produces comparable results and might be better for individuals who are not able to perform multiple calibrations. In that case, “One-time calibration” can also be done by a participant and the calibration results are used for the rest of the participants, provided the chin rest and the eye tracker positions are unaltered. The second major issue is the presence of the inherent noise in the raw gaze data, leading to systematic and variable errors. We have proposed a signal processing chain to remove these two types of errors. Two different psychological stimuli-based tasks, namely, recall-recognition test and number gazing task are used as a case study for the same. It is seen that the proposed approach gives satisfactory results even with one-time calibration. The study is also extended to test the effect of long duration task on the performance of the proposed algorithm and the results confirm that the proposed methods work well in such scenarios too.

General information

Publication status: Published
MoE publication type: A1 Journal article-refereed
Organisations: Signal Processing, Tata Consultancy Services India
Contributors: Gavas, R. D., Roy, S., Chatterjee, D., Tripathy, S. R., Chakravarty, K., Sinha, A.
Publication date: 1 Jun 2018
Peer-reviewed: Yes

Publication information

Journal: PLoS ONE
Volume: 13
Issue number: 6
Article number: e0196348
ISSN (Print): 1932-6203
Ratings: 
  • Scopus rating (2018): CiteScore 5.4 SJR 1.1 SNIP 1.167
Original language: English
ASJC Scopus subject areas: Biochemistry, Genetics and Molecular Biology(all), Agricultural and Biological Sciences(all)
Electronic versions: 
Source: Scopus
Source ID: 85048041147

Research output: Contribution to journalArticleScientificpeer-review

Evaluation of dry electrodes in canine heart rate monitoring

The functionality of three dry electrocardiogram electrode constructions was evaluated by measuring canine heart rate during four different behaviors: Standing, sitting, lying and walking. The testing was repeated (n = 9) in each of the 36 scenarios with three dogs. Two of the electrodes were constructed with spring-loaded test pins while the third electrode was a molded polymer electrode with Ag/AgCl coating. During the measurement, a specifically designed harness was used to attach the electrodes to the dogs. The performance of the electrodes was evaluated and compared in terms of heartbeat detection coverage. The effect on the respective heart rate coverage was studied by computing the heart rate coverage from the measured electrocardiogram signal using a pattern-matching algorithm to extract the R-peaks and further the beat-to-beat heart rate. The results show that the overall coverage ratios regarding the electrodes varied between 45-95% in four different activity modes. The lowest coverage was for lying and walking and the highest was for standing and sitting.

General information

Publication status: Published
MoE publication type: A1 Journal article-refereed
Organisations: Faculty of Biomedical Sciences and Engineering, Pervasive Computing, Research group: Sensor Technology and Biomeasurements (STB), University of Helsinki, Institute of Biomedical Engineering and Informatics, University of Tampere (UTA), Research Group for Emotions
Contributors: Virtanen, J., Somppi, S., Törnqvist, H., Jeyhani, V., Fiedler, P., Gizatdinova, Y., Majaranta, P., Väätäjä, H., Cardó, A. V., Lekkala, J., Tuukkanen, S., Surakka, V., Vainio, O., Vehkaoja, A.
Publication date: 1 Jun 2018
Peer-reviewed: Yes

Publication information

Journal: Sensors
Volume: 18
Issue number: 6
Article number: 1757
ISSN (Print): 1424-8220
Ratings: 
  • Scopus rating (2018): CiteScore 4.3 SJR 0.592 SNIP 1.642
Original language: English
ASJC Scopus subject areas: Analytical Chemistry, Atomic and Molecular Physics, and Optics, Biochemistry, Instrumentation, Electrical and Electronic Engineering
Keywords: Dry electrode, Heart rate canine
Electronic versions: 
Source: Scopus
Source ID: 85047961818

Research output: Contribution to journalArticleScientificpeer-review

Photo-antimicrobial efficacy of zinc complexes of porphyrin and phthalocyanine activated by inexpensive consumer LED lamp

The properties and antimicrobial efficacies of zinc complexes of tetrakis(N-methylpyridinium-4-yl) tetraiodide porphyrin and tetrakis(N-methylpyridinium-4-yl) tetraiodide phthalocyanine impregnated to paper were evaluated. Photo-inactivation of microbes using inexpensive consumer light-emitting diode lamp was assessed on surface of dyed papers. Antimicrobial experiments of phthalocyanine-dyed paper by live cell assessment through colony forming units counting demonstrated 3.72 and 4.01 log reduction against Escherichia coli (E. coli) and Acinetobacter baylyi (A. baylyi) respectively after 1 h of illumination with 35 mW/cm2 light. The porphyrin-dyed paper exhibited 1.66 and 2.01 log reduction in colony forming units against E. coli and A. baylyi respectively after 1 h exposure with 4 mW/cm2 light. Both dyed papers were photo-stable after 64 h of continuous exposure with 42 mW/cm2 light, while phthalocyanine-dyed paper exhibited superior leaching stability in phosphate-buffered saline.

General information

Publication status: Published
MoE publication type: A1 Journal article-refereed
Organisations: Chemistry and Bioengineering, Research group: Chemistry & Advanced Materials, Research group: Bio- and Circular Economy
Contributors: George, L., Hiltunen, A., Santala, V., Efimov, A.
Number of pages: 7
Pages: 94-100
Publication date: 1 Jun 2018
Peer-reviewed: Yes

Publication information

Journal: Journal of Inorganic Biochemistry
Volume: 183
ISSN (Print): 0162-0134
Ratings: 
  • Scopus rating (2018): CiteScore 3.16 SJR 0.655 SNIP 0.916
Original language: English
ASJC Scopus subject areas: Biochemistry, Inorganic Chemistry
Source: Scopus
Source ID: 85044575449

Research output: Contribution to journalArticleScientificpeer-review

Cholesterol Protects the Oxidized Lipid Bilayer from Water Injury: An All-Atom Molecular Dynamics Study

In an effort to delineate how cholesterol protects membrane structure under oxidative stress conditions, we monitored the changes to the structure of lipid bilayers comprising 30 mol% cholesterol and an increasing concentration of Class B oxidized 1-palmitoyl-2-oleoylphosphatidylcholine (POPC) glycerophospholipids, namely, 1-palmitoyl-2-(9′-oxo-nonanoyl)-sn-glycero-3-phosphocholine (PoxnoPC), and 1-palmitoyl-2-azelaoyl-sn-glycero-3-phosphocholine (PazePC), using atomistic molecular dynamics simulations. Increasing the content of oxidized phospholipids (oxPLs) from 0 to 60 mol% oxPL resulted in a characteristic reduction in bilayer thickness and increase in area per lipid, thereby increasing the exposure of the membrane hydrophobic region to water. However, cholesterol was observed to help reduce water injury by moving into the bilayer core and forming more hydrogen bonds with the oxPLs. Cholesterol also resists altering its tilt angle, helping to maintain membrane integrity. Water that enters the 1-nm-thick core region remains part of the bulk water on either side of the bilayer, with relatively few water molecules able to traverse through the bilayer. In cholesterol-rich membranes, the bilayer does not form pores at concentrations of 60 mol% oxPL as was shown in previous simulations in the absence of cholesterol.

General information

Publication status: Published
MoE publication type: A1 Journal article-refereed
Organisations: Physics, Forschungszentrum Jülich (FZJ), Masaryk University, MEMPHYS - Centre for Biomembrane Physics, University of Southern Denmark, Heinrich Heine University Düsseldorf
Contributors: Owen, M. C., Kulig, W., Rog, T., Vattulainen, I., Strodel, B.
Number of pages: 14
Pages: 521-534
Publication date: Jun 2018
Peer-reviewed: Yes
Early online date: 17 Mar 2018

Publication information

Journal: Journal of Membrane Biology
Volume: 251
Issue number: 3
ISSN (Print): 0022-2631
Ratings: 
  • Scopus rating (2018): CiteScore 1.72 SJR 0.593 SNIP 0.632
Original language: English
ASJC Scopus subject areas: Biophysics, Physiology, Cell Biology
Keywords: Cholesterol protection, Lipid oxidation, Oxidative stress, Oxidized membranes, Pore formation
Source: Scopus
Source ID: 85044078258

Research output: Contribution to journalArticleScientificpeer-review

The precision of the symmetry in Z-ring placement in Escherichia coli is hampered at critical temperatures

Cell division in Escherichia coli is morphologically symmetric due to, among other things, the ability of these cells to place the Z-ring at midcell. Studies have reported that, at sub-optimal temperatures, this symmetry decreases at the single-cell level, but the causes remain unclear. Using fluorescence microscopy, we observe FtsZ-GFP and DAPI-stained nucleoids to assess the robustness of the symmetry of Z-ring formation and positioning in individual cells under sub-optimal and critical temperatures. We find the Z-ring formation and positioning to be robust at sub-optimal temperatures, as the Z-ring's mean width, density and displacement from midcell maintain similar levels of correlation to one another as at optimal temperatures. However, at critical temperatures, the Z-ring displacement from midcell is greatly increased. We present evidence showing that this is due to enhanced distance between the replicated nucleoids and, thus, reduced Z-ring density, which explains the weaker precision in setting a morphologically symmetric division site. This also occurs in rich media and is cumulative, i.e. combining richer media and critically high temperatures enhances the asymmetries in division, which is evidence that the causes are biophysical. To further support this, we show that the effects are reversible, i.e. shifting cells from optimal to critical, and then to optimal again, reduces and then enhances the symmetry in Z-ring positioning, respectively, as the width and density of the Z-ring return to normal values. Overall, our findings show that the Z-ring positioning in E. coli is a robust biophysical process under sub-optimal temperatures, and that critical temperatures cause significant asymmetries in division.

General information

Publication status: Published
MoE publication type: A1 Journal article-refereed
Organisations: Research group: Laboratory of Biosystem Dynamics-LBD, Faculty of Biomedical Sciences and Engineering, Faculdade de Ciencias e Tecnologia, New University of Lisbon
Contributors: Neeli-Venkata, R., Oliveira, S. M., Martins, L., Startceva, S., Bahrudeen, M., Fonseca, J. M., Minoia, M., Ribeiro, A. S.
Publication date: 18 May 2018
Peer-reviewed: Yes

Publication information

Journal: Physical Biology
Volume: 15
Issue number: 5
Article number: 056002
ISSN (Print): 1478-3967
Ratings: 
  • Scopus rating (2018): CiteScore 1.93 SJR 1.066 SNIP 0.632
Original language: English
ASJC Scopus subject areas: Biophysics, Structural Biology, Molecular Biology, Cell Biology
Keywords: asymmetry in cell division, critical temperatures, Escherichia coli, single-cell microscopy, Z-ring formation and positioning
Electronic versions: 
Source: Scopus
Source ID: 85049839706

Research output: Contribution to journalArticleScientificpeer-review

Crystallization Kinetics of an Amorphous Pharmaceutical Compound Using Fluorescence-Lifetime-Imaging Microscopy

Pharmaceutical scientists are increasingly interested in amorphous drug formulations especially because of their higher dissolution rates. Consequently, the thorough characterization and analysis of these formulations are becoming more and more important for the pharmaceutical industry. Here, fluorescence-lifetime-imaging microscopy (FLIM) was used to monitor the crystallization of an amorphous pharmaceutical compound, indomethacin. Initially, we identified different solid indomethacin forms, amorphous and γ- and α-crystalline, on the basis of their time-resolved fluorescence. All of the studied indomethacin forms showed biexponential decays with characteristic fluorescence lifetimes and amplitudes. Using this information, the crystallization of amorphous indomethacin upon storage in 60 °C was monitored for 10 days with FLIM. The progress of crystallization was detected as lifetime changes both in the FLIM images and in the fluorescence-decay curves extracted from the images. The fluorescence-lifetime amplitudes were used for quantitative analysis of the crystallization process. We also demonstrated that the fluorescence-lifetime distribution of the sample changed during crystallization, and when the sample was not moved between measuring times, the lifetime distribution could also be used for the analysis of the reaction kinetics. Our results clearly show that FLIM is a sensitive and nondestructive method for monitoring solid-state transformations on the surfaces of fluorescent samples.

General information

Publication status: Published
MoE publication type: A1 Journal article-refereed
Organisations: Chemistry and Bioengineering, Research group: Chemistry & Advanced Materials
Contributors: Rautaniemi, K., Vuorimaa-Laukkanen, E., Strachan, C. J., Laaksonen, T.
Number of pages: 8
Pages: 1964-1971
Publication date: 7 May 2018
Peer-reviewed: Yes

Publication information

Journal: Molecular Pharmaceutics
Volume: 15
Issue number: 5
ISSN (Print): 1543-8384
Ratings: 
  • Scopus rating (2018): CiteScore 7.4 SJR 1.402 SNIP 1.182
Original language: English
ASJC Scopus subject areas: Molecular Medicine, Pharmaceutical Science, Drug Discovery
Keywords: amorphous materials, crystal growth, fluorescence, fluorescence lifetime, kinetics
Electronic versions: 
Source: Scopus
Source ID: 85046674658

Research output: Contribution to journalArticleScientificpeer-review

Switchable light reflectance in dilute magneto-optical colloids based on nickel ferrite nanowires

Optical properties of diluted narrow band gap magnetic semiconductor nanowire colloids are controlled by modest magnetic fields under 100 Oe. High aspect ratio NiFe2O4 nanowires are used to achieve responsiveness to magnetic field, light absorption and -scattering. Visible light reflectance of the diluted colloids can be either increased or decreased depending on the nanowire alignment relative to the direction of the light propagation. The prepared colloids can be applied as magneto-optical switches or as smart window devices.

General information

Publication status: Published
MoE publication type: A1 Journal article-refereed
Organisations: Photonics, Institute of Physics, University of Tartu, Riga Technical University, CRPP, University of Latvia
Contributors: Sutka, A., Timusk, M., Joost, U., Ignatans, R., Maiorov, M.
Number of pages: 3
Pages: 119-121
Publication date: 2 May 2018
Peer-reviewed: Yes

Publication information

Journal: e-Journal of Surface Science and Nanotechnology
Volume: 16
ISSN (Print): 1348-0391
Ratings: 
  • Scopus rating (2018): CiteScore 0.58 SJR 0.216 SNIP 0.317
Original language: English
ASJC Scopus subject areas: Biotechnology, Bioengineering, Condensed Matter Physics, Mechanics of Materials, Surfaces and Interfaces, Surfaces, Coatings and Films
Keywords: Colloid, Ferrimagnetic, Magneto-optical, Nanowire, NiFe2O4

Bibliographical note

INT=fot,"Joost, Urmas"

Source: Scopus
Source ID: 85047369076

Research output: Contribution to journalArticleScientificpeer-review

A review of connectivity map and computational approaches in pharmacogenomics

Large-scale perturbation databases, such as ConnectivityMap (CMap) or Library of Integrated Network-based Cellular Signatures (LINCS), provide enormous opportunities for computational pharmacogenomics and drug design. A reason for this is that in contrast to classical pharmacology focusing at one target at a time, the transcriptomics profiles provided by CMap and LINCS open the door for systems biology approaches on the pathway and network level. In this article, we provide a review of recent developments in computational pharmacogenomics with respect to CMap and LINCS and related applications.

General information

Publication status: Published
MoE publication type: A1 Journal article-refereed
Organisations: Faculty of Biomedical Sciences and Engineering, Research group: Computational Systems Biology, Research group: Predictive Society and Data Analytics (PSDA), Ontario Cancer Institute University of Toronto, University of Ulster, University of Arkansas for Medical Sciences, UMIT, University of Toronto, Canada
Contributors: Musa, A., Ghoraie, L. S., Zhang, S. D., Glazko, G., Yli-Harja, O., Dehmer, M., Haibe-Kains, B., Emmert-Streib, F.
Number of pages: 18
Pages: 506-523
Publication date: 1 May 2018
Peer-reviewed: Yes

Publication information

Journal: Briefings in Bioinformatics
Volume: 19
Issue number: 3
ISSN (Print): 1467-5463
Ratings: 
  • Scopus rating (2018): CiteScore 9.5 SJR 2.748 SNIP 1.512
Original language: English
ASJC Scopus subject areas: Information Systems, Molecular Biology
Keywords: Big data, Bioinformatics, Drug discovery, Drug repositioning, Drug repurposing, Pharmacogenomics
Source: Scopus
Source ID: 85040576897

Research output: Contribution to journalArticleScientificpeer-review

Non-intersecting leaf insertion algorithm for tree structure models

We present an algorithm and an implementation to insert broadleaves or needleleaves into a quantitative structure model according to an arbitrary distribution, and a data structure to store the required information efficiently. A structure model contains the geometry and branching structure of a tree. The purpose of this work is to offer a tool for making more realistic simulations of tree models with leaves, particularly for tree models developed from terrestrial laser scanning (TLS) measurements. We demonstrate leaf insertion using cylinder-based structure models, but the associated software implementation is written in a way that enables the easy use of other types of structure models. Distributions controlling leaf location, size and angles as well as the shape of individual leaves are user definable, allowing any type of distribution. The leaf generation process consist of two stages, the first of which generates individual leaf geometry following the input distributions, while in the other stage intersections are prevented by carrying out transformations when required. Initial testing was carried out on English oak trees to demonstrate the approach and to assess the required computational resources. Depending on the size and complexity of the tree, leaf generation takes between 6 and 18 min. Various leaf area density distributions were defined, and the resulting leaf covers were compared with manual leaf harvesting measurements. The results are not conclusive, but they show great potential for the method. In the future, if our method is demonstrated to work well for TLS data from multiple tree types, the approach is likely to be very useful for three-dimensional structure and radiative transfer simulation applications, including remote sensing, ecology and forestry, among others.

General information

Publication status: Published
MoE publication type: A1 Journal article-refereed
Organisations: Mathematics, Forest Research, Department of Applied Health Research, NERC National Centre for Earth Observation (NCEO), University of Salford, Newcastle University, United Kingdom, York St John University
Contributors: Åkerblom, M., Raumonen, P., Casella, E., Disney, M. I., Danson, F. M., Gaulton, R., Schofield, L. A., Kaasalainen, M.
Publication date: 6 Apr 2018
Peer-reviewed: Yes

Publication information

Journal: Interface Focus
Volume: 8
Issue number: 2
Article number: 20170045
ISSN (Print): 2042-8898
Ratings: 
  • Scopus rating (2018): CiteScore 2.97 SJR 1.138 SNIP 0.95
Original language: English
ASJC Scopus subject areas: Biotechnology, Biophysics, Bioengineering, Biochemistry, Biomaterials, Biomedical Engineering
Keywords: Laser scanning, Leaf distribution, Leaf insertion, Quantitative structure model, Tree reconstruction
Electronic versions: 
Source: Scopus
Source ID: 85043466694

Research output: Contribution to journalArticleScientificpeer-review

Uncertainty in multispectral lidar signals caused by incidence angle effects

Multispectral terrestrial laser scanning (TLS) is an emerging technology. Several manufacturers already offer commercial dual or three wavelength airborne laser scanners, while multispectral TLS is still carried out mainly with research instruments. Many of these research efforts have focused on the study of vegetation. The aim of this paper is to study the uncertainty of the measurement of spectral indices of vegetation with multispectral lidar. Using two spectral indices as examples, we find that the uncertainty is due to systematic errors caused by the wavelength dependency of laser incidence angle effects. This finding is empirical, and the error cannot be removed by modelling or instrument modification. The discovery and study of these effects has been enabled by hyperspectral and multispectral TLS, and it has become a subject of active research within the past few years. We summarize the most recent studies on multi-wavelength incidence angle effects and present new results on the effect of specular reflection from the leaf surface, and the surface structure, which have been suggested to play a key role. We also discuss the consequences to the measurement of spectral indices with multispectral TLS, and a possible correction scheme using a synthetic laser footprint.

General information

Publication status: Published
MoE publication type: A1 Journal article-refereed
Organisations: Mathematics, Department of Navigation and Positioning, FGI
Contributors: Kaasalainen, S., Åkerblom, M., Nevalainen, O., Hakala, T., Kaasalainen, M.
Publication date: 6 Apr 2018
Peer-reviewed: Yes

Publication information

Journal: Interface Focus
Volume: 8
Issue number: 2
Article number: 20170033
ISSN (Print): 2042-8898
Ratings: 
  • Scopus rating (2018): CiteScore 2.97 SJR 1.138 SNIP 0.95
Original language: English
ASJC Scopus subject areas: Biotechnology, Biophysics, Bioengineering, Biochemistry, Biomaterials, Biomedical Engineering
Keywords: Hyperspectral, Incidence angle, Laser scanning, Vegetation
Electronic versions: 
Source: Scopus
Source ID: 85043458754

Research output: Contribution to journalArticleScientificpeer-review

Weighing trees with lasers: Advances, challenges and opportunities

Terrestrial laser scanning (TLS) is providing exciting new ways to quantify tree and forest structure, particularly above-ground biomass (AGB). We show how TLS can address some of the key uncertainties and limitations of current approaches to estimating AGB based on empirical allometric scaling equations (ASEs) that underpin all large-scale estimates of AGB. TLS provides extremely detailed non-destructive measurements of tree form independent of tree size and shape. We show examples of three-dimensional (3D) TLS measurements from various tropical and temperate forests and describe how the resulting TLS point clouds can be used to produce quantitative 3D models of branch and trunk size, shape and distribution. These models can drastically improve estimates of AGB, provide new, improved large-scale ASEs, and deliver insights into a range of fundamental tree properties related to structure. Large quantities of detailed measurements of individual 3D tree structure also have the potential to open new and exciting avenues of research in areas where difficulties of measurement have until now prevented statistical approaches to detecting and understanding underlying patterns of scaling, form and function. We discuss these opportunities and some of the challenges that remain to be overcome to enable wider adoption of TLS methods.

General information

Publication status: Published
MoE publication type: A1 Journal article-refereed
Organisations: Mathematics, Department of Applied Health Research, NERC National Centre for Earth Observation (NCEO), National Physical Laboratory, Universiteit Gent, School of Geography, University of Leeds
Contributors: Disney, M. I., Boni Vicari, M., Burt, A., Calders, K., Lewis, S. L., Raumonen, P., Wilkes, P.
Publication date: 6 Apr 2018
Peer-reviewed: Yes

Publication information

Journal: Interface Focus
Volume: 8
Issue number: 2
Article number: 20170048
ISSN (Print): 2042-8898
Ratings: 
  • Scopus rating (2018): CiteScore 2.97 SJR 1.138 SNIP 0.95
Original language: English
ASJC Scopus subject areas: Biotechnology, Biophysics, Bioengineering, Biochemistry, Biomaterials, Biomedical Engineering
Keywords: Above-ground biomass, Buttress, Canopy, Lidar, Structure, Terrestrial laser scanning
Electronic versions: 

Bibliographical note

EXT="Lewis, S. L."

Source: Scopus
Source ID: 85043466280

Research output: Contribution to journalArticleScientificpeer-review

Driver Fusions and Their Implications in the Development and Treatment of Human Cancers

Gene fusions represent an important class of somatic alterations in cancer. We systematically investigated fusions in 9,624 tumors across 33 cancer types using multiple fusion calling tools. We identified a total of 25,664 fusions, with a 63% validation rate. Integration of gene expression, copy number, and fusion annotation data revealed that fusions involving oncogenes tend to exhibit increased expression, whereas fusions involving tumor suppressors have the opposite effect. For fusions involving kinases, we found 1,275 with an intact kinase domain, the proportion of which varied significantly across cancer types. Our study suggests that fusions drive the development of 16.5% of cancer cases and function as the sole driver in more than 1% of them. Finally, we identified druggable fusions involving genes such as TMPRSS2, RET, FGFR3, ALK, and ESR1 in 6.0% of cases, and we predicted immunogenic peptides, suggesting that fusions may provide leads for targeted drug and immune therapy. Gao et al. analyze a 9,624 sample TCGA cohort with 33 cancer types to detect gene fusion events. They provide a landscape of fusion events detected, relate fusions to gene expression, focus on kinase fusion structures, examine mutually exclusive mutation and fusion patterns, and highlight fusion druggability.

General information

Publication status: Published
MoE publication type: A1 Journal article-refereed
Organisations: Faculty of Biomedical Sciences and Engineering, Washington University in St. Louis, Institute for Systems Biology, Seattle, Washington, USA, H3 Biomedicine Inc.
Contributors: Gao, Q., Liang, W. W., Foltz, S. M., Mutharasu, G., Jayasinghe, R. G., Cao, S., Liao, W. W., Reynolds, S. M., Wyczalkowski, M. A., Yao, L., Yu, L., Sun, S. Q., Caesar-Johnson, S. J., Demchok, J. A., Felau, I., Kasapi, M., Ferguson, M. L., Hutter, C. M., Sofia, H. J., Tarnuzzer, R., Wang, Z., Yang, L., Zenklusen, J. C., Zhang, J. (., Chudamani, S., Liu, J., Lolla, L., Naresh, R., Pihl, T., Sun, Q., Wan, Y., Wu, Y., Cho, J., DeFreitas, T., Frazer, S., Gehlenborg, N., Getz, G., Heiman, D. I., Kim, J., Lawrence, M. S., Lin, P., Meier, S., Noble, M. S., Saksena, G., Voet, D., Zhang, H., Bernard, B., Chambwe, N., Dhankani, V., Knijnenburg, T.
Pages: 227-238.e3
Publication date: 3 Apr 2018
Peer-reviewed: Yes

Publication information

Journal: Cell Reports
Volume: 23
Issue number: 1
ISSN (Print): 2211-1247
Ratings: 
  • Scopus rating (2018): CiteScore 8.04 SJR 6.635 SNIP 1.676
Original language: English
ASJC Scopus subject areas: Biochemistry, Genetics and Molecular Biology(all)
Keywords: cancer, fusion, gene fusions, RNA, translocation
Electronic versions: 
Source: Scopus
Source ID: 85044744284

Research output: Contribution to journalArticleScientificpeer-review

The characterization of surgical smoke from various tissues and its implications for occupational safety

Electrosurgery produces surgical smoke. Different tissues produce different quantities and types of smoke, so we studied the particle characteristics of this surgical smoke in order to analyze the implications for the occupational health of the operation room personnel. We estimated the deposition of particulate matter (PM) from surgical smoke on the respiratory tract of operation room personnel using clinically relevant tissues from Finnish landrace porcine tissues including skeletal muscle, liver, subcutaneous fat, renal pelvis, renal cortex, lung, bronchus, cerebral gray and white matter, and skin. In order to standardize the electrosurgical cuts and smoke concentrations, we built a customized computer-controlled platform. The smoke particles were analyzed with an electrical low pressure impactor (ELPI), which measures the concentration and aerodynamic size distribution of particles with a diameter between 7 nm and 10 μm. There were significant differences in the mass concentration and size distribution of the surgical smoke particles depending on the electrocauter-ized tissue. Of the various tissues tested, liver yielded the highest number of particles. In order to better estimate the health hazard, we propose that the tissues can be divided into three distinct classes according to their surgical smoke production: 1) high-PM tissue for liver; 2) medium-PM tissues for renal cortex, renal pelvis, and skeletal muscle; and 3) low-PM tissues for skin, gray matter, white matter, bronchus, and subcutaneous fat.

General information

Publication status: Published
MoE publication type: A1 Journal article-refereed
Organisations: Faculty of Biomedical Sciences and Engineering, Physics, Research group: Sensor Technology and Biomeasurements (STB), Hatanpää Hospital, Tampere University Hospital
Contributors: Karjalainen, M., Kontunen, A., Saari, S., Rönkkö, T., Lekkala, J., Roine, A., Oksala, N.
Publication date: 1 Apr 2018
Peer-reviewed: Yes

Publication information

Journal: PLoS ONE
Volume: 13
Issue number: 4
Article number: e0195274
ISSN (Print): 1932-6203
Ratings: 
  • Scopus rating (2018): CiteScore 5.4 SJR 1.1 SNIP 1.167
Original language: English
ASJC Scopus subject areas: Biochemistry, Genetics and Molecular Biology(all), Agricultural and Biological Sciences(all)
Electronic versions: 
Source: Scopus
Source ID: 85045424593

Research output: Contribution to journalArticleScientificpeer-review

Depletion of nuclear import protein karyopherin alpha 7 (KPNA7) induces mitotic defects and deformation of nuclei in cancer cells

Background: Nucleocytoplasmic transport is a tightly regulated process carried out by specific transport machinery, the defects of which may lead to a number of diseases including cancer. Karyopherin alpha 7 (KPNA7), the newest member of the karyopherin alpha nuclear importer family, is expressed at a high level during embryogenesis, reduced to very low or absent levels in most adult tissues but re-expressed in cancer cells. Methods: We used siRNA-based knock-down of KPNA7 in cancer cell lines, followed by functional assays (proliferation and cell cycle) and immunofluorescent stainings to determine the role of KPNA7 in regulation of cancer cell growth, proper mitosis and nuclear morphology. Results: In the present study, we show that the silencing of KPNA7 results in a dramatic reduction in pancreatic and breast cancer cell growth, irrespective of the endogenous KPNA7 expression level. This growth inhibition is accompanied by a decrease in the fraction of S-phase cells as well as aberrant number of centrosomes and severe distortion of the mitotic spindles. In addition, KPNA7 depletion leads to reorganization of lamin A/C and B1, the main nuclear lamina proteins, and drastic alterations in nuclear morphology with lobulated and elongated nuclei. Conclusions: Taken together, our data provide new important evidence on the contribution of KPNA7 to the regulation of cancer cell growth and the maintenance of nuclear envelope environment, and thus deepens our understanding on the impact of nuclear transfer proteins in cancer pathogenesis.

General information

Publication status: Published
MoE publication type: A1 Journal article-refereed
Organisations: Faculty of Biomedical Sciences and Engineering, BioMediTech, Fimlab Laboratories Ltd
Contributors: Vuorinen, E. M., Rajala, N. K., Ihalainen, T. O., Kallioniemi, A.
Publication date: 27 Mar 2018
Peer-reviewed: Yes

Publication information

Journal: BMC Cancer
Volume: 18
Issue number: 1
Article number: 325
ISSN (Print): 1471-2407
Ratings: 
  • Scopus rating (2018): CiteScore 5 SJR 1.336 SNIP 1.068
Original language: English
ASJC Scopus subject areas: Oncology, Genetics, Cancer Research
Keywords: Cell proliferation, Importin alpha 8, KPNA7, Mitosis, Nuclear morphology, Nuclear transfer
Electronic versions: 
Source: Scopus
Source ID: 85045202860

Research output: Contribution to journalArticleScientificpeer-review

Functional Outcome of Human Adipose Stem Cell Injections in Rat Anal Sphincter Acute Injury Model

Anal incontinence is a devastating condition that significantly reduces the quality of life. Our aim was to evaluate the effect of human adipose stem cell (hASC) injections in a rat model for anal sphincter injury, which is the main cause of anal incontinence in humans. Furthermore, we tested if the efficacy of hASCs could be improved by combining them with polyacrylamide hydrogel carrier, Bulkamid. Human ASCs derived from a female donor were culture expanded in DMEM/F12 supplemented with human platelet lysate. Female virgin Sprague-Dawley rats were randomized into four groups (n = 14–15/group): hASCs in saline or Bulkamid (3 × 105/60 μl) and saline or Bulkamid without cells. Anorectal manometry (ARM) was performed before anal sphincter injury, at two (n = 58) and at four weeks after (n = 33). Additionally, the anal sphincter tissue was examined by micro-computed tomography (μCT) and the histological parameters were compared between the groups. The median resting and peak pressure during spontaneous contraction measured by ARM were significantly higher in hASC treatment groups compared with the control groups without hASCs. There was no statistical difference in functional results between the hASC-carrier groups (saline vs. Bulkamid). No difference was detected in the sphincter muscle continuation between the groups in the histology and μCT analysis. More inflammation was discovered in the group receiving saline with hASC. The hASC injection therapy with both saline and Bulkamid is a promising nonsurgical treatment for acute anal sphincter injury. Traditional histology combined with the 3D μCT image data lends greater confidence in assessing muscle healing and continuity. Stem Cells Translational Medicine 2018;7:295–304.

General information

Publication status: Published
MoE publication type: A1 Journal article-refereed
Organisations: Faculty of Biomedical Sciences and Engineering, Research group: Computational Biophysics and Imaging Group, Tampere University Hospital
Contributors: Kuismanen, K., Juntunen, M., Narra Girish, N., Tuominen, H., Huhtala, H., Nieminen, K., Hyttinen, J., Miettinen, S.
Number of pages: 10
Pages: 295-304
Publication date: 1 Mar 2018
Peer-reviewed: Yes

Publication information

Journal: Stem Cells Translational Medicine
Volume: 7
Issue number: 3
ISSN (Print): 2157-6564
Ratings: 
  • Scopus rating (2018): CiteScore 10 SJR 2.145 SNIP 1.384
Original language: English
ASJC Scopus subject areas: Developmental Biology, Cell Biology
Keywords: Adipose stem cells, Anal incontinence, Anal sphincter injury, Mesenchymal stem cells, Micro-computed tomography, Polyacrylamide hydrogel Bulkamid, Tissue engineering
Source: Scopus
Source ID: 85041170829

Research output: Contribution to journalArticleScientificpeer-review

Soft hydrazone crosslinked hyaluronan- and alginate-based hydrogels as 3D supportive matrices for human pluripotent stem cell-derived neuronal cells

Regenerative medicine, especially cell therapy combined with a supportive biomaterial scaffold, is considered to be a potential treatment for various deficits in humans. Here, we have produced and investigated the detailed properties of injectable hydrazone crosslinked hyaluronan-polyvinyl alcohol (HA-PVA) and alginate-polyvinyl alcohol (AL-PVA) hydrogels to be used as a supportive biomaterial for 3D neural cell cultures. To the best of our knowledge, this is the first time the polymerization and properties of hydrazone crosslinked AL-PVA hydrogel have been reported. The effect of the degree of substitution and molecular weight of the polymer components as well as the polymer concentration of the hydrogel on the swelling, degradation and mechanical properties of the hydrogels is reported. Furthermore, we studied the effect of the above parameters on the growth of human pluripotent stem cell-derived neuronal cells. The most neural cell supportive HA-PVA hydrogel was composed of high molecular weight HA component with brain-mimicking mechanical properties and decreased polymer concentration. AL-PVA hydrogel, with stiffness quite similar to brain tissue, was also shown to be similarly supportive. Neuronal spreading and 3D network formation was enhanced inside the softest hydrogels.

General information

Publication status: Published
MoE publication type: A1 Journal article-refereed
Organisations: Faculty of Biomedical Sciences and Engineering, Research group: Biomaterials and Tissue Engineering Group, BioMediTech Institute and Faculty of Medicine and Life Sciences
Contributors: Karvinen, J., Joki, T., Ylä-Outinen, L., Koivisto, J. T., Narkilahti, S., Kellomäki, M.
Number of pages: 11
Pages: 29-39
Publication date: 1 Mar 2018
Peer-reviewed: Yes

Publication information

Journal: Reactive and Functional Polymers
Volume: 124
ISSN (Print): 1381-5148
Ratings: 
  • Scopus rating (2018): CiteScore 4.9 SJR 0.712 SNIP 0.92
Original language: English
ASJC Scopus subject areas: Chemistry(all), Environmental Chemistry, Biochemistry, Chemical Engineering(all), Polymers and Plastics, Materials Chemistry
Keywords: 3D neuronal culture, Alginate, Hyaluronan, Hydrazone, Hydrogel
Source: Scopus
Source ID: 85040229275

Research output: Contribution to journalArticleScientificpeer-review

An activity recognition framework deploying the random forest classifier and a single optical heart rate monitoring and triaxial accelerometer wrist-band

Wrist-worn sensors have better compliance for activity monitoring compared to hip, waist, ankle or chest positions. However, wrist-worn activity monitoring is challenging due to the wide degree of freedom for the hand movements, as well as similarity of hand movements in different activities such as varying intensities of cycling. To strengthen the ability of wrist-worn sensors in detecting human activities more accurately, motion signals can be complemented by physiological signals such as optical heart rate (HR) based on photoplethysmography. In this paper, an activity monitoring framework using an optical HR sensor and a triaxial wrist-worn accelerometer is presented. We investigated a range of daily life activities including sitting, standing, household activities and stationary cycling with two intensities. A random forest (RF) classifier was exploited to detect these activities based on the wrist motions and optical HR. The highest overall accuracy of 89.6 ± 3.9% was achieved with a forest of a size of 64 trees and 13-s signal segments with 90% overlap. Removing the HR-derived features decreased the classification accuracy of high-intensity cycling by almost 7%, but did not affect the classification accuracies of other activities. A feature reduction utilizing the feature importance scores of RF was also carried out and resulted in a shrunken feature set of only 21 features. The overall accuracy of the classification utilizing the shrunken feature set was 89.4 ± 4.2%, which is almost equivalent to the above-mentioned peak overall accuracy.

General information

Publication status: Published
MoE publication type: A1 Journal article-refereed
Organisations: BioMediTech, Faculty of Biomedical Sciences and Engineering, Research group: Personal Health Informatics-PHI, Department of Future Technologies
Contributors: Mehrang, S., Pietilä, J., Korhonen, I.
Publication date: 22 Feb 2018
Peer-reviewed: Yes

Publication information

Journal: Sensors
Volume: 18
Issue number: 2
Article number: 613
ISSN (Print): 1424-8220
Ratings: 
  • Scopus rating (2018): CiteScore 4.3 SJR 0.592 SNIP 1.642
Original language: English
ASJC Scopus subject areas: Analytical Chemistry, Atomic and Molecular Physics, and Optics, Biochemistry, Instrumentation, Electrical and Electronic Engineering
Keywords: Accelerometer, Activity recognition, Context awareness, Machine learning, Photoplethysmography, Random forest, Wrist-worn sensors
Electronic versions: 
Source: Scopus
Source ID: 85042489750

Research output: Contribution to journalArticleScientificpeer-review

In a quest for engineering acidophiles for biomining applications: Challenges and opportunities

Biomining with acidophilic microorganisms has been used at commercial scale for the extraction of metals from various sulfide ores. With metal demand and energy prices on the rise and the concurrent decline in quality and availability of mineral resources, there is an increasing interest in applying biomining technology, in particular for leaching metals from low grade minerals and wastes. However, bioprocessing is often hampered by the presence of inhibitory compounds that originate from complex ores. Synthetic biology could provide tools to improve the tolerance of biomining microbes to various stress factors that are present in biomining environments, which would ultimately increase bioleaching efficiency. This paper reviews the state-of-the-art tools to genetically modify acidophilic biomining microorganisms and the limitations of these tools. The first part of this review discusses resilience pathways that can be engineered in acidophiles to enhance their robustness and tolerance in harsh environments that prevail in bioleaching. The second part of the paper reviews the efforts that have been carried out towards engineering robust microorganisms and developing metabolic modelling tools. Novel synthetic biology tools have the potential to transform the biomining industry and facilitate the extraction of value from ores and wastes that cannot be processed with existing biomining microorganisms.

General information

Publication status: Published
MoE publication type: A2 Review article in a scientific journal
Organisations: Chemistry and Bioengineering, Research group: Bio- and Circular Economy, CSIRO Energy Centre, Montana State University (MSU), School of Pathology and Laboratory Medicine, University of Western Australia
Contributors: Gumulya, Y., Boxall, N. J., Khaleque, H. N., Santala, V., Carlson, R. P., Kaksonen, A. H.
Publication date: 21 Feb 2018
Peer-reviewed: Yes

Publication information

Journal: Genes
Volume: 9
Issue number: 2
Article number: 116
ISSN (Print): 2073-4425
Ratings: 
  • Scopus rating (2018): CiteScore 3.1 SJR 1.592 SNIP 0.882
Original language: English
ASJC Scopus subject areas: Genetics, Genetics(clinical)
Keywords: Acidophile, Biohydrometallurgy, Bioleaching, Biomining, Halophile, Metal, Microorganism, Resistance, Synthetic biology, Tolerance
Electronic versions: 

Bibliographical note

EXT="Kaksonen, Anna H."

Source: Scopus
Source ID: 85042445286

Research output: Contribution to journalReview ArticleScientificpeer-review

Improved fatty aldehyde and wax ester production by overexpression of fatty acyl-CoA reductases

Background: Fatty aldehydes are industrially relevant compounds, which also represent a common metabolic intermediate in the microbial synthesis of various oleochemicals, including alkanes, fatty alcohols and wax esters. The key enzymes in biological fatty aldehyde production are the fatty acyl-CoA/ACP reductases (FARs) which reduce the activated acyl molecules to fatty aldehydes. Due to the disparity of FARs, identification and in vivo characterization of reductases with different properties are needed for the construction of tailored synthetic pathways for the production of various compounds. Results: Fatty aldehyde production in Acinetobacter baylyi ADP1 was increased by the overexpression of three different FARs: a native A. baylyi FAR Acr1, a cyanobacterial Aar, and a putative, previously uncharacterized dehydrogenase (Ramo) from Nevskia ramosa. The fatty aldehyde production was followed in real-time inside the cells with a luminescence-based tool, and the highest aldehyde production was achieved with Aar. The fate of the overproduced fatty aldehydes was studied by measuring the production of wax esters by a native downstream pathway of A. baylyi, for which fatty aldehyde is a specific intermediate. The wax ester production was improved with the overexpression of Acr1 or Ramo compared to the wild type A. baylyi by more than two-fold, whereas the expression of Aar led to only subtle wax ester production. The overexpression of FARs did not affect the length of the acyl chains of the wax esters. Conclusions: The fatty aldehyde production, as well as the wax ester production of A. baylyi, was improved with the overexpression of a key enzyme in the pathway. The wax ester titer (0.45 g/l) achieved with the overexpression of Acr1 is the highest reported without hydrocarbon supplementation to the culture. The contrasting behavior of the different reductases highlight the significance of in vivo characterization of enzymes and emphasizes the possibilities provided by the diversity of FARs for pathway and product modulation.

General information

Publication status: Published
MoE publication type: A1 Journal article-refereed
Organisations: Chemistry and Bioengineering, Research group: Bio- and Circular Economy
Contributors: Lehtinen, T., Efimova, E., Santala, S., Santala, V.
Publication date: 8 Feb 2018
Peer-reviewed: Yes

Publication information

Journal: Microbial Cell Factories
Volume: 17
Issue number: 1
Article number: 19
ISSN (Print): 1475-2859
Ratings: 
  • Scopus rating (2018): CiteScore 6.9 SJR 1.407 SNIP 1.272
Original language: English
ASJC Scopus subject areas: Biotechnology, Bioengineering, Applied Microbiology and Biotechnology
Keywords: Acinetobacter baylyi ADP1, FAR, Fatty acyl-CoA reductase, Fatty aldehyde, Wax ester
Electronic versions: 
Source: Scopus
Source ID: 85041848256

Research output: Contribution to journalArticleScientificpeer-review

Molecular mechanism for inhibition of twinfilin by phosphoinositides

Membrane phosphoinositides control organization and dynamics of the actin cytoskeleton by regulating the activities of several key actin-binding proteins. Twinfilin is an evolutionarily conserved protein that contributes to cytoskeletal dynamics by interacting with actin monomers, filaments, and the heterodimeric capping protein. Twinfilin also binds phosphoinositides, which inhibit its interactions with actin, but the underlying mechanism has remained unknown. Here, we show that the high-affinity binding site of twinfilin for phosphoinositides is located at the C-terminal tail region, whereas the two actin-depolymerizing factor (ADF)/cofilin-like ADF homology domains of twinfilin bind phosphoinositides only with low affinity. Mutagenesis and biochemical experiments combined with atomistic molecular dynamics simulations reveal that the C-terminal tail of twinfilin interacts with membranes through a multivalent electrostatic interaction with a preference toward phosphatidylinositol 3,5-bisphosphate (PI(3,5)P2), PI(4,5)P2, and PI(3,4,5)P3. This initial interaction places the actin-binding ADF homology domains of twinfilin in close proximity to the membrane and subsequently promotes their association with the membrane, thus leading to inhibition of the actin interactions. In support of this model, a twinfilin mutant lacking the C-terminal tail inhibits actin filament assembly in a phosphoinositide-insensitive manner. Our mutagenesis data also reveal that the phosphoinositide- and capping protein- binding sites overlap in the C-terminal tail of twinfilin, suggesting that phosphoinositide binding additionally inhibits the interactions of twinfilin with the heterodimeric capping protein. The results demonstrate that the conserved C-terminal tail of twinfilin is a multifunctional binding motif, which is crucial for interaction with the heterodimeric capping protein and for tethering twinfilin to phosphoinositide-rich membranes.

General information

Publication status: Published
MoE publication type: A1 Journal article-refereed
Organisations: Physics, University of Helsinki Institute of Biotechnology, Laboratory of Physics, MEMPHYS, University of Southern Denmark, University of Helsinki
Contributors: Hakala, M., Kalimeri, M., Enkavi, G., Vattulainen, I., Lappalainen, P.
Number of pages: 12
Pages: 4818-4829
Publication date: 1 Jan 2018
Peer-reviewed: Yes

Publication information

Journal: Journal of Biological Chemistry
Volume: 293
Issue number: 13
ISSN (Print): 0021-9258
Ratings: 
  • Scopus rating (2018): CiteScore 7.7 SJR 2.403 SNIP 1.089
Original language: English
ASJC Scopus subject areas: Biochemistry, Molecular Biology, Cell Biology

Bibliographical note

EXT="Enkavi, Giray"

Source: Scopus
Source ID: 85044941007

Research output: Contribution to journalArticleScientificpeer-review

A Bioscreening Technique for Ultraviolet Irradiation Protective Natural Substances

Ultraviolet radiation (UV-R) causes genotoxic and aging effects on skin, and sunscreens are used to alleviate the damage. However, sunscreens contain synthetic shielding agents that can cause harmful effects in the environment. Nature-derived substances may have potential as replacement materials for the harmful sunscreen chemicals. However, screening of a broad range of samples is tedious, and often requires a separate genotoxicity assessment. We describe a simple microplate technique for the screening of UV protective substances using a recombinant Escherichia coli biosensor. Both absorbance-based and bioactivity-based shields can be detected with simultaneous information about the sample genotoxicity. With this technique, a controversial sunscreen compound, oxybenzone offers physical or absorbance-based shield but appears genotoxic at higher concentrations (3.3 mg/mL). We also demonstrate that pine needle extract (PiNe) shields the biosensor from UV-R in a dose-dependent manner without showing genotoxicity. The physical shield of 5 mg/mL PiNe was similar to that of one of the most common UV-shielding compound TiO2 concentration 0.80 mg/mL. The bioactivity-based shield of PiNe also reaches the extent of the physical shield with the highest concentration (3.3 mg/mL). We conclude that our technique is suitable in detecting the UV-shielding potential of natural substances, and gives simultaneous information on genotoxicity.

General information

Publication status: Published
MoE publication type: A1 Journal article-refereed
Organisations: Chemistry and Bioengineering, Research group: Bio- and Circular Economy, Natural Resources Institute Finland (Luke)
Contributors: Tienaho, J., Poikulainen, E., Sarjala, T., Muilu-Mäkelä, R., Santala, V., Karp, M.
Pages: 1273-1280
Publication date: 2018
Peer-reviewed: Yes
Early online date: 2018

Publication information

Journal: Photochemistry and Photobiology
Volume: 94
Issue number: 6
ISSN (Print): 0031-8655
Ratings: 
  • Scopus rating (2018): CiteScore 2.35 SJR 0.806 SNIP 0.91
Original language: English
ASJC Scopus subject areas: Biochemistry, Physical and Theoretical Chemistry

Bibliographical note

INT=keb,"Poikulainen, Emmi"

Source: Scopus
Source ID: 85050664471

Research output: Contribution to journalArticleScientificpeer-review

Archaea are prominent members of the prokaryotic communities colonizing common forest mushrooms

In this study, the abundance and composition of prokaryotic communities associated with the inner tissue of fruiting bodies of Suillus bovinus, Boletus pinophilus, Cantharellus cibarius, Agaricus arvensis, Lycoperdon perlatum, and Piptoporus betulinus were analyzed using culture-independent methods. Our findings indicate that archaea and bacteria colonize the internal tissues of all investigated specimens and that archaea are prominent members of the prokaryotic community. The ratio of archaeal 16S rRNA gene copy numbers to those of bacteria was >1 in the fruiting bodies of four out of six fungal species included in the study. The largest proportion of archaeal 16S rRNA gene sequences belonged to thaumarchaeotal classes Terrestrial group, Miscellaneous Crenarchaeotic Group (MCG), and Thermoplasmata. Bacterial communities showed characteristic compositions in each fungal species. Bacterial classes Gammaproteobacteria, Actinobacteria, Bacilli, and Clostridia were prominent among communities in fruiting body tissues. Bacterial populations in each fungal species had different characteristics. The results of this study imply that fruiting body tissues are an important habitat for abundant and diverse populations of archaea and bacteria.

General information

Publication status: Published
MoE publication type: A1 Journal article-refereed
Organisations: Chemistry and Bioengineering, Department of Microbiology, University of Helsinki, Turku University of Applied Science
Contributors: Rinta-Kanto, J. M., Pehkonen, K., Sinkko, H., Tamminen, M. V., Timonen, S.
Number of pages: 11
Pages: 716-726
Publication date: 2018
Peer-reviewed: Yes

Publication information

Journal: Canadian Journal of Microbiology
Volume: 64
Issue number: 10
ISSN (Print): 0008-4166
Ratings: 
  • Scopus rating (2018): CiteScore 2.6 SJR 0.613 SNIP 0.662
Original language: English
ASJC Scopus subject areas: Microbiology, Immunology, Applied Microbiology and Biotechnology, Molecular Biology, Genetics
Keywords: Archaea, Bacteria, Mushroom, qPCR, Sequencing
Electronic versions: 
Source: Scopus
Source ID: 85054057146

Research output: Contribution to journalArticleScientificpeer-review

Bioactive glass induced osteogenic differentiation of human adipose stem cells is dependent on cell attachment mechanism and mitogen-activated protein kinases

Bioactive glasses (BaGs) are widely utilised in bone tissue engineering (TE) but the molecular response of cells to BaGs is poorly understood. To elucidate the mechanisms of cell attachment to BaGs and BaG-induced early osteogenic differentiation, we cultured human adipose stem cells (hASCs) on discs of two silica-based BaGs S53P4 (23.0 Na2O-20.0 CaO-4.0 P2O5-53.0 SiO2 (wt-%)) and 1-06 (5.9 Na2O-12.0 K2O-5.3 MgO-22.6 CaO-4.0 P2O5-0.2 B2O3-50.0 SiO2) in the absence of osteogenic supplements. Both BaGs induced early osteogenic differentiation by increasing alkaline phosphatase activity (ALP) and the expression of osteogenic marker genes RUNX2a and OSTERIX. Based on ALP activity, the slower reacting 1-06 glass was a stronger osteoinducer. Regarding the cell attachment, cells cultured on BaGs had enhanced integrinβ1 and vinculin production, and mature focal adhesions were smaller but more dispersed than on cell culture plastic (polystyrene). Focal adhesion kinase (FAK), extracellular signal-regulated kinase (ERK1/2) and c-Jun N-terminal kinase (JNK)-induced c-Jun phosphorylations were upregulated by glass contact. Moreover, the BaG-stimulated osteoinduction was significantly reduced by FAK and mitogen-activated protein kinase (MAPK) inhibitors, indicating an important role for FAK and MAPKs in the BaG-induced early osteogenic commitment of hASCs. Upon indirect insert culture, the ions released from the BaG discs could not reproduce the observed cellular changes, which highlighted the role of direct cell-BaG interactions in the osteopotential of BaGs. These findings gave valuable insight into the mechanism of BaG-induced osteogenic differentiation and therefore provided knowledge to aid the future design of new functional biomaterials to meet the increasing demand for clinical bone TE treatments.

General information

Publication status: Published
MoE publication type: A1 Journal article-refereed
Organisations: Faculty of Biomedical Sciences and Engineering, The National Science Centre, Poland, Tampere University Hospital, Johan Gadolin Process Chemistry Centre, Abo Akademi University, University of Tampere
Contributors: Ojansivu, M., Wang, X., Hyväri, L., Kellomäki, M., Hupa, L., Vanhatupa, S., Miettinen, S.
Number of pages: 19
Pages: 53-71
Publication date: 2018
Peer-reviewed: Yes

Publication information

Journal: European Cells and Materials
Volume: 35
ISSN (Print): 1473-2262
Ratings: 
  • Scopus rating (2018): CiteScore 6.4 SJR 1.171 SNIP 1.062
Original language: English
ASJC Scopus subject areas: Bioengineering, Biochemistry, Biomaterials, Biomedical Engineering, Cell Biology
Keywords: Bioactive glass, Cell attachment, Cell signalling, Focal adhesion, Mesenchymal stem cell, Mitogen-activated protein kinase, Osteogenic differentiation

Bibliographical note

EXT="Ojansivu, M."
EXT="Vanhatupa, S."

Source: Scopus
Source ID: 85052576307

Research output: Contribution to journalArticleScientificpeer-review

Differential processing in modality-specific Mauthner cell dendrites

Key points: The present study examines dendritic integrative processes that occur in many central neurons but have been challenging to study in vivo in the vertebrate brain. The Mauthner cell of goldfish receives auditory and visual information via two separate dendrites, providing a privileged scenario for in vivo examination of dendritic integration. The results show differential attenuation properties in the Mauthner cell dendrites arising at least partly from differences in cable properties and the nonlinear behaviour of the respective dendritic membranes. In addition to distinct modality-dependent membrane specialization in neighbouring dendrites of the Mauthner cell, we report cross-modal dendritic interactions via backpropagating postsynaptic potentials. Broadly, the results of the present study provide an exceptional example for the processing power of single neurons. Animals process multimodal information for adaptive behavioural decisions. In fish, evasion of a diving bird that breaks the water surface depends on integrating visual and auditory stimuli with very different characteristics. How do neurons process such differential sensory inputs at the dendritic level? For that, we studied the Mauthner cells (M-cells) in the goldfish startle circuit, which receive visual and auditory inputs via two separate dendrites, both accessible for in vivo recordings. We investigated whether electrophysiological membrane properties and dendrite morphology, studied in vivo, play a role in selective sensory processing in the M-cell. The results obtained show that anatomical and electrophysiological differences between the dendrites combine to produce stronger attenuation of visually evoked postsynaptic potentials (PSPs) than to auditory evoked PSPs. Interestingly, our recordings showed also cross-modal dendritic interaction because auditory evoked PSPs invade the ventral dendrite (VD), as well as the opposite where visual PSPs invade the lateral dendrite (LD). However, these interactions were asymmetrical, with auditory PSPs being more prominent in the VD than visual PSPs in the LD. Modelling experiments imply that this asymmetry is caused by active conductances expressed in the proximal segments of the VD. The results obtained in the present study suggest modality-dependent membrane specialization in M-cell dendrites suited for processing stimuli of different time domains and, more broadly, provide a compelling example of information processing in single neurons.

General information

Publication status: Published
MoE publication type: A1 Journal article-refereed
Organisations: Signal Processing, Universidad de Buenos Aires, Centre for Molecular Medicine Norway, Nordic European Molecular Biology Laboratory Partnership, University of Oslo, Simula Research Laboratory, City University of New York
Contributors: Medan, V., Mäki-Marttunen, T., Sztarker, J., Preuss, T.
Pages: 667-689
Publication date: 2018
Peer-reviewed: Yes
Early online date: 2017

Publication information

Journal: Journal of Physiology
Volume: 596
Issue number: 4
ISSN (Print): 0022-3751
Ratings: 
  • Scopus rating (2018): CiteScore 3.54 SJR 1.994 SNIP 1.19
Original language: English
ASJC Scopus subject areas: Physiology
Keywords: Cross-modal dendritic interaction, Dendritic specialization, Mauthner cell
Source: Scopus
Source ID: 85038240993

Research output: Contribution to journalArticleScientificpeer-review

Effect of N/S ratio on anoxic thiosulfate oxidation in a fluidized bed reactor: Experimental and artificial neural network model analysis

Anoxic thiosulfate (S2O3 2−) oxidation using autotrophic denitrification by a mixed culture of nitrate reducing, sulfur oxidizing bacteria (NR-SOB) was studied in a fluidized bed reactor (FBR). The long-term performance of the FBR was evaluated for 306 days at three nitrogen-to-sulfur (N/S) molar ratios (0.5, 0.3 and 0.1) and a hydraulic retention time (HRT) of 5 h. S2O3 2− removal efficiencies >99% were obtained at a N/S ratio of 0.5 and a S2O3 2− and nitrate (NO3 ) loading rate of 820 (±84) mg S-S2O3 2− L−1 d−1 and 173 (±10) mg N-NO3 L−1 d−1, respectively. The S2O3 2− removal efficiency decreased to 76% and 26% at N/S ratios of 0.3 and 0.1, respectively, and recovered to 80% within 3 days after increasing the N/S ratio from 0.1 back to 0.5. The highest observed half-saturation (Ks) and inhibition (KI) constants of the biofilm-grown NR-SOB obtained from batch cultivations were 172 and 800 mg S-S2O3 2− L−1, respectively. Thiobacilus denitrificans was the dominant microorganism in the FBR. Artificial neural network modeling successfully predicted S2O3 2− and NO3 removal efficiencies and SO4 2− production in the FBR. Additionally, results from the sensitivity analysis showed that the effluent pH was the most influential parameter affecting the S2O3 2− removal efficiency.

General information

Publication status: Published
MoE publication type: A1 Journal article-refereed
Organisations: Chemistry and Bioengineering, Hydraulic and Environmental Engineering (IHE) Inst. for Water Education, University of Cassino and Southern Lazio, ENEA/CREATE/Università Degli Studi Napoli Federico II
Contributors: Khanongnuch, R., Di Capua, F., Lakaniemi, A., Rene, E. R., Lens, P. N.
Pages: 171-181
Publication date: 2018
Peer-reviewed: Yes
Early online date: 1 Jan 2018

Publication information

Journal: Process Biochemistry
Volume: 68
ISSN (Print): 1359-5113
Ratings: 
  • Scopus rating (2018): CiteScore 4.7 SJR 0.754 SNIP 1.043
Original language: English
ASJC Scopus subject areas: Bioengineering, Biochemistry, Applied Microbiology and Biotechnology
Keywords: Anoxic thiosulfate oxidation, Artificial neutral network, Kinetic constants, Nitrate reducing-sulfur oxidizing bacteria, Thiobacilus denitrificans
URLs: 
Source: Scopus
Source ID: 85044110451

Research output: Contribution to journalArticleScientificpeer-review

Gloriosa superba Mediated Synthesis of Platinum and Palladium Nanoparticles for Induction of Apoptosis in Breast Cancer

Green chemistry approaches for designing therapeutically significant nanomedicine have gained considerable attention in the past decade. Herein, we report for the first time on anticancer potential of phytogenic platinum nanoparticles (PtNPs) and palladium nanoparticles (PdNPs) using a medicinal plant Gloriosa superba tuber extract (GSTE). The synthesis of the nanoparticles was completed within 5 hours at 100°C which was confirmed by development of dark brown and black colour for PtNPs and PdNPs, respectively, along with enhancement of the peak intensity in the UV-visible spectra. High-resolution transmission electron microscopy (HRTEM) showed that the monodispersed spherical nanoparticles were within a size range below 10 nm. Energy dispersive spectra (EDS) confirmed the elemental composition, while dynamic light scattering (DLS) helped to evaluate the hydrodynamic size of the particles. Anticancer activity against MCF-7 (human breast adenocarcinoma) cell lines was evaluated using MTT assay, flow cytometry, and confocal microscopy. PtNPs and PdNPs showed 49.65 ± 1.99% and 36.26 ± 0.91% of anticancer activity. Induction of apoptosis was most predominant in the underlying mechanism which was rationalized by externalization of phosphatidyl serine and membrane blebbing. These findings support the efficiency of phytogenic fabrication of nanoscale platinum and palladium drugs for management and therapy against breast cancer.

General information

Publication status: Published
MoE publication type: A1 Journal article-refereed
Organisations: Faculty of Biomedical Sciences and Engineering, Modern College of Arts, Savitribai Phule Pune University, Indian Institute of Science, Bangalore, Department of Biomedical Sciences and Engineering, Defense Institute of Advanced Technology, Indian Institute of Technology Bombay, RK University
Contributors: Rokade, S. S., Joshi, K. A., Mahajan, K., Patil, S., Tomar, G., Dubal, D. S., Parihar, V. S., Kitture, R., Bellare, J. R., Ghosh, S.
Publication date: 2018
Peer-reviewed: Yes

Publication information

Journal: Bioinorganic Chemistry and Applications
Volume: 2018
Article number: 4924186
ISSN (Print): 1565-3633
Ratings: 
  • Scopus rating (2018): CiteScore 2.6 SJR 0.383 SNIP 0.908
Original language: English
ASJC Scopus subject areas: Biochemistry, Organic Chemistry, Inorganic Chemistry
Electronic versions: 
Source: Scopus
Source ID: 85050376240

Research output: Contribution to journalArticleScientificpeer-review

Knitted 3D Scaffolds of Polybutylene Succinate Support Human Mesenchymal Stem Cell Growth and Osteogenesis

Polybutylene succinate (PBS) is a biodegradable polyester with better processability and different mechanical properties compared to polylactides (PLAs), the most commonly used synthetic polymers in tissue engineering (TE). Since only few studies have evaluated PBS-containing materials for bone TE, we prepared PLA-PBS blends and analyzed material properties as well as cell attachment, proliferation, and osteogenic differentiation of human mesenchymal stem cells (hMSCs) on scaffolds. In addition to PLA, PBS, and PLA-PBS blends, PLA-polycaprolactone and PLA-poly(trimethylene carbonate) blends were evaluated. Polymer fibers were prepared using melt spinning. Pure PBS was observed to have the highest crystallinity and strain at break compared to the tougher PLA and PLA blends. No degradation occurred during the 4-week hydrolysis in either of the materials. Knitted and rolled scaffolds were manufactured, seeded with hMSCs, and cultured for 27 days. Human MSC viability was good on all the materials, but cell spreading along the fibers was only detected in PBS-containing scaffolds. They also induced the strongest proliferative response and osteogenic differentiation, which diminished with decreasing PBS content. Based on these results, PBS is superior to PLA with respect to hMSC attachment, proliferation, and osteogenesis. This encourages utilizing PBS-based biomaterials more widely in bone TE applications.

General information

Publication status: Published
MoE publication type: A1 Journal article-refereed
Organisations: Faculty of Biomedical Sciences and Engineering, Research group: Computational Biophysics and Imaging Group, Adult Stem Cell Group, National Center of Science and Technology, Ministry of Education and Science, Republic of Kazakhstan, Tampere University Hospital, Department of Chemistry and Bioengineering
Contributors: Ojansivu, M., Johansson, L., Vanhatupa, S., Tamminen, I., Hannula, M., Hyttinen, J., Kellomäki, M., Miettinen, S.
Publication date: 2018
Peer-reviewed: Yes

Publication information

Journal: Stem Cells International
Volume: 2018
Article number: 5928935
ISSN (Print): 1687-966X
Original language: English
ASJC Scopus subject areas: Molecular Biology, Cell Biology
Electronic versions: 
Source: Scopus
Source ID: 85058947494

Research output: Contribution to journalArticleScientificpeer-review

Mapping microscale wetting variations on biological and synthetic water-repellent surfaces

Droplets slip and bounce on superhydrophobic surfaces, enabling remarkable functions in biology and technology. These surfaces often contain microscopic irregularities in surface texture and chemical composition, which may affect or even govern macroscopic wetting phenomena. However, effective ways to quantify and map microscopic variations of wettability are still missing, because existing contact angle and force-based methods lack sensitivity and spatial resolution. Here, we introduce wetting maps that visualize local variations in wetting through droplet adhesion forces, which correlate with wettability. We develop scanning droplet adhesion microscopy, a technique to obtain wetting maps with spatial resolution down to 10 μm and three orders of magnitude better force sensitivity than current tensiometers. The microscope allows characterization of challenging non-flat surfaces, like the butterfly wing, previously difficult to characterize by contact angle method due to obscured view. Furthermore, the technique reveals wetting heterogeneity of micropillared model surfaces previously assumed to be uniform.

General information

Publication status: Published
MoE publication type: A1 Journal article-refereed
Organisations: Faculty of Biomedical Sciences and Engineering, Research group: Micro and Nanosystems Research Group, Research group: Bioinspired Materials and Robotics (BMR), Aalto University, Helsinki University of Technology
Contributors: Liimatainen, V., Vuckovac, M., Jokinen, V., Sariola, V., Hokkanen, M. J., Zhou, Q., Ras, R. H.
Publication date: 1 Dec 2017
Peer-reviewed: Yes

Publication information

Journal: Nature Communications
Volume: 8
Issue number: 1
Article number: 1798
ISSN (Print): 2041-1723
Ratings: 
  • Scopus rating (2017): CiteScore 12.41 SJR 6.582 SNIP 2.934
Original language: English
ASJC Scopus subject areas: Chemistry(all), Biochemistry, Genetics and Molecular Biology(all), Physics and Astronomy(all)
Electronic versions: 

Bibliographical note

EXT="Zhou, Quan"

Source: Scopus
Source ID: 85035320075

Research output: Contribution to journalArticleScientificpeer-review

Lessons from the human genome project: Modesty, honesty, and realism

General information

Publication status: Published
MoE publication type: A1 Journal article-refereed
Organisations: Faculty of Biomedical Sciences and Engineering, Research group: Computational Medicine and Statistical Learning Laboratory (CMSL), Research group: Computational Systems Biology, Research group: Predictive Society and Data Analytics (PSDA), Predictive Medicine and Data Analytics Lab, Institute of Biosciences and Medical Technology, Institute for Bioinformatics and Translational Research, Nankai University, University of Applied Sciences Upper Austria, Computational Systems Biology Lab
Contributors: Emmert-Streib, F., Dehmer, M., Yli-Harja, O.
Publication date: 23 Nov 2017
Peer-reviewed: Yes

Publication information

Journal: Frontiers in Genetics
Volume: 8
Issue number: NOV
Article number: 184
ISSN (Print): 1664-8021
Ratings: 
  • Scopus rating (2017): CiteScore 3.78 SJR 2.274 SNIP 1.039
Original language: English
ASJC Scopus subject areas: Molecular Medicine, Genetics, Genetics(clinical)
Keywords: Bioinformatics and computational biology, Genomics, High-throuput technique, Medicine, Sequencing
Electronic versions: 
Source: Scopus
Source ID: 85034848228

Research output: Contribution to journalComment/debateScientificpeer-review

Evaluation of optogenetic electrophysiology tools in human stem cell-derived cardiomyocytes

Current cardiac drug safety assessments focus on hERG channel block and QT prolongation for evaluating arrhythmic risks, whereas the optogenetic approach focuses on the action potential (AP) waveform generated by a monolayer of human cardiomyocytes beating synchronously, thus assessing the contribution of several ion channels on the overall drug effect. This novel tool provides arrhythmogenic sensitizing by light-induced pacing in combination with non-invasive, all-optical measurements of cardiomyocyte APs and will improve assessment of drug-induced electrophysiological aberrancies. With the help of patch clamp electrophysiology measurements, we aimed to investigate whether the optogenetic modifications alter human cardiomyocytes' electrophysiology and how well the optogenetic analyses perform against this gold standard. Patch clamp electrophysiology measurements of non-transduced stem cell-derived cardiomyocytes compared to cells expressing the commercially available optogenetic constructs Optopatch and CaViar revealed no significant changes in action potential duration (APD) parameters. Thus, inserting the optogenetic constructs into cardiomyocytes does not significantly affect the cardiomyocyte's electrophysiological properties. When comparing the two methods against each other (patch clamp vs. optogenetic imaging) we found no significant differences in APD parameters for the Optopatch transduced cells, whereas the CaViar transduced cells exhibited modest increases in APD-values measured with optogenetic imaging. Thus, to broaden the screen, we combined optogenetic measurements of membrane potential and calcium transients with contractile motion measured by video motion tracking. Furthermore, to assess how optogenetic measurements can predict changes in membrane potential, or early afterdepolarizations (EADs), cells were exposed to cumulating doses of E-4031, a hERG potassium channel blocker, and drug effects were measured at both spontaneous and paced beating rates (1, 2 Hz). Cumulating doses of E-4031 produced prolonged APDs, followed by EADs and drug-induced quiescence. These observations were corroborated by patch clamp and contractility measurements. Similar responses, although more modest were seen with the IKs potassium channel blocker JNJ-303. In conclusion, optogenetic measurements of AP waveforms combined with optical pacing compare well with the patch clamp gold standard. Combined with video motion contractile measurements, optogenetic imaging provides an appealing alternative for electrophysiological screening of human cardiomyocyte responses in pharmacological efficacy and safety testings.

General information

Publication status: Published
MoE publication type: A1 Journal article-refereed
Organisations: Faculty of Biomedical Sciences and Engineering, Research group: Computational Biophysics and Imaging Group, BioMediTech, FIN-00014 University of Helsinki, BioMediTech Institute and Faculty of Biomedical Sciences and Engineering
Contributors: Björk, S., Ojala, E. A., Nordström, T., Ahola, A., Liljeström, M., Hyttinen, J., Kankuri, E., Mervaala, E.
Publication date: 2 Nov 2017
Peer-reviewed: Yes

Publication information

Journal: Frontiers in Physiology
Volume: 8
Issue number: NOV
Article number: 884
ISSN (Print): 1664-042X
Ratings: 
  • Scopus rating (2017): CiteScore 4.9 SJR 1.59 SNIP 1.179
Original language: English
ASJC Scopus subject areas: Physiology, Physiology (medical)
Keywords: Arrhythmia, Cardiac electrophysiology, Contractile motion, HERG, Human iPSC-derived cardiomyocytes, Optical action potential, Optogenetics, Safety pharmacology
Source: Scopus
Source ID: 85032749700

Research output: Contribution to journalArticleScientificpeer-review

Azopolymer photopatterning for directional control of angiogenesis

Understanding cellular behavior in response to microenvironmental stimuli is central to tissue engineering. An increasing number of reports emphasize the high sensitivity of cells to the physical characteristics of the surrounding milieu and in particular, topographical cues. In this work, we investigated the influence of dynamic topographic signal presentation on sprout formation and the possibility to obtain a space–time control over sprouting directionality without growth factors, in order to investigate the contribution of just topography in the angiogenic process. To test our hypothesis, we employed a 3D angiogenesis assay based on the use of spheroids derived from human umbilical vein endothelial cells (HUVECs). We then modulated the in situ presentation of topographical cues during early-stage angiogenesis through real-time photopatterning of an azobenzene-containing polymer, poly (Disperse Red 1 methacrylate) (pDR1m). Pattern inscription on the polymer surface was made using the focused laser of a confocal microscope. We demonstrate that during early-stage angiogenesis, sprouts followed the pattern direction, while spheroid cores acquired a polarized shape. These findings confirmed that sprout directionality was influenced by the photo-inscribed pattern, probably through contact guidance of leader cells, thus validating the proposed platform as a valuable tool for understanding complex processes involved in cell-topography interactions in multicellular systems. Statement of Significance The complex relationship between endothelial cells and the surrounding environment that leads to formation of a newly formed vascular network during tissue repair is currently unknown. We have developed an innovative in vitro platform to study these mechanisms in a space and time controlled fashion simulating what happens during regeneration. In particular, we combine a “smart” surface, namely a polymer film, with a three-dimensional living cell aggregate. The polymer is activated by light through which we can design a path to guide cells toward the formation of a new vessel. Our work lies at the intersection of stimuli-responsive biointerfaces and cell biology and may be particularly inspiring for those interested in designing biomaterial surface related to angiogenesis.

General information

Publication status: Published
MoE publication type: A1 Journal article-refereed
Organisations: Chemistry and Bioengineering, Center for Advanced Biomaterials for Healthcare, Italian Institute of Technology, Dipartimento di Ingegneria Chimica dei Materiali e della Produzione Industriale, ENEA/CREATE/Università Degli Studi Napoli Federico II, Laboratory of Chemistry and Bioengineering
Contributors: Fedele, C., De Gregorio, M., Netti, P. A., Cavalli, S., Attanasio, C.
Number of pages: 9
Pages: 317-325
Publication date: 1 Nov 2017
Peer-reviewed: Yes

Publication information

Journal: Acta Biomaterialia
Volume: 63
ISSN (Print): 1742-7061
Ratings: 
  • Scopus rating (2017): CiteScore 11.1 SJR 1.967 SNIP 1.825
Original language: English
ASJC Scopus subject areas: Biotechnology, Biomaterials, Biochemistry, Biomedical Engineering, Molecular Biology
Keywords: Angiogenesis, Azopolymers, Directional sprouting, Photopatterning, Topographical cues
Source: Scopus
Source ID: 85029628146

Research output: Contribution to journalArticleScientificpeer-review

Excessive aggregation of membrane proteins in the Martini model

The coarse-grained Martini model is employed extensively to study membrane protein oligomerization. While this approach is exceptionally promising given its computational efficiency, it is alarming that a significant fraction of these studies demonstrate unrealistic protein clusters, whose formation is essentially an irreversible process. This suggests that the protein–protein interactions are exaggerated in the Martini model. If this held true, then it would limit the applicability of Martini to study multi-protein complexes, as the rapidly clustering proteins would not be able to properly sample the correct dimerization conformations. In this work we first demonstrate the excessive protein aggregation by comparing the dimerization free energies of helical transmembrane peptides obtained with the Martini model to those determined from FRET experiments. Second, we show that the predictions provided by the Martini model for the structures of transmembrane domain dimers are in poor agreement with the corresponding structures resolved using NMR. Next, we demonstrate that the first issue can be overcome by slightly scaling down the Martini protein–protein interactions in a manner, which does not interfere with the other Martini interaction parameters. By preventing excessive, irreversible, and non-selective aggregation of membrane proteins, this approach renders the consideration of lateral dynamics and protein–lipid interactions in crowded membranes by the Martini model more realistic. However, this adjusted model does not lead to an improvement in the predicted dimer structures. This implicates that the poor agreement between the Martini model and NMR structures cannot be cured by simply uniformly reducing the interactions between all protein beads. Instead, a careful amino-acid specific adjustment of the protein–protein interactions is likely required.

General information

Publication status: Published
MoE publication type: A1 Journal article-refereed
Organisations: Physics, University of Helsinki, Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Memphys—Center for Biomembrane Physics, Laboratory of Physics
Contributors: Javanainen, M., Martinez-Seara, H., Vattulainen, I.
Publication date: 1 Nov 2017
Peer-reviewed: Yes

Publication information

Journal: PLoS ONE
Volume: 12
Issue number: 11
Article number: e0187936
ISSN (Print): 1932-6203
Ratings: 
  • Scopus rating (2017): CiteScore 5.7 SJR 1.164 SNIP 1.149
Original language: English
ASJC Scopus subject areas: Biochemistry, Genetics and Molecular Biology(all), Agricultural and Biological Sciences(all)
Electronic versions: 
Source: Scopus
Source ID: 85033687861

Research output: Contribution to journalArticleScientificpeer-review

Comparison of different coating techniques on the properties of FucoPol films

Plasma deposition, liquid flame spray (LFS) and atomic layer deposition (ALD) were used to form inorganic coatings in new exopolysaccharide (FucoPol) biodegradable films. Coated films were characterised in terms of surface, optical and barrier properties in order to evaluate their potential use in food packaging. FucoPol films presented dense and homogeneous surface with instant water contact angle of 95̊. Plasma deposition of perfluorohexane (PFH) on FucoPol surface has not shown significant improvement in the hydrophobic behaviour over the time. The FucoPol coating of SiO2 nanoparticles deposited by LFS and plasma deposition of PFH have shown higher instant water contact angle (135°) caused by coating surface roughness, but this hydrophobic behaviour was not stable over time. FucoPol films coated only with TiO2 deposited by ALD and combination of that with plasma deposition of PFH have shown stable water contact angle during time (90̊ and 115̊, respectively), transparency in the same order of magnitude and significantly lower permeability to water vapour (3.45 × 10−11 mol/m s Pa and 3.45 × 10−11 mol/m s Pa when compared to uncoated films with 5.32 × 10−11 mol/m s Pa). Moreover, films coated with TiO2-PFH have also shown a permeability to oxygen of 1.70 × 10−16 molm/m2s Pa which is 67% lower than uncoated films.

General information

Publication status: Published
MoE publication type: A1 Journal article-refereed
Organisations: Physics, Research group: Aerosol Synthesis, Campus FCT-UNL, Centre for Molecular Medicine Norway, Nordic European Molecular Biology Laboratory Partnership, University of Oslo, SP Technical Research Institute of Sweden, Universidade de Lisboa
Contributors: Ferreira, A. R., Haapanen, J., Mäkelä, J. M., Bratvold, J. E., Nilsen, O., Tuominen, M., Alves, V. D., Coelhoso, I. M.
Number of pages: 7
Pages: 268-274
Publication date: 1 Oct 2017
Peer-reviewed: Yes

Publication information

Journal: International Journal of Biological Macromolecules
Volume: 103
ISSN (Print): 0141-8130
Ratings: 
  • Scopus rating (2017): CiteScore 5.5 SJR 0.917 SNIP 1.328
Original language: English
ASJC Scopus subject areas: Structural Biology, Biochemistry, Molecular Biology
Keywords: ALD/Plasma/LFS coatings, Barrier properties, FucoPol films
Source: Scopus
Source ID: 85019938774

Research output: Contribution to journalArticleScientificpeer-review

Concerted regulation of npc2 binding to endosomal/lysosomal membranes by bis(monoacylglycero)phosphate and sphingomyelin

Niemann-Pick Protein C2 (npc2) is a small soluble protein critical for cholesterol transport within and from the lysosome and the late endosome. Intriguingly, npc2-mediated cholesterol transport has been shown to be modulated by lipids, yet the molecular mechanism of npc2-membrane interactions has remained elusive. Here, based on an extensive set of atomistic simulations and free energy calculations, we clarify the mechanism and energetics of npc2-membrane binding and characterize the roles of physiologically relevant key lipids associated with the binding process. Our results capture in atomistic detail two competitively favorable membrane binding orientations of npc2 with a low interconversion barrier. The first binding mode (Prone) places the cholesterol binding pocket in direct contact with the membrane and is characterized by membrane insertion of a loop (V59-M60-G61-I62-P63-V64-P65). This mode is associated with cholesterol uptake and release. On the other hand, the second mode (Supine) places the cholesterol binding pocket away from the membrane surface, but has overall higher membrane binding affinity. We determined that bis(monoacylglycero)phosphate (bmp) is specifically required for strong membrane binding in Prone mode, and that it cannot be substituted by other anionic lipids. Meanwhile, sphingomyelin counteracts bmp by hindering Prone mode without affecting Supine mode. Our results provide concrete evidence that lipids modulate npc2-mediated cholesterol transport either by favoring or disfavoring Prone mode and that they impose this by modulating the accessibility of bmp for interacting with npc2. Overall, we provide a mechanism by which npc2-mediated cholesterol transport is controlled by the membrane composition and how npc2-lipid interactions can regulate the transport rate.

General information

Publication status: Published
MoE publication type: A1 Journal article-refereed
Organisations: Physics, Research group: Biological Physics and Soft Matter, University of Helsinki, FIN-00014 University of Helsinki, Minerva Foundation Institute for Medical Research Helsinki, Memphys—Center for Biomembrane Physics, Laboratory of Physics
Contributors: Enkavi, G., Mikkolainen, H., Güngör, B., Ikonen, E., Vattulainen, I.
Publication date: 1 Oct 2017
Peer-reviewed: Yes

Publication information

Journal: PLoS Computational Biology
Volume: 13
Issue number: 10
Article number: e1005831
ISSN (Print): 1553-734X
Ratings: 
  • Scopus rating (2017): CiteScore 4.49 SJR 3.097 SNIP 1.374
Original language: English
ASJC Scopus subject areas: Ecology, Evolution, Behavior and Systematics, Modelling and Simulation, Ecology, Molecular Biology, Genetics, Cellular and Molecular Neuroscience, Computational Theory and Mathematics
Electronic versions: 

Bibliographical note

INT=fys,"Mikkolainen, Heikki"

Source: Scopus
Source ID: 85032730334

Research output: Contribution to journalArticleScientificpeer-review

Strong FGFR3 staining is a marker for FGFR3 fusions in diffuse gliomas

Background. Inhibitors of fibroblast growth factor receptors (FGFRs) have recently arisen as a promising treatment option for patients with FGFR alterations. Gene fusions involving FGFR3 and transforming acidic coiled-coil protein 3 (TACC3) have been detected in diffuse gliomas and other malignancies, and fusion-positive cases have responded well to FGFR inhibition. As high FGFR3 expression has been detected in fusion-positive tumors, we sought to determine the clinical significance of FGFR3 protein expression level as well as its potential for indicating FGFR3 fusions. Methods. We performed FGFR3 immunohistochemistry on tissue microarrays containing 676 grades II-IV astrocytomas and 116 grades II-III oligodendroglial tumor specimens. Fifty-one cases were further analyzed using targeted sequencing. Results. Moderate to strong FGFR3 staining was detected in gliomas of all grades, was more common in females, and was associated with poor survival in diffuse astrocytomas. Targeted sequencing identified FGFR3-TACC3 fusions and an FGFR3-CAMK2A fusion in 10 of 15 strongly stained cases, whereas no fusions were found in 36 negatively to moderately stained cases. Fusion-positive cases were predominantly female and negative for IDH and EGFR/PDGFRA/MET alterations. These and moderately stained cases show lower MIB-1 proliferation index than negatively to weakly stained cases. Furthermore, stronger FGFR3 expression was commonly observed in malignant tissue regions of lower cellularity in fusion-negative cases. Importantly, subregional negative FGFR3 staining was also observed in a few fusion-positive cases. Conclusions. Strong FGFR3 protein expression is indicative of FGFR3 fusions and may serve as a clinically applicable predictive marker for treatment regimens based on FGFR inhibitors.

General information

Publication status: Published
MoE publication type: A1 Journal article-refereed
Organisations: Signal Processing, Research group: Data-analytics and Optimization, Faculty of Biomedical Sciences and Engineering, Research group: Computational Systems Biology, Heart Group, Department of Pathology, University of Texas, M. D. Anderson Cancer Center, Cancer Genomics Laboratory, Houston, TX, USA, Tampere University Hospital, Fimlab Laboratories Ltd, Pori Unit, Comprehensive Cancer Center of Wake Forest Baptist Medical Center, Wake Forest Baptist Medical Center, National Center of Science and Technology, Ministry of Education and Science, Republic of Kazakhstan
Contributors: Granberg, K. J., Annala, M., Lehtinen, B., Kesseli, J., Haapasalo, J., Ruusuvuori, P., Yli-Harja, O., Visakorpi, T., Haapasalo, H., Nykter, M., Zhang, W.
Number of pages: 11
Pages: 1206-1216
Publication date: 1 Sep 2017
Peer-reviewed: Yes

Publication information

Journal: Neuro-Oncology
Volume: 19
Issue number: 9
ISSN (Print): 1522-8517
Ratings: 
  • Scopus rating (2017): CiteScore 14.6 SJR 4.064 SNIP 2.264
Original language: English
ASJC Scopus subject areas: Oncology, Clinical Neurology, Cancer Research
Keywords: Biomarker, Gene fusion, Glioblastoma, Targeted sequencing

Bibliographical note

EXT="Zhang, Wei"
EXT="Nykter, Matti"
EXT="Kesseli, Juha"
INT=tut-bmt,"Lehtinen, Birgitta"

Source: Scopus
Source ID: 85018262100

Research output: Contribution to journalArticleScientificpeer-review

Inhibition of Aβ Amyloid Growth and Toxicity by Silybins: The Crucial Role of Stereochemistry

The self-assembling of the amyloid β (Aβ) peptide into neurotoxic aggregates is considered a central event in the pathogenesis of Alzheimer's disease (AD). Based on the "amyloid hypothesis", many efforts have been devoted to designing molecules able to halt disease progression by inhibiting Aβ self-assembly. Here, we combine biophysical (ThT assays, TEM and AFM imaging), biochemical (WB and ESI-MS), and computational (all-atom molecular dynamics) techniques to investigate the capacity of four optically pure components of the natural product silymarin (silybin A, silybin B, 2,3-dehydrosilybin A, 2,3-dehydrosilybin B) to inhibit Aβ aggregation. Despite TEM analysis demonstrated that all the four investigated flavonoids prevent the formation of mature fibrils, ThT assays, WB and AFM investigations showed that only silybin B was able to halt the growth of small-sized protofibrils thus promoting the formation of large, amorphous aggregates. Molecular dynamics (MD) simulations indicated that silybin B interacts mainly with the C-terminal hydrophobic segment 35MVGGVV40 of Aβ40. Consequently to silybin B binding, the peptide conformation remains predominantly unstructured along all the simulations. By contrast, silybin A interacts preferentially with the segments 17LVFF20 and 27NKGAII32 of Aβ40 which shows a high tendency to form bend, turn, and β-sheet conformation in and around these two domains. Both 2,3-dehydrosilybin enantiomers bind preferentially the segment 17LVFF20 but lead to the formation of different small-sized, ThT-positive Aβ aggregates. Finally, in vivo studies in a transgenic Caenorhabditis elegans strain expressing human Aβ indicated that silybin B is the most effective of the four compounds in counteracting Aβ proteotoxicity. This study underscores the pivotal role of stereochemistry in determining the neuroprotective potential of silybins and points to silybin B as a promising lead compound for further development in anti-AD therapeutics.

General information

Publication status: Published
MoE publication type: A1 Journal article-refereed
Organisations: Physics, Centro S3, ENEA/CREATE/Università Degli Studi Napoli Federico II, STMicroelectronics, Università degli Studi di Catania, IRCCS-Istituto di Ricerche Farmacologiche Mario Negri
Contributors: Sciacca, M. F., Romanucci, V., Zarrelli, A., Monaco, I., Lolicato, F., Spinella, N., Galati, C., Grasso, G., D'Urso, L., Romeo, M., Diomede, L., Salmona, M., Bongiorno, C., Di Fabio, G., La Rosa, C., Milardi, D.
Number of pages: 12
Pages: 1767-1778
Publication date: 16 Aug 2017
Peer-reviewed: Yes

Publication information

Journal: ACS Chemical Neuroscience
Volume: 8
Issue number: 8
ISSN (Print): 1948-7193
Ratings: 
  • Scopus rating (2017): CiteScore 5.9 SJR 1.442 SNIP 0.991
Original language: English
ASJC Scopus subject areas: Physiology, Biochemistry, Cognitive Neuroscience, Cell Biology
Keywords: Alzheimer's disease, Chiral drugs, natural compounds, neurodegeneration, neuroprotection
Source: Scopus
Source ID: 85027418392

Research output: Contribution to journalArticleScientificpeer-review

Nanofibrillar cellulose-alginate hydrogel coated surgical sutures as cell-carrier systems

Hydrogel nanomaterials, especially those that are of non-human and non-animal origins, have great potential in biomedical and pharmaceutical sciences due to their versatility and inherent soft-tissue like properties. With the ability to simulate native tissue function, hydrogels are potentially well suited for cellular therapy applications. In this study, we have fabricated nanofibrillar cellulose-alginate (NFCA) suture coatings as biomedical devices to help overcome some of the limitations related to cellular therapy, such as low cell survivability and distribution out of target tissue. The addition of sodium alginate 8% (w/v) increased the NFCA hydrogel viscosity, storage and loss moduli by slightly under one order of magnitude, thus contributing significantly to coating strength. Confocal microscopy showed nearly 100% cell viability throughout the 2-week incubation period within and on the surface of the coating. Additionally, typical morphologies in the dual cell culture of spheroid forming HepG2 and monolayer type SK-HEP-1 were observed. Twelve out of 14 NFCA coated surgical sutures remained intact during the suturing operation with various mice and rat tissue; however, partial peeling off was observed in 2 of the coated sutures. We conclude that NFCA suture coatings could perform as cell-carrier systems for cellular based therapy and post-surgical treatment.

General information

Publication status: Published
MoE publication type: A1 Journal article-refereed
Organisations: Chemistry and Bioengineering, Research group: Chemistry & Advanced Materials, University of Helsinki, Aalto University, Ita-Suomen yliopisto, Made Consulting, Centre for Drug Research
Contributors: Laurén, P., Somersalo, P., Pitkänen, I., Lou, Y. R., Urtti, A., Partanen, J., Seppälä, J., Madetoja, M., Laaksonen, T., Mäkitie, A., Yliperttula, M.
Publication date: 1 Aug 2017
Peer-reviewed: Yes

Publication information

Journal: PLoS ONE
Volume: 12
Issue number: 8
Article number: e0183487
ISSN (Print): 1932-6203
Ratings: 
  • Scopus rating (2017): CiteScore 5.7 SJR 1.164 SNIP 1.149
Original language: English
ASJC Scopus subject areas: Medicine(all), Biochemistry, Genetics and Molecular Biology(all), Agricultural and Biological Sciences(all)
Electronic versions: 
Source: Scopus
Source ID: 85028334326

Research output: Contribution to journalArticleScientificpeer-review

How management intensity and neighborhood composition affect the structure of beech (Fagus sylvatica L.) trees

Key message: The intensity of silvicultural interventions and the neighborhood composition determine branching patterns, crown shape, and trunk attributes of beech (Fagus sylvaticaL.) trees.Abstract: The intensity of silvicultural interventions and the composition of tree species are important forest management decisions. Both determine tree shape and thus influence the value of a tree, be it in terms of economy (trunk form, branchiness), or in terms of ecology (microhabitats). However, our knowledge on the distinct changes in tree architecture due to silvicultural management intensity or different neighborhood diversities is still limited, especially if the focus is on single tree attributes, e.g., branching patterns or crown shapes. We used terrestrial laser scanner data to calculate 25 structural measures for 55 European beech (Fagus sylvatica L.) trees that grew either in pure stands along a gradient of management intensity or in intra or interspecific neighborhoods in unmanaged stands. We found a lower height of maximal horizontal crown extension, a higher crown surface area, and straighter trunks with increasing management intensity. Moreover, our study revealed that beech trees surrounded by valuable hardwoods showed a lower height of maximal horizontal crown extension, a lower height–diameter ratio, and longer branches with flatter branch angles than beech trees surrounded by conspecific neighbors. Our findings provide evidence of phenotypic plasticity of European beech to diverse environmental conditions. The differences in tree structure indicate an increasing crown competition with decreasing management intensity and stronger competitive pressure for beech surrounded by conspecific neighbors in comparison to alien neighbors.

General information

Publication status: Published
MoE publication type: A1 Journal article-refereed
Organisations: Mathematics, Research group: Inverse Problems, University of Goettingen, Department of Applied Health Research
Contributors: Juchheim, J., Annighöfer, P., Ammer, C., Calders, K., Raumonen, P., Seidel, D.
Number of pages: 13
Pages: 1723–1735
Publication date: 14 Jul 2017
Peer-reviewed: Yes

Publication information

Journal: TREES-STRUCTURE AND FUNCTION
Volume: 31
Issue number: 5
ISSN (Print): 0931-1890
Ratings: 
  • Scopus rating (2017): CiteScore 1.88 SJR 0.726 SNIP 0.945
Original language: English
ASJC Scopus subject areas: Forestry, Physiology, Ecology, Plant Science
Keywords: Competition, Crown plasticity, Quantitative structural models, Terrestrial laser scanning, Thinning, Tree architecture
Source: Scopus
Source ID: 85023781959

Research output: Contribution to journalArticleScientificpeer-review

sgnesR: An R package for simulating gene expression data from an underlying real gene network structure considering delay parameters

Background: sgnesR (Stochastic Gene Network Expression Simulator in R) is an R package that provides an interface to simulate gene expression data from a given gene network using the stochastic simulation algorithm (SSA). The package allows various options for delay parameters and can easily included in reactions for promoter delay, RNA delay and Protein delay. A user can tune these parameters to model various types of reactions within a cell. As examples, we present two network models to generate expression profiles. We also demonstrated the inference of networks and the evaluation of association measure of edge and non-edge components from the generated expression profiles. Results: The purpose of sgnesR is to enable an easy to use and a quick implementation for generating realistic gene expression data from biologically relevant networks that can be user selected. Conclusions: sgnesR is freely available for academic use. The R package has been tested for R 3.2.0 under Linux, Windows and Mac OS X.

General information

Publication status: Published
MoE publication type: A1 Journal article-refereed
Organisations: BioMediTech, Faculty of Biomedical Sciences and Engineering, Signal Processing, Research group: Laboratory of Biosystem Dynamics-LBD, Research group: Computational Systems Biology, Research group: Computational Medicine and Statistical Learning Laboratory (CMSL), Research group: Predictive Society and Data Analytics (PSDA), Harvard T.H. Chan School of Public Health, Harvard School of Public Health, Mathematics and Operations Research
Contributors: Tripathi, S., Lloyd-Price, J., Ribeiro, A., Yli-Harja, O., Dehmer, M., Emmert-Streib, F.
Publication date: 4 Jul 2017
Peer-reviewed: Yes

Publication information

Journal: BMC Bioinformatics
Volume: 18
Issue number: 1
Article number: 325
ISSN (Print): 1471-2105
Ratings: 
  • Scopus rating (2017): CiteScore 4.3 SJR 1.479 SNIP 0.907
Original language: English
ASJC Scopus subject areas: Structural Biology, Biochemistry, Molecular Biology, Computer Science Applications, Applied Mathematics
Keywords: Gene expression data, Gene network, Simulation
Electronic versions: 
Source: Scopus
Source ID: 85021637056

Research output: Contribution to journalArticleScientificpeer-review

Atomistic fingerprint of hyaluronan–CD44 binding

Hyaluronan is a polyanionic, megadalton-scale polysaccharide, which initiates cell signaling by interacting with several receptor proteins including CD44 involved in cell-cell interactions and cell adhesion. Previous studies of the CD44 hyaluronan binding domain have identified multiple widespread residues to be responsible for its recognition capacity. In contrast, the X-ray structural characterization of CD44 has revealed a single binding mode associated with interactions that involve just a fraction of these residues. In this study, we show through atomistic molecular dynamics simulations that hyaluronan can bind CD44 with three topographically different binding modes that in unison define an interaction fingerprint, thus providing a plausible explanation for the disagreement between the earlier studies. Our results confirm that the known crystallographic mode is the strongest of the three binding modes. The other two modes represent metastable configurations that are readily available in the initial stages of the binding, and they are also the most frequently observed modes in our unbiased simulations. We further discuss how CD44, fostered by the weaker binding modes, diffuses along HA when attached. This 1D diffusion combined with the constrained relative orientation of the diffusing proteins is likely to influence the aggregation kinetics of CD44. Importantly, CD44 aggregation has been suggested to be a possible mechanism in CD44-mediated signaling.

General information

Publication status: Published
MoE publication type: A1 Journal article-refereed
Organisations: Physics, Research group: Biological Physics and Soft Matter, University of Helsinki, MEMPHYS - Centre for Biomembrane Physics, University of Southern Denmark, Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic
Contributors: Vuorio, J., Vattulainen, I., Martinez-Seara, H.
Publication date: 1 Jul 2017
Peer-reviewed: Yes

Publication information

Journal: PLoS Computational Biology
Volume: 13
Issue number: 7
Article number: e1005663
ISSN (Print): 1553-734X
Ratings: 
  • Scopus rating (2017): CiteScore 4.49 SJR 3.097 SNIP 1.374
Original language: English
ASJC Scopus subject areas: Ecology, Evolution, Behavior and Systematics, Modelling and Simulation, Ecology, Molecular Biology, Genetics, Cellular and Molecular Neuroscience, Computational Theory and Mathematics
Source: Scopus
Source ID: 85026671290

Research output: Contribution to journalArticleScientificpeer-review

The relationship between loading history and proximal femoral diaphysis cross-sectional geometry

Objectives: We investigated the relationship between loading history and bone biomechanical properties used in physical activity reconstructions. These bone properties included bone bending and torsional strength (J), cortical area (CA), the direction of the major axis (theta angle), and element shape ratios determined from cross sections of standardized bone length. In addition, we explored the applicability of anatomically determined cross sections. Methods: Our material consisted of hip and proximal thigh magnetic resonance images of Finnish female athletes (N = 91) engaged in high-jump, triple-jump, endurance running, swimming, power-lifting, soccer and squash; along with a group of active non-athlete individuals (N = 20). We used regression analysis for size-adjustment, and the extracted residuals were then used to compare differences in the bone properties between groups. Results: We found that triple-jumpers, soccer players, and squash players had the greatest values in CA and J, swimmers and non-athletes had the smallest, whereas high-jumpers, power-lifters, and endurance runners exhibited interim values. No between-the-group differences in element shape ratios or theta angles were found. We found that influences of activity were similar regardless of whether standardized length or anatomically determined cross sections were used. Conclusions: Extreme (triple-jump) and directionally inconsistent loading (soccer and squash) necessitate a more robust skeleton compared to directionally consistent loading (high-jump, power-lifting, and endurance running) or non-impact loading (swimming and non-athletes). However, not all of these relationships were statistically significant. Thus, information gained about physical activity using bone properties is informative but limited. Accounting for the limitations, the method is applicable on fragmented skeletal material as anatomically determined cross sections can be used.

General information

Publication status: Published
MoE publication type: A1 Journal article-refereed
Organisations: Faculty of Biomedical Sciences and Engineering, Civil Engineering, Research group: Computational Biophysics and Imaging Group, Univ of Oulu, Ita-Suomen yliopisto, Jyväskylän yliopisto, GeroCenter Foundation, Jyvaskyla Central Hospital, et Anthropologie (PACEA), UKK Institute Finland
Contributors: Niinimäki, S., Narra, N., Härkönen, L., Abe, S., Nikander, R., Hyttinen, J., Knüsel, C., Sievänen, H.
Publication date: 1 Jul 2017
Peer-reviewed: Yes

Publication information

Journal: American Journal of Human Biology
Volume: 29
Issue number: 4
Article number: e22965
ISSN (Print): 1042-0533
Ratings: 
  • Scopus rating (2017): CiteScore 3.1 SJR 0.736 SNIP 0.951
Original language: English
ASJC Scopus subject areas: Anatomy, Ecology, Evolution, Behavior and Systematics, Anthropology, Genetics

Bibliographical note

EXT="Sievänen, Harri"

Source: Scopus
Source ID: 85012016858

Research output: Contribution to journalArticleScientificpeer-review

Dynamics of a True Moving Bed separation process: Linear model identification and advanced process control

The control of Simulated Moving Bed (SMB) units is challenging due to their complex dynamic behaviour and the difficulty of measuring their main properties. Furthermore, for the SMB units, the transfer function identification when the unit is operating at its optimal point is not easy to be done through the usual way. This work presents the development of a novel strategy to identify transfer functions of TMB/SMB and its application on classical linear model predictive controllers (MPC). However, for the process in study, due its unique dynamics, only the identification of the linear model is not enough to solve its control problem. Therefore, it is proposed a modification in the MPC prediction, that consists in a strategy based on a switching system where the most adequate transfer function is employed in the controller to overcome the problems related with the process dynamic behaviour. The results show that the used methodology enables the easy identification of transfer functions at the process optimal operating point and that the MPC can control the process in both the servo and regulator problem cases. It is also showed that the transfer function identified can be applied in the control of a SMB unit with four columns, under its optimal conditions.

General information

Publication status: Published
MoE publication type: A1 Journal article-refereed
Organisations: Automation and Hydraulic Engineering, Research area: Information Systems in Automation
Contributors: Nogueira, I. B., Ribeiro, A. M., Martins, M. A., Rodrigues, A. E., Koivisto, H., Loureiro, J. M.
Publication date: 30 Jun 2017
Peer-reviewed: Yes

Publication information

Journal: Journal of Chromatography A
Volume: 1504
ISSN (Print): 0021-9673
Ratings: 
  • Scopus rating (2017): CiteScore 3.81 SJR 1.378 SNIP 1.23
Original language: English
ASJC Scopus subject areas: Analytical Chemistry, Biochemistry, Organic Chemistry
Keywords: Enantiomers separation, Model predictive control, Process transfer function, Simulated moving bed
Source: Scopus
Source ID: 85019248239

Research output: Contribution to journalArticleScientificpeer-review

Calcium Assists Dopamine Release by Preventing Aggregation on the Inner Leaflet of Presynaptic Vesicles

In this study, the dopamine-lipid bilayer interactions were probed with three physiologically relevant ion compositions using atomistic molecular dynamics simulations and free energy calculations. The in silico results indicate that calcium is able to decrease significantly the binding of dopamine to a neutral (zwitterionic) phosphatidylcholine lipid bilayer model mimicking the inner leaflet of a presynaptic vesicle. We argue that the observed calcium-induced effect is likely in crucial role in the neurotransmitter release from the presynaptic vesicles docked in the active zone of nerve terminals. The inner leaflets of presynaptic vesicles, which are responsible for releasing neurotransmitters into the synaptic cleft, are mainly composed of neutral lipids such as phosphatidylcholine and phosphatidylethanolamine. The neutrality of the lipid head group region, enhanced by a low pH level, should limit membrane aggregation of transmitters. In addition, the simulations suggest that the high calcium levels inside presynaptic vesicles prevent even the most lipophilic transmitters such as dopamine from adhering to the inner leaflet surface, thus rendering unhindered neurotransmitter release feasible.

General information

Publication status: Published
MoE publication type: A1 Journal article-refereed
Organisations: Physics, Research group: Biological Physics and Soft Matter, Structural Bioinformatics Laboratory, Abo Akad Univ, Abo Akademi University, Dept Phys, University of Helsinki, MEMPHYS, University of Southern Denmark
Contributors: Mokkila, S., Postila, P. A., Rissanen, S., Juhola, H., Vattulainen, I., Róg, T.
Number of pages: 9
Pages: 1242-1250
Publication date: 21 Jun 2017
Peer-reviewed: Yes

Publication information

Journal: ACS Chemical Neuroscience
Volume: 8
Issue number: 6
ISSN (Print): 1948-7193
Ratings: 
  • Scopus rating (2017): CiteScore 5.9 SJR 1.442 SNIP 0.991
Original language: English
ASJC Scopus subject areas: Physiology, Biochemistry, Cognitive Neuroscience, Cell Biology
Keywords: binding free energy, dopamine, molecular dynamics simulations, neurotransmitter release, phosphatidylcholine, presynaptic vesicle, Synaptic neurotransmission

Bibliographical note

INT=fys,"Mokkila, Sini"
EXT="Postila, Pekka A."

Source: Scopus
Source ID: 85021076435

Research output: Contribution to journalArticleScientificpeer-review

Androgen Receptor Deregulation Drives Bromodomain-Mediated Chromatin Alterations in Prostate Cancer

Global changes in chromatin accessibility may drive cancer progression by reprogramming transcription factor (TF) binding. In addition, histone acetylation readers such as bromodomain-containing protein 4 (BRD4) have been shown to associate with these TFs and contribute to aggressive cancers including prostate cancer (PC). Here, we show that chromatin accessibility defines castration-resistant prostate cancer (CRPC). We show that the deregulation of androgen receptor (AR) expression is a driver of chromatin relaxation and that AR/androgen-regulated bromodomain-containing proteins (BRDs) mediate this effect. We also report that BRDs are overexpressed in CRPCs and that ATAD2 and BRD2 have prognostic value. Finally, we developed gene stratification signature (BROMO-10) for bromodomain response and PC prognostication, to inform current and future trials with drugs targeting these processes. Our findings provide a compelling rational for combination therapy targeting bromodomains in selected patients in which BRD-mediated TF binding is enhanced or modified as cancer progresses.

General information

Publication status: Published
MoE publication type: A1 Journal article-refereed
Organisations: BioMediTech, Faculty of Biomedical Sciences and Engineering, Prostate cancer research center (PCRC), Oslo University Hospital, Fred Hutchinson Cancer Research Center, Rikshospitalet-Radiumhospitalet HF, Tampere University Hospital, Hamburg-Eppendorf, University of Michigan, Research and Development, University of California San Francisco, Department of Urology, Johns Hopkins Medical Institutions, Northwestern University Feinberg School of Medicine, University of Chicago, Goethe-University Frankfurt, Thomas Jefferson University, Queen's University, Belfast, Northern Ireland, Centre for Molecular Medicine Norway, Nordic European Molecular Biology Laboratory Partnership, University of Oslo, Department of Chemistry and Bioengineering, School of Management (JKK)
Contributors: Urbanucci, A., Barfeld, S. J., Kytölä, V., Itkonen, H. M., Coleman, I. M., Vodák, D., Sjöblom, L., Sheng, X., Tolonen, T., Minner, S., Burdelski, C., Kivinummi, K. K., Kohvakka, A., Kregel, S., Takhar, M., Alshalalfa, M., Davicioni, E., Erho, N., Lloyd, P., Karnes, R. J., Ross, A. E., Schaeffer, E. M., Vander Griend, D. J., Knapp, S., Corey, E., Feng, F. Y., Nelson, P. S., Saatcioglu, F., Knudsen, K. E., Tammela, T. L., Sauter, G., Schlomm, T., Nykter, M., Visakorpi, T., Mills, I. G.
Number of pages: 15
Pages: 2045-2059
Publication date: 6 Jun 2017
Peer-reviewed: Yes

Publication information

Journal: Cell Reports
Volume: 19
Issue number: 10
ISSN (Print): 2211-1247
Ratings: 
  • Scopus rating (2017): CiteScore 8.24 SJR 7.552 SNIP 1.675
Original language: English
ASJC Scopus subject areas: Biochemistry, Genetics and Molecular Biology(all)
Keywords: androgen receptor, ATAD2, BRD2, BRD4, BROMO-10, bromodomain inhibitor, castration-resistant prostate cancer, chromatin
Source: Scopus
Source ID: 85020289723

Research output: Contribution to journalArticleScientificpeer-review

Phase partitioning of GM1 and its bodipy-labeled analog determine their different binding to Cholera Toxin

Driven by interactions between lipids and proteins, biological membranes display lateral heterogeneity that manifests itself in a mosaic of liquid-ordered (Lo) or raft, and liquid-disordered (Ld) or non-raft domains with a wide range of different properties and compositions. In giant plasma membrane vesicles and giant unilamellar vesicles, specific binding of Cholera Toxin (CTxB) to GM1 glycolipids is a commonly used strategy to label raft domains or Lo membrane environments. However, these studies often use acyl-chain labeled bodipy-GM1 (bdGM1), whose headgroup accessibility and membrane order or phase partitioning may differ from those of GM1, rendering the interpretation of CTxB binding data quite problematic. To unravel the molecular basis of CTxB binding to GM1 and bdGM1, we explored the partitioning and the headgroup presentation of these gangliosides in the Lo and Ld phases using atomistic molecular dynamics simulations complemented by CTxB binding experiments. The conformation of both GM1 and bdGM1 was shown to be largely similar in the Lo and Ld phases. However, bdGM1 showed reduction in receptor availability when reconstituted into synthetic bilayer mixtures, highlighting that membrane phase partitioning of the gangliosides plays a considerable role in CTxB binding. Our results suggest that the CTxB binding is predominately modulated by the partitioning of the receptor to an appropriate membrane phase. Further, given that the Lo and Ld partitioning of bdGM1 differs from those of GM1, usage of bdGM1 for studying GM1 behavior in cells can lead to invalid interpretation of experimental data.

General information

Publication status: Published
MoE publication type: A1 Journal article-refereed
Organisations: Physics, Research group: Biological Physics and Soft Matter, German Center for Diabetes Research, University of Helsinki, University of Texas Health Science Center at Houston, Weatherall Institute of Molecular Medicine, MEMPHYS - Centre for Biomembrane Physics, University of Southern Denmark
Contributors: Rissanen, S., Grzybek, M., Orlowski, A., Róg, T., Cramariuc, O., Levental, I., Eggeling, C., Sezgin, E., Vattulainen, I.
Publication date: 9 May 2017
Peer-reviewed: Yes

Publication information

Journal: Frontiers in Physiology
Volume: 8
Issue number: MAY
Article number: 252
ISSN (Print): 1664-042X
Ratings: 
  • Scopus rating (2017): CiteScore 4.9 SJR 1.59 SNIP 1.179
Original language: English
ASJC Scopus subject areas: Physiology, Physiology (medical)
Keywords: Cholera toxin, Ganglioside, GM1, Membrane domains, Model membranes, Molecular dynamics simulations
Electronic versions: 
Source: Scopus
Source ID: 85019691532

Research output: Contribution to journalArticleScientificpeer-review