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PLoS Computational Biology

Yani Zhao, Pawel Dabrowski-Tumanski, Szymon Niewieczerzal, Joanna I Sulkowska
The folding of proteins with a complex knot is still an unresolved question. Based on representative members of Ubiquitin C-terminal Hydrolases (UCHs) that contain the 52 knot in the native state, we explain how UCHs are able to unfold and refold in vitro reversibly within the structure-based model. In particular, we identify two, topologically different folding/unfolding pathways and corroborate our results with experiment, recreating the chevron plot. We show that confinement effect of chaperonin or weak crowding greatly facilitates folding, simultaneously slowing down the unfolding process of UCHs, compared with bulk conditions...
March 16, 2018: PLoS Computational Biology
Christopher Ebsch, Robert Rosenbaum
Understanding the relationship between external stimuli and the spiking activity of cortical populations is a central problem in neuroscience. Dense recurrent connectivity in local cortical circuits can lead to counterintuitive response properties, raising the question of whether there are simple arithmetical rules for relating circuits' connectivity structure to their response properties. One such arithmetic is provided by the mean field theory of balanced networks, which is derived in a limit where excitatory and inhibitory synaptic currents precisely balance on average...
March 15, 2018: PLoS Computational Biology
Núria Folguera-Blasco, Elisabet Cuyàs, Javier A Menéndez, Tomás Alarcón
Understanding the control of epigenetic regulation is key to explain and modify the aging process. Because histone-modifying enzymes are sensitive to shifts in availability of cofactors (e.g. metabolites), cellular epigenetic states may be tied to changing conditions associated with cofactor variability. The aim of this study is to analyse the relationships between cofactor fluctuations, epigenetic landscapes, and cell state transitions. Using Approximate Bayesian Computation, we generate an ensemble of epigenetic regulation (ER) systems whose heterogeneity reflects variability in cofactor pools used by histone modifiers...
March 15, 2018: PLoS Computational Biology
Jun Ding, James S Hagood, Namasivayam Ambalavanan, Naftali Kaminski, Ziv Bar-Joseph
The Dynamic Regulatory Events Miner (DREM) software reconstructs dynamic regulatory networks by integrating static protein-DNA interaction data with time series gene expression data. In recent years, several additional types of high-throughput time series data have been profiled when studying biological processes including time series miRNA expression, proteomics, epigenomics and single cell RNA-Seq. Combining all available time series and static datasets in a unified model remains an important challenge and goal...
March 14, 2018: PLoS Computational Biology
Britta U Westner, Sarang S Dalal, Simon Hanslmayr, Tobias Staudigl
Single-trial analyses have the potential to uncover meaningful brain dynamics that are obscured when averaging across trials. However, low signal-to-noise ratio (SNR) can impede the use of single-trial analyses and decoding methods. In this study, we investigate the applicability of a single-trial approach to decode stimulus modality from magnetoencephalographic (MEG) high frequency activity. In order to classify the auditory versus visual presentation of words, we combine beamformer source reconstruction with the random forest classification method...
March 12, 2018: PLoS Computational Biology
Hao Ge, Pingping Wu, Hong Qian, Sunney Xiaoliang Xie
Within an isogenic population, even in the same extracellular environment, individual cells can exhibit various phenotypic states. The exact role of stochastic gene-state switching regulating the transition among these phenotypic states in a single cell is not fully understood, especially in the presence of positive feedback. Recent high-precision single-cell measurements showed that, at least in bacteria, switching in gene states is slow relative to the typical rates of active transcription and translation...
March 12, 2018: PLoS Computational Biology
Guillaume Pernelle, Wilten Nicola, Claudia Clopath
Cortical oscillations are thought to be involved in many cognitive functions and processes. Several mechanisms have been proposed to regulate oscillations. One prominent but understudied mechanism is gap junction coupling. Gap junctions are ubiquitous in cortex between GABAergic interneurons. Moreover, recent experiments indicate their strength can be modified in an activity-dependent manner, similar to chemical synapses. We hypothesized that activity-dependent gap junction plasticity acts as a mechanism to regulate oscillations in the cortex...
March 12, 2018: PLoS Computational Biology
Stefan Gahbauer, Kristyna Pluhackova, Rainer A Böckmann
Chemokine receptors, a subclass of G protein coupled receptors (GPCRs), play essential roles in the human immune system, they are involved in cancer metastasis as well as in HIV-infection. A plethora of studies show that homo- and heterodimers or even higher order oligomers of the chemokine receptors CXCR4, CCR5, and CCR2 modulate receptor function. In addition, membrane cholesterol affects chemokine receptor activity. However, structural information about homo- and heterodimers formed by chemokine receptors and their interplay with cholesterol is limited...
March 12, 2018: PLoS Computational Biology
Jinbo Chen, Uwe Scholz, Ruonan Zhou, Matthias Lange
In order to access and filter content of life-science databases, full text search is a widely applied query interface. But its high flexibility and intuitiveness is paid for with potentially imprecise and incomplete query results. To reduce this drawback, query assistance systems suggest those combinations of keywords with the highest potential to match most of the relevant data records. Widespread approaches are syntactic query corrections that avoid misspelling and support expansion of words by suffixes and prefixes...
March 12, 2018: PLoS Computational Biology
James Elber Duverger, Vincent Jacquemet, Alain Vinet, Philippe Comtois
The biological pacemaker approach is an alternative to cardiac electronic pacemakers. Its main objective is to create pacemaking activity from added or modified distribution of spontaneous cells in the myocardium. This paper aims to assess how automaticity strength of pacemaker cells (i.e. their ability to maintain robust spontaneous activity with fast rate and to drive neighboring quiescent cells) and structural linear anisotropy, combined with density and spatial distribution of pacemaker cells, may affect the macroscopic behavior of the biological pacemaker...
March 12, 2018: PLoS Computational Biology
Michael Pablo, Samuel A Ramirez, Timothy C Elston
Polarity establishment, the spontaneous generation of asymmetric molecular distributions, is a crucial component of many cellular functions. Saccharomyces cerevisiae (yeast) undergoes directed growth during budding and mating, and is an ideal model organism for studying polarization. In yeast and many other cell types, the Rho GTPase Cdc42 is the key molecular player in polarity establishment. During yeast polarization, multiple patches of Cdc42 initially form, then resolve into a single front. Because polarization relies on strong positive feedback, it is likely that the amplification of molecular-level fluctuations underlies the generation of multiple nascent patches...
March 12, 2018: PLoS Computational Biology
James A Grogan, Anthony J Connor, Joe M Pitt-Francis, Philip K Maini, Helen M Byrne
The corneal micropocket angiogenesis assay is an experimental protocol for studying vessel network formation, or neovascularization, in vivo. The assay is attractive due to the ease with which the developing vessel network can be observed in the same animal over time. Measurements from the assay have been used in combination with mathematical modeling to gain insights into the mechanisms of angiogenesis. While previous modeling studies have adopted planar domains to represent the assay, the hemispherical shape of the cornea and asymmetric positioning of the angiogenic source can be seen to affect vascular patterning in experimental images...
March 9, 2018: PLoS Computational Biology
Nicholas B DeFelice, Zachary D Schneider, Eliza Little, Christopher Barker, Kevin A Caillouet, Scott R Campbell, Dan Damian, Patrick Irwin, Herff M P Jones, John Townsend, Jeffrey Shaman
Ecological and laboratory studies have demonstrated that temperature modulates West Nile virus (WNV) transmission dynamics and spillover infection to humans. Here we explore whether inclusion of temperature forcing in a model depicting WNV transmission improves WNV forecast accuracy relative to a baseline model depicting WNV transmission without temperature forcing. Both models are optimized using a data assimilation method and two observed data streams: mosquito infection rates and reported human WNV cases...
March 9, 2018: PLoS Computational Biology
Ibai Irastorza-Azcarate, Rafael D Acemel, Juan J Tena, Ignacio Maeso, José Luis Gómez-Skarmeta, Damien P Devos
The use of 3C-based methods has revealed the importance of the 3D organization of the chromatin for key aspects of genome biology. However, the different caveats of the variants of 3C techniques have limited their scope and the range of scientific fields that could benefit from these approaches. To address these limitations, we present 4Cin, a method to generate 3D models and derive virtual Hi-C (vHi-C) heat maps of genomic loci based on 4C-seq or any kind of 4C-seq-like data, such as those derived from NG Capture-C...
March 9, 2018: PLoS Computational Biology
Sarah Jarvis, Konstantin Nikolic, Simon R Schultz
The mechanisms by which the gain of the neuronal input-output function may be modulated have been the subject of much investigation. However, little is known of the role of dendrites in neuronal gain control. New optogenetic experimental paradigms based on spatial profiles or patterns of light stimulation offer the prospect of elucidating many aspects of single cell function, including the role of dendrites in gain control. We thus developed a model to investigate how competing excitatory and inhibitory input within the dendritic arbor alters neuronal gain, incorporating kinetic models of opsins into our modeling to ensure it is experimentally testable...
March 9, 2018: PLoS Computational Biology
Carl Barton, Sandro Morganella, Øyvind Ødegård-Fougner, Stephanie Alexander, Jonas Ries, Tomas Fitzgerald, Jan Ellenberg, Ewan Birney
The 3D structure of chromatin plays a key role in genome function, including gene expression, DNA replication, chromosome segregation, and DNA repair. Furthermore the location of genomic loci within the nucleus, especially relative to each other and nuclear structures such as the nuclear envelope and nuclear bodies strongly correlates with aspects of function such as gene expression. Therefore, determining the 3D position of the 6 billion DNA base pairs in each of the 23 chromosomes inside the nucleus of a human cell is a central challenge of biology...
March 9, 2018: PLoS Computational Biology
Alexander E Moskalensky, Maxim A Yurkin, Artem R Muliukov, Alena L Litvinenko, Vyacheslav M Nekrasov, Andrei V Chernyshev, Valeri P Maltsev
We present a simple physically based quantitative model of blood platelet shape and its evolution during agonist-induced activation. The model is based on the consideration of two major cytoskeletal elements: the marginal band of microtubules and the submembrane cortex. Mathematically, we consider the problem of minimization of surface area constrained to confine the marginal band and a certain cellular volume. For resting platelets, the marginal band appears as a peripheral ring, allowing for the analytical solution of the minimization problem...
March 8, 2018: PLoS Computational Biology
David O Holland, Margaret E Johnson
Stoichiometric balance, or dosage balance, implies that proteins that are subunits of obligate complexes (e.g. the ribosome) should have copy numbers expressed to match their stoichiometry in that complex. Establishing balance (or imbalance) is an important tool for inferring subunit function and assembly bottlenecks. We show here that these correlations in protein copy numbers can extend beyond complex subunits to larger protein-protein interactions networks (PPIN) involving a range of reversible binding interactions...
March 8, 2018: PLoS Computational Biology
Elizabeth C Lee, Ali Arab, Sandra M Goldlust, Cécile Viboud, Bryan T Grenfell, Shweta Bansal
The surveillance of influenza activity is critical to early detection of epidemics and pandemics and the design of disease control strategies. Case reporting through a voluntary network of sentinel physicians is a commonly used method of passive surveillance for monitoring rates of influenza-like illness (ILI) worldwide. Despite its ubiquity, little attention has been given to the processes underlying the observation, collection, and spatial aggregation of sentinel surveillance data, and its subsequent effects on epidemiological understanding...
March 7, 2018: PLoS Computational Biology
Laura Martinez-Mateu, Lucia Romero, Ana Ferrer-Albero, Rafael Sebastian, José F Rodríguez Matas, José Jalife, Omer Berenfeld, Javier Saiz
Anatomically based procedures to ablate atrial fibrillation (AF) are often successful in terminating paroxysmal AF. However, the ability to terminate persistent AF remains disappointing. New mechanistic approaches use multiple-electrode basket catheter mapping to localize and target AF drivers in the form of rotors but significant concerns remain about their accuracy. We aimed to evaluate how electrode-endocardium distance, far-field sources and inter-electrode distance affect the accuracy of localizing rotors...
March 5, 2018: PLoS Computational Biology
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