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PLoS Computational Biology

Nathalie Van Humbeeck, Tom Putzeys, Johan Wagemans
Two stimuli alternately presented at different locations can evoke a percept of a stimulus continuously moving between the two locations. The neural mechanism underlying this apparent motion (AM) is thought to be increased activation of primary visual cortex (V1) neurons tuned to locations along the AM path, although evidence remains inconclusive. AM masking, which refers to the reduced detectability of stimuli along the AM path, has been taken as evidence for AM-related V1 activation. AM-induced neural responses are thought to interfere with responses to physical stimuli along the path and as such impair the perception of these stimuli...
October 2016: PLoS Computational Biology
Max Schelker, Caroline Maria Mair, Fabian Jolmes, Robert-William Welke, Edda Klipp, Andreas Herrmann, Max Flöttmann, Christian Sieben
After endocytic uptake, influenza viruses transit early endosomal compartments and eventually reach late endosomes. There, the viral glycoprotein hemagglutinin (HA) triggers fusion between endosomal and viral membrane, a critical step that leads to release of the viral segmented genome destined to reach the cell nucleus. Endosomal maturation is a complex process involving acidification of the endosomal lumen as well as endosome motility along microtubules. While the pH drop is clearly critical for the conformational change and membrane fusion activity of HA, the effect of intracellular transport dynamics on the progress of infection remains largely unclear...
October 2016: PLoS Computational Biology
Kerstin Reuter, Alexander Biehl, Laurena Koch, Volkhard Helms
Translation of mRNA sequences into proteins typically starts at an AUG triplet. In rare cases, translation may also start at alternative non-AUG codons located in the annotated 5' UTR which leads to an increased regulatory complexity. Since ribosome profiling detects translational start sites at the nucleotide level, the properties of these start sites can then be used for the statistical evaluation of functional open reading frames. We developed a linear regression approach to predict in-frame and out-of-frame translational start sites within the 5' UTR from mRNA sequence information together with their translation initiation confidence...
October 2016: PLoS Computational Biology
Beibei Wang, Joshua Francis, Monika Sharma, Sean M Law, Alexander V Predeus, Michael Feig
Allostery is conformation regulation by propagating a signal from one site to another distal site. This study focuses on the long-range communication in DNA mismatch repair proteins MutS and its homologs where intramolecular signaling has to travel over 70 Å to couple lesion detection to ATPase activity and eventual downstream repair. Using dynamic network analysis based on extensive molecular dynamics simulations, multiple preserved communication pathways were identified that would allow such long-range signaling...
October 2016: PLoS Computational Biology
Ruben Perez-Carrasco, Pilar Guerrero, James Briscoe, Karen M Page
During tissue development, patterns of gene expression determine the spatial arrangement of cell types. In many cases, gradients of secreted signalling molecules-morphogens-guide this process by controlling downstream transcriptional networks. A mechanism commonly used in these networks to convert the continuous information provided by the gradient into discrete transitions between adjacent cell types is the genetic toggle switch, composed of cross-repressing transcriptional determinants. Previous analyses have emphasised the steady state output of these mechanisms...
October 2016: PLoS Computational Biology
Matthieu Barbier, James R Watson
Predators of all kinds, be they lions hunting in the Serengeti or fishermen searching for their catch, display various collective strategies. A common strategy is to share information about the location of prey. However, depending on the spatial characteristics and mobility of predators and prey, information sharing can either improve or hinder individual success. Here, our goal is to investigate the interacting effects of space and information sharing on predation efficiency, represented by the expected rate at which prey are found and consumed...
October 2016: PLoS Computational Biology
Soya Shinkai, Tadasu Nozaki, Kazuhiro Maeshima, Yuichi Togashi
The mammalian genome is organized into submegabase-sized chromatin domains (CDs) including topologically associating domains, which have been identified using chromosome conformation capture-based methods. Single-nucleosome imaging in living mammalian cells has revealed subdiffusively dynamic nucleosome movement. It is unclear how single nucleosomes within CDs fluctuate and how the CD structure reflects the nucleosome movement. Here, we present a polymer model wherein CDs are characterized by fractal dimensions and the nucleosome fibers fluctuate in a viscoelastic medium with memory...
October 2016: PLoS Computational Biology
Jason Karslake, Jeff Maltas, Peter Brumm, Kevin B Wood
The inoculum effect (IE) is an increase in the minimum inhibitory concentration (MIC) of an antibiotic as a function of the initial size of a microbial population. The IE has been observed in a wide range of bacteria, implying that antibiotic efficacy may depend on population density. Such density dependence could have dramatic effects on bacterial population dynamics and potential treatment strategies, but explicit measures of per capita growth as a function of density are generally not available. Instead, the IE measures MIC as a function of initial population size, and population density changes by many orders of magnitude on the timescale of the experiment...
October 2016: PLoS Computational Biology
David T Manallack, Elizabeth Yuriev
No abstract text is available yet for this article.
October 2016: PLoS Computational Biology
Edmund M Hart, Pauline Barmby, David LeBauer, François Michonneau, Sarah Mount, Patrick Mulrooney, Timothée Poisot, Kara H Woo, Naupaka B Zimmerman, Jeffrey W Hollister
No abstract text is available yet for this article.
October 2016: PLoS Computational Biology
Qie He, Junfeng Zhu, David Dingli, Jasmine Foo, Kevin Zox Leder
Over the past decade, several targeted therapies (e.g. imatinib, dasatinib, nilotinib) have been developed to treat Chronic Myeloid Leukemia (CML). Despite an initial response to therapy, drug resistance remains a problem for some CML patients. Recent studies have shown that resistance mutations that preexist treatment can be detected in a substantial number of patients, and that this may be associated with eventual treatment failure. One proposed method to extend treatment efficacy is to use a combination of multiple targeted therapies...
October 2016: PLoS Computational Biology
Daifeng Wang, Fei He, Sergei Maslov, Mark Gerstein
Gene expression is controlled by the combinatorial effects of regulatory factors from different biological subsystems such as general transcription factors (TFs), cellular growth factors and microRNAs. A subsystem's gene expression may be controlled by its internal regulatory factors, exclusively, or by external subsystems, or by both. It is thus useful to distinguish the degree to which a subsystem is regulated internally or externally-e.g., how non-conserved, species-specific TFs affect the expression of conserved, cross-species genes during evolution...
October 2016: PLoS Computational Biology
Yoonsik Shim, Andrew Philippides, Kevin Staras, Phil Husbands
We propose a biologically plausible architecture for unsupervised ensemble learning in a population of spiking neural network classifiers. A mixture of experts type organisation is shown to be effective, with the individual classifier outputs combined via a gating network whose operation is driven by input timing dependent plasticity (ITDP). The ITDP gating mechanism is based on recent experimental findings. An abstract, analytically tractable model of the ITDP driven ensemble architecture is derived from a logical model based on the probabilities of neural firing events...
October 2016: PLoS Computational Biology
Lars Hahn, Chris-André Leimeister, Rachid Ounit, Stefano Lonardi, Burkhard Morgenstern
Many algorithms for sequence analysis rely on word matching or word statistics. Often, these approaches can be improved if binary patterns representing match and don't-care positions are used as a filter, such that only those positions of words are considered that correspond to the match positions of the patterns. The performance of these approaches, however, depends on the underlying patterns. Herein, we show that the overlap complexity of a pattern set that was introduced by Ilie and Ilie is closely related to the variance of the number of matches between two evolutionarily related sequences with respect to this pattern set...
October 2016: PLoS Computational Biology
Duncan K Ralph, Frederick A Matsen
The human immune system depends on a highly diverse collection of antibody-making B cells. B cell receptor sequence diversity is generated by a random recombination process called "rearrangement" forming progenitor B cells, then a Darwinian process of lineage diversification and selection called "affinity maturation." The resulting receptors can be sequenced in high throughput for research and diagnostics. Such a collection of sequences contains a mixture of various lineages, each of which may be quite numerous, or may consist of only a single member...
October 2016: PLoS Computational Biology
Jumpei F Yamagishi, Nen Saito, Kunihiko Kaneko
As cells grow and divide under a given environment, they become crowded and resources are limited, as seen in bacterial biofilms and multicellular aggregates. These cells often show strong interactions through exchanging chemicals, as evident in quorum sensing, to achieve mutualism and division of labor. Here, to achieve stable division of labor, three characteristics are required. First, isogenous cells differentiate into several types. Second, this aggregate of distinct cell types shows better growth than that of isolated cells without interaction and differentiation, by achieving division of labor...
October 2016: PLoS Computational Biology
(no author information available yet)
[This corrects the article DOI: 10.1371/journal.pcbi.1004884.].
October 2016: PLoS Computational Biology
Richard A Gray, Pras Pathmanathan
Elucidating the underlying mechanisms of fatal cardiac arrhythmias requires a tight integration of electrophysiological experiments, models, and theory. Existing models of transmembrane action potential (AP) are complex (resulting in over parameterization) and varied (leading to dissimilar predictions). Thus, simpler models are needed to elucidate the "minimal physiological requirements" to reproduce significant observable phenomena using as few parameters as possible. Moreover, models have been derived from experimental studies from a variety of species under a range of environmental conditions (for example, all existing rabbit AP models incorporate a formulation of the rapid sodium current, INa, based on 30 year old data from chick embryo cell aggregates)...
October 2016: PLoS Computational Biology
Guillermo Rodrigo, Juan F Poyatos
Cellular decision making is based on regulatory circuits that associate signal thresholds to specific physiological actions. This transmission of information is subjected to molecular noise what can decrease its fidelity. Here, we show instead how such intrinsic noise enhances information transfer in the presence of multiple circuit copies. The result is due to the contribution of noise to the generation of autonomous responses by each copy, which are altogether associated with a common decision. Moreover, factors that correlate the responses of the redundant units (extrinsic noise or regulatory cross-talk) contribute to reduce fidelity, while those that further uncouple them (heterogeneity within the copies) can lead to stronger information gain...
October 2016: PLoS Computational Biology
Braden A W Brinkman, Alison I Weber, Fred Rieke, Eric Shea-Brown
Neural circuits reliably encode and transmit signals despite the presence of noise at multiple stages of processing. The efficient coding hypothesis, a guiding principle in computational neuroscience, suggests that a neuron or population of neurons allocates its limited range of responses as efficiently as possible to best encode inputs while mitigating the effects of noise. Previous work on this question relies on specific assumptions about where noise enters a circuit, limiting the generality of the resulting conclusions...
October 2016: PLoS Computational Biology
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