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PLoS Computational Biology

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https://www.readbyqxmd.com/read/29351276/static-length-changes-of-cochlear-outer-hair-cells-can-tune-low-frequency-hearing
#1
Nikola Ciganović, Rebecca L Warren, Batu Keçeli, Stefan Jacob, Anders Fridberger, Tobias Reichenbach
The cochlea not only transduces sound-induced vibration into neural spikes, it also amplifies weak sound to boost its detection. Actuators of this active process are sensory outer hair cells in the organ of Corti, whereas the inner hair cells transduce the resulting motion into electric signals that propagate via the auditory nerve to the brain. However, how the outer hair cells modulate the stimulus to the inner hair cells remains unclear. Here, we combine theoretical modeling and experimental measurements near the cochlear apex to study the way in which length changes of the outer hair cells deform the organ of Corti...
January 19, 2018: PLoS Computational Biology
https://www.readbyqxmd.com/read/29351275/a-mathematical-model-for-il-6-mediated-stem-cell-driven-tumor-growth-and-targeted-treatment
#2
Fereshteh Nazari, Alexander T Pearson, Jacques Eduardo Nör, Trachette L Jackson
Targeting key regulators of the cancer stem cell phenotype to overcome their critical influence on tumor growth is a promising new strategy for cancer treatment. Here we present a modeling framework that operates at both the cellular and molecular levels, for investigating IL-6 mediated, cancer stem cell driven tumor growth and targeted treatment with anti-IL6 antibodies. Our immediate goal is to quantify the influence of IL-6 on cancer stem cell self-renewal and survival, and to characterize the subsequent impact on tumor growth dynamics...
January 19, 2018: PLoS Computational Biology
https://www.readbyqxmd.com/read/29346368/mechanical-feedback-coordinates-cell-wall-expansion-and-assembly-in-yeast-mating-morphogenesis
#3
Samhita P Banavar, Carlos Gomez, Michael Trogdon, Linda R Petzold, Tau-Mu Yi, Otger Campàs
The shaping of individual cells requires a tight coordination of cell mechanics and growth. However, it is unclear how information about the mechanical state of the wall is relayed to the molecular processes building it, thereby enabling the coordination of cell wall expansion and assembly during morphogenesis. Combining theoretical and experimental approaches, we show that a mechanical feedback coordinating cell wall assembly and expansion is essential to sustain mating projection growth in budding yeast (Saccharomyces cerevisiae)...
January 18, 2018: PLoS Computational Biology
https://www.readbyqxmd.com/read/29342146/a-theory-of-how-active-behavior-stabilises-neural-activity-neural-gain-modulation-by-closed-loop-environmental-feedback
#4
Christopher L Buckley, Taro Toyoizumi
During active behaviours like running, swimming, whisking or sniffing, motor actions shape sensory input and sensory percepts guide future motor commands. Ongoing cycles of sensory and motor processing constitute a closed-loop feedback system which is central to motor control and, it has been argued, for perceptual processes. This closed-loop feedback is mediated by brainwide neural circuits but how the presence of feedback signals impacts on the dynamics and function of neurons is not well understood. Here we present a simple theory suggesting that closed-loop feedback between the brain/body/environment can modulate neural gain and, consequently, change endogenous neural fluctuations and responses to sensory input...
January 17, 2018: PLoS Computational Biology
https://www.readbyqxmd.com/read/29338008/interactions-between-species-introduce-spurious-associations-in-microbiome-studies
#5
Rajita Menon, Vivek Ramanan, Kirill S Korolev
Microbiota contribute to many dimensions of host phenotype, including disease. To link specific microbes to specific phenotypes, microbiome-wide association studies compare microbial abundances between two groups of samples. Abundance differences, however, reflect not only direct associations with the phenotype, but also indirect effects due to microbial interactions. We found that microbial interactions could easily generate a large number of spurious associations that provide no mechanistic insight. Using techniques from statistical physics, we developed a method to remove indirect associations and applied it to the largest dataset on pediatric inflammatory bowel disease...
January 16, 2018: PLoS Computational Biology
https://www.readbyqxmd.com/read/29338006/a-model-for-cooperative-gating-of-l-type-ca2-channels-and-its-effects-on-cardiac-alternans-dynamics
#6
Daisuke Sato, Rose E Dixon, Luis F Santana, Manuel F Navedo
In ventricular myocytes, membrane depolarization during the action potential (AP) causes synchronous activation of multiple L-type CaV1.2 channels (LTCCs), which trigger the release of calcium (Ca2+) from the sarcoplasmic reticulum (SR). This results in an increase in intracellular Ca2+ (Cai) that initiates contraction. During pulsus alternans, cardiac contraction is unstable, going from weak to strong in successive beats despite a constant heart rate. These cardiac alternans can be caused by the instability of membrane potential (Vm) due to steep AP duration (APD) restitution (Vm-driven alternans), instability of Cai cycling (Ca2+-driven alternans), or both, and may be modulated by functional coupling between clustered CaV1...
January 16, 2018: PLoS Computational Biology
https://www.readbyqxmd.com/read/29338005/inferring-cell-state-by-quantitative-motility-analysis-reveals-a-dynamic-state-system-and-broken-detailed-balance
#7
Jacob C Kimmel, Amy Y Chang, Andrew S Brack, Wallace F Marshall
Cell populations display heterogeneous and dynamic phenotypic states at multiple scales. Similar to molecular features commonly used to explore cell heterogeneity, cell behavior is a rich phenotypic space that may allow for identification of relevant cell states. Inference of cell state from cell behavior across a time course may enable the investigation of dynamics of transitions between heterogeneous cell states, a task difficult to perform with destructive molecular observations. Cell motility is one such easily observed cell behavior with known biomedical relevance...
January 16, 2018: PLoS Computational Biology
https://www.readbyqxmd.com/read/29338004/interrupting-behaviour-minimizing-decision-costs-via-temporal-commitment-and-low-level-interrupts
#8
Kevin Lloyd, Peter Dayan
Ideal decision-makers should constantly assess all sources of information about opportunities and threats, and be able to redetermine their choices promptly in the face of change. However, perpetual monitoring and reassessment impose inordinate sensing and computational costs, making them impractical for animals and machines alike. The obvious alternative of committing for extended periods of time to limited sensory strategies associated with particular courses of action can be dangerous and wasteful. Here, we explore the intermediate possibility of making provisional temporal commitments whilst admitting interruption based on limited broader observation...
January 16, 2018: PLoS Computational Biology
https://www.readbyqxmd.com/read/29337991/hasappy-a-tool-for-candidate-identification-in-pooled-forward-genetic-screens-of-haploid-mammalian-cells
#9
Giulio Di Minin, Andreas Postlmayr, Anton Wutz
Haploid cells are increasingly used for screening of complex pathways in animal genomes. Hemizygous mutations introduced through viral insertional mutagenesis can be directly selected for phenotypic changes. Here we present HaSAPPy a tool for analysing sequencing datasets of screens using insertional mutations in large pools of haploid cells. Candidate gene prediction is implemented through identification of enrichment of insertional mutations after selection by simultaneously evaluating several parameters...
January 16, 2018: PLoS Computational Biology
https://www.readbyqxmd.com/read/29337990/clustering-gene-expression-time-series-data-using-an-infinite-gaussian-process-mixture-model
#10
Ian C McDowell, Dinesh Manandhar, Christopher M Vockley, Amy K Schmid, Timothy E Reddy, Barbara E Engelhardt
Transcriptome-wide time series expression profiling is used to characterize the cellular response to environmental perturbations. The first step to analyzing transcriptional response data is often to cluster genes with similar responses. Here, we present a nonparametric model-based method, Dirichlet process Gaussian process mixture model (DPGP), which jointly models cluster number with a Dirichlet process and temporal dependencies with Gaussian processes. We demonstrate the accuracy of DPGP in comparison to state-of-the-art approaches using hundreds of simulated data sets...
January 16, 2018: PLoS Computational Biology
https://www.readbyqxmd.com/read/29337986/the-e2-65a-mutation-disrupts-dynamic-binding-poses-of-sb269652-at-the-dopamine-d2-and-d3-receptors
#11
Ravi Kumar Verma, Ara M Abramyan, Mayako Michino, R Benjamin Free, David R Sibley, Jonathan A Javitch, J Robert Lane, Lei Shi
The dopamine D2 and D3 receptors (D2R and D3R) are important targets for antipsychotics and for the treatment of drug abuse. SB269652, a bitopic ligand that simultaneously binds both the orthosteric binding site (OBS) and a secondary binding pocket (SBP) in both D2R and D3R, was found to be a negative allosteric modulator. Previous studies identified Glu2.65 in the SBP to be a key determinant of both the affinity of SB269652 and the magnitude of its cooperativity with orthosteric ligands, as the E2.65A mutation decreased both of these parameters...
January 16, 2018: PLoS Computational Biology
https://www.readbyqxmd.com/read/29329285/a-direct-interaction-of-cholesterol-with-the-dopamine-transporter-prevents-its-out-to-inward-transition
#12
Talia Zeppelin, Lucy Kate Ladefoged, Steffen Sinning, Xavier Periole, Birgit Schiøtt
Monoamine transporters (MATs) carry out neurotransmitter reuptake from the synaptic cleft, a key step in neurotransmission, which is targeted in the treatment of neurological disorders. Cholesterol (CHOL), a major component of the synaptic plasma membrane, has been shown to exhibit a modulatory effect on MATs. Recent crystal structures of the dopamine transporter (DAT) revealed the presence of two conserved CHOL-like molecules, suggesting a functional protein-CHOL direct interaction. Here, we present extensive atomistic molecular dynamics (MD) simulations of DAT in an outward-facing conformation...
January 12, 2018: PLoS Computational Biology
https://www.readbyqxmd.com/read/29329283/modeling-the-assembly-order-of-multimeric-heteroprotein-complexes
#13
Lenna X Peterson, Yoichiro Togawa, Juan Esquivel-Rodriguez, Genki Terashi, Charles Christoffer, Amitava Roy, Woong-Hee Shin, Daisuke Kihara
Protein-protein interactions are the cornerstone of numerous biological processes. Although an increasing number of protein complex structures have been determined using experimental methods, relatively fewer studies have been performed to determine the assembly order of complexes. In addition to the insights into the molecular mechanisms of biological function provided by the structure of a complex, knowing the assembly order is important for understanding the process of complex formation. Assembly order is also practically useful for constructing subcomplexes as a step toward solving the entire complex experimentally, designing artificial protein complexes, and developing drugs that interrupt a critical step in the complex assembly...
January 12, 2018: PLoS Computational Biology
https://www.readbyqxmd.com/read/29324853/disentangling-and-modeling-interactions-in-fish-with-burst-and-coast-swimming-reveal-distinct-alignment-and-attraction-behaviors
#14
Daniel S Calovi, Alexandra Litchinko, Valentin Lecheval, Ugo Lopez, Alfonso Pérez Escudero, Hugues Chaté, Clément Sire, Guy Theraulaz
The development of tracking methods for automatically quantifying individual behavior and social interactions in animal groups has open up new perspectives for building quantitative and predictive models of collective behavior. In this work, we combine extensive data analyses with a modeling approach to measure, disentangle, and reconstruct the actual functional form of interactions involved in the coordination of swimming in Rummy-nose tetra (Hemigrammus rhodostomus). This species of fish performs burst-and-coast swimming behavior that consists of sudden heading changes combined with brief accelerations followed by quasi-passive, straight decelerations...
January 11, 2018: PLoS Computational Biology
https://www.readbyqxmd.com/read/29324768/identifying-human-diamine-sensors-for-death-related-putrescine-and-cadaverine-molecules
#15
Cristina Izquierdo, José C Gómez-Tamayo, Jean-Christophe Nebel, Leonardo Pardo, Angel Gonzalez
Pungent chemical compounds originating from decaying tissue are strong drivers of animal behavior. Two of the best-characterized death smell components are putrescine (PUT) and cadaverine (CAD), foul-smelling molecules produced by decarboxylation of amino acids during decomposition. These volatile polyamines act as 'necromones', triggering avoidance or attractive responses, which are fundamental for the survival of a wide range of species. The few studies that have attempted to identify the cognate receptors for these molecules have suggested the involvement of the seven-helix trace amine-associated receptors (TAARs), localized in the olfactory epithelium...
January 11, 2018: PLoS Computational Biology
https://www.readbyqxmd.com/read/29320496/bayesian-inference-of-phylogenetic-networks-from-bi-allelic-genetic-markers
#16
Jiafan Zhu, Dingqiao Wen, Yun Yu, Heidi M Meudt, Luay Nakhleh
Phylogenetic networks are rooted, directed, acyclic graphs that model reticulate evolutionary histories. Recently, statistical methods were devised for inferring such networks from either gene tree estimates or the sequence alignments of multiple unlinked loci. Bi-allelic markers, most notably single nucleotide polymorphisms (SNPs) and amplified fragment length polymorphisms (AFLPs), provide a powerful source of genome-wide data. In a recent paper, a method called SNAPP was introduced for statistical inference of species trees from unlinked bi-allelic markers...
January 10, 2018: PLoS Computational Biology
https://www.readbyqxmd.com/read/29315306/modeling-the-genetic-relatedness-of-plasmodium-falciparum-parasites-following-meiotic-recombination-and-cotransmission
#17
Wesley Wong, Edward A Wenger, Daniel L Hartl, Dyann F Wirth
Unlike in most pathogens, multiple-strain (polygenomic) infections of P. falciparum are frequently composed of genetic siblings. These genetic siblings are the result of sexual reproduction and can coinfect the same host when cotransmitted by the same mosquito. The degree with which coinfecting strains are related varies among infections and populations. Because sexual recombination occurs within the mosquito, the relatedness of cotransmitted strains could depend on transmission dynamics, but little is actually known of the factors that influence the relatedness of cotransmitted strains...
January 9, 2018: PLoS Computational Biology
https://www.readbyqxmd.com/read/29309407/bowhead-bayesian-modelling-of-cell-velocity-during-concerted-cell-migration
#18
Mathias Engel, James Longden, Jesper Ferkinghoff-Borg, Xavier Robin, Gaye Sağınç, Rune Linding
Cell migration is a central biological process that requires fine coordination of molecular events in time and space. A deregulation of the migratory phenotype is also associated with pathological conditions including cancer where cell motility has a causal role in tumor spreading and metastasis formation. Thus cell migration is of critical and strategic importance across the complex disease spectrum as well as for the basic understanding of cell phenotype. Experimental studies of the migration of cells in monolayers are often conducted with 'wound healing' assays...
January 8, 2018: PLoS Computational Biology
https://www.readbyqxmd.com/read/29309406/robust-and-efficient-coding-with-grid-cells
#19
Lajos Vágó, Balázs B Ujfalussy
The neuronal code arising from the coordinated activity of grid cells in the rodent entorhinal cortex can uniquely represent space across a large range of distances, but the precise conditions for optimal coding capacity are known only for environments with finite size. Here we consider a coding scheme that is suitable for unbounded environments, and present a novel, number theoretic approach to derive the grid parameters that maximise the coding range in the presence of noise. We derive an analytic upper bound on the coding range and provide examples for grid scales that achieve this bound and hence are optimal for encoding in unbounded environments...
January 8, 2018: PLoS Computational Biology
https://www.readbyqxmd.com/read/29309405/cardinal-features-of-involuntary-force-variability-can-arise-from-the-closed-loop-control-of-viscoelastic-afferented-muscles
#20
Akira Nagamori, Christopher M Laine, Francisco J Valero-Cuevas
Involuntary force variability below 15 Hz arises from, and is influenced by, many factors including descending neural drive, proprioceptive feedback, and mechanical properties of muscles and tendons. However, their potential interactions that give rise to the well-structured spectrum of involuntary force variability are not well understood due to a lack of experimental techniques. Here, we investigated the generation, modulation, and interactions among different sources of force variability using a physiologically-grounded closed-loop simulation of an afferented muscle model...
January 8, 2018: PLoS Computational Biology
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