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Plos Computational Biology : a MacAque’s-eye View of Human Inserti...

By: Wen-hsiung Li

Description : Insertions and deletions (indels) cause numerous genetic diseases and lead to pronounced evolutionary differences among genomes. The macaque sequences provide an opportunity to gain insights into the mechanisms generating these mutations on a genome-wide scale by establishing the polarity of indels occurring in the human lineage since its divergence from the chimpanzee. Here we apply novel regression techniques and multiscale analyses to demonstrate an exte...

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Plos Computational Biology : Essential Requirements for Robust Sig...

By: David N. Adamson

Description : Bacteria possess networks of small RNAs (sRNAs) that are important for modulating gene expression. At the center of many of these sRNA networks is the Hfq protein. Hfq’s role is to quickly match cognate sRNAs and target mRNAs from among a large number of possible combinations and anneal them to form duplexes. Here we show using a kinetic model that Hfq can efficiently and robustly achieve this difficult task by minimizing the sequestration of sRNAs and targ...

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Plos Computational Biology : Smoothing Of, and Parameter Estimatio...

By: Karl J. Friston

Description : Biophysically detailed models of single cells are difficult to fit to real data. Recent advances in imaging techniques allow simultaneous access to various intracellular variables, and these data can be used to significantly facilitate the modelling task. These data, however, are noisy, and current approaches to building biophysically detailed models are not designed to deal with this. We extend previous techniques to take the noisy nature of the measuremen...

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Plos Computational Biology : Adaptive Temperature Compensation in ...

By: Paul Franc¸ Ois

Description : A temperature independent period and temperature entrainment are two defining features of circadian oscillators. A default model of distributed temperature compensation satisfies these basic facts yet is not easily reconciled with other properties of circadian clocks, such as many mutants with altered but temperature compensated periods. The default model also suggests that the shape of the circadian limit cycle and the associated phase response curves (PRC...

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Plos Computational Biology : Analysis of Gene Regulatory Networks ...

By: Jeffrey M. Gimble

Description : Circadian rhythm is fundamental in regulating a wide range of cellular, metabolic, physiological, and behavioral activities in mammals. Although a small number of key circadian genes have been identified through extensive molecular and genetic studies in the past, the existence of other key circadian genes and how they drive the genomewide circadian oscillation of gene expression in different tissues still remains unknown. Here we try to address these quest...

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Plos Computational Biology : Multi-scale Inference of Interaction ...

By: Olaf Sporns

Description : Inference of interaction rules of animals moving in groups usually relies on an analysis of large scale system behaviour. Models are tuned through repeated simulation until they match the observed behaviour. More recent work has used the fine scale motions of animals to validate and fit the rules of interaction of animals in groups. Here, we use a Bayesian methodology to compare a variety of models to the collective motion of glass prawns (Paratya australie...

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Plos Computational Biology : Dynamical Modeling of Collective Beha...

By: Graciano Dieck Kattas
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Plos Computational Biology : Exploring Volatile General Anesthetic...

By: S. G. Raju

Description : Despite the clinical ubiquity of anesthesia, the molecular basis of anesthetic action is poorly understood. Amongst the many molecular targets proposed to contribute to anesthetic effects, the voltage gated sodium channels (VGSCs) should also be considered relevant, as they have been shown to be sensitive to all general anesthetics tested thus far. However, binding sites for VGSCs have not been identified. Moreover, the mechanism of inhibition is still larg...

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Plos Computational Biology : Canalization of Gene Expression and D...

By: Stanislav Shvartsman

Description : The variation in the expression patterns of the gap genes in the blastoderm of the fruit fly Drosophila melanogaster reduces over time as a result of cross regulation between these genes, a fact that we have demonstrated in an accompanying article in PLoS Biology (see Manu et al., doi:10.1371/journal.pbio.1000049). This biologically essential process is an example of the phenomenon known as canalization. It has been suggested that the developmental trajecto...

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Plos Computational Biology : Timing the Emergence of Resistance to...

By: Christophe Fraser

Description : New antiretroviral drugs that offer large genetic barriers to resistance, such as the recently approved inhibitors of HIV-1 protease, tipranavir and darunavir, present promising weapons to avert the failure of current therapies for HIV infection. Optimal treatment strategies with the new drugs, however, are yet to be established. A key limitation is the poor understanding of the process by which HIV surmounts large genetic barriers to resistance. Extant mod...

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Plos Computational Biology : Neocortical Axon Arbors Trade-off Mat...

By: Budd Julian M. L.
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Plos Computational Biology : Eradication of Chronic Myeloid Leukem...

By: Jasmine Foo

Description : Imatinib mesylate induces complete cytogenetic responses in patients with chronic myeloid leukemia (CML), yet many patients have detectable BCR-ABL transcripts in peripheral blood even after prolonged therapy. Bone marrow studies have shown that this residual disease resides within the stem cell compartment. Quiescence of leukemic stem cells has been suggested as a mechanism conferring insensitivity to imatinib, and exposure to the Granulocyte-Colony Stimul...

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Plos Computational Biology : Chapter 8 ; Biological Knowledge Asse...

By: Fran Lewitter

Description : Kim JH (2012) Chapter 8 : Biological Knowledge Assembly and Interpretation.

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Plos Computational Biology : Pathway Analysis of Expression Data ;...

By: Frank Emmert-streib
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Plos Computational Biology : Multi-scale Modeling of Hiv Infection...

By: Iraj Hosseini
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Plos Computational Biology : a Correspondence Between Solution-sta...

By: Ruth Nussinov

Description : Conformational ensembles are increasingly recognized as a useful representation to describe fundamental relationships between protein structure, dynamics and function. Here we present an ensemble of ubiquitin in solution that is created by sampling conformational space without experimental information using ‘‘Backrub’’ motions inspired by alternative conformations observed in sub-Angstrom resolution crystal structures. Backrub-generated structures are then ...

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Plos Computational Biology : a Circadian Clock-regulated Toggle Sw...

By: Christoph Schmal

Description : The circadian clock controls many physiological processes in higher plants and causes a large fraction of the genome to be expressed with a 24h rhythm. The transcripts encoding the RNA-binding proteins AtGRP7 (Arabidopsis thaliana Glycine Rich Protein 7) and AtGRP8 oscillate with evening peaks. The circadian clock components CCA1 and LHY negatively affect AtGRP7 expression at the level of transcription. AtGRP7 and AtGRP8, in turn, negatively auto-regulate a...

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Plos Computational Biology : Quasispecies Made Simple, Volume 1

By: J. J. Bull

Description : Quasispecies are clouds of genotypes that appear in a population at mutation–selection balance. This concept has recently attracted the attention of virologists, because many RNA viruses appear to generate high levels of genetic variation that may enhance the evolution of drug resistance and immune escape. The literature on these important evolutionary processes is, however, quite challenging. Here we use simple models to link mutation–selection balance the...

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Plos Computational Biology : How Evolving Heterogeneity Distributi...

By: Yann Le Cunff

Description : It is well established that individuals age differently. Yet the nature of these inter-individual differences is still largely unknown. For humans, two main hypotheses have been recently formulated : individuals may experience differences in aging rate or aging timing. This issue is central because it directly influences predictions for human lifespan and provides strong insights into the biological determinants of aging. In this article, we propose a model...

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Plos Computational Biology : Coalescent Tree Imbalance and a Simpl...

By: Haipeng Li

Description : Selective sweeps are at the core of adaptive evolution. We study how the shape of coalescent trees is affected by recent selective sweeps. To do so we define a coarse-grained measure of tree topology. This measure has appealing analytical properties, its distribution is derived from a uniform, and it is easy to estimate from experimental data. We show how it can be cast into a test for recent selective sweeps using microsatellite markers and present an appl...

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