PLoS Computational BiologyThis is an RSS file. You can use it to subscribe to this data in your favourite RSS reader, such as GoogleReader, or to display this data on your own website or blog. Subscribe to this data using MyMedWorm.Subscribe to this data using GoogleReader.Subscribe to this data using Bloglines.Subscribe to this data using MyYahoo.

This page shows you the latest items in this publication.

Pages: 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22

1070 records returned

Computational Model of Membrane Fission Catalyzed by ESCRT-IIIEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Author Summary Membrane fission is a key step of fundamental intracellular processes such as endocytosis, membrane trafficking, cytokinesis and virus budding. The fission reaction requires substantial energy inputs provided by specialized proteins. Recently, the ESCRT-III proteins have been implicated in membrane budding and fission involved in multivesicular body formation, cytokinesis and virus budding. The ESCRT-III proteins self-assemble into circular filaments and flat spirals in the membrane plane and generate tubular structures with dome-like end caps. We suggest and elaborate computationally on a mechanism by whic...
Source: PLoS Computational Biology - November 20, 2009 Category: Biology Authors: Gur Fabrikant et al. Source Type: journals

Dynamic Allostery in the Methionine Repressor Revealed by Force Distribution AnalysisEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Author Summary Proteins carry out most of the cellular processes, from metabolic reactions to the regulation and expression of genes. Tight and effective regulation of the executing protein machinery is commonly achieved by allostery. The only general requirement for allosteric communication is the transmission of a signal, e.g., the binding of a cofactor, from the ligand binding site to the allosteric (active) protein site; in other words an internal propagation of strain. Based on molecular dynamics simulations, we recently presented a method that allows visualization of force distribution in proteins. We here applied t...
Source: PLoS Computational Biology - November 20, 2009 Category: Biology Authors: Wolfram Stacklies et al. Source Type: journals

Evaluation of the Oscillatory Interference Model of Grid Cell Firing through Analysis and Measured Period Variance of Some Biological OscillatorsEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Author Summary For many animals, including rats, accurate spatial memory over relatively large areas is important in order to find food and shelter. Just as unique points in time can be efficiently represented by combinations of repeating elements like hours, days, and months, points in space can be represented as combinations of elements that repeat at different spatial scales. Just such a code has been identified in the brains of rats and it shows an intriguing triangular spacing of encoded locations. Two different explanations have been developed as to what general mechanism in the brain might be able to generate this ...
Source: PLoS Computational Biology - November 20, 2009 Category: Biology Authors: Eric A. Zilli et al. Source Type: journals

Stochastic Drift in Mitochondrial DNA Point Mutations: A Novel Perspective Ex SilicoEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Author Summary Aging is characterized by a systemic decline of an organism's capacity in responding to internal and external stresses, leading to increased mortality. The mitochondrial Free Radical Theory of Aging (mFRTA) attributes this decline to the accumulation of damages, in the form of mitochondrial DNA (mtDNA) mutations, caused by free radical byproducts of metabolism. However, there is still a great deal of uncertainty with this theory due to the difficulties in quantifying mtDNA mutation burden. In this modeling study, we have shown that a random drift in mtDNA point mutation during life, in combination with the ...
Source: PLoS Computational Biology - November 20, 2009 Category: Biology Authors: Suresh Kumar Poovathingal et al. Source Type: journals

Exon Array Analysis of Head and Neck Cancers Identifies a Hypoxia Related Splice Variant of LAMA3 Associated with a Poor PrognosisEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Author Summary Alternative splicing is the process by which cells express a set of different, but related, transcripts from a single gene. When translated, each transcript results in a different protein, resulting in additional cellular complexity. Affymetrix Exon microarrays, which feature multiple probesets targeting different locations throughout each gene, allow the changes in transcription that result from alternative splicing to be investigated in a single genome-wide assay. In addition, the increased number of probesets targeting each gene offers the potential to combine signals in order to increase statistical pow...
Source: PLoS Computational Biology - November 20, 2009 Category: Biology Authors: Carla S. Moller-Levet et al. Source Type: journals

A Novel Extended Granger Causal Model Approach Demonstrates Brain Hemispheric Differences during Face Recognition LearningEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Author Summary The right temporal cortex has previously been shown to play a greater role in the discrimination of faces in both sheep and humans. In the frequency domain, analysis of the relative causal contributions of low (theta 4–8Hz) and high (gamma 30–70Hz) frequency oscillations reveals that prior to learning, theta activity is more predominant in right than in left hemisphere processing, and that learning reduces this so that high frequency oscillations gain more control. We have been able to demonstrate that the frequency of connections increases in the right hemisphere and decreases between the left and righ...
Source: PLoS Computational Biology - November 20, 2009 Category: Biology Authors: Tian Ge et al. Source Type: journals

Spatial Analysis of Expression Patterns Predicts Genetic Interactions at the Mid-Hindbrain BoundaryEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Author Summary Understanding brain formation during development is a tantalizing challenge. It is also essential for the fight against neurodegenerative diseases. In vertebrates, the central nervous system arises from a structure called the neural plate. This tissue is divided into four regions, which continue to develop into forebrain, midbrain, hindbrain and spinal cord. Interactions between locally expressed genes and signaling molecules are responsible for this patterning. Two key signaling molecules in this process are Fgf8 and Wnt1 proteins. They are secreted from a signaling center located at the boundary between p...
Source: PLoS Computational Biology - November 20, 2009 Category: Biology Authors: Dominik M. Wittmann et al. Source Type: journals

Circadian KaiC Phosphorylation: A Multi-Layer NetworkEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Author Summary Circadian clocks are endogenous timing mechanisms that allow living organisms to coordinate their activities with daily environmental fluctuations. In cyanobacteria, almost all the genes are rhythmically expressed with the same ~24 h period yet exhibit a variety of phase relationships and waveforms. Remarkably, the core pacemaker ticks robustly via simple biochemical reactions carried out by three Kai proteins: KaiC undergoes circadian phosphorylation in the presence of KaiA, KaiB and ATP. In this work, we propose a reaction network modeling the Kai oscillator based on the differentiation of dual phosphoryl...
Source: PLoS Computational Biology - November 20, 2009 Category: Biology Authors: Congxin Li et al. Source Type: journals

A Threading-Based Method for the Prediction of DNA-Binding Proteins with Application to the Human GenomeEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Author Summary DNA-binding proteins represent only a small fraction of proteins encoded in genomes, yet they play a critical role in a variety of biological activities. Identifying these proteins and understanding how they function are important issues. The structures of solved DNA protein complexes of different protein families provide an invaluable knowledge base not only for understanding DNA-protein interactions, but also for developing methods that predict whether or not a protein binds DNA. While such methods are useful, they require an experimental structure as input. To overcome this obstacle, we have developed a ...
Source: PLoS Computational Biology - November 13, 2009 Category: Biology Authors: Mu Gao et al. Source Type: journals

Discovery and Annotation of Functional Chromatin Signatures in the Human GenomeEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Author Summary Recent studies have observed that histone tails can be modified in a variety of ways. Analyzing a collection of 21 histone modifications, we attempted to determine what common signatures are associated with different classes of regulatory elements and whether they mark places of distinct function. Indeed, at promoters, we identified a number of distinct signatures, each associated with a different class of expressed and functional genes. We also observed several unexpected signatures marking exons that directly correlate with the expression of exons. Finally, we recovered many places marked by two distinct ...
Source: PLoS Computational Biology - November 13, 2009 Category: Biology Authors: Gary Hon et al. Source Type: journals

The Evolutionary Dynamics of a Rapidly Mutating Virus within and between Hosts: The Case of Hepatitis C VirusEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Author Summary Rapidly mutating viruses, such as hepatitis C virus, can escape host immunity by generating new strains that avoid the immune system. Existing data support the idea that such within-host evolution affects the outcome of the infection. Few theoretical models address this question and most follow viral diversity or qualitative traits, such as drug resistance. Here, we study the evolution of two virus quantitative traits—the replication rate and the ability to be recognised by the immune response—during an infection. We develop an epidemiological framework where transmission events are driven by within-hos...
Source: PLoS Computational Biology - November 13, 2009 Category: Biology Authors: Fabio Luciani et al. Source Type: journals

Identifying Changes in Selective Constraints: Host Shifts in InfluenzaEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Author Summary Influenza A's natural reservoir is waterfowl. Sometimes avian virus genomic segments are able to shift to a human host, either in toto or by combining with those that underwent a previous host shift event. Such host shift events can cause worldwide pandemics in their immunologically naive hosts. In order for these host shifts to establish a stable lineage, the virus has to adapt to the new host. Identifying the changes that have occurred in the past can provide important clues about how this process happens, and how surveillance for new influenza threats should be targeted. Unfortunately, it is difficult to...
Source: PLoS Computational Biology - November 13, 2009 Category: Biology Authors: Asif U. Tamuri et al. Source Type: journals

Discovery of Regulatory Elements is Improved by a Discriminatory ApproachEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Author Summary In the years following the sequencing of the human genome focus have shifted towards trying to understand how this blueprint results in the diversity of cells that we observe. Part of the answer lies in the regulation of transcription and how the proteins responsible for this recognize where they should attach to the DNA. This is a well studied problem, but most methods developed for this have a hard time dealing with the heterogeneity of the mammalian genomes. Here we present a method that greatly improves the efficiency of this search by contrasting the DNA with a large number of background DNA sequences....
Source: PLoS Computational Biology - November 13, 2009 Category: Biology Authors: Eivind Valen et al. Source Type: journals

Dynamics of Trimming the Content of Face Representations for Categorization in the BrainEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
We describe this elimination of irrelevant and redundant information as ‘trimming’. We suggest that this may be an example of the brain optimizing categorical representations. (Source: PLoS Computational Biology)
Source: PLoS Computational Biology - November 13, 2009 Category: Biology Authors: Nicola J. van Rijsbergen et al. Source Type: journals

Interactions between Connected Half-Sarcomeres Produce Emergent Mechanical Behavior in a Mathematical Model of MuscleEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Author Summary Quantitative muscle biophysics has been dominated for the last 60 years by reductionist theories that try to explain the mechanical properties of an entire muscle fiber as the scaled behavior of a single half-sarcomere (typical muscle fibers contain ~106 such structures). This work tests the hypothesis that a fiber's mechanical properties are irreducible, meaning that the fiber exhibits more complex behavior than the half-sarcomeres do. The key finding is that a system composed of many interacting half-sarcomeres has mechanical properties that are very different from that of a single half-sarcomere. This co...
Source: PLoS Computational Biology - November 13, 2009 Category: Biology Authors: Kenneth S. Campbell Source Type: journals

Looking at Cerebellar Malformations through Text-Mined Interactomes of Mice and HumansEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
We described and made publicly available the largest existing set of text-mined statements; we also presented its application to an important biological problem. We have extracted and purified two large molecular networks, one for humans and one for mouse. We characterized the data sets, described the methods we used to generate them, and presented a novel biological application of the networks to study the etiology of five cerebellum phenotypes. We demonstrated quantitatively that the development-related malformations differ in their system-level properties from degeneration-related genes. We showed that there is a high d...
Source: PLoS Computational Biology - November 6, 2009 Category: Biology Authors: Ivan Iossifov et al. Source Type: journals

Optimal Experimental Design for Parameter Estimation of a Cell Signaling ModelEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Author Summary Differential equation models of signaling processes are useful to gain a molecular and quantitative understanding of cellular information flow. Although these models are typically based on simple kinetic rules, they can often qualitatively describe the behavior of biological systems. However, in the quest to transform biomedical research into an engineering discipline, biologists face the challenge of estimating important parameters of such models from laboratory data. Measurement noise as well as the robust architecture of biological circuits are causes for large uncertainty of parameter estimates. This ma...
Source: PLoS Computational Biology - November 6, 2009 Category: Biology Authors: Samuel Bandara et al. Source Type: journals

Evolution of Resistance to Targeted Anti-Cancer Therapies during Continuous and Pulsed Administration StrategiesEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Author Summary Recently, the field of anti-cancer therapy has witnessed a revolution by the discovery of targeted therapy, which refers to compounds targeting specific pathways causing abnormal growth of cancer cells. The clinical success of such drugs has been limited by the evolution of acquired resistance to these compounds, which leads to a relapse after initial response to therapy. Current dosing procedures are not designed to optimally delay the emergence of resistance; the identification of such optimal dosing schedules represents an important challenge in clinical cancer research. Here, we design a novel methodolo...
Source: PLoS Computational Biology - November 6, 2009 Category: Biology Authors: Jasmine Foo et al. Source Type: journals

A Hidden Markov Model for Single Particle Tracks Quantifies Dynamic Interactions between LFA-1 and the Actin CytoskeletonEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Author Summary Many important biological processes begin when a target molecule binds to a cell surface receptor protein. This event leads to a series of biochemical reactions involving the receptor and signalling molecules, and ultimately a cellular response. Surface receptors are mobile on the cell surface and their mobility is influenced by their interaction with intracellular proteins. We wish to understand the details of these interactions and how they are affected by cellular activation. An experimental technique called single particle tracking (SPT) uses optical microscopy to study the motion of cell-surface recept...
Source: PLoS Computational Biology - November 6, 2009 Category: Biology Authors: Raibatak Das et al. Source Type: journals

Robust Models for Optic Flow Coding in Natural Scenes Inspired by Insect BiologyEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Author Summary Building artificial vision systems that work robustly in a variety of environments has been difficult, with systems often only performing well under restricted conditions. In contrast, animal vision operates effectively under extremely variable situations. Many attempts to emulate biological vision have met with limited success, often because multiple seemingly appropriate approximations to neural coding resulted in a compromised system. We have constructed a full model for motion processing in the insect visual pathway incorporating known or suspected elements in as much detail as possible. We have found t...
Source: PLoS Computational Biology - November 6, 2009 Category: Biology Authors: Russell S. A. Brinkworth et al. Source Type: journals

Alternative Splicing in the Differentiation of Human Embryonic Stem Cells into Cardiac PrecursorsEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Author Summary The reprogramming of pluripotent stem cells from adult cells is a crucial step toward producing patient-specific cells for transplant therapy. Critical to this goal is the ability to reproducibly drive the differentiation of these cells to specific fates, such as cardiac and neural cells. While gene expression is important in tissue specific differentiation, the impact of alternative splicing on the biology of differentiating cells has not been fully realized. To identify specific splicing events that may determine cell-type-specific differentiation, we compared splicing profiles of human embryonic stem cel...
Source: PLoS Computational Biology - November 6, 2009 Category: Biology Authors: Nathan Salomonis et al. Source Type: journals

Intrinsic Structural Disorder Confers Cellular Viability on Oncogenic Fusion ProteinsEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Author Summary Chromosomal translocations generate chimeric proteins by fusing segments of two distinct genes and are frequently associated with cancer. The proteins involved are large and fairly heterogeneous in sequence and typically have only a few dispersed structural domains connected by long uncharacterized regions. It has never been studied from a structural perspective how these chimeras survive losing significant portions of the original proteins and acquire new oncogenic functions. By analyzing a collection of 406 human translocation proteins we show here that the answer to both questions lies to a large extent ...
Source: PLoS Computational Biology - October 30, 2009 Category: Biology Authors: Hedi Hegyi et al. Source Type: journals

Specific Entrainment of Mitral Cells during Gamma Oscillation in the Rat Olfactory BulbEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
In this study, we first characterize in vivo the detailed activity of individual neurons relative to the oscillation and find that, depending on their state, neurons can exhibit periodic activity patterns. We also find, at least qualitatively, a relation between this activity and a particular odor. This is reminiscent of general physical phenomena—the entrainment by an oscillation—and to verify this hypothesis, in a second phase, we build a biologically realistic model mimicking these in vivo conditions. Our model confirms quantitatively this hypothesis and reveals that entrainment is maximal in the gamma range. Taken ...
Source: PLoS Computational Biology - October 30, 2009 Category: Biology Authors: François O. David et al. Source Type: journals

Structure of Protein Interaction Networks and Their Implications on Drug DesignEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
This study revealed that the architectural properties of the backbones of protein interaction networks (PINs) were similar to those of the Internet router-level topology by using statistical analyses of genome-wide budding yeast and human PINs. This type of network is known as a highly optimized tolerance (HOT) network that is robust against failures in its components and that ensures high levels of communication. Moreover, we also found that a large number of the most successful drug-target proteins are on the backbone of the human PIN. We made a list of proteins on the backbone of the human PIN, which may help drug compa...
Source: PLoS Computational Biology - October 30, 2009 Category: Biology Authors: Takeshi Hase et al. Source Type: journals

Tipping the Balance: Robustness of Tip Cell Selection, Migration and Fusion in AngiogenesisEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Author Summary Abnormal vasculature exacerbates many diseases such as cancer and diabetic retinopathy. In angiogenesis new blood vessels, headed by a migrating tip cell, sprout from pre-existing vessels in response to chemical signals. The signals are released from newly oxygen deficient tissue. The signals are known to be different in disease and are thought to cause the process of angiogenesis to progress abnormally, though the reasons for this remain unclear. Normalisation of angiogenesis has great potential as a therapeutic strategy; it has been shown to reduce metastasis and improve drug delivery in tumours. Here we ...
Source: PLoS Computational Biology - October 30, 2009 Category: Biology Authors: Katie Bentley et al. Source Type: journals

Gene Circuit Analysis of the Terminal Gap Gene huckebeinEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Author Summary Currently, there are two very different approaches to the study of pattern formation: Traditional developmental genetics investigates the role of particular factors in great mechanistic detail, while newly developed systems-biology methods study many factors in parallel but usually remain rather general in their conclusions. Here, we attempt to bridge the gap between the two by studying the expression pattern and function of a particular developmental gene—the terminal gap gene huckebein (hkb) in the fruit fly Drosophila melanogaster—in great quantitative detail using a systems-level approach called the...
Source: PLoS Computational Biology - October 30, 2009 Category: Biology Authors: Maksat Ashyraliyev et al. Source Type: journals

Mechanical Strength of 17 134 Model Proteins and Cysteine SlipknotsEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Author Summary The advances in nanotechnology have allowed for manipulation of single biomolecules and determination of their elastic properties. Titin was among the first proteins studied in this way. Its unravelling by stretching requires a 204 pN force. The resistance to stretching comes mostly from a localized region known as a force clamp. In titin, the force clamp is simple as it is formed by two parallel β-strands that are sheared on pulling. Studies of a set of under a hundred proteins accomplished in the last decade have revealed a variety of the force clamps that lead to forces ranging from under 20 pN to about...
Source: PLoS Computational Biology - October 30, 2009 Category: Biology Authors: Mateusz Sikora et al. Source Type: journals

Investigation of the Interaction between the Large and Small Subunits of Potato ADP-Glucose PyrophosphorylaseEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
This study will enable us to use a rational approach to obtain better assembled mutant AGPase variants and use them for the improvement of the plant yield. (Source: PLoS Computational Biology)
Source: PLoS Computational Biology - October 30, 2009 Category: Biology Authors: Ibrahim Barıs et al. Source Type: journals

Getting Started in Gene Expression Microarray AnalysisEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
(Source: PLoS Computational Biology)
Source: PLoS Computational Biology - October 30, 2009 Category: Biology Authors: Donna K. Slonim et al. Source Type: journals

Computational Biology in ColombiaEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
(Source: PLoS Computational Biology)
Source: PLoS Computational Biology - October 30, 2009 Category: Biology Authors: Silvia Restrepo et al. Source Type: journals

PLoS Computational Biology Issue Image | Vol. 5(10) October 2009Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Cloud topology in the yeast protein interaction network. This figure represents the protein-protein interaction network topology of budding yeast. The outermost circle shows proteins with smaller numbers of interactions (gray dots) and proteins that interact with these are located on inner circles. Most large hubs are placed here (blue dots). Inner circles are dominated by medium size hubs (red dots) that are extensively connected to each other. This topology is mathematically similar to the router-level topology of the internet and represents networks according to highly optimized tolerance (see Hase et al., doi:10.1371/j...
Source: PLoS Computational Biology - October 30, 2009 Category: Biology Authors: PLoS Source Type: journals

The Role of Medical Structural Genomics in Discovering New Drugs for Infectious DiseasesEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
(Source: PLoS Computational Biology)
Source: PLoS Computational Biology - October 26, 2009 Category: Biology Authors: Wesley C. Van Voorhis et al. Source Type: journals

Discovering the Phylodynamics of RNA VirusesEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
(Source: PLoS Computational Biology)
Source: PLoS Computational Biology - October 26, 2009 Category: Biology Authors: Edward C. Holmes et al. Source Type: journals

Computational Resources in Infectious Disease: Limitations and ChallengesEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
(Source: PLoS Computational Biology)
Source: PLoS Computational Biology - October 26, 2009 Category: Biology Authors: Eva C. Berglund et al. Source Type: journals

Invariant Distribution of Promoter Activities in Escherichia coliEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Author Summary Cells respond to a changing environment by regulating the activity of genes. Here, we sought to understand how E. coli cells distribute their limited transcriptional resources among their target genes, and how this allocation varies with growth rate and growth conditions. To achieve this, we assayed the expression of a comprehensive library of transcriptional reporter strains under different conditions. High-temporal resolution measurements of promoter activities were obtained for different growth rates spanning recovery from stationary phase into exponential phase and eventually deep stationary phase again...
Source: PLoS Computational Biology - October 22, 2009 Category: Biology Authors: Alon Zaslaver et al. Source Type: journals

Perturbation-Response Scanning Reveals Ligand Entry-Exit Mechanisms of Ferric Binding ProteinEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Author Summary Upon binding ligands, many proteins undergo structural changes compared to the unbound form. We introduce a methodology to monitor these changes and to study which mechanisms arrange conformational shifts between the liganded and free forms. Our method is simple, yet it efficiently characterizes the response of proteins to a given perturbation on systematically selected residues. The coherent responses predicted are validated by molecular dynamics simulations. The results indicate that the iron uptake by the ferric binding protein is favorable in a thermally fluctuating environment, while release of iron is...
Source: PLoS Computational Biology - October 22, 2009 Category: Biology Authors: Canan Atilgan et al. Source Type: journals

An Atlas of the Thioredoxin Fold Class Reveals the Complexity of Function-Enabling AdaptationsEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Author Summary For any large class of proteins, far more protein sequences are known than can be examined experimentally. This is the case with the thioredoxin fold class, a large and diverse collection of proteins, some of which are known to catalyze important steps in metabolism. Some others participate in key processes like protein folding and detoxification of foreign compounds. Many of the unstudied proteins likely participate in other important biological processes and have useful applications in medicine and industry. We used a new network-based computational approach to create similarity-based maps of the thioredo...
Source: PLoS Computational Biology - October 22, 2009 Category: Biology Authors: Holly J. Atkinson et al. Source Type: journals

Steps in the Bacterial Flagellar MotorEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Author Summary Many species of bacteria swim to find food or to avoid toxins. Swimming motility depends on helical flagella that act as propellers. Each flagellum is driven by a rotary molecular engine–the bacterial flagellar motor–which draws its energy from an ion flux entering the cell. Despite much progress, the detailed mechanisms underlying the motor's extraordinary power output, as well as its near 100% efficiency, have yet to be understood. Surprisingly, recent experiments have shown that, at low speeds, the motor proceeds by small steps (~26 per rotation), providing new insight into motor operation. Here we s...
Source: PLoS Computational Biology - October 22, 2009 Category: Biology Authors: Thierry Mora et al. Source Type: journals

A Model of Cardiovascular Disease Giving a Plausible Mechanism for the Effect of Fractionated Low-Dose Ionizing Radiation ExposureEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Author Summary Atherosclerosis is the main cause of coronary heart disease and stroke, the two major causes of death in developed society. There is emerging evidence of excess risk of cardiovascular disease in various occupationally exposed groups, exposed to fractionated radiation doses with small doses/fraction. The mechanisms for such effects of fractionated low-dose radiation exposures on cardiovascular disease are unclear. We outline a spatial reaction-diffusion model for early stage atherosclerotic lesion formation and perform a stability analysis, based on experimentally derived parameters. We show that following m...
Source: PLoS Computational Biology - October 22, 2009 Category: Biology Authors: Mark P. Little et al. Source Type: journals

Multilevel Selection in Models of Prebiotic Evolution II: A Direct Comparison of Compartmentalization and Spatial Self-OrganizationEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Author Summary The origin of life has ever been attracting scientific inquiries. The RNA world hypothesis suggests that, before the evolution of DNA and protein, primordial life was based on RNA-like molecules both for information storage and chemical catalysis. In the simplest form, an RNA world consists of RNA molecules that can catalyze the replication of their own copies. Thus, an interesting question is whether a system of RNA-like replicators can increase its complexity through Darwinian evolution and approach the modern form of life. It is, however, known that simple natural selection acting on individual replicato...
Source: PLoS Computational Biology - October 15, 2009 Category: Biology Authors: Nobuto Takeuchi et al. Source Type: journals

Grasping Objects with Environmentally Induced Position UncertaintyEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Author Summary Optimal sensorimotor control models actions as decisions that maximize the desirableness of outcomes, where the desirableness is captured by an expected cost or utility to each action sequence. These models provide explanations for many aspects of our ability to compensate for uncertainty, but they have not been applied to understanding purposive movements—movements involving the application of forces to change the relative position of objects and the actor in the environment. Using time efficiency as a natural cost function, we present a statistical optimal control analysis of uncertainty compensation st...
Source: PLoS Computational Biology - October 15, 2009 Category: Biology Authors: Vassilios N. Christopoulos et al. Source Type: journals

Subbarrel Patterns in Somatosensory Cortical Barrels Can Emerge from Local Dynamic InstabilitiesEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Author Summary Complex spatial patterning, common in the brain as well as in other biological systems, can emerge as a result of dynamic interactions that occur locally within developing structures. In rodent somatosensory cortex, groups of neurons called “barrels” correspond to individual whiskers on the contralateral face. Barrels themselves often contain subbarrels organized into one of a few characteristic patterns. We suggest that these so-called subbarrel patterns arise spontaneously during development through a pattern-forming instability. We use a simple chemotaxis and branching model to explain the patterns a...
Source: PLoS Computational Biology - October 15, 2009 Category: Biology Authors: Bard Ermentrout et al. Source Type: journals

Antigenic Diversity, Transmission Mechanisms, and the Evolution of PathogensEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Author Summary Infectious diseases vary widely in how they affect those who get infected and how they are transmitted. As an example, the duration of a single infection can range from days to years, while transmission can occur via the respiratory route, water or sexual contact. Measles and HIV are contrasting examples—both are caused by RNA viruses, but one is a genetically diverse, lethal sexually transmitted infection (STI) while the other is a relatively mild respiratory childhood disease with low antigenic diversity. We investigate why the most transmissible respiratory diseases such as measles and rubella are anti...
Source: PLoS Computational Biology - October 15, 2009 Category: Biology Authors: Alexander Lange et al. Source Type: journals

‘Glocal’ Robustness Analysis and Model Discrimination for Circadian OscillatorsEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Author Summary Robustness is an intrinsic property of many biological systems. To quantify the robustness of a model that represents such a system, two approaches exist: global methods assess the volume in parameter space that is compliant with the proper functioning of the system; and local methods, in contrast, study the model for a given parameter set and determine its robustness. Local methods are fundamentally biased due to the a priori choice of a particular parameter set. Our ‘glocal’ analysis combines the two complementary approaches and provides an objective measure of robustness. We apply this method to two ...
Source: PLoS Computational Biology - October 15, 2009 Category: Biology Authors: Marc Hafner et al. Source Type: journals

Modeling Latently Infected Cell Activation: Viral and Latent Reservoir Persistence, and Viral Blips in HIV-infected Patients on Potent TherapyEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Author Summary Current combination therapy can suppress viral loads in HIV-1-infected individuals to below the detection limit of standard commercial assays. However, it cannot eradicate the virus from patients. HIV-1 can generally be identified in resting memory CD4+ T cells and persists in patients on potent treatment for a long time. These latently infected cells decay slowly, but can produce new virions when activated by relevant antigens. Many patients experience transient episodes of viremia, or blips, even though they have “undetectable” plasma viral loads for many years. Here, we develop a new mathematical mod...
Source: PLoS Computational Biology - October 15, 2009 Category: Biology Authors: Libin Rong et al. Source Type: journals