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headings list	keywords list	title stringlengths 20 281	id stringlengths 20 20	toc stringlengths 57 522 ⌀	sections list	abstract list	summary list	year stringclasses 13 values
[ "Introduction", "Results and Discussion", "Materials and Methods", "Supporting Information" ]	[ "biochemistry" ]	Capturing Hammerhead Ribozyme Structures in Action by Modulating General Base Catalysis	journal.pbio.0060234	The hammerhead ribozyme exploits acid/base catalysis as an enzymatic mechanism. Weakening the general base, G12, by mutating it into an A, greatly slows the reaction. As a result, the before and after cleavage structures could be captured in a crystal lattice.	[ [ "The hammerhead ribozyme , since its discovery in satellite virus RNA genomes [1 , 2] , has been a central focus of experiments designed to correlate RNA structure with RNA catalysis , as it is a comparatively small RNA whose biochemistry has been intensively investigated using a wide variety of approaches [3...	[ "We have obtained precatalytic ( enzyme–substrate complex ) and postcatalytic ( enzyme–product complex ) crystal structures of an active full-length hammerhead RNA that cleaves in the crystal .", "Using the natural satellite tobacco ringspot virus hammerhead RNA sequence , the self-cleavage reaction was modulated...	[ "Enzymes use variations of a few standard approaches to catalyze reactions .", "One of these approaches , acid–base catalysis , is of such fundamental importance that it is common to both protein enzymes and RNA-based enzymes , or ribozymes .", "The hammerhead ribozyme is one such ribozyme that uses an invarian...	2008
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "blood cells", "medicine and health sciences", "immune cells", "pathology and laboratory medicine", "respiratory infections", "influenza", "pathogens", "immunology", "microbiology", "orthomyxoviruses", "pulmonology", "epithelial cells", "viruses", "rna viruses", "cytotoxic t cells", "r...	A20 Deficiency in Lung Epithelial Cells Protects against Influenza A Virus Infection	journal.ppat.1005410	null	[ [ "Disease outcome upon exposure to a certain pathogen relies on the capacity of the host to resist and tolerate the infection [1] .", "Resistance protects the host by suppressing pathogen replication and promoting clearance of the pathogen , a process that is mostly mediated by the innate and adaptive immu...	[ "A20 negatively regulates multiple inflammatory signalling pathways .", "We here addressed the role of A20 in club cells ( also known as Clara cells ) of the bronchial epithelium in their response to influenza A virus infection .", "Club cells provide a niche for influenza virus replication , but little is know...	[ "Influenza viruses are a major public health threat .", "Each year , the typical seasonal flu epidemic affects millions of people with sometimes fatal outcomes , especially in high risk groups such as young children and elderly .", "The sporadic pandemic outbreaks can have even more disastrous consequences .", ...	2016
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "learning", "cognitive neurology", "medicine and health sciences", "neural networks", "brain damage", "brain", "social sciences", "neuroscience", "learning and memory", "cognitive neuroscience", "cognitive psychology", "cognition", "network analysis", "memory", "computer and information ...	Network supporting contextual fear learning after dorsal hippocampal damage has increased dependence on retrosplenial cortex	journal.pcbi.1006207	null	[ [ "Brain lesions provide evidence primarily about the extent to which a brain function can persevere in the absence of the damaged region .", "A preserved cognitive function or behavior after lesion is generally interpreted as alternative ‘brain routes’ being still able to meet the cognitive demands [1 , 2]...	[ "Hippocampal damage results in profound retrograde , but no anterograde amnesia in contextual fear conditioning ( CFC ) .", "Although the content learned in the latter have been discussed , alternative regions supporting CFC learning were seldom proposed and never empirically addressed .", "Here , we employed n...	[ "When determined cognitive performances are not affected by brain lesions of regions generally involved in that performance , the interpretation is that the remaining regions can promote function despite of ( or compensate ) the damaged one .", "In contextual fear conditioning , a memory model largely used in lab...	2018
[ "Introduction", "Methods", "Results", "Discussion" ]	[]	The Relative Contribution of Immigration or Local Increase for Persistence of Urban Schistosomiasis in Salvador, Bahia, Brazil	journal.pntd.0003521	null	[ [ "Urbanization , the concentration of regional populations in cities , has been the great global demographic trend of the last 100 years , and the urban context has influence the nature and distribution of parasitic diseases , such as schistosomiasis .", "While the disease is usually thought of as a rural ...	[ "Urbanization is increasing across the globe , and diseases once considered rural can now be found in urban areas due to the migration of populations from rural endemic areas , local transmission within the city , or a combination of factors .", "We investigated the epidemiologic characteristics of urban immigran...	[ "Urban transmission of schistosomiasis is becoming more recognized as rural disease is becoming less common and urbanization increases .", "Characteristics of infection of the immigrant population to cities and genetic characteristics of the parasite population itself indicate local transmission is the most impor...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Determinants of Cell-to-Cell Variability in Protein Kinase Signaling	journal.pcbi.1003357	null	[ [ "External stimuli typically induce cellular responses by binding to cell surface receptors .", "Intracellular signaling networks transduce the signal , ultimately triggering gene expression responses in the nucleus .", "The basic building blocks of eukaryotic signaling networks are protein kinase casc...	[ "Cells reliably sense environmental changes despite internal and external fluctuations , but the mechanisms underlying robustness remain unclear .", "We analyzed how fluctuations in signaling protein concentrations give rise to cell-to-cell variability in protein kinase signaling using analytical theory and numer...	[ "Cells sense their surroundings and respond to soluble factors in the extracellular space .", "Extracellular factors frequently induce heterogeneous responses , thereby restricting the biological outcome to a fraction of the cell population .", "However , the question arises how such cell-to-cell variability ca...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "h7n9", "medicine and health sciences", "viral vaccines", "enzyme-linked immunoassays", "immune physiology", "pathology and laboratory medicine", "pathogens", "split-decomposition method", "immunology", "microbiology", "orthomyxoviruses", "viruses", "animal models", "multiple alignment cal...	Broadly-Reactive Neutralizing and Non-neutralizing Antibodies Directed against the H7 Influenza Virus Hemagglutinin Reveal Divergent Mechanisms of Protection	journal.ppat.1005578	null	[ [ "In 2013 , zoonotic infections with H7N9 influenza virus were reported in Eastern China [1] .", "Since then numerous human cases have been confirmed , revealing a trend of local outbreaks coinciding with annual seasonal influenza virus epidemics [2] .", "Although human-to-human transmission of the vir...	[ "In the early spring of 2013 , Chinese health authorities reported several cases of H7N9 influenza virus infections in humans .", "Since then the virus has established itself at the human-animal interface in Eastern China and continues to cause several hundred infections annually .", "In order to characterize t...	[ "Several hundred human avian H7N9 virus infections with a case fatality rate of approximately 37% have occurred in China since 2013 .", "The emergence of this virus has raised concerns about its pandemic potential and has triggered the development of H7N9 vaccines .", "Using the traditional correlate of protect...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "molecular biology/histone modification", "genetics and genomics/gene function", "genetics and genomics/cancer genetics", "molecular biology/chromatin structure", "molecular biology/dna repair" ]	Dynamics of Rad9 Chromatin Binding and Checkpoint Function Are Mediated by Its Dimerization and Are Cell Cycle–Regulated by CDK1 Activity	journal.pgen.1001047	null	[ [ "The DNA damage checkpoint coordinates cell cycle progression , DNA repair , replication , recombination , apoptosis and senescence in response to genotoxic stress .", "Defects in this surveillance mechanism lead to increased genomic instability , cancer susceptibility , ageing and several human pathologi...	[ "Saccharomyces cerevisiae Rad9 is required for an effective DNA damage response throughout the cell cycle .", "Assembly of Rad9 on chromatin after DNA damage is promoted by histone modifications that create docking sites for Rad9 recruitment , allowing checkpoint activation .", "Rad53 phosphorylation is also de...	[ "In response to DNA damage all eukaryotic cells activate a surveillance mechanism , known as the DNA damage checkpoint , which delays cell cycle progression and modulates DNA repair .", "Yeast RAD9 was the first DNA damage checkpoint gene identified .", "The genetic tools available in this model system allow to...	2010
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "computational biology/systems biology", "computational biology/transcriptional regulation" ]	Patterns of Subnet Usage Reveal Distinct Scales of Regulation in the Transcriptional Regulatory Network of Escherichia coli	journal.pcbi.1000836	null	[ [ "An interesting topological feature of the transcriptional regulatory network ( TRN ) of the bacterium Escherichia coli is its almost tree-like structure with only few loops ( see [1] for a detailed discussion and comparison with the TRN of the yeast Saccharomyces cerevisiae ) .", "This observation has se...	[ "The set of regulatory interactions between genes , mediated by transcription factors , forms a species' transcriptional regulatory network ( TRN ) .", "By comparing this network with measured gene expression data , one can identify functional properties of the TRN and gain general insight into transcriptional co...	[ "Bacterial cells can adapt to various genomic mutations and intriguingly many environmental changes .", "They do this by adjusting their gene expression profile to meet the requirements of a new condition .", "In this work , we study the interplay of different mechanisms of gene regulatory control driving this ...	2010
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "homo (human)", "genetics and genomics", "computational biology" ]	Global and Local Architecture of the Mammalian microRNA–Transcription Factor Regulatory Network	journal.pcbi.0030131	null	[ [ "microRNAs ( miRs ) are short RNAs that post transcriptionally regulate messenger RNAs .", "Two main mechanisms for such effects are degradation of the target mRNA , and inhibition of its translation [1] .", "In recent years considerable progress within multiple genomes was obtained in the experimenta...	[ "microRNAs ( miRs ) are small RNAs that regulate gene expression at the posttranscriptional level .", "It is anticipated that , in combination with transcription factors ( TFs ) , they span a regulatory network that controls thousands of mammalian genes .", "Here we set out to uncover local and global architect...	[ "It is becoming increasingly appreciated that a new type of gene which does not code for proteins , the regulatory RNAs , constitutes a considerable portion of mammalian genomes , and these genes serve as key players in the regulatory network of living cells .", "Among these regulatory RNAs are the microRNAs ( mi...	2007
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "developmental biology/cell differentiation", "genetics and genomics/epigenetics", "developmental biology/plant growth and development", "genetics and genomics/plant genetics and gene expression" ]	CHD3 Proteins and Polycomb Group Proteins Antagonistically Determine Cell Identity in Arabidopsis	journal.pgen.1000605	null	[ [ "Dynamic regulation of chromatin structure is the underlying scheme for modulating genome activities in higher eukaryotes .", "There are two major classes of proteins with enzymatic activities directed at chromatin - histone modifying enzymes and ATP dependent chromatin remodelers .", "Histone modifyi...	[ "Dynamic regulation of chromatin structure is of fundamental importance for modulating genomic activities in higher eukaryotes .", "The opposing activities of Polycomb group ( PcG ) and trithorax group ( trxG ) proteins are part of a chromatin-based cellular memory system ensuring the correct expression of specif...	[ "In higher eukaryotes only a small proportion of genomic information is required in any specific cell type at a given developmental stage .", "The intricate decision whether a gene should be active or repressed is made by the counteractive activities of trithorax group ( trxG ) and Polycomb group ( PcG ) proteins...	2009
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "neuroscience/psychology", "neuroscience/theoretical neuroscience", "computational biology/computational neuroscience" ]	Structure Learning in Human Sequential Decision-Making	journal.pcbi.1001003	null	[ [ "From a squirrel deciding where to bury its nuts to a scientist selecting the next experiment , all decision-making organisms must balance exploration of alternatives against exploitation of known options in developing action plans .", "Finding a balance is equivalent to knowing when you can profit from l...	[ "Studies of sequential decision-making in humans frequently find suboptimal performance relative to an ideal actor that has perfect knowledge of the model of how rewards and events are generated in the environment .", "Rather than being suboptimal , we argue that the learning problem humans face is more complex ,...	[ "Every decision-making experiment has a structure that specifies how rewards are obtained , which is usually explained to the subject at the beginning of the experiment .", "Participants frequently fail to act as if they understand the experimental structure , even in tasks as simple as determining which of two b...	2010
[ "Introduction", "Results/Discussion", "Materials and Methods" ]	[ "bacteriology", "genome-wide association studies", "microbial metabolism", "plant biology", "microbiology", "chemical biology", "gene function", "genome sequencing", "plant science", "plant pathology", "plant microbiology", "chemistry", "comparative genomics", "biology", "microbial ecolo...	Comparative Genomics of Plant-Associated Pseudomonas spp.: Insights into Diversity and Inheritance of Traits Involved in Multitrophic Interactions	journal.pgen.1002784	null	[ [ "Pseudomonas is a large genus within the γ subclass of Proteobacteria known for its ubiquity in the environment , utilization of a striking variety of organic compounds as energy sources [1] , [2] , and production of an array of secondary metabolites [3]–[5] .", "Some species include well-known pathogens ...	[ "We provide here a comparative genome analysis of ten strains within the Pseudomonas fluorescens group including seven new genomic sequences .", "These strains exhibit a diverse spectrum of traits involved in biological control and other multitrophic interactions with plants , microbes , and insects .", "Multil...	[ "We sequenced the genomes of seven strains of the Pseudomonas fluorescens group that colonize plant surfaces and function as biological control agents , protecting plants from disease .", "In this study , we demonstrated the genomic diversity of the group by comparing these strains to each other and to three othe...	2012
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "protozoology", "biology", "microbiology", "parasitology" ]	Impact of Continuous Axenic Cultivation in Leishmania infantum Virulence	journal.pntd.0001469	null	[ [ "Protozoan parasites of the genus Leishmania undergo several developmental transitions during their life cycle .", "Ingestion of infected macrophages during a blood meal by the sandfly vector leads to the release of intracellular amastigotes into the vector's midgut .", "This abrupt change in environm...	[ "Experimental infections with visceral Leishmania spp .", "are frequently performed referring to stationary parasite cultures that are comprised of a mixture of metacyclic and non-metacyclic parasites often with little regard to time of culture and metacyclic purification .", "This may lead to misleading or irr...	[ "Protozoan of the genus Leishmania undergo several developmental transitions during its life cycle .", "Leishmania alternates between two morphologically distinct forms , promastigotes ( insect stage ) and amastigotes ( vertebrate stage ) .", "Most of the available information about Leishmania spp .", "has be...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Circulating Pneumolysin Is a Potent Inducer of Cardiac Injury during Pneumococcal Infection	journal.ppat.1004836	null	[ [ "Streptococcus pneumoniae ( the pneumococcus ) is a major human pathogen responsible for severe invasive diseases such as pneumonia , sepsis and meningitis in young children and immunocompromised individuals worldwide [1] , while also being the main cause of community acquired pneumonia ( CAP ) in the elderly...	[ "Streptococcus pneumoniae accounts for more deaths worldwide than any other single pathogen through diverse disease manifestations including pneumonia , sepsis and meningitis .", "Life-threatening acute cardiac complications are more common in pneumococcal infection compared to other bacterial infections .", "D...	[ "Cardiac complications frequently accompany invasive disease caused by the pathogen Streptococcus pneumoniae and are associated with significant increases in mortality , however the underlying mechanisms remain elusive .", "Here , we describe a new mechanism by which pneumococci in the blood stream induce elevati...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "rna processing", "molecular biology", "gene expression", "immunology", "biology", "molecular cell biology", "chromatin", "dna transcription", "histone modification" ]	Mechanisms Establishing TLR4-Responsive Activation States of Inflammatory Response Genes	journal.pgen.1002401	null	[ [ "Precise control of gene expression in response to external cues is essential for normal development , homeostasis and immunity .", "In the case of the innate immune system , which provides initial protection against bacterial and viral pathogens through the utilization of germ line-encoded pattern recogn...	[ "Precise control of the innate immune response is required for resistance to microbial infections and maintenance of normal tissue homeostasis .", "Because this response involves coordinate regulation of hundreds of genes , it provides a powerful biological system to elucidate the molecular strategies that underl...	[ "The innate immune response is a complex biological program that is configured to allow host cells to rapidly respond to infection and tissue injury .", "An essential feature of this response is the sequential activation of large numbers of genes that play roles in amplification of the initial inflammatory respon...	2011
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "infectious diseases", "computer and information sciences", "medicine and health sciences", "systems science", "mathematics", "sexually transmitted diseases", "population modeling", "aids", "biology and life sciences", "infectious disease modeling", "computational biology", "nonlinear dynamics...	Quantifying and Predicting the Effect of Exogenous Interleukin-7 on CD4+T Cells in HIV-1 Infection	journal.pcbi.1003630	null	[ [ "Human Immunodeficiency virus ( HIV ) infection is characterized by a profound depletion of CD4+ T cell numbers and function .", "Immune restoration with combination antiretroviral therapies ( cART ) has substantially improved patients' outcomes .", "Unfortunately , this restoration may be delayed , n...	[ "Exogenous Interleukin-7 ( IL-7 ) , in supplement to antiretroviral therapy , leads to a substantial increase of all CD4+ T cell subsets in HIV-1 infected patients .", "However , the quantitative contribution of the several potential mechanisms of action of IL-7 is unknown .", "We have performed a mathematical ...	[ "HIV infection is characterized by a decrease of CD4+ T-lymphocytes in the blood .", "Whereas antiretroviral treatment succeeds to control viral replication , some patients fail to reconstitute their CD4+ T cell count to normal value .", "IL-7 is a promising cytokine under evaluation for its use in HIV infectio...	2014
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "parasite evolution", "population genetics", "social sciences", "cloning", "parasitology", "kernel functions", "mutation", "probability distribution", "mathematics", "animal behavior", "molecular biology techniques", "population biology", "zoology", "research and analysis methods", "oper...	Spatial soft sweeps: Patterns of adaptation in populations with long-range dispersal	journal.pgen.1007936	null	[ [ "Rare beneficial alleles can rapidly increase their frequency in a population in response to a new selective pressure .", "When adaptation is limited by the availability of mutations , a single beneficial mutation may sweep through the entire population in the classical scenario of a “hard sweep” .", ...	[ "Adaptation in extended populations often occurs through multiple independent mutations responding in parallel to a common selection pressure .", "As the mutations spread concurrently through the population , they leave behind characteristic patterns of polymorphism near selected loci—so-called soft sweeps—which ...	[ "When a species is spread out over a large geographic range , different regions may adapt to the same selection pressure by acquiring distinct beneficial mutations .", "The resulting pattern of genetic variation in the population is called a soft sweep .", "Dispersal strongly influences soft sweep patterns , as...	2019
[ "Introduction", "Methods", "Results", "Discussion" ]	[]	Detecting and Removing Inconsistencies between Experimental Data and Signaling Network Topologies Using Integer Linear Programming on Interaction Graphs	journal.pcbi.1003204	null	[ [ "Given a single experimental scenario , we fix the states of the perturbed nodes ( according to the experimental interventions ) and then search for a sign-consistent node labeling having a minimal mismatch with the given measurements .", "In the ideal case , where the associated labeling of the experimen...	[ "Cross-referencing experimental data with our current knowledge of signaling network topologies is one central goal of mathematical modeling of cellular signal transduction networks .", "We present a new methodology for data-driven interrogation and training of signaling networks .", "While most published metho...	[ "Cellular signal transduction is orchestrated by communication networks of signaling proteins commonly depicted on signaling pathway maps .", "However , each cell type may have distinct variants of signaling pathways , and wiring diagrams are often altered in disease states .", "The identification of truly acti...	2013
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "blood cells", "medicine and health sciences", "body fluids", "microtubules", "radii", "platelet activation", "light", "geometry", "electromagnetic radiation", "light scattering", "mathematics", "platelets", "cellular structures and organelles", "cytoskeleton", "animal cells", "hematol...	Method for the simulation of blood platelet shape and its evolution during activation	journal.pcbi.1005899	null	[ [ "Human blood platelets are the paramount element of hemostasis and also contribute to a variety of other normal and pathological processes , including thrombosis , inflammation , and tumor development .", "These corpuscles attracted attention of early microscopists by the outstanding capacity to change ph...	[ "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...	[ "Blood platelets are the second most numerous component of blood after red blood cells .", "Their main function is to stop bleeding upon vessel wall injury .", "Contact with foreign substances , normally absent inside the bloodstream , leads to platelet activation .", "After this , platelets adhere to the dam...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "cell death", "genetic networks", "gene regulation", "cell processes", "network analysis", "genome analysis", "bioassays and physiological analysis", "mapk signaling cascades", "research and analysis methods", "computer and information sciences", "gene expression", "metabolic pathways", "met...	MinePath: Mining for Phenotype Differential Sub-paths in Molecular Pathways	journal.pcbi.1005187	null	[ [ "MinePath aims to address and cope with the aforementioned traditional pathway analysis problems and overcome the gene-set oriented visualization limitations , i . e . , what color should be assigned to a target gene when , for one phenotype it is activated by an activator source gene , and for another phenot...	[ "Pathway analysis methodologies couple traditional gene expression analysis with knowledge encoded in established molecular pathway networks , offering a promising approach towards the biological interpretation of phenotype differentiating genes .", "Early pathway analysis methodologies , named as gene set analys...	[ "It is generally recognized that using different sources of information and knowledge is better than just using a single source .", "This is most profound in the post-genomics era .", "On one hand , the advent of genomic high-throughput technologies realized by DNA microarray and next generation RNAseq technolo...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "cognitive science", "specimen preparation and treatment", "mechanical treatment of specimens", "cognitive neuroscience", "specimen disruption", "cognition", "decision making", "biology and life sciences", "electroporation", "neuroscience", "research and analysis methods" ]	Motivational Salience Signal in the Basal Forebrain Is Coupled with Faster and More Precise Decision Speed	journal.pbio.1001811	Avila and Lin report that the speed and variability of the decision-making process are tightly coupled and jointly determined by the motivational salience signal in the basal forebrain.	[ [ "The overall speed of information processing and decision-making has been studied for more than a century by measuring reaction time ( RT ) [1]–[3] .", "Significant increases in RT , reflecting a slower decision speed , represents a key feature in several conditions such as depression [4] , [5] , dementia...	[ "The survival of animals depends critically on prioritizing responses to motivationally salient stimuli .", "While it is generally believed that motivational salience increases decision speed , the quantitative relationship between motivational salience and decision speed , measured by reaction time ( RT ) , rema...	[ "Humans and animals face the constant challenge of identifying the subset of incoming sensory stimuli that are most behaviorally relevant and prioritizing behavioral responses accordingly .", "Critical to this decision is the ability to determine whether a stimulus is motivationally salient—that is , whether the ...	2014
[ "Introduction", "Design and Implementation", "Results", "Availability and Future Directions" ]	[ "sequencing techniques", "taxonomy", "microbiome", "microbiology", "cloning", "data management", "metagenomics", "shotgun sequencing", "molecular biology techniques", "dna cloning", "microbial genomics", "research and analysis methods", "sequence analysis", "computer and information scienc...	MEGAN Community Edition - Interactive Exploration and Analysis of Large-Scale Microbiome Sequencing Data	journal.pcbi.1004957	null	[ [ "In microbiome analysis , 16S rRNA amplicon sequencing [1] is often used when a high-level analysis of taxonomic content suffices , and/or computational resources are limited .", "However , metagenomic shotgun sequencing allows a more detailed analysis of taxonomic composition and also provides a detailed...	[ "There is increasing interest in employing shotgun sequencing , rather than amplicon sequencing , to analyze microbiome samples .", "Typical projects may involve hundreds of samples and billions of sequencing reads .", "The comparison of such samples against a protein reference database generates billions of al...	[ "Microbiome sequencing projects continue to grow rapidly , both in the number of samples considered and sequencing reads collected .", "With MEGAN Community Edition ( CE ) , we provide a highly efficient program for interactive analysis and comparison of such data , allowing one to explore hundreds of samples and...	2016
[ "Introduction", "Methods", "Discussion" ]	[ "infectious diseases/helminth infections", "infectious diseases/hiv infection and aids", "infectious diseases/neglected tropical diseases" ]	Treatment of Helminth Co-Infection in Individuals with HIV-1: A Systematic Review of the Literature	journal.pntd.0000102	null	[ [ "Many individuals living in areas of the world hardest hit by the HIV-1 epidemic are also infected with other common pathogens .", "These infections may have detrimental effects on the host's ability to control the HIV-1 virus [1] .", "Some studies have suggested that these infections may result in a ...	[ "The HIV-1 pandemic has disproportionately affected individuals in resource-constrained settings .", "It is important to determine if other prevalent infections affect the progression of HIV-1 in co-infected individuals in these settings .", "Some observational studies suggest that helminth infection may advers...	[ "Many people living in areas of the world most affected by the HIV/AIDS pandemic are also exposed to other common infections .", "Parasitic infections with helminths ( intestinal worms ) are common in Africa and affect over half of the population in some areas .", "There are plausible biological reasons why tre...	2007
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "computational biology/systems biology", "computational biology/signaling networks" ]	Temporal Controls of the Asymmetric Cell Division Cycle in Caulobacter crescentus	journal.pcbi.1000463	null	[ [ "The molecular network relevant to our model of the stalked cell division cycle of Caulobacter has been described in great detail previously [25] , so here we describe only those new components of the model involved in the swarmed-to-stalked cell transition , and some details related to improvements of our co...	[ "The asymmetric cell division cycle of Caulobacter crescentus is orchestrated by an elaborate gene-protein regulatory network , centered on three major control proteins , DnaA , GcrA and CtrA .", "The regulatory network is cast into a quantitative computational model to investigate in a systematic fashion how the...	[ "Because of its small genome size and the ease by which it can be manipulated genetically and biochemically , Caulobacter crescentus provides unique opportunities to study the molecular circuitry controlling the asymmetric cell division cycle of bacteria .", "A large amount of experimental data accumulated on thi...	2009
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "genetics of the immune system", "immunology", "biology", "genomics", "genetics and genomics" ]	Genome-Wide Association Study for Serum Complement C3 and C4 Levels in Healthy Chinese Subjects	journal.pgen.1002916	null	[ [ "The complement has been recognized as one pivotal part of innate and adaptive immune system , and it had three well-known physiologic activities , including host defense against infection , bridging interface between innate and adaptive immunity , and disposal of waste immune complexes or apoptotic cells [1]...	[ "Complement C3 and C4 play key roles in the main physiological activities of complement system , and their deficiencies or over-expression are associated with many clinical infectious or immunity diseases .", "A two-stage genome-wide association study ( GWAS ) was performed for serum levels of C3 and C4 .", "Th...	[ "The complement system plays important roles in the innate and adaptive immune functions .", "C3 and C4 participate in almost all physiological activities and activated pathways as key complement members and host defense proteins .", "Identifying the genes that influence serum levels of C3 and C4 may help to el...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genetics and genomics/genetics of disease", "genetics and genomics/bioinformatics", "genetics and genomics/medical genetics" ]	Genome-Wide Interaction-Based Association Analysis Identified Multiple New Susceptibility Loci for Common Diseases	journal.pgen.1001338	null	[ [ "Recent genome-wide association studies ( GWAS ) have identified many common genetic variants associated with common diseases .", "This has rapidly expanded our knowledge of the genetic architecture of these diseases .", "For example , the Wellcome Trust Case Control Consortium ( WTCCC ) study [1] and...	[ "Genome-wide interaction-based association ( GWIBA ) analysis has the potential to identify novel susceptibility loci .", "These interaction effects could be missed with the prevailing approaches in genome-wide association studies ( GWAS ) .", "However , no convincing loci have been discovered exclusively from ...	[ "Recent studies on the genetic basis of common diseases have identified many loci that confer disease susceptibility .", "However , much of the heritability of these diseases remains unexplained .", "Loci involved in gene–gene interactions are considered cryptic , because they confer susceptibility , but may no...	2011
[ "Introduction", "Results", "Discussion", "Materials and Methods", "Supporting Information" ]	[ "developmental biology", "neuroscience", "drosophila", "genetics and genomics" ]	Specification of Neuronal Identities by Feedforward Combinatorial Coding	journal.pbio.0050037	By studying the differential peptidergic fate of two lineage-related neurons in theDrosophila ventral nerve cord, the authors provide deeper insights into how, in a feedforward mechanism, earlier developmental determinants become critical players in later combinatorial codes defining cell identity.	[ [ "Animals have a daunting number of different cell types , and this cellular diversity is profound in the nervous system .", "During the last two decades , it has become increasingly apparent that neuronal cell fate is not dictated by the action of any single regulatory gene , but results from the combinat...	[ "Neuronal specification is often seen as a multistep process: earlier regulators confer broad neuronal identity and are followed by combinatorial codes specifying neuronal properties unique to specific subtypes .", "However , it is still unclear whether early regulators are re-deployed in subtype-specific combina...	[ "The nervous system contains a daunting number of different cell types , perhaps as many as 10 , 000 in mammals , far outnumbering regulatory genes in many animal species .", "Studies of the determinants of cell fate in many systems during the last decade have supported the conclusion that cell fate is not determ...	2007
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Increased Susceptibility of Humanized NSG Mice to Panton-Valentine Leukocidin and Staphylococcus aureus Skin Infection	journal.ppat.1005292	null	[ [ "Staphylococcus aureus is an aggressive human pathogen that causes a wide range of diseases and represents a major threat to public health .", "S . aureus is the most common cause of bacterial skin and soft tissue infection in the United States and is responsible for over 70% of soft tissue infections tre...	[ "Staphylococcus aureus is a leading cause of skin and soft-tissue infections worldwide .", "Mice are the most commonly used animals for modeling human staphylococcal infections .", "However a supra-physiologic S . aureus inoculum is required to establish gross murine skin pathology .", "Moreover , many staphy...	[ "S . aureus infection has emerged in the past decade as a major burden to public health and is responsible for a surge in preclinical research .", "Mice are the most commonly studied animals for modeling of human S . aureus infection .", "However , it is increasingly evident that available murine models poorly ...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biomacromolecule-ligand interactions", "cell death", "immune cells", "immunology", "signaling networks", "protein structure", "signaling pathways", "apoptotic signaling", "glycoproteins", "immunomodulation", "signaling in cellular processes", "gene expression", "biology", "molecular biolo...	Structure of Human Cytomegalovirus UL141 Binding to TRAIL-R2 Reveals Novel, Non-canonical Death Receptor Interactions	journal.ppat.1003224	null	[ [ "The immune system has evolved to protect against the many pathogens that are encountered throughout the lifetime of an individual .", "In turn , the selective pressure that is exerted by the immune system has shaped pathogen evolution .", "This co-evolutionary relationship between host and pathogen i...	[ "The TRAIL ( TNF-related apoptosis inducing ligand ) death receptors ( DRs ) of the tumor necrosis factor receptor superfamily ( TNFRSF ) can promote apoptosis and regulate antiviral immunity by maintaining immune homeostasis during infection .", "In turn , human cytomegalovirus ( HCMV ) expresses immunomodulator...	[ "Natural killer ( NK ) cells are critical to the innate immune system along with their ability to detect and destroy cells infected by viruses .", "To avoid discovery by cytotoxic lymphocytes and to allow for longtime persistence in the host , human cytomegalovirus ( HCMV ) evolved a number of genes to evade or i...	2013
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "physics", "sequence analysis", "forms of evolution", "statistical mechanics", "coevolution", "evolutionary modeling", "protein structure", "biology", "computational biology", "evolutionary biology", "proteomics", "evolutionary processes", "macromolecular structure analysis" ]	From Principal Component to Direct Coupling Analysis of Coevolution in Proteins: Low-Eigenvalue Modes are Needed for Structure Prediction	journal.pcbi.1003176	null	[ [ "Data are given in form of a multiple sequence alignment ( MSA ) , in which each row contains the amino-acid sequence of one protein , and each column one residue position in these proteins , which is aligned based on amino-acid similarity .", "We denote the MSA by with index running over the columns of t...	[ "Various approaches have explored the covariation of residues in multiple-sequence alignments of homologous proteins to extract functional and structural information .", "Among those are principal component analysis ( PCA ) , which identifies the most correlated groups of residues , and direct coupling analysis (...	[ "Extracting functional and structural information about protein families from the covariation of residues in multiple sequence alignments is an important challenge in computational biology .", "Here we propose a statistical-physics inspired framework to analyze those covariations , which naturally unifies existin...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biology" ]	Substitutions in the Amino-Terminal Tail of Neurospora Histone H3 Have Varied Effects on DNA Methylation	journal.pgen.1002423	null	[ [ "The primary structures of histones , the small basic proteins that are complexed with DNA to form chromatin in eukaryotes , are highly conserved but not invariant [1] , [2] .", "For example , comparisons between a sea urchin and the filamentous fungus Neurospora crassa reveal that the two most highly con...	[ "Eukaryotic genomes are partitioned into active and inactive domains called euchromatin and heterochromatin , respectively .", "In Neurospora crassa , heterochromatin formation requires methylation of histone H3 at lysine 9 ( H3K9 ) by the SET domain protein DIM-5 .", "Heterochromatin protein 1 ( HP1 ) reads th...	[ "DNA methylation is a common feature of eukaryotic genomes .", "Methylation is typically associated with silenced chromosomal domains and is essential for development of plants and animals .", "Although the control of DNA methylation is not well understood , recent findings with model organisms , including the ...	2011
[ "Introduction", "Methods", "Results", "Discussion" ]	[]	Epilepsy and Neurocysticercosis in Latin America: A Systematic Review and Meta-analysis	journal.pntd.0002480	null	[ [ "Epilepsy is one of the most prevalent non-communicable neurologic diseases [1] , with an estimated aggregate burden of around 0 . 5% of the total disease burden [2] .", "It affects approximately 70 million people worldwide [3] and at least five million people in Latin American Countries ( LAC ) [4] .", ...	[ "The difference in epilepsy burden existing among populations in tropical regions has been attributed to many factors , including the distribution of infectious diseases with neurologic sequels .", "To define the burden of epilepsy in Latin American Countries ( LAC ) and to investigate the strength of association...	[ "Epilepsy affects approximately 70 million people worldwide and at least five million people in Latin America .", "Many researchers have pointed out a different distribution of epilepsy in Latin American countries , with some regions presenting higher frequencies and others presenting lower frequencies .", "Thi...	2013
[ "Introduction", "Materials and methods", "Results", "Discussion" ]	[ "medicine and health sciences", "body fluids", "trypanosoma congolense", "social sciences", "neuroscience", "parasitic diseases", "parasitic protozoans", "protozoans", "genome analysis", "mechanoreceptors", "gene expression", "sensory receptors", "gene ontologies", "signal transduction", ...	Molecular characterization of tsetse’s proboscis and its response to Trypanosoma congolense infection	journal.pntd.0006057	null	[ [ "Tsetse flies ( Glossina spp . ) are vectors of African trypanosomes , which are protozoan parasites that cause human and animal African trypanosomiases ( HAT and AAT , respectively ) throughout sub-Saharan Africa [1] .", "AAT caused by Trypanosoma brucei brucei , Trypanosoma vivax and Trypanosoma congole...	[ "Tsetse flies ( Glossina spp . ) transmit parasitic African trypanosomes ( Trypanosoma spp . ) , including Trypanosoma congolense , which causes animal African trypanosomiasis ( AAT ) .", "AAT detrimentally affects agricultural activities in sub-Saharan Africa and has negative impacts on the livelihood and nutrie...	[ "Tsetse flies are economically important insects responsible for transmitting African trypanosomes , which cause debilitating and fatal diseases in humans and animals in sub-Saharan Africa .", "In the tsetse vector , trypanosomes undergo complex developmental processes in the midgut , culminating with the generat...	2017
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "hiv epidemiology", "infectious disease surveillance", "infectious diseases", "hiv infections", "plant science", "medicine and health sciences", "amebiasis", "epidemiology", "disease surveillance", "plant pathology", "biology and life sciences", "viral diseases", "protozoan infections", "p...	Prevalent and Incident HIV Diagnoses among Entamoeba histolytica-Infected Adult Males: A Changing Epidemiology Associated with Sexual Transmission — Taiwan, 2006–2013	journal.pntd.0003222	null	[ [ "Entamoeba histolytica is a fecal-orally transmitted protozoan that generally causes asymptomatic infection but can lead to invasive diseases such as colitis and liver abscess [1] , [2] .", "E . histolytica infection ( EHI , also known as amebiasis ) is endemic in areas of inadequate sanitation , particul...	[ "Sexually transmitted Entamoeba histolytica infection ( EHI ) has been increasingly recognized among men who have sex with men ( MSM ) .", "We used the National Disease Surveillance Systems ( NDSS ) to identify prevalent and incident HIV diagnoses among adults with EHI and to determine the associated factors .", ...	[ "Although sexually transmitted Entamoeba histolytica infection has been increasingly recognized among men who have sex with men ( MSM ) in Australia , Japan , Korea , and Taiwan , particularly those with HIV infection , no studies have examined E . histolytica infection in relation to HIV and attribution of sexual ...	2014
[ "Introduction", "Material and Methods", "Results", "Discussion" ]	[]	The SUMOylation Pathway Restricts Gene Transduction by Adeno-Associated Viruses	journal.ppat.1005281	null	[ [ "Adeno-associated viruses ( AAV ) are members of the family parvoviridae which encompasses the subfamily of dependoparvovirus so named because they require helper viruses such as adenovirus , herpes simplex virus or human papillomavirus for replication in cell culture [1–5] .", "They comprise a single str...	[ "Adeno-associated viruses are members of the genus dependoviruses of the parvoviridae family .", "AAV vectors are considered promising vectors for gene therapy and genetic vaccination as they can be easily produced , are highly stable and non-pathogenic .", "Nevertheless , transduction of cells in vitro and in ...	[ "SUMOylation is a post-translational modification in which a small protein ( SUMO ) is covalently attached to target proteins .", "Three key enzymes are controlling this modification: The E1 activating complex composed of the heterodimer Sae1/Sae2 , the E2 conjugation enzyme Ubc9 and one of many E3 enzymes which ...	2015
[ "Introduction", "Models and methods", "Results", "Discussion" ]	[ "epidemiological statistics", "medicine and health sciences", "epidemiological methods and statistics", "mathematics", "diagnostic medicine", "pathology and laboratory medicine", "simulation and modeling", "epidemiology", "statistics", "pathogens", "biology and life sciences", "physical scienc...	Model diagnostics and refinement for phylodynamic models	journal.pcbi.1006955	null	[ [ "Pathogen dynamics are shaped collectively and interdependently by biological processes occurring at the epidemiological , immunological and evolutionary levels .", "Conventionally , however , each of these processes has been studied independently , revealing only a partial picture of the pathogen dynamic...	[ "Phylodynamic modelling , which studies the joint dynamics of epidemiological and evolutionary processes , has made significant progress in recent years due to increasingly available genomic data and advances in statistical modelling .", "These advances have greatly improved our understanding of transmission dyna...	[ "Integrated modelling of conventional epidemiological data and modern genomic data ( i . e . phylodynamics ) has made significant progress in recent years , due to the ever-increasing availability of genomic data and development of statistical methods .", "However , there is a lack of tools for carrying out effec...	2019
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "cell physiology", "meiosis", "cell cycle and cell division", "cell processes", "light microscopy", "fungi", "model organisms", "microscopy", "experimental organism systems", "cell nucleus", "cellular structures and organelles", "schizosaccharomyces", "nuclear pores", "research and analysi...	Asymmetrical localization of Nup107-160 subcomplex components within the nuclear pore complex in fission yeast	journal.pgen.1008061	null	[ [ "In eukaryotes , the nuclear envelope ( NE ) separates the nucleus from the cytoplasm .", "Molecular transport between the nucleus and cytoplasm across the NE occurs through nuclear pore complexes ( NPCs ) .", "These complexes are cylindrical , eight-fold symmetrical structures that perforate the NE a...	[ "The nuclear pore complex ( NPC ) forms a gateway for nucleocytoplasmic transport .", "The outer ring protein complex of the NPC ( the Nup107-160 subcomplex in humans ) is a key component for building the NPC .", "Nup107-160 subcomplexes are believed to be symmetrically localized on the nuclear and cytoplasmic ...	[ "The nuclear pore complexes ( NPCs ) form gateways to transport intracellular molecules between the nucleus and the cytoplasm across the nuclear envelope .", "The Nup107-160 subcomplex , that forms nuclear and cytoplasmic outer rings , is a key complex responsible for building the NPC by symmetrical localization ...	2019
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "blood cells", "genome-wide association studies", "medicine and health sciences", "body fluids", "quantitative trait loci", "blood counts", "alleles", "genome analysis", "platelets", "hemoglobin", "animal cells", "proteins", "genetic loci", "hematology", "biochemistry", "blood", "ana...	Rare coding variants pinpoint genes that control human hematological traits	journal.pgen.1006925	null	[ [ "Although genome-wide association studies ( GWAS ) have identified thousands of associations with the number or distributional characteristics of red blood cells , white blood cells , and platelets [1] , the genes responsible for this phenotypic variation remain elusive at most of these loci .", "For the ...	[ "The identification of rare coding or splice site variants remains the most straightforward strategy to link genes with human phenotypes .", "Here , we analyzed the association between 137 , 086 rare ( minor allele frequency ( MAF ) <1% ) coding or splice site variants and 15 hematological traits in up to 308 , 5...	[ "Genome-wide association studies ( GWAS ) have identified thousand of genetic associations between common DNA sequence variants ( e . g . single nucleotide polymorphisms ( SNPs ) ) and complex human diseases or traits .", "In most cases , these associations highlight non-coding variants , and thus fall short of i...	2017
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "immunology/immunomodulation", "infectious diseases/helminth infections", "immunology/immunity to infections" ]	Filarial Lymphedema Is Characterized by Antigen-Specific Th1 and Th17 Proinflammatory Responses and a Lack of Regulatory T Cells	journal.pntd.0000420	null	[ [ "Although two-thirds of the 120 million people infected with Wuchereria bancrofti , the major causative agent of human lymphatic filariasis , have subclinical infections , ∼40 million have lymphedema and/or other pathologic manifestations including hydroceles ( and other forms of urogenital disease ) , episod...	[ "Lymphatic filariasis can be associated with development of serious pathology in the form of lymphedema , hydrocele , and elephantiasis in a subset of infected patients .", "To elucidate the role of CD4+ T cell subsets in the development of lymphatic pathology , we examined specific sets of cytokines in individua...	[ "Lymphatic filariasis afflicts over 120 million people worldwide .", "While the infection is mostly clinically asymptomatic , approximately 40 million people suffer from overt , morbid clinical pathology , characterized by swelling of the scrotal area and lower limbs ( hydrocele and lymphedema ) .", "Host immun...	2009
[ "Introduction", "Methods", "Results", "Discussion" ]	[]	Long Term Control of Scabies Fifteen Years after an Intensive Treatment Programme	journal.pntd.0004246	null	[ [ "Scabies , caused by infestation with the Sarcoptes scabiei mite , remains a major public health problem in developing countries worldwide[1] .", "In addition to the direct manifestations of infestation , scabies is associated with an increased risk of bacterial skin infections due to Staphylococcus aureu...	[ "Scabies is a major public health problem in the Pacific and is associated with an increased risk of bacterial skin infections , glomerulonephritis and rheumatic fever .", "Mass drug administration with ivermectin is a promising strategy for the control of scabies .", "Mass treatment with ivermectin followed by...	[ "Scabies is a parasitic infection caused by the mite Sarcoptes scabiei .", "Scabies is a risk factor for bacterial skin infections and as a result of these secondary infections , individuals with scabies are also at risk of kidney disease and possibly rheumatic heart disease .", "Traditionally the management of...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "animal models", "animal models of infection", "zebrafish", "viral clearance", "model organisms", "host cells", "neuroinvasiveness", "immunity", "viral transmission and infection", "virology", "innate immunity", "immunity to infections", "immunology", "host-pathogen interaction", "biolog...	Real-Time Whole-Body Visualization of Chikungunya Virus Infection and Host Interferon Response in Zebrafish	journal.ppat.1003619	null	[ [ "Chikungunya virus ( CHIKV ) is a mosquito-transmitted virus that causes serious illness and has reemerged in Africa and Asia since 2000 , causing outbreaks with millions of cases after decades of near-absence [1] .", "The epidemic spread to previously CHIKV-free areas , such as La Reunion Island in the I...	[ "Chikungunya Virus ( CHIKV ) , a re-emerging arbovirus that may cause severe disease , constitutes an important public health problem .", "Herein we describe a novel CHIKV infection model in zebrafish , where viral spread was live-imaged in the whole body up to cellular resolution .", "Infected cells emerged in...	[ "Chikungunya , a re-emerging disease caused by a mosquito-transmitted virus , is an important public health problem .", "We developed a zebrafish model for chikungunya virus infection .", "For the first time , rise and death of virus-infected cells could be live imaged in the entire body of a vertebrate .", "...	2013
[ "Introduction", "Methods", "Discussion" ]	[ "medicine", "infectious diseases", "mosquitoes", "entomology", "vector biology", "neglected tropical diseases", "dengue", "biology", "microbiology", "viral diseases", "zoology" ]	Fluctuations at a Low Mean Temperature Accelerate Dengue Virus Transmission by Aedes aegypti	journal.pntd.0002190	null	[ [ "The ability of Aedes aegypti to transmit viruses , in particular dengue viruses ( DENV ) , has long been known to be influenced by temperature [1]–[6] .", "It is generally assumed that higher mean temperatures facilitate DENV transmission due to faster virus propagation and dissemination within the vecto...	[ "Environmental factors such as temperature can alter mosquito vector competence for arboviruses .", "Results from recent studies indicate that daily fluctuations around an intermediate mean temperature ( 26°C ) reduce vector competence of Aedes aeygpti for dengue viruses ( DENV ) .", "Theoretical predictions su...	[ "Mosquitoes in the wild are exposed to daily fluctuations in temperature , but in the laboratory , the effect of temperature on vector competence is generally assessed using constant temperatures .", "Recent studies demonstrate that realistic fluctuations in temperature around an intermediate mean ( 26°C ) can al...	2013
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "cell motility", "medicine and health sciences", "cancer treatment", "clinical oncology", "biological cultures", "cancers and neoplasms", "blastomas", "cell processes", "surgical and invasive medical procedures", "oncology", "neurological tumors", "clinical medicine", "cell cultures", "pop...	The role of Allee effect in modelling post resection recurrence of glioblastoma	journal.pcbi.1005818	null	[ [ "The growth of a malignant tumour is driven by the uncontrolled proliferation of cancer cells , and their invasion into healthy tissue .", "While the primary therapy often involves the surgical removal of the tumour , unfortunately , the surgery often leaves a small population of cancer cells infiltrated ...	[ "Resection of the bulk of a tumour often cannot eliminate all cancer cells , due to their infiltration into the surrounding healthy tissue .", "This may lead to recurrence of the tumour at a later time .", "We use a reaction-diffusion equation based model of tumour growth to investigate how the invasion front i...	[ "Mathematical models of propagating fronts have been used to represent a wide variety of biological phenomena from action potentials in neural cells to invasive species in ecology and epidemic spreading .", "Here we show that when such models are used to predict the effects of external perturbations the results c...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Insulin/IGF-Regulated Size Scaling of Neuroendocrine Cells Expressing the bHLH Transcription Factor Dimmed in Drosophila	journal.pgen.1004052	null	[ [ "Neurons and other cells display substantial variation in size in an organism .", "Thus , some neuron types in the brain have large cell bodies and extensive axonal processes , whereas others are minute with restricted branches .", "An important question is to what extent neuron size is genetically pr...	[ "Neurons and other cells display a large variation in size in an organism .", "Thus , a fundamental question is how growth of individual cells and their organelles is regulated .", "Is size scaling of individual neurons regulated post-mitotically , independent of growth of the entire CNS ?", "Although the rol...	[ "Nerve cells display a large variation in size in an organism .", "Thus , a fundamental question is how growth of individual cells and their organelles is regulated .", "We ask if there is a regulatory mechanism for scaling the size of individual nerve cells , independent of the growth of the entire central ner...	2013
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "systems biology", "immune cells", "t cells", "immunology", "biology", "computational biology", "immune response" ]	Virus Replication Strategies and the Critical CTL Numbers Required for the Control of Infection	journal.pcbi.1002274	null	[ [ "The majority of vaccine design approaches to date have used neutralizing antibody titers as a correlate of efficacy .", "However , major infectious diseases such as HIV-AIDS , TB and Malaria have not yet fully yielded to vaccines aimed at eliciting antibodies .", "There is currently much interest in ...	[ "Vaccines that elicit protective cytotoxic T lymphocytes ( CTL ) may improve on or augment those designed primarily to elicit antibody responses .", "However , we have little basis for estimating the numbers of CTL required for sterilising immunity at an infection site .", "To address this we begin with a theor...	[ "In the search for vaccines that provide reliable protection against major diseases such as HIV-AIDS , TB and Malaria , there is now a focus on generating populations of antigen-specific cytotoxic T lymphocytes ( CTL ) , immune cells that recognise and kill infected cells .", "However , we have little idea of the...	2011
[ "Introduction", "Materials and methods", "Results", "Discussion" ]	[ "dna damage", "mathematics", "statistics (mathematics)", "dna", "cellular structures and organelles", "research and analysis methods", "mathematical and statistical techniques", "chemistry", "monte carlo method", "biophysics", "ribosomes", "cytoplasm", "physics", "biochemistry", "biochem...	Activation of the DNA-repair mechanism through NBS1 and MRE11 diffusion	journal.pcbi.1006362	null	[ [ "Once a DNA strand inside a cell nucleus breaks , the ruptured strands are sought mended by a biological multi-step process [1–4] .", "This breakage and repair can happen in various different ways .", "The double strand breaks are for example repaired by non-homologous end-joining ( NHEJ ) , where bro...	[ "The non-homologous end joining of a DNA double strand break is initiated by the MRE11-NBS1-RAD50 complex whose subunits are the first three proteins to arrive to the breakage site thereby making the recruitment time of MRE11 , NBS1 and RAD50 essential for cell survival .", "In the present investigation , the nat...	[ "The DNA repair mechanism is crucial for a cell to avoid apoptosis , and is a complicated process involving many different repair proteins .", "The mean of transportation of these repair proteins is largely unknown as their transportation mechanisms need clarification .", "We have focused on the transportation ...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Dynamic Endothelial Cell Rearrangements Drive Developmental Vessel Regression	journal.pbio.1002125	A study of mouse retina and zebrafish vasculature shows how differential blood flow patterns direct the orientation and migration of endothelial cells as a mechanism for stabilizing or pruning individual blood vessel segments.	[ [ "The formation of a functionally perfused and hierarchically branched network of blood vessels is essential for vertebrate development , tissue growth , and organ physiology [1] .", "Together , vasculogenic vessel assembly and angiogenic sprouting establish the major axial vessels and form a rough draft o...	[ "Patterning of functional blood vessel networks is achieved by pruning of superfluous connections .", "The cellular and molecular principles of vessel regression are poorly understood .", "Here we show that regression is mediated by dynamic and polarized migration of endothelial cells , representing anastomosis...	[ "The question of how blood vessel networks achieve their branching patterns is key to our understanding of organ formation as well as diseases that involve vascular anomalies .", "Regression ( or pruning ) of blood vessel segments is required for functional vascular branching patterns; however , the molecular bas...	2015
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "blood cells", "innate immune system", "medicine and health sciences", "immune cells", "immune physiology", "cytokines", "cd coreceptors", "immunology", "tropical diseases", "cell-mediated immunity", "bacterial diseases", "developmental biology", "molecular development", "cytotoxic t cells...	TIM3 Mediates T Cell Exhaustion during Mycobacterium tuberculosis Infection	journal.ppat.1005490	null	[ [ "In countries where tuberculosis exists with a low prevalence , T cell immunity to Mycobacterium tuberculosis enforces latency in 90% of infected people and prevents the development of clinical disease .", "However , in countries with endemic tuberculosis the cumulative risk for developing active tubercul...	[ "While T cell immunity initially limits Mycobacterium tuberculosis infection , why T cell immunity fails to sterilize the infection and allows recrudescence is not clear .", "One hypothesis is that T cell exhaustion impairs immunity and is detrimental to the outcome of M . tuberculosis infection .", "Here we pr...	[ "Tuberculosis is a leading cause of morbidity and mortality across the globe .", "Fortunately , most people infected with M . tuberculosis mount a protective immune response and only a small fraction develops active disease .", "Impairment of immunity late during the course of disease can lead to bacterial recr...	2016
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "genome-wide association studies", "body weight", "medicine and health sciences", "statistics", "metaanalysis", "physiological parameters", "mathematics", "obesity", "genome analysis", "research and analysis methods", "genomic signal processing", "mathematical and statistical techniques", "s...	Genetic architecture of human thinness compared to severe obesity	journal.pgen.1007603	null	[ [ "The rising prevalence of obesity is driven by changes in the environment including the consumption of high calorie foods and reduced levels of physical activity [1] .", "However , within a given environment , there is considerable variation in body weight; some people are particularly susceptible to seve...	[ "The variation in weight within a shared environment is largely attributable to genetic factors .", "Whilst many genes/loci confer susceptibility to obesity , little is known about the genetic architecture of healthy thinness .", "Here , we characterise the heritability of thinness which we found was comparable...	[ "Obesity-associated disorders are amongst the leading causes of morbidity and mortality worldwide .", "Most genome-wide association studies ( GWAS ) have focused on body mass index ( BMI = weight in Kg divided by height squared ( m2 ) ) and obesity , but to date no genetic association study testing thin and healt...	2019
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "invertebrates", "medicine and health sciences", "pathology and laboratory medicine", "chemical compounds", "aliphatic amino acids", "pathogens", "vibrio", "microbiology", "organic compounds", "animals", "animal models", "vibrio cholerae", "model organisms", "drosophila melanogaster", "g...	Vibrio cholerae ensures function of host proteins required for virulence through consumption of luminal methionine sulfoxide	journal.ppat.1006428	null	[ [ "Childhood diarrheal disease is a leading cause of morbidity and mortality , particularly in the developing world , and bacterial pathogens figure prominently in this entity [1] .", "Traditional virulence factors are pathogen-specific and synthesized expressly for the purpose of colonizing , entering , an...	[ "Vibrio cholerae is a diarrheal pathogen that induces accumulation of lipid droplets in enterocytes , leading to lethal infection of the model host Drosophila melanogaster .", "Through untargeted lipidomics , we provide evidence that this process is the product of a host phospholipid degradation cascade that indu...	[ "The virulence program of intestinal pathogens such as Vibrio cholerae depends on the continued function of target host proteins .", "If these proteins are inactivated by methionine oxidation , virulence may also depend on repair of these proteins by host methionine sulfoxide reductases such as MsrA .", "Dietar...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "plant science", "gene expression", "genetics", "plant genetics", "epigenetics", "molecular genetics", "biology", "dna modification", "dna transcription" ]	How a Retrotransposon Exploits the Plant's Heat Stress Response for Its Activation	journal.pgen.1004115	null	[ [ "Transposable elements ( TEs ) and their host organisms depend on each other for better or for worse .", "New TE insertions can give rise to deleterious mutations [1] or overall genetic instability [2] , but they can also make a positive contribution to gene regulation and adaptation [3] , [4] .", "Ho...	[ "Retrotransposons are major components of plant and animal genomes .", "They amplify by reverse transcription and reintegration into the host genome but their activity is usually epigenetically silenced .", "In plants , genomic copies of retrotransposons are typically associated with repressive chromatin modifi...	[ "Transposons are programmed to amplify within their host genomes .", "In defense , hosts have evolved mechanisms to impede transposon activation , often by epigenetic transcriptional silencing .", "A constant and likely unending arms race between host and invader has brought about different strategies to mutual...	2014
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "cognitive neurology", "medicine and health sciences", "nervous system", "astrocytes", "tropical diseases", "brain", "parasitic diseases", "neuroscience", "macroglial cells", "microglial cells", "animal models", "cognitive neuroscience", "model organisms", "experimental organism systems", ...	IL-33 receptor ST2 regulates the cognitive impairments associated with experimental cerebral malaria	journal.ppat.1006322	null	[ [ "Malaria is still one of the most devastating infectious diseases worldwide with 300–500 million cases each year and one million deaths every year ( WHO ) .", "Cerebral malaria is a frequent cause of death from Plasmodium falciparum infection [1] , with severe anemia , shock , lung vascular leakage , acut...	[ "Cerebral malaria ( CM ) is associated with a high mortality rate and long-term neurocognitive impairment in survivors .", "The murine model of experimental cerebral malaria ( ECM ) induced by Plasmodium berghei ANKA ( PbA ) -infection reproduces several of these features .", "We reported recently increased lev...	[ "The cerebral complication of malaria caused by Plasmodium falciparum infection , is associated with long-term neurological sequelae in survivors .", "The mechanisms involved in neurocognitive impairments during cerebral malaria development are still unknown .", "We reported recently the essential role of IL-33...	2017
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "invertebrates", "medicine and health sciences", "specific gravity", "helminths", "tropical diseases", "hookworms", "parasitic diseases", "animals", "developmental biology", "ascaris", "materials science", "neglected tropical diseases", "surfactants", "chemical properties", "physical che...	Detecting and enumerating soil-transmitted helminth eggs in soil: New method development and results from field testing in Kenya and Bangladesh	journal.pntd.0005522	null	[ [ "Almost one quarter of the world’s population is infected with at least one species of soil-transmitted helminth ( STH ) [1] .", "South Asia , Southeast Asia , and Sub-Saharan Africa are the regions with the highest prevalence [1] .", "Ascaris and Trichuris infection is spread via an environmentally-m...	[ "Globally , about 1 . 5 billion people are infected with at least one species of soil-transmitted helminth ( STH ) .", "Soil is a critical environmental reservoir of STH , yet there is no standard method for detecting STH eggs in soil .", "We developed a field method for enumerating STH eggs in soil and tested ...	[ "Intestinal worm infections are common in populations living in tropical , low-income countries .", "People primarily become infected when they consume intestinal worm eggs from contaminated water , hands , and food .", "Intestinal worm eggs are transmitted from infected people and spread through the environmen...	2017
[ "Introduction", "Results", "Discussion", "Methods" ]	[]	Nxf1 Natural Variant E610G Is a Semi-dominant Suppressor of IAP-Induced RNA Processing Defects	journal.pgen.1005123	null	[ [ "Endogenized retroviruses and other molecular parasites frequently influence expression of host genes at sites of insertion .", "Chromosomal insertions of these mobile elements can alter initiation , splicing , or termination of host gene transcripts , in quality or amount .", "Remnants of ancient ins...	[ "Endogenous retroviruses and retrotransposons contribute functional genetic variation in animal genomes .", "In mice , Intracisternal A Particles ( IAPs ) are a frequent source of both new mutations and polymorphism across laboratory strains .", "Intronic IAPs can induce alternative RNA processing choices , inc...	[ "Transposable elements , including endogenous retroviruses , have long been hypothesized as a substrate for creating or modulating gene regulatory networks , particularly through effects on transcription .", "However , several classes of elements are also known to affect alternative RNA processing events .", "W...	2015
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "taeniasis", "medicine", "infectious diseases", "zoonoses", "veterinary epidemiology", "infectious disease epidemiology", "epidemiology", "cysticercosis", "neglected tropical diseases", "parasitic diseases", "veterinary science" ]	Relationship between Serum Antibodies and Taenia solium Larvae Burden in Pigs Raised in Field Conditions	journal.pntd.0002192	null	[ [ "Taenia solium/cysticercosis infection is an endemic parasitic disease in less developed countries where pigs are raised as a food source [1] .", "The life cycle of Taenia solium includes the pig as the normal intermediate host , harboring the larval vesicles or cysticerci , and the human as the definitiv...	[ "Serological tests have been used for the diagnosis of Taenia solium infection in pigs .", "However , those serological results do not necessarily correlate with the actual infection burden after performing pig necropsy .", "This study aimed to evaluate the Electro Immuno Transfer Blot ( EITB ) seropositivity w...	[ "Taenia solium is a parasite that infects humans .", "The parasite eggs are released into the environment with human feces in villages with inadequate sanitation .", "Pigs might ingest the parasite eggs and develop the larval stage named cysticercosis ( cysts ) , mainly in the muscles and heart .", "If a huma...	2013
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "cdna libraries", "transfer rna", "nucleases", "enzymes", "dna-binding proteins", "enzymology", "fungi", "forms of dna", "dna libraries", "molecular biology techniques", "dna", "cellular structures and organelles", "genetic footprinting", "research and analysis methods", "proteins", "g...	Lso2 is a conserved ribosome-bound protein required for translational recovery in yeast	journal.pbio.2005903	null	[ [ "The ribosome is a universally conserved , multi-megadalton machine that carries out protein synthesis in all organisms .", "Accurate and efficient translation in eukaryotes requires the interaction of nearly 30 translation factors with the ribosome to ensure orderly execution of the translation cycle , i...	[ "Ribosome-binding proteins function broadly in protein synthesis , gene regulation , and cellular homeostasis , but the complete complement of functional ribosome-bound proteins remains unknown .", "Using quantitative mass spectrometry , we identified late-annotated short open reading frame 2 ( Lso2 ) as a riboso...	[ "Translation , or the production of protein from messenger RNA ( mRNA ) , is catalyzed by a universally conserved macromolecular machine known as the ribosome .", "Ribosome-binding factors are also required for all substeps of translation , from initial recruitment of mRNA to peptide chain elongation to release o...	2018
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "schistosoma", "invertebrates", "schistosoma mansoni", "medicine and health sciences", "body fluids", "immune physiology", "helminths", "immunology", "microbiology", "viral structure", "parasitic diseases", "animals", "urine", "antibodies", "immune system proteins", "schistosoma haemat...	In-depth proteomic characterization of Schistosoma haematobium: Towards the development of new tools for elimination	journal.pntd.0007362	null	[ [ "Schistosomiasis is a neglected tropical and debilitating disease caused by different trematodes from the genus Schistosoma [1] .", "It affects over 250 million people worldwide , particularly in developing and tropical regions [2–4] .", "Despite widespread use of the anthelmintic praziquantel in mass...	[ "Schistosomiasis is a neglected disease affecting hundreds of millions worldwide .", "Of the three main species affecting humans , Schistosoma haematobium is the most common , and is the leading cause of urogenital schistosomiasis .", "S . haematobium infection can cause different urogenital clinical complicati...	[ "Schistosomiasis is a neglected tropical disease affecting millions of people worldwide .", "Of the main three species affecting humans , Schistosoma haematobium is the most common , and is the leading cause of urogenital schistosomiasis .", "This parasite can cause a range of clinical complications associated ...	2019
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "organismal evolution", "computer and information sciences", "genome complexity", "genomics", "genome evolution", "network analysis", "eukaryotic evolution", "genetics", "biology and life sciences", "metabolic networks", "comparative genomics", "computational biology", "evolutionary biology"...	A Lack of Parasitic Reduction in the Obligate Parasitic Green Alga Helicosporidium	journal.pgen.1004355	null	[ [ "Helicosporidia are parasitic protists characterized by mature discoid cysts each containing a single filamentous and three ovoid cells [1] , [2] .", "These parasites invade their invertebrate hosts per os and initiate their replicative stage within the digestive tract [3] , [4] .", "The cysts , trigg...	[ "The evolution of an obligate parasitic lifestyle is often associated with genomic reduction , in particular with the loss of functions associated with increasing host-dependence .", "This is evident in many parasites , but perhaps the most extreme transitions are from free-living autotrophic algae to obligate pa...	[ "Helicosporidium is a highly-adapted obligate parasite of animals .", "Its evolutionary origins were unclear for almost a century , but molecular analysis ultimately and surprisingly showed that it is a green alga , which means it has undergone an evolutionary transition from autotrophy to parasitism comparable t...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "systems biology", "genetics", "biology", "genomics", "evolutionary biology", "genetics and genomics" ]	Genome-Wide Location Analysis Reveals Distinct Transcriptional Circuitry by Paralogous Regulators Foxa1 and Foxa2	journal.pgen.1002770	null	[ [ "Expansion of transcription factor gene families has greatly contributed to the complexity of metazoan genomes [1] .", "Newly duplicated genes must acquire new functions in order to remain relevant , otherwise they are lost via mutation over time .", "Transcription factor paralogs diversify either by ...	[ "Gene duplication is a powerful driver of evolution .", "Newly duplicated genes acquire new roles that are relevant to fitness , or they will be lost over time .", "A potential path to functional relevance is mutation of the coding sequence leading to the acquisition of novel biochemical properties , as analyze...	[ "The duplication of a gene from a common ancestor , resulting in two copies known as paralogs , plays an important role in evolution .", "Newly duplicated genes must acquire new functions in order to remain relevant , otherwise they are lost via mutation over time .", "We have performed genome-wide location ana...	2012
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "nuclear import", "phosphorylation", "medicine and health sciences", "pathology and laboratory medicine", "gene regulation", "pathogens", "cell processes", "signaling networks", "microbiology", "orthomyxoviruses", "viruses", "wireless sensor networks", "rna viruses", "network analysis", ...	Phospholipid scramblase 1 interacts with influenza A virus NP, impairing its nuclear import and thereby suppressing virus replication	journal.ppat.1006851	null	[ [ "Influenza A virus ( IAV ) , a single-stranded , negative-sense RNA virus with an eight-segmented genome , is the causative agent of influenza in many animal species , including humans .", "Inside the virion , all eight viral RNA ( vRNA ) segments bind to the three RNA polymerases ( polymerase basic prote...	[ "Transcription and replication of the influenza A virus ( IAV ) genome occur in the nucleus of infected cells and are carried out by the viral ribonucleoprotein complex ( vRNP ) .", "As a major component of the vRNP complex , the viral nucleoprotein ( NP ) mediates the nuclear import of the vRNP complex via its n...	[ "Influenza viral RNA is encapsidated by three polymerase proteins and the NP protein to form the vRNP complex , which is transported to the nucleus of infected cells for viral transcription and replication .", "The active nuclear import of the vRNP complex is mediated by the interaction between NP and importin α ...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genome-wide association studies", "population genetics", "mathematics", "statistics (mathematics)", "test statistics", "genome analysis", "population biology", "research and analysis methods", "statistical distributions", "lipids", "fats", "mathematical and statistical techniques", "statist...	Accounting for Population Structure in Gene-by-Environment Interactions in Genome-Wide Association Studies Using Mixed Models	journal.pgen.1005849	null	[ [ "Over the past decade , genome-wide association studies ( GWASs ) have been a predominant approach to identify genetic variants involved in many complex traits and diseases .", "[1–3] While GWASs have discovered associations of many genetic variants , a large proportion of phenotypic variance for most tra...	[ "Although genome-wide association studies ( GWASs ) have discovered numerous novel genetic variants associated with many complex traits and diseases , those genetic variants typically explain only a small fraction of phenotypic variance .", "Factors that account for phenotypic variance include environmental facto...	[ "Although genome-wide association studies ( GWASs ) have discovered numerous novel genetic variants associated with many complex traits and diseases , those genetic variants typically explain only a small fraction of phenotypic variance .", "Factors that account for phenotypic variance include environmental facto...	2016
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "ecology and environmental sciences", "gene regulation", "brassica", "rna extraction", "plant physiology", "suppressor genes", "plant science", "model organisms", "experimental organism systems", "gene types", "plant pathology", "seedlings", "plant ecology", "plants", "extraction techniq...	An Arabidopsis Nucleoporin NUP85 modulates plant responses to ABA and salt stress	journal.pgen.1007124	null	[ [ "Nucleocytoplasmic transport plays vital roles in eukaryotic systems [1 , 2] .", "The exchange of macromolecules such as RNAs and proteins is predominantly regulated by highly conserved nuclear pore complexes ( NPCs ) , which consist of multi-nucleoporins ( Nups ) arranged in distinct sub-complexes [3 , 4...	[ "Several nucleoporins in the nuclear pore complex ( NPC ) have been reported to be involved in abiotic stress responses in plants .", "However , the molecular mechanism of how NPC regulates abiotic stress responses , especially the expression of stress responsive genes remains poorly understood .", "From a forw...	[ "Nuclear pore complex ( NPC ) mediates the traffic between nucleus and cytoplasm .", "This work identified NUCLEOPORIN 85 ( NUP85 ) as an important factor for the expression of stress-responsive luciferase reporter gene RD29A-LUC in response to ABA and salt stress from a forward genetics screen .", "Mutation in...	2017
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "blood cells", "cell death", "medicine and health sciences", "immune cells", "microtubules", "cell cycle and cell division", "cell processes", "immunology", "immunoprecipitation", "epigenetics", "dna", "molecular biology techniques", "cellular structures and organelles", "dna methylation",...	EBNA3C facilitates RASSF1A downregulation through ubiquitin-mediated degradation and promoter hypermethylation to drive B-cell proliferation	journal.ppat.1007514	null	[ [ "Epstein-Barr virus ( EBV ) , a double-stranded DNA gammaherpesvirus , was the first recognized and one of the most common oncogenic viruses in humans [1] .", "It contributes to multiple lymphoid and epithelial malignancies , including Burkitt’s lymphoma ( BL ) , gastric cancer ( GC ) , nasopharyngeal car...	[ "EBV latent antigen 3C ( EBNA3C ) is essential for EBV-induced primary B-cell transformation .", "Infection by EBV induces hypermethylation of a number of tumor suppressor genes , which contributes to the development of human cancers .", "The Ras association domain family isoform 1A ( RASSF1A ) is a cellular tu...	[ "Epstein-Barr virus ( EBV ) which is associated with multiple lymphoid and epithelial malignancies was the first recognized oncogenic virus in humans .", "EBNA3C , an essential latent antigen encoded by EBV interacts with numerous host transcription factors and plays an important role in the transformation of pri...	2019
[ "Introduction", "Materials and methods", "Results", "Discussion" ]	[ "medicine and health sciences", "immune physiology", "enzyme-linked immunoassays", "pathology and laboratory medicine", "pathogens", "vibrio", "immunology", "tropical diseases", "microbiology", "vaccines", "diarrhea", "bacterial diseases", "vibrio cholerae", "signs and symptoms", "gastro...	Anti-O-specific polysaccharide (OSP) immune responses following vaccination with oral cholera vaccine CVD 103-HgR correlate with protection against cholera after infection with wild-type Vibrio cholerae O1 El Tor Inaba in North American volunteers	journal.pntd.0006376	null	[ [ "Vibrio cholerae can be characterized into over 200 serogroups [1] .", "V . cholerae serogroups O1 and O139 are the causes of epidemic cholera , a severe dehydrating illness of humans [2] .", "V . cholerae O1 and O139 are noninvasive intestinal pathogens that express cholera toxin within the intestine...	[ "Cholera is an acute voluminous dehydrating diarrheal disease caused by toxigenic strains of Vibrio cholerae O1 and occasionally O139 .", "A growing body of evidence indicates that immune responses targeting the O-specific polysaccharide ( OSP ) of V . cholerae are involved in mediating protection against cholera...	[ "Cholera is a severe watery diarrheal disease , caused by pathogenic strains of V . cholerae .", "Protective immunity against cholera is serogroup specific , and serogroup specificity is determined by the O-specific polysaccharide ( OSP ) of V . cholerae lipopolysaccharide ( LPS ) .", "Despite this , no previou...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine and health sciences", "pathology and laboratory medicine", "host-pathogen interactions", "medical microbiology", "microbial pathogens", "biology and life sciences", "microbiology", "pathogenesis", "bacterial pathogens" ]	The Machinery at Endoplasmic Reticulum-Plasma Membrane Contact Sites Contributes to Spatial Regulation of Multiple Legionella Effector Proteins	journal.ppat.1004222	null	[ [ "Intracellular pathogens co-opt host processes to facilitate pathogen survival and replication within the eukaryotic host .", "To do this , many bacterial pathogens possess secretion systems that transport bacterial proteins into host cells to orchestrate their intracellular survival .", "After uptake...	[ "The Dot/Icm system of the intracellular pathogen Legionella pneumophila has the capacity to deliver over 270 effector proteins into host cells during infection .", "Important questions remain as to spatial and temporal mechanisms used to regulate such a large array of virulence determinants after they have been ...	[ "The intracellular pathogen Legionella pneumophila encodes at least 270 effectors that modulate trafficking of the pathogen-occupied vacuole .", "The mechanisms by which effectors are controlled in host cells are of key interest .", "Spatial and temporal regulation of effector function has been proposed to invo...	2014
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "genome-wide association studies", "medicine and health sciences", "gene regulation", "computational biology", "renal cancer", "alleles", "genetic mapping", "genome analysis", "epigenetics", "chromatin", "small interfering rnas", "chromosome biology", "gene expression", "genetic loci", "...	Multiple renal cancer susceptibility polymorphisms modulate the HIF pathway	journal.pgen.1006872	null	[ [ "Successive advances in genetic analysis have provided insights into the biology of cancer .", "To date , such analyses have focused mainly on mutations that affect the integrity of transcribed genes .", "In contrast , it has so far proved difficult to interpret alterations in extragenic sequences , d...	[ "Un-physiological activation of hypoxia inducible factor ( HIF ) is an early event in most renal cell cancers ( RCC ) following inactivation of the von Hippel-Lindau tumor suppressor .", "Despite intense study , how this impinges on cancer development is incompletely understood .", "To test for the impact of ge...	[ "Though numerous DNA polymorphisms that modulate the risk of developing cancer have been identified , understanding the functional role of extra-genic variation has so far proved difficult , in part because it is difficult to link such variation to a functional framework .", "To address this , we aligned extragen...	2017
[ "Introduction", "Results", "Discussion", "Material and methods" ]	[ "invertebrates", "medicine and health sciences", "vesicles", "ocular anatomy", "social sciences", "neuroscience", "animals", "pigments", "animal models", "drosophila melanogaster", "model organisms", "materials science", "experimental organism systems", "energy-producing organelles", "mi...	Physiological and pathological roles of FATP-mediated lipid droplets in Drosophila and mice retina	journal.pgen.1007627	null	[ [ "Photoreceptor neurons are among the highest energy consumers in the body .", "They are sustained by a layer of retinal pigment epithelial cells ( here termed retinal pigment cells [RPC] , S1 Fig ) that provide photoreceptors with a constant supply of substrates for energy production by mitochondrial oxid...	[ "Increasing evidence suggests that dysregulation of lipid metabolism is associated with neurodegeneration in retinal diseases such as age-related macular degeneration and in brain disorders such as Alzheimer’s and Parkinson’s diseases .", "Lipid storage organelles ( lipid droplets , LDs ) , accumulate in many cel...	[ "Lipids are major cell constituents and are present in the membranes , as free lipids in the cytoplasm , or stored in vesicles called lipid droplets ( LDs ) .", "Under conditions of stress , lipids stored in LDs can be released to serve as substrates for energy metabolism by mitochondria .", "However , lipid st...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "virology/virus evolution and symbiosis", "virology/immunodeficiency viruses", "virology/animal models of infection", "virology/mechanisms of resistance and susceptibility, including host genetics", "virology/immune evasion" ]	Species-Specific Activity of SIV Nef and HIV-1 Vpu in Overcoming Restriction by Tetherin/BST2	journal.ppat.1000429	null	[ [ "Efforts to elucidate the function of the HIV-1 Vpu protein recently led to the identification of an interferon-inducible , host-cell factor that interferes with the detachment of virions from infected cells [1] , [2] .", "Vpu-deleted strains of HIV-1 exhibit a cell-type dependent defect in the release of...	[ "Tetherin , also known as BST2 , CD317 or HM1 . 24 , was recently identified as an interferon-inducible host–cell factor that interferes with the detachment of virus particles from infected cells .", "HIV-1 overcomes this restriction by expressing an accessory protein , Vpu , which counteracts tetherin .", "Sin...	[ "Tetherin was recently identified as a host–cell factor that interferes with the detachment of virus particles from infected cells .", "HIV-1 overcomes the antiviral effects of tetherin by expressing Vpu , which mediates the degradation of tetherin .", "While tetherin has broad activity against diverse types of...	2009
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "medicine and health sciences", "ocular anatomy", "social sciences", "neuroscience", "animal models", "retinal disorders", "age groups", "developmental biology", "adults", "model organisms", "experimental organism systems", "eyes", "cellular structures and organelles", "morphogenesis", "...	BBSome function is required for both the morphogenesis and maintenance of the photoreceptor outer segment	journal.pgen.1007057	null	[ [ "Photoreceptor outer segments are a specialized cellular compartment organized into stacked membranous discs where proteins for the initiation of the phototransduction cascade are enriched .", "Proteins that do not have an active role in the outer segment are excluded from this compartment , and are retai...	[ "Genetic mutations disrupting the structure and function of primary cilia cause various inherited retinal diseases in humans .", "Bardet-Biedl syndrome ( BBS ) is a genetically heterogeneous , pleiotropic ciliopathy characterized by retinal degeneration , obesity , postaxial polydactyly , intellectual disability ...	[ "The BBSome is a protein complex that regulates ciliary trafficking in primary cilia , and mutations that impair BBSome function cause Bardet-Biedl Syndrome ( BBS ) .", "BBS patients have retinal degeneration leading to blindness , but the disease pathophysiology has not been fully elucidated .", "In this study...	2017
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "applied mathematics", "brassica", "sequence assembly tools", "simulation and modeling", "algorithms", "alternative splicing", "optimization", "model organisms", "mathematics", "experimental organism systems", "genome analysis", "plants", "research and analysis methods", "arabidopsis thali...	Strawberry: Fast and accurate genome-guided transcript reconstruction and quantification from RNA-Seq	journal.pcbi.1005851	null	[ [ "Strawberry consists of two modules: assembly module and quantification module .", "The two modules work in a sequential manner ( Fig 1 ) .", "Strawberry is a genome-guided transcript-level assembler and quantification tool .", "It takes aligned RNA-Seq data in BAM format and output a gene annotat...	[ "We propose a novel method and software tool , Strawberry , for transcript reconstruction and quantification from RNA-Seq data under the guidance of genome alignment and independent of gene annotation .", "Strawberry consists of two modules: assembly and quantification .", "The novelty of Strawberry is that the...	[ "Transcript assembly and quantification are important bioinformatics applications of RNA-Seq .", "The difficulty of solving these problem arises from the ambiguity of reads assignment to isoforms uniquely .", "This challenge is twofold: statistically , it requires a high-dimensional mixture model , and computat...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "molecular cell biology", "cell biology", "cell adhesion", "virology", "gene expression", "biology", "microbiology", "host-pathogen interaction", "molecular biology", "dna transcription" ]	The Human Papillomavirus E6 Oncogene Represses a Cell Adhesion Pathway and Disrupts Focal Adhesion through Degradation of TAp63β upon Transformation	journal.ppat.1002256	null	[ [ "Infection of the anogenital mucosal epithelium with high risk Human Papilloma Virus ( HPV ) is linked to 99% of cervical carcinomas [1] .", "Cell lines derived from these cervical carcinomas remain associated with HPV and contain part of the viral genome integrated in the cellular genome .", "However...	[ "Cervical carcinomas result from cellular transformation by the human papillomavirus ( HPV ) E6 and E7 oncogenes which are constitutively expressed in cancer cells .", "The E6 oncogene degrades p53 thereby modulating a large set of p53 target genes as shown previously in the cervical carcinoma cell line HeLa .", ...	[ "High-risk human papillomavirus infection can cause cancer of the uterine cervix .", "The viral proteins leading to transformation of the infected keratinocytes are the E6 and E7 oncogenes which interact with and induce degradation of the cell cycle regulators p53 and pRB .", "In cervical carcinoma cells , repr...	2011
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "invertebrates", "typhus", "medicine and health sciences", "china", "atmospheric science", "geographical locations", "vertebrates", "animals", "mammals", "bacterial diseases", "materials science", "surface properties", "humidity", "surface temperature", "climate change", "infectious di...	Climate variability, animal reservoir and transmission of scrub typhus in Southern China	journal.pntd.0005447	null	[ [ "Scrub typhus , also known as tsutsugamushi disease , is a rickettsial disease that is highly endemic in East Asia and the western Pacific Ocean areas [1] .", "In recent years , scrub typhus has been increasingly reported and has become a significant health concern in China[2–5] .", "Currently , scrub...	[ "We aimed to evaluate the relationships between climate variability , animal reservoirs and scrub typhus incidence in Southern China .", "We obtained data on scrub typhus cases in Guangzhou every month from 2006 to 2014 from the Chinese communicable disease network .", "Time-series Poisson regression models and...	[ "Scrub typhus has been endemic in southern China for several decades .", "In recent years , it has been increasingly reported and has become a significant health concern in China .", "The incidence of scrub typhus , a vector-borne disease , is influenced by the density of rats and changes in climate .", "Seve...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "infectious diseases/helminth infections", "ecology/evolutionary ecology", "infectious diseases/epidemiology and control of infectious diseases", "infectious diseases/neglected tropical diseases" ]	Bidirectional Introgressive Hybridization between a Cattle and Human Schistosome Species	journal.ppat.1000571	null	[ [ "The increasing use of molecular techniques in ecological studies has revealed many cases of hybridization and introgression in plants and animals [1]–[3] , but examples in metazoan parasites are rare [2] .", "Hybridization can have a major impact on adaptive radiation and diversification of the species u...	[ "Schistosomiasis is a disease of great medical and veterinary importance in tropical and subtropical regions , caused by parasitic flatworms of the genus Schistosoma ( subclass Digenea ) .", "Following major water development schemes in the 1980s , schistosomiasis has become an important parasitic disease of chil...	[ "Schistosome blood flukes cause significant disease in humans and their livestock in tropical and subtropical regions of the world .", "They have a two host-life cycle with a sexual stage within the mammalian host and are transmitted through water contact .", "Understanding the biology of these dioecious parasi...	2009
[ "Introduction", "Results/Discussion", "Materials and Methods" ]	[ "genetics and genomics/microbial evolution and genomics", "molecular biology/molecular evolution", "genetics and genomics/population genetics" ]	Selection at a Single Locus Leads to Widespread Expansion of Toxoplasma gondii Lineages That Are Virulent in Mice	journal.pgen.1000404	null	[ [ "Toxoplasma gondii provides a valuable model for studying the evolution of pathogens because it is widespread and infects virtually all warm-blooded vertebrates , including companion and agricultural animals .", "This remarkably successful parasite is easily acquired by ingesting either oocysts ( excreted...	[ "Pathogenicity differences among laboratory isolates of the dominant clonal North American and European lineages of Toxoplasma gondii are largely controlled by polymorphisms and expression differences in rhoptry secretory proteins ( ROPs ) .", "However , the extent to which such differences control virulence in n...	[ "The determinants of virulence are rarely defined for eukaryotic parasites such as T . gondii , a widespread parasite of mammals that also infects humans , sometimes with serious consequences .", "Recent laboratory studies have established that variation in a single secreted protein , a serine/threonine kinase kn...	2009
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine", "immune cells", "clinical immunology", "immunology", "biology" ]	TGF-β1 Down-Regulation of NKG2D/DAP10 and 2B4/SAP Expression on Human NK Cells Contributes to HBV Persistence	journal.ppat.1002594	null	[ [ "Hepatitis B virus ( HBV ) infects more than 350 million people worldwide , accounting for over 1 million deaths annually due to immune-mediated chronic liver damage [1]–[3] .", "The course of HBV infection is complicated .", "Three phases of chronic HBV ( CHB ) infection are now widely accepted:", ...	[ "The mechanism underlying persistent hepatitis B virus ( HBV ) infection remains unclear .", "We investigated the role of innate immune responses to persistent HBV infection in 154 HBV-infected patients and 95 healthy controls .", "The expression of NKG2D- and 2B4-activating receptors on NK cells was significan...	[ "NK cells have been viewed as the most important effectors of the initial antiviral innate immune response .", "Their activation depends on the integration of signals from “co-activation” receptors , and the cytotoxic effects of NK cells on target cells are tempered by a need for combined signals from multiple ac...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "molecular cell biology", "immunology", "biology", "microbiology" ]	DHX36 Enhances RIG-I Signaling by Facilitating PKR-Mediated Antiviral Stress Granule Formation	journal.ppat.1004012	null	[ [ "Cellular responses against various stresses are crucial for maintaining homeostasis .", "Virus infection is one class of cellular stress that induces a number of host responses through the activation of pattern recognition receptors ( PRRs ) , which detect pathogen-associated molecular patterns ( PAMPs )...	[ "RIG-I is a DExD/H-box RNA helicase and functions as a critical cytoplasmic sensor for RNA viruses to initiate antiviral interferon ( IFN ) responses .", "Here we demonstrate that another DExD/H-box RNA helicase DHX36 is a key molecule for RIG-I signaling by regulating double-stranded RNA ( dsRNA ) -dependent pro...	[ "Cellular responses to environmental stress are critical for maintaining homeostasis in living organisms .", "In one type of response , eukaryotic cells exhibit rapid formation of aggregates with RNA and multiple RNA-binding proteins in the cytoplasm termed stress granules ( SGs ) .", "Over the past decade , SG...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "rna transport", "macromolecular assemblies", "microbiology", "gene function", "model organisms", "gene expression", "biology", "biochemistry", "rna", "nucleic acids", "genetic screens", "genetics", "yeast and fungal models", "saccharomyces cerevisiae", "genetics and genomics" ]	Role of Mex67-Mtr2 in the Nuclear Export of 40S Pre-Ribosomes	journal.pgen.1002915	null	[ [ "All living cells expend a significant proportion of their cellular energy to manufacture ribosomal subunits [1] .", "To construct ribosomal subunits , eukaryotic cells assemble >70 ribosomal proteins ( r-proteins ) with four different ribosomal RNA ( rRNA ) species [2] , [3] .", "Transcription machin...	[ "Nuclear export of mRNAs and pre-ribosomal subunits ( pre40S and pre60S ) is fundamental to all eukaryotes .", "While genetic approaches in budding yeast have identified bona fide export factors for mRNAs and pre60S subunits , little is known regarding nuclear export of pre40S subunits .", "The yeast heterodime...	[ "Eukaryotic pre-ribosomal subunits ( pre40S and pre60S ) are one of the largest RNA containing cargos that are transported from the nucleus through the nuclear pore complex ( NPC ) into the cytoplasm .", "While genetic approaches in budding yeast have identified bona fide export factors for pre60S subunits , litt...	2012
[ "Introduction", "Methods", "Results", "Discussion", "Final Conclusions" ]	[]	A Review of Factors That Influence Individual Compliance with Mass Drug Administration for Elimination of Lymphatic Filariasis	journal.pntd.0002447	null	[ [ "The Global Programme to Eliminate Lymphatic Filariasis ( GPELF ) is one of the most ambitious , exciting , and challenging public health programs of our time .", "Part of the challenge is in the large numbers of people that either have lymphatic filariasis ( LF ) ( an estimated 120 million ) or who are a...	[ "The success of programs to eliminate lymphatic filariasis ( LF ) depends in large part on their ability to achieve and sustain high levels of compliance with mass drug administration ( MDA ) .", "This paper reports results from a comprehensive review of factors that affect compliance with MDA .", "Papers publi...	[ "Lymphatic filariasis ( LF , also known as “elephantiasis” ) is a deforming and disabling disease that is caused by roundworm parasites that are transmitted by mosquitoes .", "The Global Programme to Eliminate Lymphatic Filariasis is the largest public health intervention program attempted to date based on mass d...	2013
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[]	Differential Impact of LPG-and PG-Deficient Leishmania major Mutants on the Immune Response of Human Dendritic Cells	journal.pntd.0004238	null	[ [ "Leishmaniasis constitutes a group of vector-borne parasitic diseases that affects approximately 12 million people worldwide and results in diverse clinical pathologies [1] .", "The causative intracellular protozoa belonging to the genus Leishmania , generally dictate disease outcome in a distinct species...	[ "Leishmania major infection induces robust interleukin-12 ( IL12 ) production in human dendritic cells ( hDC ) , ultimately resulting in Th1-mediated immunity and clinical resolution .", "The surface of Leishmania parasites is covered in a dense glycocalyx consisting of primarily lipophosphoglycan ( LPG ) and oth...	[ "Leishmaniasis is a group of parasitic diseases caused by intracellular protozoa belonging to the genus Leishmania , pathological manifestations ranging from self-healing cutaneous forms to severe visceral infections that result in death .", "These clinical outcomes are dictated by the Leishmania species initiati...	2015
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "computational biology/synthetic biology", "computational biology/systems biology", "mathematics", "computational biology/metabolic networks", "biotechnology/bioengineering", "biochemistry/theory and simulation", "biochemistry/transcription and translation", "biophysics/transcription and translation",...	The Origins of Time-Delay in Template Biopolymerization Processes	journal.pcbi.1000726	null	[ [ "Time-delay models are common in mathematical biology , as is demonstrated by the use of mathematical models incorporating time-delays in a wide range of applications .", "These include population dynamics , the chemostat , neural networks , blood cell maturation , transcriptional regulator dynamics , vir...	[ "Time-delays are common in many physical and biological systems and they give rise to complex dynamic phenomena .", "The elementary processes involved in template biopolymerization , such as mRNA and protein synthesis , introduce significant time delays .", "However , there is not currently a systematic mapping...	[ "Genetic networks display exceedingly complex and rich behavior which is modulated by multiple mechanisms , including many diverse types of interactions between DNA , mRNA and protein molecules .", "Mathematical models of gene networks must necessarily consider the essential mechanistic details of the processes i...	2010
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine", "biology" ]	Down-Regulating Sphingolipid Synthesis Increases Yeast Lifespan	journal.pgen.1002493	null	[ [ "Most of us dream of a long life and wonder if we can increase our time on earth .", "Except for caloric restriction ( CR ) , there has been little prospect for increasing lifespan .", "But recent studies offer hope for developing drugs that increase lifespan by reducing the incidence of age-related d...	[ "Knowledge of the mechanisms for regulating lifespan is advancing rapidly , but lifespan is a complex phenotype and new features are likely to be identified .", "Here we reveal a novel approach for regulating lifespan .", "Using a genetic or a pharmacological strategy to lower the rate of sphingolipid synthesis...	[ "Studies with rats in the 1930s showed a surprising increase in lifespan when the diet contained 30%–40% fewer calories than normal .", "This experiment has been repeated on many organisms and is the gold standard for extending lifespan .", "While we are beginning to understand how calorie restriction regulates...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "evolutionary modeling", "biology", "computational biology" ]	Selection for Replicases in Protocells	journal.pcbi.1003051	null	[ [ "The origin of life must have required a series of transitions building new levels of molecular interaction .", "However , a tension often exists between the fitness of an individual sequence and the fitness of the collective [1] , [2] .", "This tension would be important for the earliest replicase en...	[ "We consider a world of nucleotide sequences and protocells .", "The sequences have the property of spontaneous self-replication .", "Some sequences - so-called replicases - have enzymatic activity in the sense of enhancing the replication rate of all ( or almost all ) sequences .", "In a well-mixed medium , ...	[ "The origin of life , proceeding from chemical reactions to cells , must have included a critical transitional period in which catalytically active sequences arose .", "A fundamental problem exists for the first catalytic sequences: their activity would not enhance their own fitness directly , and might even decr...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "viruses", "medicine and health sciences", "pathology and laboratory medicine", "medical microbiology", "viral pathogens", "microbial pathogens", "pathogens", "biology and life sciences", "microbiology", "kaposi's sarcoma-associated herpesvirus", "herpesviruses", "organisms" ]	Kaposi's Sarcoma-Associated Herpesvirus Induces Nrf2 during De Novo Infection of Endothelial Cells to Create a Microenvironment Conducive to Infection	journal.ppat.1004460	null	[ [ "Kaposi's sarcoma-associated herpesvirus ( KSHV ) or human herpesvirus 8 ( HHV-8 ) , a γ-2 lymphotropic herpesvirus with a double-stranded DNA genome of ∼160 kb in length , is the etiological agent of hyper-proliferative disorders such as Kaposi's sarcoma ( KS ) , primary effusion B-cell lymphoma ( PEL ) , an...	[ "Kaposi's sarcoma-associated herpesvirus ( KSHV ) is the etiological agent of Kaposi's sarcoma ( KS ) and primary effusion B-cell lymphoma .", "KSHV induces reactive oxygen species ( ROS ) early during infection of human dermal microvascular endothelial ( HMVEC-d ) cells that are critical for virus entry .", "O...	[ "KSHV infection of endothelial cells in vivo causes Kaposi's sarcoma and understanding the steps involved in de novo KSHV infection of these cells and the consequences is important to develop therapies to counter KSHV pathogenesis .", "Infection of endothelial cells in vitro is preceded by the induction of a netw...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "blood cells", "cell physiology", "medicine and health sciences", "immune cells", "pathology and laboratory medicine", "pathogens", "immunology", "microbiology", "cloning", "retroviruses", "viruses", "immunodeficiency viruses", "rna viruses", "molecular biology techniques", "research and...	A Conserved HIV-1-Derived Peptide Presented by HLA-E Renders Infected T-cells Highly Susceptible to Attack by NKG2A/CD94-Bearing Natural Killer Cells	journal.ppat.1005421	null	[ [ "It was realized even as early as the mid-1980s that HIV-1-infected cells are refractory to Natural Killer ( NK ) cell-induced lysis [1 , 2] .", "About fifteen years later it was revealed that HIV-1 selectively down-modulates HLA-A and -B to avoid cytotoxic T-lymphocyte ( CTL ) while leaving HLA-C and -E ...	[ "Major histocompatibility class I ( MHC-I ) -specific inhibitory receptors on natural killer ( NK ) cells ( iNKRs ) tolerize mature NK cell responses toward normal cells .", "NK cells generate cytolytic responses to virus-infected or malignant target cells with altered or decreased MHC-I surface expression due to...	[ "A critical mechanism by which the immune system controls viruses is through destruction of infected cells .", "One way to avoid cytotoxic T-lymphocytes ( CTL ) is by down modulating ligands that present virus peptides , the major histocompatibility complex class I molecules ( MHC-I ) .", "However , MHC-I negat...	2016
[ "Introduction", "Results/Discussion", "Methods" ]	[ "biophysics/protein folding", "biophysics/experimental biophysical methods", "biophysics/theory and simulation", "computational biology/molecular dynamics", "physics/interdisciplinary physics" ]	Is Protein Folding Sub-Diffusive?	journal.pcbi.1000921	null	[ [ "A free energy surface ( FES ) projected onto one or a small number of coordinates is often used to describe the equilibrium and kinetic properties of complex systems with a very large number ( 100 to 1 , 000 or more ) of degrees of freedom .", "Studies of protein folding are an important case where this ...	[ "Protein folding dynamics is often described as diffusion on a free energy surface considered as a function of one or few reaction coordinates .", "However , a growing number of experiments and models show that , when projected onto a reaction coordinate , protein dynamics is sub-diffusive .", "This raises the ...	[ "To understand dynamics of complex systems with many degrees of freedom , one often projects it onto one or several collective variables .", "Protein folding , the complex , concerted motion of a protein chain towards a unique three-dimensional structure , is one example of where such reduction of complexity is u...	2010
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "infectious diseases/helminth infections", "molecular biology/molecular evolution" ]	The bandit, a New DNA Transposon from a Hookworm—Possible Horizontal Genetic Transfer between Host and Parasite	journal.pntd.0000035	null	[ [ "Almost one billion people throughout tropical and sub-tropical latitudes are infected with hookworms .", "In the countries affected , hookworm infection is often the major contributor to iron-deficiency anemia , a direct consequence of the parasite's blood-feeding activities [1] .", "Comparatively li...	[ "An enhanced understanding of the hookworm genome and its resident mobile genetic elements should facilitate understanding of the genome evolution , genome organization , possibly host-parasite co-evolution and horizontal gene transfer , and from a practical perspective , development of transposon-based transgenesi...	[ "Because of its importance to public health , the hookworm parasite has become the focus of increased research over the past decade—research that will ultimately decipher its genetic code .", "We now report a gene from hookworm chromosomes known as a transposon .", "Transposons are genes that can move around in...	2007
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "blood cells", "t helper cells", "humoral immunity", "medicine and health sciences", "parasite groups", "immune cells", "immune physiology", "plasmodium", "immunology", "tropical diseases", "cloning", "parasitic diseases", "parasitic protozoans", "parasitology", "apicomplexa", "protozo...	Type I Interferons Induce T Regulatory 1 Responses and Restrict Humoral Immunity during Experimental Malaria	journal.ppat.1005945	null	[ [ "Malaria , caused by mosquito-borne Plasmodium parasites , remains a significant burden on public health that is responsible for over 400 , 000 deaths annually [1] .", "Immunological studies in humans and mice have identified parasite-specific antibodies as critical for Plasmodium control and parasite cle...	[ "CD4 T cell-dependent antibody responses are essential for limiting Plasmodium parasite replication and the severity of malaria; however , the factors that regulate humoral immunity during highly inflammatory , Th1-biased systemic infections are poorly understood .", "Using genetic and biochemical approaches , we...	[ "Humoral immunity is essential for host resistance to pathogens that trigger highly inflammatory immune responses , including Plasmodium parasites , the causative agents of malaria .", "Long-lived , secreted antibody responses depend on a specialized subset of CD4 T cells called T follicular helper ( Tfh ) cells ...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "bacteriology", "bacterial physiology", "gram negative", "medical microbiology", "microbial pathogens", "biology and life sciences", "microbiology", "bacterial pathogens" ]	Concerted Spatio-Temporal Dynamics of Imported DNA and ComE DNA Uptake Protein during Gonococcal Transformation	journal.ppat.1004043	null	[ [ "Natural competence for transformation is widespread among different bacterial species [1] .", "Transformation is thought to speed up adaptive evolution but it is also discussed in the context of genome maintenance [2] [3] .", "The currently available data from Gram-positive species strongly supports ...	[ "Competence for transformation is widespread among bacterial species .", "In the case of Gram-negative systems , a key step to transformation is the import of DNA across the outer membrane .", "Although multiple factors are known to affect DNA transport , little is known about the dynamics of DNA import .", "...	[ "Bacterial transformation is the import and inheritable integration of external DNA .", "As such , it is believed to be a major evolutionary force .", "A key step is the import of DNA through the outer membrane .", "Here , we have characterized the spatio-temporal dynamics of DNA during import and residence i...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	ZASC1 Stimulates HIV-1 Transcription Elongation by Recruiting P-TEFb and TAT to the LTR Promoter	journal.ppat.1003712	null	[ [ "The Retroviridae family includes human immunodeficiency viruses type-1 and 2 ( HIV-1 and HIV-2 ) , the causative agents of acquired immune deficiency syndrome ( AIDS ) .", "Retroviruses are unique among RNA viruses in that after virus entry into the cell , the viral RNA is reverse transcribed into double...	[ "Transcription from the HIV-1 LTR promoter efficiently initiates but rapidly terminates because of a non-processive form of RNA polymerase II .", "This premature termination is overcome by assembly of an HIV-1 TAT/P-TEFb complex at the transactivation response region ( TAR ) , a structured RNA element encoded by ...	[ "The human immunodeficiency virus 1 ( HIV-1 ) promoter exhibits a strong block to transcription elongation that is a critical regulator of the viral life cycle .", "Failure to overcome this restriction during provirus establishment results in a transcriptionally silent , latent provirus .", "Similarly , reactiv...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "systems biology", "synthetic biology", "biology", "computational biology", "molecular biology", "genetics and genomics" ]	Fine-Tuning Tomato Agronomic Properties by Computational Genome Redesign	journal.pcbi.1002528	null	[ [ "Considering a cell as a DNA-based molecular factory [1] and applying principles drawn from industrial engineering provides new approaches to optimize cellular performance ( Figure S1 ) .", "This approach adopts the new philosophy implemented nowadays by large industries that is known as Lean Manufacturin...	[ "Considering cells as biofactories , we aimed to optimize its internal processes by using the same engineering principles that large industries are implementing nowadays: lean manufacturing .", "We have applied reverse engineering computational methods to transcriptomic , metabolomic and phenomic data obtained fr...	[ "Considering cells as biofactories , we aimed to optimize their internal processes by using existing design principles acquired from engineering .", "Herein , we present a synthetic biology approach based on experimental and computational methodology that integrates genomic , transcriptomic , metabolomic and phen...	2012
[ "Introduction", "Results", "Discussion", "Material and Methods" ]	[ "genetics and genomics/comparative genomics", "evolutionary biology/human evolution", "computational biology/comparative sequence analysis", "evolutionary biology/genomics", "computational biology/evolutionary modeling", "genetics and genomics/population genetics" ]	The Impact of Recombination on Nucleotide Substitutions in the Human Genome	journal.pgen.1000071	null	[ [ "Genomic landscapes are not uniform across vertebrate chromosomes .", "Notably , the genomes of amniotes ( mammals , birds and reptiles ) show a very strong heterogeneity of base composition along chromosomes ( the so-called isochores ) ( for review , [1] ) .", "These Mb-scale variations in GC-content...	[ "Unraveling the evolutionary forces responsible for variations of neutral substitution patterns among taxa or along genomes is a major issue for detecting selection within sequences .", "Mammalian genomes show large-scale regional variations of GC-content ( the isochores ) , but the substitution processes at the ...	[ "Mammalian genomes show a very strong heterogeneity of base composition along chromosomes ( the so-called isochores ) .", "The functional significance of these peculiar genomic landscapes is highly debated: do isochores confer some selective advantage , or are they simply the by-product of neutral evolutionary pr...	2008
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Mycobacterial MazG Safeguards Genetic Stability via Housecleaning of 5-OH-dCTP	journal.ppat.1003814	null	[ [ "Oxidative damage to DNA and the DNA precursors , deoxynucleotides ( dNTPs ) is an inevitable mutagenic challenge occurring in normal aerobic metabolism , generating a large amount of reactive oxygen species ( ROS ) as by-products during respiration or oxidation-reduction reaction [1]-[3] .", "Oxidative D...	[ "Generation of reactive oxygen species and reactive nitrogen species in phagocytes is an important innate immune response mechanism to eliminate microbial pathogens .", "It is known that deoxynucleotides ( dNTPs ) , the precursor nucleotides to DNA synthesis , are one group of the significant targets for these ox...	[ "The cellular nucleotide pool is a significant target for oxidation by reactive oxygen species and reactive nitrogen species .", "Misincorporation of these oxidized non-canonical nucleotides into DNA is known to cause mutations , and may be related to carcinogenesis , aging and neurodegeneration .", "Cells have...	2013
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "luciferase assay", "chemical compounds", "carbohydrates", "organic compounds", "glucose", "dna transcription", "circadian oscillators", "biochemical analysis", "fungi", "enzyme assays", "chronobiology", "epigenetics", "bioassays and physiological analysis", "chromatin", "research and an...	Transcriptional repression of frequency by the IEC-1-INO80 complex is required for normal Neurospora circadian clock function	journal.pgen.1006732	null	[ [ "From the filamentous fungus Neurospora crassa to animals , circadian oscillation is a conserved mechanism based on an auto-regulatory feedback loop composed of negative and positive elements [1–6] .", "In Neurospora , the heterodimeric WHITE COLLAR ( WC ) complex , consisting of WC-1 and WC-2 , acts as t...	[ "Rhythmic activation and repression of the frequency ( frq ) gene are essential for normal function of the Neurospora circadian clock .", "WHITE COLLAR ( WC ) complex , the positive element of the Neurospora circadian system , is responsible for stimulation of frq transcription .", "We report that a C2H2 finger...	[ "Circadian clocks organize inner physiology to anticipate changes in the external environment .", "These clocks are controlled by the oscillation of central clock proteins which form the central oscillator .", "Transcriptional regulation is a critical step in the regulation of the oscillation of these core prot...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine", "genome expression analysis", "pathology", "immunology", "cancer risk factors", "cancers and neoplasms", "biomarkers", "gastrointestinal tumors", "algorithms", "oncology", "general pathology", "genetics and genomics", "immunologic techniques", "immunohistochemical analysis", ...	Google Goes Cancer: Improving Outcome Prediction for Cancer Patients by Network-Based Ranking of Marker Genes	journal.pcbi.1002511	null	[ [ "In the past decade , several studies have used microarray gene expression data from tumors to predict the clinical outcome of patients ( see Table S1 ) .", "The tumors included breast cancer [1]–[5] , lung cancer [6]–[8] , lymphomas [9]–[13] , leukemia [14] , [15] , and others [16]–[18] .", "Outcome ...	[ "Predicting the clinical outcome of cancer patients based on the expression of marker genes in their tumors has received increasing interest in the past decade .", "Accurate predictors of outcome and response to therapy could be used to personalize and thereby improve therapy .", "However , state of the art met...	[ "Why do some people with the same type of cancer die early and some live long ?", "Apart from influences from the environment and personal lifestyle , we believe that differences in the individual tumor genome account for different survival times .", "Recently , powerful methods have become available to systema...	2012
[ "Introduction", "Results and Discussion", "Materials and Methods" ]	[ "bacteriology", "sequencing techniques", "gram negative bacteria", "horizontal gene transfer", "transcription activators", "evolutionary biology", "gene regulation", "plasmids", "nucleic acid sequencing", "dna-binding proteins", "microbiology", "gene transfer", "vibrio cholerae", "genetic ...	The Master Activator of IncA/C Conjugative Plasmids Stimulates Genomic Islands and Multidrug Resistance Dissemination	journal.pgen.1004714	null	[ [ "Multidrug resistance ( MDR ) is steadily increasing in Gram-negative bacteria in both community and hospital settings , and represents a growing concern worldwide [1] .", "MDR usually results from the adaptation of microorganisms through various mutations or from the acquisition of foreign DNA by horizon...	[ "Dissemination of antibiotic resistance genes occurs mostly by conjugation , which mediates DNA transfer between cells in direct contact .", "Conjugative plasmids of the IncA/C incompatibility group have become a substantial threat due to their broad host-range , the extended spectrum of antimicrobial resistance ...	[ "Multidrug resistance is a major health concern that complicates treatments of even the most common infections caused by bacteria .", "In recent years , IncA/C plasmids have emerged and spread in bacteria infecting humans , food-producing animals and food products , driving at the same time the dissemination of a...	2014
[ "Introduction", "Materials and methods", "Results", "Discussion" ]	[ "medicine and health sciences", "toxins", "pathology and laboratory medicine", "enzymes", "metalloproteases", "tropical diseases", "enzymology", "toxic agents", "toxicology", "collagens", "muscle regeneration", "developmental biology", "muscle proteins", "organism development", "neglecte...	Mechanisms underpinning the permanent muscle damage induced by snake venom metalloprotease	journal.pntd.0007041	null	[ [ "Snakebite envenomation is a recently reinstated neglected tropical disease [1] that causes around 100 , 000 deaths annually [2 , 3] and innumerable permanent disabilities predominantly on the rural population living in the lower income regions of the world [4–6] .", "The significant rate of mortality and...	[ "Snakebite is a major neglected tropical health issue that affects over 5 million people worldwide resulting in around 1 . 8 million envenomations and 100 , 000 deaths each year .", "Snakebite envenomation also causes innumerable morbidities , specifically loss of limbs as a result of excessive tissue/muscle dama...	[ "Snakebite is a major neglected tropical disease that affects thousands of people in the rural areas of developing countries .", "As well as the deaths , snakebites result in a significant number of disabilities including permanent loss of limbs that alter the lifestyle of the victims .", "Snake venom is a mixt...	2019
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "none", "computational biology" ]	Distributed Representations Accelerate Evolution of Adaptive Behaviours	journal.pcbi.0030147	null	[ [ "Before considering how FLL can accelerate evolution of certain types of behaviours , FLL will be described in its original context of spontaneous recovery of memory in humans [9] and in neural network models [10] .", "Note that FLL is not unique to a specific class of network architectures , although it ...	[ "Animals with rudimentary innate abilities require substantial learning to transform those abilities into useful skills , where a skill can be considered as a set of sensory–motor associations .", "Using linear neural network models , it is proved that if skills are stored as distributed representations , then wi...	[ "Some behaviours are purely innate ( e . g . , blinking ) , whereas other , “apparently innate , ” behaviours require a degree of learning to refine them into a useful skill ( e . g . , nest building ) .", "In terms of biological fitness , it matters how quickly such learning occurs , because time spent learning ...	2007
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "microarrays", "systems biology", "medicine", "chronic obstructive pulmonary diseases", "genomics", "functional genomics", "regulatory networks", "respiratory medicine", "biology", "computational biology", "pulmonology" ]	Suppressed Expression of T-Box Transcription Factors Is Involved in Senescence in Chronic Obstructive Pulmonary Disease	journal.pcbi.1002597	null	[ [ "Chronic obstructive pulmonary disease ( COPD ) is characterized by a progressive decline in lung function , with an irreversible airflow obstruction , caused either by chronic bronchitis , emphysema or both [1] .", "It is a leading cause of morbidity and mortality worldwide , and thus a global health pro...	[ "Chronic obstructive pulmonary disease ( COPD ) is a major global health problem .", "The etiology of COPD has been associated with apoptosis , oxidative stress , and inflammation .", "However , understanding of the molecular interactions that modulate COPD pathogenesis remains only partly resolved .", "We co...	[ "Chronic obstructive pulmonary disease or COPD is among the most lethal of respiratory diseases .", "While this disease has been well characterized , more studies are needed to learn the interaction of macromolecules involved in the progression towards illness .", "We explored possible interactions involved in ...	2012
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "learning", "medicine and health sciences", "neurogenesis", "neural networks", "nervous system", "brain", "social sciences", "electrophysiology", "neuroscience", "learning and memory", "cognitive psychology", "cognition", "network analysis", "memory", "granule cells", "computer and inf...	Top-down inputs drive neuronal network rewiring and context-enhanced sensory processing in olfaction	journal.pcbi.1006611	null	[ [ "A key property of the mammalian brain that is essential for its vast computational power is the pervasiveness of centrifugal , top-down feedback from higher to lower brain areas [1–5] .", "The top-down projections can provide the receiving brain area with information that is not available in the feedforw...	[ "Much of the computational power of the mammalian brain arises from its extensive top-down projections .", "To enable neuron-specific information processing these projections have to be precisely targeted .", "How such a specific connectivity emerges and what functions it supports is still poorly understood .",...	[ "In mammalian sensory processing , extensive top-down feedback from higher brain areas reshapes the feedforward , bottom-up information processing .", "The structure of the top-down connectivity , the mechanisms leading to its specificity , and the functions it supports are still poorly understood .", "Using co...	2019
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "growth plate", "cell death", "medicine and health sciences", "chondrocytes", "protein aggregation", "cell processes", "animal models", "model organisms", "bone", "connective tissue cells", "experimental organism systems", "bioassays and physiological analysis", "cartilage", "research and ...	XBP1 signalling is essential for alleviating mutant protein aggregation in ER-stress related skeletal disease	journal.pgen.1008215	null	[ [ "The unfolded protein response ( UPR ) is one of the canonical cellular stress pathways that is triggered by unfolded proteins accumulating in the ER lumen .", "The pathway is active in both health and disease and many secretory cells have a highly active UPR to allow a greater secretory output [1] .", ...	[ "The unfolded protein response ( UPR ) is a conserved cellular response to the accumulation of proteinaceous material in endoplasmic reticulum ( ER ) , active both in health and disease to alleviate cellular stress and improve protein folding .", "Multiple epiphyseal dysplasia ( EDM5 ) is a genetic skeletal condi...	[ "A significant proportion of genetic skeletal diseases result from misfolding of structural proteins within the endoplasmic reticulum ( ER ) of cartilage cells ( chondrocytes ) .", "Interestingly , these diseases often share transcriptomic changes with non-skeletal conditions such as Alzheimer’s disease and diabe...	2019

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