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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/Discussion", "Materials and Methods" ]	[ "infectious diseases", "evolutionary biology/evolutionary and comparative genetics" ]	A New Malaria Agent in African Hominids	journal.ppat.1000446	null	[ [ "Malaria is a major parasitic worldwide scourge , infecting and killing several million people each year [1] .", "Among the numerous Plasmodium species that infect reptiles , birds and mammals , four of them are human-specific: P . falciparum , P . vivax , P . malariae and P . ovale .", "The most viru...	[ "Plasmodium falciparum is the major human malaria agent responsible for 200 to 300 million infections and one to three million deaths annually , mainly among African infants .", "The origin and evolution of this pathogen within the human lineage is still unresolved .", "A single species , P . reichenowi , which...	[ "In 2002 , the publication of the genome of Plasmodium falciparum , the most malignant agent of malaria , generated hopes in the fight against this deadly disease by the opportunities it offered to discover new drug targets .", "Since then results have not lived up to the expectations .", "The development of co...	2009
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biomacromolecule-ligand interactions", "biochemistry", "enzyme structure", "cell motility", "actin filaments", "enzymes", "biology", "enzyme kinetics", "biophysics" ]	Direct Observation of the Myosin Va Recovery Stroke That Contributes to Unidirectional Stepping along Actin	journal.pbio.1001031	null	[ [ "Myosin is an ATP-driven linear molecular motor that produces force and unidirectional", "movement along actin filaments .", "The “swinging lever arm” hypothesis", "proposes that small nucleotide-dependent movements at the catalytic ATPase active", "site are amplified by rotation of the myosin...	[ "Myosins are ATP-driven linear molecular motors that work as cellular force", "generators , transporters , and force sensors .", "These functions are driven by", "large-scale nucleotide-dependent conformational changes , termed", "“strokes”; the “power stroke” is the force-generating", "swinging of the my...	[ "Myosin Va is a “two-legged” ATP-dependent linear molecular motor that", "transports cellular organelles by “stepping” along actin filaments", "in a processive manner analogous to human walking , the two “feet”", "alternating between forward and backward positions .", "During stepping , the lifted", "leg ...	2011
[ "Introduction", "Concluding Remarks" ]	[ "sequencing techniques", "parasite groups", "plasmodium", "gene regulation", "regulatory proteins", "dna-binding proteins", "parasitic protozoans", "parasitology", "developmental biology", "apicomplexa", "review", "protozoans", "transcription factors", "sequence motif analysis", "molecul...	Comparative Bioinformatics Analysis of Transcription Factor Genes Indicates Conservation of Key Regulatory Domains among Babesia bovis, Babesia microti, and Theileria equi	journal.pntd.0004983	null	[ [ "The presence of AP2 genes in apicomplexans was initially described by Balaji et al . [22] , who first reported the identification of members of the AP2 gene family in the genomes of Plasmodium , Theileria , Cryptosporidium , and Toxoplasma .", "Initial genome characterization in the B . bovis T2Bo strain...	[ "Apicomplexa tick-borne hemoparasites , including Babesia bovis , Babesia microti , and Theileria equi are responsible for bovine and human babesiosis and equine theileriosis , respectively .", "These parasites of vast medical , epidemiological , and economic impact have complex life cycles in their vertebrate an...	[ "The tick-borne apicomplexan parasites Babesia and Theileria are responsible for costly and devastating diseases globally .", "Improved control is needed , but the biology of these parasites remains poorly understood .", "Significant gaps include better understanding of the mechanisms involved in control of gen...	2016
[ "Introduction", "Results/Discussion", "Materials and Methods", "Supporting Information" ]	[ "evolutionary biology", "mus (mouse)" ]	Adaptive Variation in Beach Mice Produced by Two Interacting Pigmentation Genes	journal.pbio.0050219	Species of oldfield mice have coat colors adapted for their environment. By using genome-wide linkage mapping, the authors show that three chromosomal regions are associated with differences in pigmentation traits.	[ [ "Animal pigmentation has attracted substantial evolutionary interest because changes in color , be they driven by natural or sexual selection , can have profound effects on fitness .", "Dissecting the genetic basis of morphological variation , such as adaptive pigmentation , allows us to answer several lo...	[ "Little is known about the genetic basis of ecologically important morphological variation such as the diverse color patterns of mammals .", "Here we identify genetic changes contributing to an adaptive difference in color pattern between two subspecies of oldfield mice ( Peromyscus polionotus ) .", "One mainla...	[ "The tremendous amount of variation in color patterns among organisms helps individuals survive and reproduce in the wild , yet we know surprisingly little about the genes that produce these adaptive patterns .", "Here we used a genomic analysis to uncover the molecular basis of a pale color pattern that camoufla...	2007
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "death rates", "invertebrates", "medicine and health sciences", "markov models", "dose prediction methods", "applied mathematics", "tropical diseases", "social sciences", "parasitic diseases", "animals", "health care", "simulation and modeling", "algorithms", "mathematics", "ectoparasiti...	Scabies in residential care homes: Modelling, inference and interventions for well-connected population sub-units	journal.pcbi.1006046	null	[ [ "Stochastic ( random ) models play a pivotal role in the description of transmission and control of infection within small closely-connected populations .", "The typical example of such populations is households [2–5] , although the household methodology is generalisable to any well-connected population s...	[ "In the context of an ageing population , understanding the transmission of infectious diseases such as scabies through well-connected sub-units of the population , such as residential care homes , is particularly important for the design of efficient interventions to mitigate against the effects of those diseases ...	[ "Our work makes five main contributions .", "( 1 ) We study a previously under-modelled scenario—transmission of scabies in residential care homes—that is of significant and growing public health importance in the context of an ageing population .", "( 2 ) We develop a Markov-chain-based modelling framework tha...	2018
[ "Introduction", "Results", "Discussion", "Methods" ]	[]	Adaptation Dynamics in Densely Clustered Chemoreceptors	journal.pcbi.1003230	null	[ [ "High-resolution microscopy has revealed the exquisite spatial organization of signaling pathways and their molecular constituents .", "Understanding the computations performed by biological networks therefore requires taking the spatiotemporal organization of the reactants into account [1] .", "One f...	[ "In many sensory systems , transmembrane receptors are spatially organized in large clusters .", "Such arrangement may facilitate signal amplification and the integration of multiple stimuli .", "However , this organization likely also affects the kinetics of signaling since the cytoplasmic enzymes that modulat...	[ "To navigate their environments , organisms must remain sensitive to small changes in their surroundings while adapting to persistent conditions .", "Bacteria travel by performing a random walk biased toward nutrients and away from toxins .", "The decision of a bacterium to continue in a given direction or to r...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Smc5/6-Mms21 Prevents and Eliminates Inappropriate Recombination Intermediates in Meiosis	journal.pgen.1004067	null	[ [ "Sexual reproduction in eukaryotes relies on the generation of haploid gametes from diploid somatic cells by a process called meiosis .", "Meiosis achieves the required reduction in ploidy by executing a single round of DNA replication followed by two consecutive rounds of chromosome segregation .", "...	[ "Repairing broken chromosomes via joint molecule ( JM ) intermediates is hazardous and therefore strictly controlled in most organisms .", "Also in budding yeast meiosis , where production of enough crossovers via JMs is imperative , only a subset of DNA breaks are repaired via JMs , closely regulated by the ZMM ...	[ "Homologous recombination allows repair of DNA breaks from intact templates of identical sequence by a “copy-and-paste” like mechanism .", "However , the double Holliday Junction ( dHJ ) is a hazardous intermediate that can form during homologous recombination , if single stranded DNA from both ends of a lesion p...	2013
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "neuroscience/behavioral neuroscience", "neuroscience", "neuroscience/theoretical neuroscience" ]	An Imperfect Dopaminergic Error Signal Can Drive Temporal-Difference Learning	journal.pcbi.1001133	null	[ [ "In this article we focus on a specific variant of TD learning: the TD algorithm as implemented by the actor-critic architecture [36] .", "Here , we summarize the basic principles; a thorough introduction can be found in [1] .", "The goal of a TD learning agent , as for every reinforcement learning ag...	[ "An open problem in the field of computational neuroscience is how to link synaptic plasticity to system-level learning .", "A promising framework in this context is temporal-difference ( TD ) learning .", "Experimental evidence that supports the hypothesis that the mammalian brain performs temporal-difference ...	[ "What are the physiological changes that take place in the brain when we solve a problem or learn a new skill ?", "It is commonly assumed that behavior adaptations are realized on the microscopic level by changes in synaptic efficacies .", "However , this is hard to verify experimentally due to the difficulties...	2011
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "medicine", "infectious diseases", "neglected tropical diseases", "lymphatic filariasis" ]	The Impact of a Filariasis Control Program on Lihir Island, Papua New Guinea	journal.pntd.0001286	null	[ [ "Lymphatic filariasis ( LF ) , caused by the mosquito-borne nematode Wuchereria Bancrofti , is a major public-health problem in many tropical and subtropical regions .", "Papua New Guinea represents the biggest remaining challenge for elimination of the disease .", "The Global Program to Eliminate Lym...	[ "Annual mass drug administration ( MDA ) over five years is the WHO's recommended strategy to eliminate lymphatic filariasis ( LF ) .", "Some experts , however , consider that longer periods of treatment might be necessary in certain high prevalence and transmission environments based upon past unsuccessful field...	[ "Large-scale intervention programmes to control filariasis are currently underway worldwide .", "However , a major unresolved question remains: what is the appropriate duration for these programmes ?", "Recent theoretical work and clinical field experience has highlighted how the ecological diversity between di...	2011
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "agriculture", "biology" ]	A Rice Plastidial Nucleotide Sugar Epimerase Is Involved in Galactolipid Biosynthesis and Improves Photosynthetic Efficiency	journal.pgen.1002196	null	[ [ "Plants possess a sophisticated sugar biosynthetic machinery comprised of families of nucleotide sugars that can be modified at their glycosyl moieties by nucleotide sugar interconversion enzymes to generate different sugars [1] , [2] .", "UDP-glucose 4-epimerase ( also UDP-galactose 4-epimerase , UGE; EC...	[ "Photosynthesis is the final determinator for crop yield .", "To gain insight into genes controlling photosynthetic capacity , we selected from our large T-DNA mutant population a rice stunted growth mutant with decreased carbon assimilate and yield production named photoassimilate defective1 ( phd1 ) .", "Mole...	[ "Photosynthesis is carried out in chloroplast , a plant-specific organelle .", "Photosynthetic membranes in chloroplasts contain high levels of glycolipids , and UDP-galactose is a dominating donor for glycolipid biosynthesis .", "Although glycolipid assembly of photosynthetic membranes has been characterized a...	2011
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "kala-azar", "antimicrobials", "medicine and health sciences", "drugs", "tropical diseases", "microbiology", "geographical locations", "antifungals", "parasitic diseases", "data management", "pharmaceutics", "neglected tropical diseases", "pharmacology", "veterinary science", "bangladesh...	Relationship between treatment regimens for visceral leishmaniasis and development of post-kala-azar dermal leishmaniasis and visceral leishmaniasis relapse: A cohort study from Bangladesh	journal.pntd.0007653	null	[ [ "Visceral leishmaniasis ( VL ) or kala-azar has been a public health problem in Bangladesh over the centuries [1] .", "About 150 , 000 people have suffered from VL since 1994 in Bangaldesh [2] .", "Victims of VL are the poorest of the poor living in the rural areas of the country .", "The epidemio...	[ "We investigated the relationship of treatment regimens for visceral leishmaniasis ( VL ) with post-kala-azar dermal leishmaniasis ( PKDL ) and visceral leishmaniasis relapse ( VLR ) development .", "Study subjects included cohorts of patients cured of VL since treatment with monotherapy by sodium stibogluconate ...	[ "Post-kala-azar Dermal Leishmaniasis ( PKDL ) , a sequale of visceral leishmaniasis ( VL ) , and reappearance VL ( visceral leishmaniasis relapse , VLR ) are intra-epidemic reservoirs of VL and threats control of VL in long run .", "Currently there is no strategy for prevention of PKDL and VLR .", "If a relatio...	2019
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Broadly Neutralizing Antibody Responses in a Large Longitudinal Sub-Saharan HIV Primary Infection Cohort	journal.ppat.1005369	null	[ [ "The humoral immune response to HIV-1 infection comprises in a subset of individuals broad and potent neutralizing antibodies ( bnAbs ) [1–6] .", "The elicitation of such Abs prior to infection would presumably protect against infection by most circulating HIV strains and is thus considered one of the hig...	[ "Broadly neutralizing antibodies ( bnAbs ) are thought to be a critical component of a protective HIV vaccine .", "However , designing vaccines immunogens able to elicit bnAbs has proven unsuccessful to date .", "Understanding the correlates and immunological mechanisms leading to the development of bnAb respon...	[ "Understanding how HIV-1-broadly neutralizing antibodies ( bnAbs ) develop during natural infection is essential to the design of an efficient HIV vaccine .", "We studied kinetics and correlates of neutralization breadth in a large sub-Saharan African longitudinal cohort of 439 participants with primary HIV-1 inf...	2016
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "parasite groups", "medicine and health sciences", "immune physiology", "plasmodium", "immunology", "geographical locations", "tropical diseases", "parasitic diseases", "parasitology", "apicomplexa", "regional geography", "antibodies", "antibody response", "immune system proteins", "geog...	Naturally acquired antibody responses to more than 300 Plasmodium vivax proteins in three geographic regions	journal.pntd.0005888	null	[ [ "Plasmodium vivax is the most geographically widespread of the Plasmodium spp .", "causing malaria in humans , and accounts for the majority of cases outside Africa [1] .", "The leaders of Central American and East Asian countries have declared their intention for elimination of malaria within their r...	[ "Plasmodium vivax remains an important cause of malaria in South America and the Asia-Pacific .", "Naturally acquired antibody responses against multiple P . vivax proteins have been described in numerous countries , however , direct comparison of these responses has been difficult with different methodologies em...	[ "In the pursuit of eliminating all species of malaria , Plasmodium vivax presents one of the most substantial challenges , particularly in countries in Asia , the Western-Pacific and South America .", "This is primarily due to the ability of P . vivax to cause relapse infections months to years after the initial ...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "immunology", "biology" ]	The Molecular Basis for Recognition of CD1d/α-Galactosylceramide by a Human Non-Vα24 T Cell Receptor	journal.pbio.1001412	Human Vα24− CD1d-restricted T cells use variation in their CDR1α loop to respond to lipid antigens presented by CD1d, altering their specificities from that of invariant natural killer T cells.	[ [ "Natural killer T ( NKT ) cells are a highly conserved lineage of T lymphocytes found in both human and mice that are involved in the modulation of the immune response in autoimmunity , infection , and tumor development [1] .", "Unlike conventional CD4+ and CD8+ αβ T cells that recognize peptides presente...	[ "CD1d-mediated presentation of glycolipid antigens to T cells is capable of initiating powerful immune responses that can have a beneficial impact on many diseases .", "Molecular analyses have recently detailed the lipid antigen recognition strategies utilized by the invariant Vα24-Jα18 TCR rearrangements of iNKT...	[ "Certain lineages of T cells can recognize lipids as stimulatory antigens when presented in the context of CD1 molecules .", "We know how most Natural Killer T ( NKT ) cells react with this unusual ligand because they use a single invariant T cell receptor ( TCR ) alpha chain to do the job .", "NKT cells place ...	2012
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "invertebrates", "carbohydrate metabolism", "chemical compounds", "symbiosis", "statistics", "metaanalysis", "carbohydrates", "glucose metabolism", "animals", "organic compounds", "glucose", "organisms", "mathematics", "research and analysis methods", "amino acid metabolism", "mathemat...	Host-dependent nitrogen recycling as a mechanism of symbiont control in Aiptasia	journal.pgen.1008189	null	[ [ "The symbiotic relationship between photosynthetic dinoflagellates in the family Symbiodiniaceae [1] and corals is the foundation of the coral reef ecosystem .", "This metabolic symbiosis is thought to enable corals to thrive in the oligotrophic environment of tropical oceans by allowing efficient recycli...	[ "The metabolic symbiosis with photosynthetic algae allows corals to thrive in the oligotrophic environments of tropical seas .", "Different aspects of this relationship have been investigated using the emerging model organism Aiptasia .", "However , many fundamental questions , such as the nature of the symbiot...	[ "The symbiotic relationship with photosynthetic algae is key to the success of reef building corals in the nutrient poor environment of tropical waters .", "Extensive insight has been obtained from both physiological and “omics” level studies , yet , there are still gaps in our knowledge with respect to the metab...	2019
[ "Introduction", "Materials and methods", "Results", "Discussion" ]	[ "orchards", "medicine and health sciences", "infectious disease epidemiology", "kernel functions", "plant science", "farms", "probability distribution", "mathematics", "plant pathology", "infectious disease control", "infectious diseases", "operator theory", "probability density", "epidemi...	Estimation of the dispersal distances of an aphid-borne virus in a patchy landscape	journal.pcbi.1006085	null	[ [ "Infectious diseases of humans , animals and plants severely impact the world’s health and economy .", "To gain knowledge on disease dynamics , powerful mathematical models have been developed [1–3] .", "However , for predicting the relative efficacies of competing control strategies across realistic ...	[ "Characterising the spatio-temporal dynamics of pathogens in natura is key to ensuring their efficient prevention and control .", "However , it is notoriously difficult to estimate dispersal parameters at scales that are relevant to real epidemics .", "Epidemiological surveys can provide informative data , but ...	[ "In spatial epidemiology , dispersal kernels quantify how the probability of pathogen dissemination varies with distance from an infection source .", "Spatial models of pathogen spread are sensitive to kernel parameters; yet these parameters have rarely been estimated using field data gathered at relevant scales ...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "animal models", "medicine", "neurobiology of disease and regeneration", "model organisms", "neurological disorders", "neurology", "neurodegenerative diseases", "biology", "neuroscience", "cerebellar disorders" ]	Oxr1 Is Essential for Protection against Oxidative Stress-Induced Neurodegeneration	journal.pgen.1002338	null	[ [ "Reactive oxygen species ( ROS ) are the natural by-products of many essential biological processes such as mitochondrial respiration , although they are also potentially damaging to cells .", "Consequently , eukaryotic organisms have evolved a comprehensive range of proteins to detoxify ROS and repair ag...	[ "Oxidative stress is a common etiological feature of neurological disorders , although the pathways that govern defence against reactive oxygen species ( ROS ) in neurodegeneration remain unclear .", "We have identified the role of oxidation resistance 1 ( Oxr1 ) as a vital protein that controls the sensitivity o...	[ "Oxygen is vital for life , but it can also cause damage to cells .", "Consequently , protective proteins ( antioxidants ) are utilised to maintain the fine balance between oxygen metabolism and the production of potentially toxic reactive oxygen species ( ROS ) .", "If this balance is not maintained , oxidativ...	2011
[ "Background and motivation", "Discussion" ]	[ "learning", "education", "engineering and technology", "sociology", "social sciences", "teachers", "neuroscience", "learning and memory", "cell phones", "computers", "cognitive psychology", "research and analysis methods", "computer and information sciences", "bioinformatics", "human lea...	Bioinformatics calls the school: Use of smartphones to introduce Python for bioinformatics in high schools	journal.pcbi.1006473	null	[ [ "Biology-oriented programming workshops using Python for students and teachers were performed in one private and two public schools from La Plata , the capital city of the province of Buenos Aires , Argentina .", "These schools were selected on the basis of their willingness to take part in the project an...	[ "The dynamic nature of technological developments invites us to rethink the learning spaces .", "In this context , science education can be enriched by the contribution of new computational resources , making the educational process more up-to-date , challenging , and attractive .", "Bioinformatics is a key int...	[ "Bioinformatics is an interdisciplinary activity that complements and connects several fields with biology and can also be used as an educational tool for science .", "During 2017 , the Structural Bioinformatics Group at National University of Quilmes in Buenos Aires , Argentina , worked together with public and ...	2019
[ "Introduction", "Material and methods", "Results", "Discussion" ]	[ "medicine and health sciences", "body fluids", "pathology and laboratory medicine", "pathogens", "sociology", "tropical diseases", "microbiology", "geographical locations", "ebola hemorrhagic fever", "social sciences", "health care", "viruses", "filoviruses", "rna viruses", "neglected tr...	"We are survivors and not a virus:" Content analysis of media reporting on Ebola survivors in Liberia	journal.pntd.0005845	null	[ [ "The Ebola virus disease epidemic in West Africa 2013–2016 was unprecedented and resulted in over 28 . 000 cases .", "Up to 10 . 000 persons are estimated to have survived the disease [1] .", "In Liberia , there are over 1500 survivors registered in the database of the Liberian Ministry of Health [2] ...	[ "The Ebola virus disease epidemic between 2013 and 2016 in West Africa was unprecedented .", "It resulted in approximately 28 . 000 cases and 10 . 000 Ebola survivors .", "Many survivors face social , economic and health-related predicaments and media reporting is crucially important in infectious disease outbr...	[ "The largest Ebola epidemic occurred in West Africa between 2013 and 2016 .", "Liberia was one of the most affected countries with more than 1500 survivors registered .", "In the height of the Ebola outbreak survivors were increasingly included in the treatment and care of patients and in health sensitizing and...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "cell physiology", "invertebrates", "medicine and health sciences", "reproductive system", "senescence", "gonads", "caenorhabditis", "cell cycle and cell division", "cell processes", "animals", "germ cells", "animal models", "physiological processes", "developmental biology", "caenorhabd...	Intermittent Stem Cell Cycling Balances Self-Renewal and Senescence of the C. elegans Germ Line	journal.pgen.1005985	null	[ [ "An important goal of aging research is not just to extend lifespan—which in C . elegans can be simply achieved by a pause in developmental and reproductive activities in the “dauer” state [1]—but to do so in a way that increases “healthspan” without diminishing organ activity .", "To this end , it is cri...	[ "Self-renewing organs often experience a decline in function in the course of aging .", "It is unclear whether chronological age or external factors control this decline , or whether it is driven by stem cell self-renewal—for example , because cycling cells exhaust their replicative capacity and become senescent ...	[ "Stem cell cycling is expected to be beneficial because it helps delay aging , by ensuring organ self-renewal .", "Yet stem cell cycling is best used sparingly: cycling likely causes mutation accumulation—increasing the likelihood of cancer—and may eventually cause stem cells to senesce and thus stop contributing...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "blood cells", "cell motility", "medicine and health sciences", "immune cells", "classical mechanics", "fluid mechanics", "immunology", "mathematical models", "simulation and modeling", "mathematics", "brownian motion", "statistics (mathematics)", "stochastic processes", "neutrophils", "...	Leukocyte Motility Models Assessed through Simulation and Multi-objective Optimization-Based Model Selection	journal.pcbi.1005082	null	[ [ "Cellular motility and interactions underlie many processes in the immune response , including lymphocyte recirculation through blood and lymphoid organs , their interactions with cells presenting specific antigen , and relocation to the specific tissues where they engage in protective immunity [1] .", "I...	[ "The advent of two-photon microscopy now reveals unprecedented , detailed spatio-temporal data on cellular motility and interactions in vivo .", "Understanding cellular motility patterns is key to gaining insight into the development and possible manipulation of the immune response .", "Computational simulation...	[ "Advances in imaging technology allow investigators to monitor the movements and interactions of immune cells in a live animal , processes essential to understanding and manipulating how an immune response is generated .", "T cells in the brains of Toxoplasma gondii-infected mice have previously been described as...	2016
[ "Introduction", "Materials and Methods", "Results", "Discussion", "Supporting Information" ]	[ "primates", "developmental biology", "infectious diseases", "cell biology", "entamoeba", "caenorhabditis", "human", "computational biology", "evolutionary biology", "drosophila", "molecular biology", "genetics and genomics" ]	Human Subtelomeric WASH Genes Encode a New Subclass of the WASP Family	journal.pgen.0030237	null	[ [ "Human chromosome termini are unusual in their sequence content and frequency of structural rearrangement .", "Their ends are capped with telomeres that protect chromosomes against degradation and fusion [1] and that can exert a silencing effect on nearby genes [2 , 3] .", "Patchworks of large DNA seg...	[ "Subtelomeres are duplication-rich , structurally variable regions of the human genome situated just proximal of telomeres .", "We report here that the most terminally located human subtelomeric genes encode a previously unrecognized third subclass of the Wiskott-Aldrich Syndrome Protein family , whose known memb...	[ "Human subtelomeres are rearrangement-prone regions near chromosome ends .", "They are concentrations of large , recent interchromosomal duplications .", "Over half of subtelomeric sequences changed copy number or location since humans and chimpanzee diverged , and subtelomeric content varies greatly among huma...	2007
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "medicine", "infectious diseases", "diagnostic medicine", "global health", "neglected tropical diseases", "loiasis" ]	Rapid Molecular Assays for Specific Detection and Quantitation of Loa loa Microfilaremia	journal.pntd.0001299	null	[ [ "Loa loa is a filarial nematode that infects between 3 and 13 million people in Central and Western Africa .", "Although infected individuals may exhibit a range of symptoms , indigenous inhabitants of endemic areas are typically clinically asymptomatic even in the setting of high parasite burden .", ...	[ "Accurate diagnosis of Loa loa infection is essential to the success of mass drug administration efforts to eliminate onchocerciasis and lymphatic filariasis , due to the risk of fatal encephalopathic reactions to ivermectin occurring among highly microfilaremic Loa-infected individuals living in areas co-endemic f...	[ "Loa loa is a filarial nematode that infects over 10 million people in Africa .", "Most infections cause no symptoms , but individuals with large numbers of blood-stage microfilariae are at risk for fatal reactions to ivermectin , an antiparasitic agent used to treat and prevent infections with Onchocerca volvulu...	2011
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "antimicrobials", "cell death", "medicine and health sciences", "body fluids", "pathology and laboratory medicine", "pathogens", "drugs", "immunology", "cell processes", "microbiology", "mathematical models", "vancomycin", "staphylococcus aureus", "bacterial diseases", "methicillin-resis...	Identifying determinants of persistent MRSA bacteremia using mathematical modeling	journal.pcbi.1007087	null	[ [ "Staphylococcus aureus ( SA ) is one of the most common life-threatening human pathogens [1–3] .", "Methicillin-resistant strains ( MRSA ) exhibit high rates of morbidity and mortality [1–3] .", "MRSA bacteremia may be treated with anti-MRSA antibiotics , such as vancomycin or daptomycin .", "Howe...	[ "Persistent bacteremia caused by Staphylococcus aureus ( SA ) , especially methicillin-resistant SA ( MRSA ) , is a significant cause of morbidity and mortality .", "Despite susceptibility phenotypes in vitro , persistent MRSA strains fail to clear with appropriate anti-MRSA therapy during bacteremia in vivo .", ...	[ "Staphylococcus aureus causes potentially lethal infections of the bloodstream and target organs when able to enter the body , often via skin trauma or catheterization .", "Methicillin-resistant Staphylococcus aureus ( MRSA ) resist common antibiotics , but are often successfully treated with vancomycin .", "Ho...	2019
[ "Introduction", "Materials and methods", "Results", "Discussion" ]	[ "blood cells", "humoral immunity", "blood serum", "medicine and health sciences", "enzyme-linked immunoassays", "immune physiology", "body fluids", "immune cells", "immunology", "vaccines", "animal models", "model organisms", "experimental organism systems", "infectious disease control", ...	Protective immunity by an engineered DNA vaccine for Mayaro virus	journal.pntd.0007042	null	[ [ "Mayaro virus ( MAYV ) is an alphavirus in the Togaviridae family originally identified on the island of Trinidad in 1954 .", "MAYV infection can result in an acute febrile illness lasting 3 to 5 days with symptoms including rash , headache , nausea , vomiting , and diarrhea .", "Similar to chikunguny...	[ "Mayaro virus ( MAYV ) of the genus alphavirus is a mosquito-transmitted emerging infectious disease that causes an acute febrile illness , rash , headaches , and nausea that may turn into incapacitating , persistent arthralgias in some victims .", "Since its discovery in Trinidad in 1954 , cases of MAYV infectio...	[ "Mayaro virus ( MAYV ) is a mosquito-transmitted virus that causes fever , headache , chills , nausea and joint pain that can last for months after infection .", "The rising number of cases , due to increased mosquito circulation , and the threat of an epidemic emphasize its importance as an emerging virus , but ...	2019
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "animal genetics", "veterinary neurology", "animal management", "animal breeding", "neuroscience", "genetics and genomics", "veterinary science", "veterinary medicine" ]	A One Base Pair Deletion in the Canine ATP13A2 Gene Causes Exon Skipping and Late-Onset Neuronal Ceroid Lipofuscinosis in the Tibetan Terrier	journal.pgen.1002304	null	[ [ "Neuronal ceroid lipofuscinosis ( NCL ) is a progressive neurodegenerative diseases characterized by brain and retinal atrophy and the intracellular accumulation of autofluorescent lysosomal storage bodies resembling lipofuscin in neurons and other cells .", "NCL has been reported in several domestic anim...	[ "Neuronal ceroid lipofuscinosis ( NCL ) is a progressive neurodegenerative disease characterized by brain and retinal atrophy and the intracellular accumulation of autofluorescent lysosomal storage bodies resembling lipofuscin in neurons and other cells .", "Tibetan terriers show a late-onset lethal form of NCL m...	[ "The neuronal ceroid lipofuscinosis ( NCL ) is a neurodegenerative storage diseases characterized by psychomotor retardation , blindness , and premature death .", "NCL has been reported in several dog breeds .", "NCL is characterized by progressive brain and retinal atrophy and the intracellular accumulation of...	2011
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "immune cells", "immunity", "immunity to infections", "immunology", "immunoregulation", "biology", "zoology", "immunomodulation", "parasitology", "helminthology" ]	Foxp3+ Regulatory T Cells Delay Expulsion of Intestinal Nematodes by Suppression of IL-9-Driven Mast Cell Activation in BALB/c but Not in C57BL/6 Mice	journal.ppat.1003913	null	[ [ "Helminths are large multicellular parasites that may survive for years within their mammalian hosts despite their potential exposure to the immune system .", "This is achieved by active suppression of their host's immune response utilizing regulatory pathways that are intrinsic parts of the mammalian imm...	[ "Accumulating evidence suggests that IL-9-mediated immunity plays a fundamental role in control of intestinal nematode infection .", "Here we report a different impact of Foxp3+ regulatory T cells ( Treg ) in nematode-induced evasion of IL-9-mediated immunity in BALB/c and C57BL/6 mice .", "Infection with Stron...	[ "Parasitic worms are large multicellular organisms that manage completion of their life cycles despite exposure to their host's immune system .", "To avoid expulsion , parasitic worms actively suppress their host's immune response .", "Here we show that the pathogenic nematode Strongyloides ratti induces the ex...	2014
[ "Introduction", "Results", "Discussion", "Material and methods" ]	[ "material fatigue", "medicine and health sciences", "legs", "classical mechanics", "pathology and laboratory medicine", "fatigue", "skeletal muscles", "limbs (anatomy)", "neuroscience", "biomechanics", "muscle contraction", "motor neurons", "simulation and modeling", "signs and symptoms", ...	A motor unit-based model of muscle fatigue	journal.pcbi.1005581	null	[ [ "Muscle fatigue is a temporary decline in the force and power capacity of skeletal muscle resulting from muscle activity .", "Muscle fatigue can adversely affect the lives of workers , athletes , patients , and the elderly—and is a quotidian ( and bothersome ) presence in the lives of most people .", ...	[ "Muscle fatigue is a temporary decline in the force and power capacity of skeletal muscle resulting from muscle activity .", "Because control of muscle is realized at the level of the motor unit ( MU ) , it seems important to consider the physiological properties of motor units when attempting to understand and p...	[ "Skeletal muscle fatigue reduces strength during work and play and profoundly impairs motor function in many neuromuscular disorders .", "Muscle is composed of groupings of fibres called motor units and these have an extensive range of characteristics from small , weak , and fatigue-resistant to large , strong , ...	2017
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "blood cells", "medicine and health sciences", "immune cells", "pathology and laboratory medicine", "gene regulation", "pathogens", "immunology", "microbiology", "streptococcus pyogenes", "signs and symptoms", "sequence motif analysis", "epigenetics", "dna", "bacteria", "dna methylation"...	DNA methylation from a Type I restriction modification system influences gene expression and virulence in Streptococcus pyogenes	journal.ppat.1007841	null	[ [ "DNA methylation has been shown to regulate diverse pathways across all domains of life [1] .", "In eukaryotes , cytosine methylation regulates developmental gene expression and aberrant DNA methylation patterns have been implicated in many disease states , including cancer [2 , 3] .", "Although studi...	[ "DNA methylation is pervasive across all domains of life .", "In bacteria , the presence of N6-methyladenosine ( m6A ) has been detected among diverse species , yet the contribution of m6A to the regulation of gene expression is unclear in many organisms .", "Here we investigated the impact of DNA methylation o...	[ "DNA methylation is common among many bacterial species , yet the contribution of DNA methylation to the regulation of gene expression is unclear outside of a limited number of gram-negative species .", "We characterized sites of DNA methylation throughout the genome of the gram-positive pathogen Streptococcus py...	2019
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	IL-4 Induced Innate CD8+ T Cells Control Persistent Viral Infection	journal.ppat.1005193	null	[ [ "Conventional T cells take on naive phenotypes when they emigrate out from the thymus , whereas innate T cells from the thymus are phenotypically of the effector/memory form [1] .", "Compared with conventional T cells , these innate T cells , such as natural killer T ( NKT ) cells , mucosal-associated inv...	[ "Memory-like CD8+ T cells expressing eomesodermin are a subset of innate T cells initially identified in a number of genetically modified mice , and also exist in wild mice and human .", "The acquisition of memory phenotype and function by these T cells is dependent on IL–4 produced by PLZF+ innate T cells; howev...	[ "Over the course of viral infection there may be a limited time period during which the host system can eliminate the virus .", "When viruses are not eliminated within this period of time , virus can establish persistent infection .", "Here , we show that IL-4-induced innate CD8+ T cells are able to effectively...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	A Structure-Guided Mutation in the Major Capsid Protein Retargets BK Polyomavirus	journal.ppat.1003688	null	[ [ "Interactions of a virus with receptors on host cells are crucial for viral entry and infection , and determine host range and tissue tropism of the virus .", "As a result , receptor specificity and affinity are tightly regulated , with changes in either producing a virus with different spread and infecti...	[ "Viruses within a family often vary in their cellular tropism and pathogenicity .", "In many cases , these variations are due to viruses switching their specificity from one cell surface receptor to another .", "The structural requirements that underlie such receptor switching are not well understood especially...	[ "Viruses need to bind to receptors on host cells for viral entry and infection , and the type of receptor bound determines the range of hosts and tissues the virus can infect .", "Viruses within a family often vary in their tissue distribution and pathogenicity because changes in receptor specificity can produce ...	2013
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "genome expression analysis", "mutation", "sexual selection", "chromosomal inheritance", "chromosome biology", "natural selection", "sexual conflict", "heredity", "gene expression", "genetics", "genome evolution", "biology", "genomics", "evolutionary biology", "evolutionary processes" ]	Masculinization of the X Chromosome in the Pea Aphid	journal.pgen.1003690	null	[ [ "As males and females differ in their optimal values for most phenotypic traits , selection often runs in opposite directions in the two sexes , a situation called sexual antagonism [1] .", "Since males and females share most of their genome , intra-locus conflicts appear when the same gene is selected fo...	[ "Evolutionary theory predicts that sexually antagonistic mutations accumulate differentially on the X chromosome and autosomes in species with an XY sex-determination system , with effects ( masculinization or feminization of the X ) depending on the dominance of mutations .", "Organisms with alternative modes of...	[ "Males and females differ in their optimal values for most phenotypic traits , which makes intra-locus genetic conflicts among sexes common .", "Sex chromosomes have a sex-biased transmission , a pattern which might create favourable conditions for the spread of sexually antagonistic alleles ( i . e . alleles ben...	2013
[ "Introduction", "Results", "Discussion", "Methods" ]	[]	Clustered Desynchronization from High-Frequency Deep Brain Stimulation	journal.pcbi.1004673	null	[ [ "High frequency deep brain stimulation ( DBS ) , a medical treatment in which high-frequency , pulsatile current is injected into an appropriate brain region , is a well established technique for alleviating tremors , rigidity , and bradykinesia in patients with Parkinson’s disease [1 , 2] .", "While the ...	[ "While high-frequency deep brain stimulation is a well established treatment for Parkinson’s disease , its underlying mechanisms remain elusive .", "Here , we show that two competing hypotheses , desynchronization and entrainment in a population of model neurons , may not be mutually exclusive .", "We find that...	[ "While high-frequency deep brain stimulation ( DBS ) is a decades old treatment for alleviating the motor symptoms Parkinsons disease , the way in which it alleviates these symptoms is not well understood .", "Making matters more complicated , some experimental results suggest that DBS works by making neurons fir...	2015
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "antimicrobials", "medicine and health sciences", "cell division analysis", "cell cycle and cell division", "drugs", "cell processes", "microbiology", "streptomycin", "protein expression", "probability distribution", "mathematics", "antibiotics", "bioassays and physiological analysis", "ph...	Inferring fitness landscapes and selection on phenotypic states from single-cell genealogical data	journal.pgen.1006653	null	[ [ "Selection is a process in which the interaction of organisms with their environment determines which types of individuals thrive and proliferate more than others .", "Genetic information encoded in the genome is a primary determinant of reproductivity , but epigenetic and fluctuating phenotypic traits ca...	[ "Recent advances in single-cell time-lapse microscopy have revealed non-genetic heterogeneity and temporal fluctuations of cellular phenotypes .", "While different phenotypic traits such as abundance of growth-related proteins in single cells may have differential effects on the reproductive success of cells , ri...	[ "Selection is a ubiquitous process in biological populations in which individuals are endowed with heterogeneous reproductive abilities , and it occurs even among genetically homogeneous cells due to the existence of phenotypic noise .", "Unlike genotypes , which can remain stable for many generations , phenotypi...	2017
[ "Introduction", "Methods", "Results and Discussion" ]	[ "genetics and genomics/genome projects", "genetics and genomics/bioinformatics", "genetics and genomics/genomics" ]	New Assembly, Reannotation and Analysis of the Entamoeba histolytica Genome Reveal New Genomic Features and Protein Content Information	journal.pntd.0000716	null	[ [ "Although many infectious diseases receive little attention in today's world , the pathogenic intestinal parasite E . histolytica occupies a major place in the list of ignored illnesses .", "The parasite is the causative agent of amoebiasis , causes a significant level of morbidity and mortality in develo...	[ "In order to maintain genome information accurately and relevantly , original genome annotations need to be updated and evaluated regularly .", "Manual reannotation of genomes is important as it can significantly reduce the propagation of errors and consequently diminishes the time spent on mistaken research .", ...	[ "Entamoeba histolytica is an anaerobic parasitic protozoan that causes amoebic dysentery .", "The parasites colonize the large intestine , but under some circumstances may invade the intestinal mucosa , enter the bloodstream and lead to the formation of abscesses such amoebic liver abscesses .", "The draft geno...	2010
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine and health sciences", "diagnostic radiology", "functional magnetic resonance imaging", "personality traits", "social sciences", "biomarkers", "neuroscience", "magnetic resonance imaging", "fear", "anxiety", "cognition", "brain mapping", "personality", "neuroimaging", "research ...	Decoding Spontaneous Emotional States in the Human Brain	journal.pbio.2000106	null	[ [ "Functional neuroimaging offers unique insight into how mental representations are encoded in brain activity [1 , 2] .", "Seminal cognitive neuroscience studies demonstrated that distributed patterns of cortical activity measured with functional magnetic resonance imaging ( fMRI ) contain information capa...	[ "Pattern classification of human brain activity provides unique insight into the neural underpinnings of diverse mental states .", "These multivariate tools have recently been used within the field of affective neuroscience to classify distributed patterns of brain activation evoked during emotion induction proce...	[ "Functional brain imaging techniques provide a window into neural activity underpinning diverse cognitive processes , including visual perception , decision-making , and memory , among many others .", "By treating functional imaging data as a pattern-recognition problem , similar to face- or character-recognition...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods", "Supporting Information" ]	[ "genetics and genomics", "cell biology", "developmental biology", "saccharomyces" ]	Life Span Extension by Calorie Restriction Depends on Rim15 and Transcription Factors Downstream of Ras/PKA, Tor, and Sch9	journal.pgen.0040013	null	[ [ "The effect of restricting calorie intake on life span extension has been known for more than 70 years [1 , 2] .", "Although many hypotheses on how calorie restriction ( CR ) modulates aging have been proposed , the underlying mechanism for CR is still elusive [3] .", "Evidence from genetic studies ut...	[ "Calorie restriction ( CR ) , the only non-genetic intervention known to slow aging and extend life span in organisms ranging from yeast to mice , has been linked to the down-regulation of Tor , Akt , and Ras signaling .", "In this study , we demonstrate that the serine/threonine kinase Rim15 is required for yeas...	[ "Reduction in calorie intake is a well-established intervention that extends the life span of a variety of biological model organisms studied .", "Calorie restriction also delays and attenuates age-related changes in primates , although its longevity-promoting effect has not been demonstrated .", "Here , we uti...	2008
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "medicine and health sciences", "mali", "pathology and laboratory medicine", "pathogens", "immunology", "geographical locations", "microbiology", "pediatrics", "vaccines", "preventive medicine", "bacterial diseases", "enterobacteriaceae", "vaccination and immunization", "bacteria", "bact...	Modeling the Potential for Vaccination to Diminish the Burden of Invasive Non-typhoidal Salmonella Disease in Young Children in Mali, West Africa	journal.pntd.0005283	null	[ [ "In industrialized countries , non-typhoidal Salmonella ( NTS ) predominately causes gastroenteritis [1 , 2] .", "However , in sub-Saharan Africa the NTS serovars S . Typhimurium and S . Enteritidis have become recognized as important causes of severe invasive bacterial disease ( e . g . , septicemia , me...	[ "In sub-Saharan Africa , systematic surveillance of young children with suspected invasive bacterial disease ( e . g . , septicemia , meningitis ) has revealed non-typhoidal Salmonella ( NTS ) to be a major pathogen exhibiting high case fatality ( ~20% ) .", "Where infant vaccination against Haemophilus influenza...	[ "A surveillance program at Gabriel Touré Hospital in Mali observed a high burden of invasive disease caused by non-typhoidal Salmonella ( iNTS ) .", "This surveillance program was originally instituted to measure the amount of invasive disease ( e . g . , septicemia , meningitis ) caused by two bacteria that inva...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "developmental biology", "plant biology" ]	The Making of a Compound Inflorescence in Tomato and Related Nightshades	journal.pbio.0060288	Plant flower production is largely determined by the number of inflorescences, the branches produced on flower stems. Two genes identified in tomato reveal a new phase transition that may explain the mechanism of evolution of compound inflorescences in the Solanaceae family.	[ [ "A striking manifestation of plant evolution is observed in the diverse branching and patterning of inflorescences , which are the shoots that bear flowers [1 , 2] Inflorescences are derived from the growth of dome-shaped groups of pluripotent cells called apical meristems .", "Apical meristems first prod...	[ "Variation in the branching of plant inflorescences determines flower number and , consequently , reproductive success and crop yield .", "Nightshade ( Solanaceae ) species are models for a widespread , yet poorly understood , program of eudicot growth , where short side branches are initiated upon floral termina...	[ "Among the most distinguishing features of plants are the flower-bearing shoots , called inflorescences .", "Despite a solid understanding of flower development , the molecular mechanisms that control inflorescence architecture remain obscure .", "We have explored this question in tomato , where mutations in tw...	2008
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "neuroscience/behavioral neuroscience", "neuroscience/motor systems", "neuroscience/theoretical neuroscience", "computational biology/computational neuroscience" ]	Distinct Timing Mechanisms Produce Discrete and Continuous Movements	journal.pcbi.1000061	null	[ [ "Discrete movements constitute singularly occurring events preceded and followed by a period without motion ( i . e . , with zero velocity ) for a reasonable amount of time , such as a single finger flexion or flexion-extension cycle [1] , [2] .", "Continuous movements lack such recognizable endpoints , a...	[ "The differentiation of discrete and continuous movement is one of the pillars of motor behavior classification .", "Discrete movements have a definite beginning and end , whereas continuous movements do not have such discriminable end points .", "In the past decade there has been vigorous debate whether this c...	[ "A fundamental question in motor control research is whether distinct movement classes exist .", "Candidate classes are discrete and continuous movement .", "Discrete movements have a definite beginning and end , whereas continuous movements do not have such discriminable end points .", "In the past decade th...	2008
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "humoral immunity", "infectious diseases", "medicine and health sciences", "clinical laboratory sciences", "immune cells", "diagnostic medicine", "cell biology", "animal cells", "immunity", "clinical immunology", "immunity to infections", "biology and life sciences", "cellular types", "imm...	Field-Evaluation of a New Lateral Flow Assay for Detection of Cellular and Humoral Immunity against Mycobacterium leprae	journal.pntd.0002845	null	[ [ "Leprosy , a curable infectious disease caused by Mycobacterium leprae ( M . leprae ) that affects the skin and peripheral nerves , is one of the six diseases considered by the WHO as a major threat in developing countries [1] .", "Despite being treatable , leprosy often results in severe , life-long disa...	[ "Field-applicable tests detecting asymptomatic Mycobacterium leprae ( M . leprae ) infection or predicting progression to leprosy , are urgently required .", "Since the outcome of M . leprae infection is determined by cellular- and humoral immunity , we aim to develop diagnostic tests detecting pro-/anti-inflamma...	[ "Leprosy is one of the six diseases considered by WHO as a major threat in developing countries and often results in severe , life-long disabilities and deformities due to delayed diagnosis .", "Early detection of Mycobacterium leprae ( M . leprae ) infection , followed by effective interventions , is considered ...	2014
[ "Introduction", "Materials and methods", "Results", "Discussion" ]	[ "crystal structure", "chemical compounds", "oxides", "split-decomposition method", "condensed matter physics", "enzymology", "organic compounds", "multiple alignment calculation", "flavin", "crystallography", "hydrogen peroxide", "alcohols", "enzyme chemistry", "research and analysis metho...	The ins and outs of vanillyl alcohol oxidase: Identification of ligand migration paths	journal.pcbi.1005787	null	[ [ "Vanillyl alcohol oxidase ( VAO ) is a flavoenzyme involved in the mineralisation of aromatic compounds in the soil fungus Penicillium simplicissimum .", "VAO is active with a wide range of para-substituted phenolic compounds , but received its name because the enzyme initially was found to catalyse the o...	[ "Vanillyl alcohol oxidase ( VAO ) is a homo-octameric flavoenzyme belonging to the VAO/PCMH family .", "Each VAO subunit consists of two domains , the FAD-binding and the cap domain .", "VAO catalyses , among other reactions , the two-step conversion of p-creosol ( 2-methoxy-4-methylphenol ) to vanillin ( 4-hyd...	[ "Enzymes are bionanomachines , which speed up chemical reactions in organisms .", "To understand how they achieve that , we need to study their mechanisms .", "Computational enzymology can show us what happens in the enzyme’s active site during a reaction .", "But molecules need first to reach the active site...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biochemistry/replication and repair", "genetics and genomics/cancer genetics", "genetics and genomics/animal genetics", "genetics and genomics/chromosome biology" ]	Incremental Genetic Perturbations to MCM2-7 Expression and Subcellular Distribution Reveal Exquisite Sensitivity of Mice to DNA Replication Stress	journal.pgen.1001110	null	[ [ "In late mitosis to early G1 phase of the cell cycle , DNA replication origins are selected and bound by the hexameric origin recognition complex ( ORC; [1] ) .", "ORC then recruits the initiation factors CDC6 and CDT1 , which are required for loading MCM2-7 , thereby forming the “pre-replicative complex”...	[ "Mutations causing replication stress can lead to genomic instability ( GIN ) .", "In vitro studies have shown that drastic depletion of the MCM2-7 DNA replication licensing factors , which form the replicative helicase , can cause GIN and cell proliferation defects that are exacerbated under conditions of replic...	[ "Proper replication of the genome is essential for maintenance of the genetic material and normal cell proliferation .", "DNA replication can be compromised by exogenous factors and genetic disruptions .", "Such compromise can lead to disease such as cancer , which is characterized by genomic instability ( an e...	2010
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "developmental biology", "theoretical biology", "gene regulatory networks", "natural selection", "neutral theory", "biology and life sciences", "population genetics", "computational biology", "evolutionary biology", "evolutionary processes", "evolutionary developmental biology" ]	Stability Depends on Positive Autoregulation in Boolean Gene Regulatory Networks	journal.pcbi.1003916	null	[ [ "Gene regulatory networks ( GRNs ) are believed to play a central role in organismal development and evolution [1]–[3] .", "Recent theoretical and experimental studies have revealed that GRNs have many interesting quantitative and qualitative features , including scale-free structure [4] , recurring motif...	[ "Network motifs have been identified as building blocks of regulatory networks , including gene regulatory networks ( GRNs ) .", "The most basic motif , autoregulation , has been associated with bistability ( when positive ) and with homeostasis and robustness to noise ( when negative ) , but its general importan...	[ "Multicellular organisms show an incredible diversity of cell types in their different tissues .", "Functional classes of cells can be attributed to the activation and repression of genes , which enable each cell type to support different functions within the organism .", "These patterns of activity have been s...	2014
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "bacteriology", "infographics", "organismal evolution", "interaction networks", "population dynamics", "microbiology", "fungal evolution", "microbial evolution", "population biology", "computer and information sciences", "mycology", "molecular biology", "data visualization", "natural selec...	Motion, fixation probability and the choice of an evolutionary process	journal.pcbi.1007238	null	[ [ "The study of the success of mutants in evolving populations is a well-established focus area of research in computational biology .", "Approaches to this problem range from mostly theoretical work to direct application to specific biological systems [1–26] .", "The simplest way of modelling evolution...	[ "Seemingly minor details of mathematical and computational models of evolution are known to change the effect of population structure on the outcome of evolutionary processes .", "For example , birth-death dynamics often result in amplification of selection , while death-birth processes have been associated with ...	[ "Whether a mutation spreads in a population or not is one of the most important questions in biology .", "The evolution of cancer and antibiotic resistance , for example , are mediated by invading mutants .", "Recent work has shown that population structure can have important consequences for the outcome of evo...	2019
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "blastocysts", "sequencing techniques", "population genetics", "neuronal differentiation", "neuroscience", "cell differentiation", "developmental biology", "molecular biology techniques", "population biology", "embryos", "rna sequencing", "research and analysis methods", "embryology", "rna...	Visualizing the structure of RNA-seq expression data using grade of membership models	journal.pgen.1006599	null	[ [ "We assume that the RNA-seq data on N samples has been summarized by a table of counts CN×G = ( cng ) , where cng is the number of reads from sample n mapped to gene g ( or other unit , such as transcript or exon ) [19] .", "The GoM model is a generalization of a cluster model , which allows that each sam...	[ "Grade of membership models , also known as “admixture models” , “topic models” or “Latent Dirichlet Allocation” , are a generalization of cluster models that allow each sample to have membership in multiple clusters .", "These models are widely used in population genetics to model admixed individuals who have an...	[ "Gene expression profile of a biological sample ( either from single cells or pooled cells ) results from a complex interplay of multiple related biological processes .", "Consequently , for example , distal tissue samples may share a similar gene expression profile through some common underlying biological proce...	2017
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "medicine and health sciences", "pathology and laboratory medicine", "immunofluorescence staining", "immunology", "epithelial cells", "animal models", "developmental biology", "model organisms", "signs and symptoms", "experimental organism systems", "digestive system", "research and analysis m...	hnRNP I regulates neonatal immune adaptation and prevents colitis and colorectal cancer	journal.pgen.1006672	null	[ [ "Increasing evidence indicates that proper host-microbe interaction in the gastrointestinal tract is critical for the balance of immune tolerance and active immune responses [1 , 2] .", "Dysregulated host response to gut microbiota is the major cause of autoimmune diseases , inflammatory disorders and can...	[ "The intestinal epithelium plays a critical role in host-microbe homeostasis by sensing gut microbes and subsequently initiating proper immune responses .", "During the neonatal stage , the intestinal epithelium is under immune repression , allowing the transition for newborns from a relatively sterile intra-uter...	[ "Precisely controlled host-microbe interactions in the gastrointestinal tract are crucial for human overall health and well-being .", "Dysregulated host responses to gut microbiota are the major cause of autoimmune diseases , inflammatory disorders and cancers .", "The intestinal epithelium lines the gastrointe...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "cancer detection and diagnosis", "medicine", "breast tumors", "cancers and neoplasms", "basic cancer research", "algorithms", "oncology", "neurological tumors", "developmental biology", "organism development", "regulatory networks", "biology", "microarrays", "systems biology", "computer...	Protein Networks as Logic Functions in Development and Cancer	journal.pcbi.1002180	null	[ [ "Biological complexity , it is thought , is not a simple function of the number of genes in a genome .", "It likely stems from a variety of factors , including the number of protein states and , as importantly , the number of combinations in which proteins assemble into functional modules [1] , [2] .", ...	[ "Many biological and clinical outcomes are based not on single proteins , but on modules of proteins embedded in protein networks .", "A fundamental question is how the proteins within each module contribute to the overall module activity .", "Here , we study the modules underlying three representative biologic...	[ "Biological outcomes are often determined by modules of proteins working in combination .", "In classic biological studies , these modules have been shown to encode a diverse repertoire of logic functions which provide the means to express complex regulatory programs using a limited number of proteins .", "Here...	2011
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "infectious diseases/helminth infections", "pediatrics and child health", "chemistry/organic chemistry", "infectious diseases/neglected tropical diseases" ]	Taste, A New Incentive to Switch to (R)-Praziquantel in Schistosomiasis Treatment	journal.pntd.0000357	null	[ [ "Praziquantel [1] ( PZQ ) is the drug compound of choice in the control and treatment of schistosomiasis [2] , in fact , it is the only commercially readily available drug .", "So far , no backup compound for PZQ of comparable efficacy and breadth of application is available .", "Clinically relevant r...	[ "Praziquantel ( PZQ ) is the drug compound of choice in the control and treatment of schistosomiasis .", "PZQ is administered as a racemate , i .", "e .", "1∶1 mixture of enantiomers .", "The schistosomicidal activity arises from one PZQ-enantiomer , whereas the other enantiomer does not contribute to the a...	[ "Schistosomiasis , or Bilharzia , is a parasitic disease caused by flatworms , which affects about 200 million people worldwide .", "Praziquantel ( PZQ ) is the drug compound of choice in the control and treatment of this disease .", "Only half of the drug dose currently administered actually has activity again...	2009
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "medicine and health sciences", "action potentials", "membrane potential", "ocular anatomy", "electrophysiology", "neuroscience", "probability distribution", "mathematics", "ganglion cells", "systems science", "neuronal tuning", "computer and information sciences", "animal cells", "probabi...	The structured ‘low temperature’ phase of the retinal population code	journal.pcbi.1005792	null	[ [ "The past decade has witnessed a rapid development of new techniques for recording simultaneously from large populations of neurons [1–4] .", "As the experimentally accessible populations increase in size , a natural question arises: how can we model and understand the activity of large populations of neu...	[ "Recent advances in experimental techniques have allowed the simultaneous recordings of populations of hundreds of neurons , fostering a debate about the nature of the collective structure of population neural activity .", "Much of this debate has focused on the empirical findings of a phase transition in the par...	[ "Neurons encoding the natural world are correlated in their activities .", "The structure of this correlation fundamentally changes the population code , and these effects increase in larger neural populations .", "We experimentally recorded from populations of 100+ retinal ganglion cells and probed the structu...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Parathyroid-Specific Deletion of Klotho Unravels a Novel Calcineurin-Dependent FGF23 Signaling Pathway That Regulates PTH Secretion	journal.pgen.1003975	null	[ [ "Calcium plays a pivotal role in many biological processes , such as intra-cellular signaling , cell membrane depolarization and excitation , energy metabolism and skeletal mineralization .", "Accordingly , a fine-tuned regulation of serum calcium level is a prerequisite for normal cellular and organ func...	[ "Klotho acts as a co-receptor for and dictates tissue specificity of circulating FGF23 .", "FGF23 inhibits PTH secretion , and reduced Klotho abundance is considered a pathogenic factor in renal secondary hyperparathyroidism .", "To dissect the role of parathyroid gland resident Klotho in health and disease , w...	[ "Inorganic calcium is a critical element for a diverse range of cellular processes ranging from cell signaling to energy metabolism , and its extracellular concentration is controlled by parathyroid hormone ( PTH ) .", "Klotho is expressed in parathyroid chief cells and reported to facilitate PTH secretion during...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genetics and genomics/genetics of disease", "diabetes and endocrinology/bone and mineral metabolism", "rheumatology/bone and mineral metabolism" ]	Genome-Wide Association Study Using Extreme Truncate Selection Identifies Novel Genes Affecting Bone Mineral Density and Fracture Risk	journal.pgen.1001372	null	[ [ "Osteoporotic fracture is a leading cause of morbidity and mortality in the community ,", "particularly amongst the elderly .", "In 2004 ten million Americans were estimated to", "have osteoporosis , resulting in 1 . 5 million fractures per annum [1] .", "Hip fracture is", "associated with...	[ "Osteoporotic fracture is a major cause of morbidity and mortality worldwide .", "Low", "bone mineral density ( BMD ) is a major predisposing factor to fracture and is", "known to be highly heritable .", "Site- , gender- , and age-specific genetic effects", "on BMD are thought to be significant , but have...	[ "Osteoporotic fracture is a major cause of early mortality and morbidity in the", "community .", "To identify genes associated with osteoporosis , we have performed a", "genome-wide association study .", "In order to improve study power and to address", "the demographic group of highest risk from osteopor...	2011
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "genome-wide association studies", "cancer genetics", "genetics", "biology", "genetics and genomics" ]	GWAS Identifies Novel Susceptibility Loci on 6p21.32 and 21q21.3 for Hepatocellular Carcinoma in Chronic Hepatitis B Virus Carriers	journal.pgen.1002791	null	[ [ "Hepatocellular carcinoma ( HCC ) is the sixth common cancer and the third common cause of cancer mortality worldwide [1] .", "The incidence rate of HCC varies considerably in the world , with the highest in East , Southeast Asia and Sub-Saharan Africa , and China alone accounts for approximately half of ...	[ "Genome-wide association studies ( GWAS ) have recently identified KIF1B as susceptibility locus for hepatitis B virus ( HBV ) –related hepatocellular carcinoma ( HCC ) .", "To further identify novel susceptibility loci associated with HBV–related HCC and replicate the previously reported association , we perform...	[ "Previous studies strongly suggest the importance of genetic susceptibility for hepatocellular carcinoma ( HCC ) .", "However , the studies about genetic etiology on HBV–related HCC were limited .", "Our genome-wide association study included 523 , 663 autosomal SNPs in 1 , 538 HBV–positive HCC patients and 1 ,...	2012
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "blood cells", "medicine and health sciences", "immune cells", "pathology and laboratory medicine", "engineering and technology", "signal processing", "immunology", "population genetics", "gene pool", "simulation and modeling", "mathematics", "signs and symptoms", "statistics (mathematics)",...	Robust Inference of Cell-to-Cell Expression Variations from Single- and K-Cell Profiling	journal.pcbi.1005016	null	[ [ "Transcriptomic profiling is widely used in biomedical research , but until recently it often relies on measuring mRNAs pooled from thousands to millions of cells , thus obscuring the well-appreciated biological variation that exists among individual cells of the profiled population .", "Quantifying varia...	[ "Quantifying heterogeneity in gene expression among single cells can reveal information inaccessible to cell-population averaged measurements .", "However , the expression level of many genes in single cells fall below the detection limit of even the most sensitive technologies currently available .", "One prop...	[ "Different cells can make different amounts of biomolecules such as RNA transcripts of genes .", "New technologies are emerging to measure the transcript level of many genes in single cells .", "However , accurate quantification of the biological variation from cell to cell can be challenging due to the low tra...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genetics and genomics/epigenetics", "genetics and genomics", "biochemistry/rna structure", "molecular biology/rna-protein interactions" ]	SINE RNA Induces Severe Developmental Defects in Arabidopsis thaliana and Interacts with HYL1 (DRB1), a Key Member of the DCL1 Complex	journal.pgen.1000096	null	[ [ "Short Interspersed Elements ( SINEs ) are repetitive sequences , present in the genome of most eukaryotes and ancestrally derived from small functional RNAs ( tRNAs , 7SL RNAs or 5S RNAs ) [1] .", "SINEs can be transcribed by the RNA polymerase III ( polIII ) machinery [2] .", "They propagate in geno...	[ "The proper temporal and spatial expression of genes during plant development is governed , in part , by the regulatory activities of various types of small RNAs produced by the different RNAi pathways .", "Here we report that transgenic Arabidopsis plants constitutively expressing the rapeseed SB1 SINE retroposo...	[ "Short interspersed elements ( SINEs ) are transposable elements in eukaryotic genomes that mobilize through an RNA intermediate .", "Recently , mammalian SINE RNAs were shown to have roles as noncoding riboregulators in stress situations or in specific tissues .", "Mammalian SINE RNAs modulate the level of mRN...	2008
[ "Introduction", "Materials and methods", "Results", "Discussion" ]	[ "learning", "anthropogenic climate change", "ecology and environmental sciences", "chemical compounds", "atmospheric science", "social sciences", "neuroscience", "learning and memory", "physical geography", "simulation and modeling", "cognitive psychology", "research and analysis methods", "...	Charting pathways to climate change mitigation in a coupled socio-climate model	journal.pcbi.1007000	null	[ [ "According to many ancient myths , humans did not invent fire-making de novo but rather learned it from personalities like Prometheus and subsequently spread the practice amongst themselves .", "These stories reveal how ancient myth-makers already grasped the fundamental importance of social learning—the ...	[ "Geophysical models of climate change are becoming increasingly sophisticated , yet less effort is devoted to modelling the human systems causing climate change and how the two systems are coupled .", "Here , we develop a simple socio-climate model by coupling an Earth system model to a social dynamics model .", ...	[ "The importance of anthropogenic CO2 emissions on climate change trajectories is widely acknowledged .", "However , geophysical climate models rarely account for dynamic human behaviour , which determines the emissions trajectory , and is itself affected by the climate system .", "Here , using a coupled socio-c...	2019
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "infectious diseases/viral infections", "immunology/immunity to infections", "immunology/immune response", "immunology/innate immunity" ]	T Cell-Dependence of Lassa Fever Pathogenesis	journal.ppat.1000836	null	[ [ "Lassa virus ( LASV ) is the causative agent of Lassa fever ( LF ) [1] .", "It accounts for an estimated number of 300′000 infections and several thousand deaths in endemic areas each year [2] , while imported cases have been reported from around the globe [3] .", "The virus is listed category A by th...	[ "Lassa virus ( LASV ) , the causative agent of Lassa fever ( LF ) , is endemic in West Africa , accounting for substantial morbidity and mortality .", "In spite of ongoing research efforts , LF pathogenesis and mechanisms of LASV immune control remain poorly understood .", "While normal laboratory mice are resi...	[ "Lassa virus ( LASV ) is the causative agent of Lassa fever ( LF ) , accounting for substantial morbidity and mortality in West Africa .", "Yet the mechanisms leading to disease remain poorly understood .", "Here we propose a concept whereby the body's immune defense either defeats LASV rapidly or , if unsucces...	2010
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine and health sciences" ]	The Epithelial αvβ3-Integrin Boosts the MYD88-Dependent TLR2 Signaling in Response to Viral and Bacterial Components	journal.ppat.1004477	null	[ [ "The toll like receptors ( TLRs ) constitute a major defensive system of the cell against invasion from bacteria and viruses , and endogenous DAMPs ( danger associated molecular patterns ) [1] .", "Some of them , including TLR2 and 4 , are present at the cell surface and mount the immediate branch of the ...	[ "TLR2 is a cell surface receptor which elicits an immediate response to a wide repertoire of bacteria and viruses .", "Its response is usually thought to be proinflammatory rather than an antiviral .", "In monocytic cells TLR2 cooperates with coreceptors , e . g . CD14 , CD36 and αMβ2-integrin .", "In an earl...	[ "In an earlier work we showed that a relevant contribution to the overall IFN-based antiviral response of the cell to herpes simplex virus is exerted by αvβ3-integrin which acts in concert with TLR2 in eliciting this response .", "Major characteristics of this branch of the innate response are the secretion of IF...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine", "infectious diseases", "gastroenterology and hepatology", "hiv", "biology", "genomics", "viral diseases", "genetics and genomics" ]	Absence of HIV-1 Evolution in the Gut-Associated Lymphoid Tissue from Patients on Combination Antiviral Therapy Initiated during Primary Infection	journal.ppat.1002506	null	[ [ "Acute infection with human immunodeficiency virus type 1 ( HIV-1 ) is a critical time during which host factors including innate and adaptive immunity converge with virologic characteristics to determine the course of clinical progression in infected individuals [1]–[3] .", "In the absence of combination...	[ "Mucosal mononuclear ( MMC ) CCR5+CD4+ T cells of the gastrointestinal ( GI ) tract are selectively infected and depleted during acute HIV-1 infection .", "Despite early initiation of combination antiretroviral therapy ( cART ) , gut-associated lymphoid tissue ( GALT ) CD4+ T cell depletion and activation persist...	[ "This study was undertaken to determine if the gastrointestinal tract is a site of ongoing viral replication during suppressive combination antiretroviral therapy ( cART ) ( defined by plasma HIV-1 RNA levels below 50 copies/ml ) .", "We found no evidence of substantial viral evolution in HIV-1 envelope sequences...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "cell physiology", "medicine and health sciences", "vesicles", "pathology and laboratory medicine", "pathogens", "cell processes", "microbiology", "viral structure", "neurites", "neuroscience", "motor neurons", "viruses", "rna viruses", "cellular structures and organelles", "neuronal den...	Rabies Internalizes into Primary Peripheral Neurons via Clathrin Coated Pits and Requires Fusion at the Cell Body	journal.ppat.1005753	null	[ [ "Rabies virus ( RABV ) , a member of the Rhabdoviridae family , is a neurotropic pathogen that causes fatal encephalitis in animals and humans .", "The neurotropism of RABV is conferred by its single attachment and fusion glycoprotein ( G ) [1] .", "Virulence of specific RABV strains correlates with t...	[ "The single glycoprotein ( G ) of rabies virus ( RABV ) dictates all viral entry steps from receptor engagement to membrane fusion .", "To study the uptake of RABV into primary neuronal cells in culture , we generated a recombinant vesicular stomatitis virus in which the G protein was replaced with that of the ne...	[ "Rabies virus is the causative agent of a generally fatal and incurable disease of the central nervous system ( CNS ) .", "Rabies lethality requires that the virus invade the brain , a feat accomplished by neuronal transmission from the site of infection to the CNS .", "Using cultures of peripheral neurons and ...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Hybrid Spreading Mechanisms and T Cell Activation Shape the Dynamics of HIV-1 Infection	journal.pcbi.1004179	null	[ [ "The course of HIV-1 infection is typified by three phases; acute infection characterized by a rapid viraemia peak ( 3–6 weeks post-infection ) followed by a rapid fall in virus levels , a stable chronic phase of variable length characterized by low level viraemia and slowly declining CD4+ T cell numbers , an...	[ "HIV-1 can disseminate between susceptible cells by two mechanisms: cell-free infection following fluid-phase diffusion of virions and by highly-efficient direct cell-to-cell transmission at immune cell contacts .", "The contribution of this hybrid spreading mechanism , which is also a characteristic of some impo...	[ "The ability to spread using more than once mechanism , named hybrid spreading , is a ubiquitous feature of many real world epidemics including HIV and Hepatitis C virus infection in vivo , and computer worms spreading on the Internet .", "Hybrid spreading of HIV is well documented experimentally but its importan...	2015
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "gram negative", "microbial pathogens", "biology", "microbiology", "host-pathogen interaction", "bacterial pathogens", "pathogenesis" ]	Pdl1 Is a Putative Lipase that Enhances Photorhabdus Toxin Complex Secretion	journal.ppat.1002692	null	[ [ "Photorhabdus are Gram-negative members of the Enterobacteriaceae that live in a symbiotic association with entomopathogenic nematodes which invade and kill insects .", "Upon insect invasion the nematode regurgitates the bacteria which grow within the insect open blood system releasing a plethora of toxin...	[ "The Toxin Complex ( TC ) is a large multi-subunit toxin first characterized in the insect pathogens Photorhabdus and Xenorhabdus , but now seen in a range of pathogens , including those of humans .", "These complexes comprise three protein subunits , A , B and C which in the Xenorhabdus toxin are found in a 4∶1∶...	[ "Bacterial pathogens of insects deploy a range of toxins to combat the innate immune system and kill the host .", "There is significant interest in developing these toxins as candidates for crop protection strategies .", "To date , transgenic crops expressing Bacillus thuringiensis Cry toxins have been used to ...	2012
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "biogeography", "taxonomy", "ecology and environmental sciences", "medicine and health sciences", "population dynamics", "population genetics", "geographical locations", "tropical diseases", "bacterial diseases", "phylogenetics", "data management", "phylogenetic analysis", "paleontology", ...	A Mycobacterial Perspective on Tuberculosis in West Africa: Significant Geographical Variation of M. africanum and Other M. tuberculosis Complex Lineages	journal.pntd.0004408	null	[ [ "West Africa consists of 15 countries with 245 million inhabitants ( S1A Fig ) , 13 of which belong to the world’s 42 countries with the lowest human development index [1] .", "Consequently , it faces great challenges in controlling infectious diseases , such as tuberculosis ( TB ) .", "Clinical trial...	[ "Phylogenetically distinct Mycobacterium tuberculosis lineages differ in their phenotypes and pathogenicity .", "Consequently , understanding mycobacterial population structures phylogeographically is essential for design , interpretation and generalizability of clinical trials .", "Comprehensive efforts are la...	[ "Tuberculosis is caused by bacteria belonging to the Mycobacterium tuberculosis complex ( MTBc ) , which consists of seven major , phylogenetically distinct lineages and their families .", "West Africa is the only region in the world where , besides the common M . tuberculosis lineages , the two M . africanum lin...	2016
[ "Introduction", "Results", "Discussion" ]	[ "evolutionary biology/evolutionary ecology", "evolutionary biology/human evolution", "mathematics", "computational biology/evolutionary modeling", "evolutionary biology" ]	Calculating Evolutionary Dynamics in Structured Populations	journal.pcbi.1000615	null	[ [ "Constant selection implies that the fitness of individuals does not depend on the composition of the population .", "In general , however , the success of individuals is affected by what others are doing .", "Then we are in the realm of game theory [1]–[3] or evolutionary game theory [4]–[8] .", ...	[ "Evolution is shaping the world around us .", "At the core of every evolutionary process is a population of reproducing individuals .", "The outcome of an evolutionary process depends on population structure .", "Here we provide a general formula for calculating evolutionary dynamics in a wide class of struct...	[ "At the center of any evolutionary process is a population of reproducing individuals .", "The structure of this population can greatly affect the outcome of evolution .", "If the fitness of an individual is determined by its interactions with others , then we are in the world of evolutionary game theory .", ...	2009
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "phosphorylation", "invertebrates", "medicine and health sciences", "nervous system", "electrophysiology", "neuroscience", "animals", "motor neurons", "animal models", "organisms", "developmental biology", "drosophila melanogaster", "model organisms", "bioassays and physiological analysis"...	A Novel, Noncanonical BMP Pathway Modulates Synapse Maturation at the Drosophila Neuromuscular Junction	journal.pgen.1005810	null	[ [ "Bone morphogenetic proteins ( BMPs ) modulate a wide variety of cellular processes via canonical and noncanonical signaling pathways [1–3] .", "BMP signaling is initiated when extracellular dimeric BMP ligands bind to a heterotetrameric complex of Ser/Thr kinases , known as type I and type II BMP recepto...	[ "At the Drosophila NMJ , BMP signaling is critical for synapse growth and homeostasis .", "Signaling by the BMP7 homolog , Gbb , in motor neurons triggers a canonical pathway—which modulates transcription of BMP target genes , and a noncanonical pathway—which connects local BMP/BMP receptor complexes with the cyt...	[ "Synaptic activity and synapse development are intimately linked , but our understanding of the coupling mechanisms remains limited .", "Anterograde and retrograde signals together with trans-synaptic complexes enable intercellular communications .", "How synapse activity status is monitored and relayed across ...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biochemistry", "proteins", "protein folding", "protein structure", "biology and life sciences", "computational biology", "biophysics" ]	Fast Protein Loop Sampling and Structure Prediction Using Distance-Guided Sequential Chain-Growth Monte Carlo Method	journal.pcbi.1003539	null	[ [ "Protein loops connect regular secondary structures and are flexible regions on protein surface .", "They often play important functional roles in recognition and binding of small molecules or other proteins [1]–[3] .", "The flexibility and irregularity of loops make their structures difficult to reso...	[ "Loops in proteins are flexible regions connecting regular secondary structures .", "They are often involved in protein functions through interacting with other molecules .", "The irregularity and flexibility of loops make their structures difficult to determine experimentally and challenging to model computati...	[ "Loops in proteins are flexible regions connecting regular secondary structures .", "They are often involved in protein functions through interacting with other molecules .", "The irregularity and flexibility of loops make their structures difficult to determine experimentally and challenging to model computati...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Evolutionary Analyses Suggest a Function of MxB Immunity Proteins Beyond Lentivirus Restriction	journal.ppat.1005304	null	[ [ "Ancient , pathogenic viruses have played a major role in shaping the extant host innate immune repertoire .", "Understanding how pathogen-driven evolution has shaped host-virus interfaces can reveal insights into the molecular basis of cross-species transmission , including human susceptibility to zoonos...	[ "Viruses impose diverse and dynamic challenges on host defenses .", "Diversifying selection of codons and gene copy number variation are two hallmarks of genetic innovation in antiviral genes engaged in host-virus genetic conflicts .", "The myxovirus resistance ( Mx ) genes encode interferon-inducible GTPases t...	[ "Evolutionary analyses have the potential to reveal not only biochemical details about host-virus arms-races but also the nature of the pathogens that drove them .", "Primate MxB was recently shown to restrict the replication of primate lentiviruses , including HIV-1 .", "However , we find that positive selecti...	2015
[ "Results", "Discussion", "Methods" ]	[ "neuroscience/theoretical neuroscience" ]	Spike-Based Reinforcement Learning in Continuous State and Action Space: When Policy Gradient Methods Fail	journal.pcbi.1000586	null	[ [ "We consider a Spike Response Model neuron with index that receives input from other neurons .", "The input spike from neuron arrives at time at a synapses onto neuron and causes there an excitatory ( or inhibitory ) postsynaptic potential ( EPSP or IPSP ) of time course and amplitude .", "The EPSPs a...	[ "Changes of synaptic connections between neurons are thought to be the physiological basis of learning .", "These changes can be gated by neuromodulators that encode the presence of reward .", "We study a family of reward-modulated synaptic learning rules for spiking neurons on a learning task in continuous spa...	[ "Humans and animals learn if they receive reward .", "Such reward is likely to be communicated throughout the brain by neuromodulatory signals .", "In this paper we present a network of model neurons , which communicate by short electrical pulses ( spikes ) .", "Learning is achieved by modifying the input con...	2009
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "adaptive immunity", "immune cells", "aging and immunity", "streptococci", "immunity", "t cells", "immunology", "biology", "microbiology", "immunoregulation", "bacterial pathogens", "immune response" ]	Acquisition of Pneumococci Specific Effector and Regulatory Cd4+ T Cells Localising within Human Upper Respiratory-Tract Mucosal Lymphoid Tissue	journal.ppat.1002396	null	[ [ "Global estimates suggest that approximately one and a half million deaths due to pneumonia , bacteraemia and meningitis are associated with pneumococcal infection annually , around two thirds of these occur in children in resource-poor countries [1]–[3] .", "In addition to this high disease burden , S . ...	[ "The upper respiratory tract mucosa is the location for commensal Streptococcus ( S . ) pneumoniae colonization and therefore represents a major site of contact between host and bacteria .", "The CD4+ T cell response to pneumococcus is increasingly recognised as an important mediator of immunity that protects aga...	[ "The S . pneumoniae bacteria is a major cause of disease ( e . g . pneumonia and meningitis ) particularly affecting infants .", "In most cases bacteria can colonise the nose without causing harm , however colonisation is thought to be a prerequisite of disease .", "With increasing age colonization and disease ...	2011
[ "Introduction", "Materials and methods", "Results", "Discussion" ]	[ "invertebrates", "medicine and health sciences", "pathology and laboratory medicine", "pathogens", "microbiology", "invertebrate genomics", "animals", "animal models", "age groups", "fungi", "drosophila melanogaster", "model organisms", "experimental organism systems", "genome analysis", ...	High GC content causes orphan proteins to be intrinsically disordered	journal.pcbi.1005375	null	[ [ "Proteins without any detectable homology are often referred to as orphans .", "The presence of orphans can be attributed to several causes; rapid sequence divergence beyond the point of homology recognition [1 , 2] , lateral transfer of genetic material [3] , and de novo gene creation [4] .", "The la...	[ "De novo creation of protein coding genes involves the formation of short ORFs from noncoding regions; some of these ORFs might then become fixed in the population .", "These orphan proteins need to , at the bare minimum , not cause serious harm to the organism , meaning that they should for instance not aggregat...	[ "We show that the GC content of a genome is of great importance for the properties of an orphan protein .", "GC content affects the frequency of the codons and this affects the probability for each amino acid to be included in a de novo created protein .", "The codons encoding for Ala , Pro and Gly contain 80% ...	2017
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "parasite groups", "medicine and health sciences", "pathology and laboratory medicine", "plasmodium", "parasite evolution", "tropical diseases", "vertebrates", "parasitic diseases", "animals", "mammals", "parasitology", "parasitic protozoans", "apicomplexa", "protozoans", "evolutionary a...	High rate of adaptation of mammalian proteins that interact with Plasmodium and related parasites	journal.pgen.1007023	null	[ [ "Malaria is one of the world's most notorious infectious diseases , responsible for billions of illnesses and millions of deaths in the last fifty years alone [1] .", "Human malaria is caused by five species in the genus Plasmodium , which are evolutionarily related to Babesia , Theileria , and other para...	[ "Plasmodium parasites , along with their Piroplasm relatives , have caused malaria-like illnesses in terrestrial mammals for millions of years .", "Several Plasmodium-protective alleles have recently evolved in human populations , but little is known about host adaptation to blood parasites over deeper evolutiona...	[ "Malaria caused by the parasite Plasmodium falciparum remains the third-most deadly infectious disease of humans .", "Over the last 75 , 000 years , partial genetic resistance to malaria has evolved several times , earning malaria the title of \"one of the strongest selective forces on the human genome . \"", "...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "neurological disorders/peripheral neuropathies", "neuroscience/neuronal signaling mechanisms", "neuroscience/neurobiology of disease and regeneration", "neurological disorders/spinal disorders" ]	Endogenous Nmnat2 Is an Essential Survival Factor for Maintenance of Healthy Axons	journal.pbio.1000300	We conclude that endogenous Nmnat2 prevents spontaneous degeneration of healthy axons and propose that, when present, the more long-lived, functionally related WldS protein substitutes for Nmnat2 loss after axon injury. Endogenous Nmnat2 represents an exciting new therapeutic target for axonal disorders.	[ [ "The endogenous molecular trigger for Wallerian degeneration remains unknown .", "Recent progress towards understanding how the slow Wallerian degeneration fusion protein ( WldS ) delays degeneration of injured and sick axons has not addressed this wider question [1]–[8] , and this aberrant protein is onl...	[ "The molecular triggers for axon degeneration remain unknown .", "We identify endogenous Nmnat2 as a labile axon survival factor whose constant replenishment by anterograde axonal transport is a limiting factor for axon survival .", "Specific depletion of Nmnat2 is sufficient to induce Wallerian-like degenerati...	[ "In a normally functioning neuron , the cell body supplies the axon with materials needed to keep it healthy .", "This complex logistical activity breaks down completely after injury and often becomes compromised in neurodegenerative diseases , leading to degeneration of the isolated axon .", "Whilst there are ...	2010
[ "Introduction", "Results and discussion", "Conclusion", "Methods" ]	[ "medicine and health sciences", "body fluids", "parasitic diseases", "parasitic protozoans", "protozoans", "mitochondria", "bioenergetics", "infectious disease control", "cellular structures and organelles", "cardia", "digestive system", "infectious diseases", "gene expression", "exocrine ...	A fine-tuned vector-parasite dialogue in tsetse's cardia determines peritrophic matrix integrity and trypanosome transmission success	journal.ppat.1006972	null	[ [ "Insects are essential vectors for the transmission of microbes that cause devastating diseases in humans and livestock .", "Many of these diseases lack effective vaccines and drugs for control in mammalian hosts .", "Hence , reduction of insect populations , as well as approaches that reduce the tran...	[ "Arthropod vectors have multiple physical and immunological barriers that impede the development and transmission of parasites to new vertebrate hosts .", "These barriers include the peritrophic matrix ( PM ) , a chitinous barrier that separates the blood bolus from the midgut epithelia and modulates vector-patho...	[ "Insects are responsible for transmission of parasites that cause deadly diseases in humans and animals .", "Understanding the key factors that enhance or interfere with parasite transmission processes can result in new control strategies .", "Here , we report that a proportion of tsetse flies with African tryp...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "immunology/immunomodulation", "hematology/bone marrow and stem cell transplantation", "immunology/immune response" ]	Regulatory T Cells and Human Myeloid Dendritic Cells Promote Tolerance via Programmed Death Ligand-1	journal.pbio.1000302	Human regulatory T cells inhibit graft-versus-host disease that can occur after tissue transplantation, in part through expression of programmed death ligand 1 and modulation of antigen-presenting cells.	[ [ "Regulatory T cells ( Tregs ) promote immune tolerance to self-antigens and alloantigens ( reviewed in [1] ) .", "Genetic deficiency of Tregs mediated by lack of Foxp3 transcription factor yields autoimmunity in mice [2] and humans [3] .", "Numerical or functional deficiency of Tregs in murine models ...	[ "Immunotherapy using regulatory T cells ( Treg ) has been proposed , yet cellular and molecular mechanisms of human Tregs remain incompletely characterized .", "Here , we demonstrate that human Tregs promote the generation of myeloid dendritic cells ( DC ) with reduced capacity to stimulate effector T cell respon...	[ "Graft-versus-host disease ( GVHD ) is the most serious complication of bone marrow transplants between individuals ( so-called allogenic transplants ) .", "The class of suppressor immune cells called regulatory T cells ( Tregs ) inhibit GVHD by dampening the effects of donor immune cells in the grafted tissue ."...	2010
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biochemistry", "cell biology/cell signaling", "cell biology", "biochemistry/chemical biology of the cell", "chemical biology/protein chemistry and proteomics", "chemical biology/chemical biology of the cell" ]	Elevation of Intact and Proteolytic Fragments of Acute Phase Proteins Constitutes the Earliest Systemic Antiviral Response in HIV-1 Infection	journal.ppat.1000893	null	[ [ "Although human immunodeficiency virus type 1 ( HIV-1 ) induces a chronic infection ultimately culminating in the development of an acquired immunodeficiency syndrome , it is now recognized that critical damage to the host immune system is mediated during the acute phase of infection , when an exponential bur...	[ "The earliest immune responses activated in acute human immunodeficiency virus type 1 infection ( AHI ) exert a critical influence on subsequent virus spread or containment .", "During this time frame , components of the innate immune system such as macrophages and DCs , NK cells , β-defensins , complement and ot...	[ "Acquired immune deficiency syndrome ( AIDS ) remains a major health problem worldwide , affecting predominantly the adult population in the western world and in developing countries in particular .", "Despite a tremendous effort to develop a cure or a vaccine that confers protection against human immunodeficienc...	2010
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "blood cells", "medicine and health sciences", "immune cells", "pathology and laboratory medicine", "atrophy", "immunology", "cloning", "age groups", "adults", "signs and symptoms", "stem cells", "molecular biology techniques", "cytotoxic t cells", "research and analysis methods", "speci...	mTORC1 in Thymic Epithelial Cells Is Critical for Thymopoiesis, T-Cell Generation, and Temporal Control of γδT17 Development and TCRγ/δ Recombination	journal.pbio.1002370	The thymus is essential for making T cells but undergoes age- or stress-associated atrophy. This study demonstrates that mTOR complex 1 in thymic epithelial cells is crucial for correct thymic architecture and the production of mature T cells.	[ [ "The thymus is the primary organ for T cell development and generation of a diverse repertoire of T cells that are crucial for host defense but are also self-tolerated .", "Thymic epithelial cells ( TECs ) are essential for thymopoiesis and establish an environment that properly nurtures T cell developmen...	[ "Thymus is crucial for generation of a diverse repertoire of T cells essential for adaptive immunity .", "Although thymic epithelial cells ( TECs ) are crucial for thymopoiesis and T cell generation , how TEC development and function are controlled is poorly understood .", "We report here that mTOR complex 1 ( ...	[ "The thymus is the primary organ for T cell generation .", "Abnormal thymus function profoundly affects host immunity and numerous diseases .", "Thymopoiesis and thymus function rely on orchestrated interaction between multiple cell types representing different origins .", "Among them , thymic epithelial cell...	2016
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "spatial and landscape ecology", "medicine", "infectious diseases", "public health and epidemiology", "chagas disease", "ecology", "epidemiology", "genetics", "population genetics", "biology", "population ecology", "parasitic diseases", "genetics and genomics" ]	Hidden Sylvatic Foci of the Main Vector of Chagas Disease Triatoma infestans: Threats to the Vector Elimination Campaign?	journal.pntd.0001365	null	[ [ "Disease eradication or elimination programs depend on time-limited intensive campaigns and are likely to fail if resistance to insecticides or drugs ( i . e . , malaria ) or sylvatic transmission cycles ( i . e . , yellow fever ) occur .", "Chagas disease is the most important vector-borne disease in Lat...	[ "Establishing the sources of reinfestation after residual insecticide spraying is crucial for vector elimination programs .", "Triatoma infestans , traditionally considered to be limited to domestic or peridomestic ( abbreviated as D/PD ) habitats throughout most of its range , is the target of an elimination pro...	[ "Triatoma infestans , a highly domesticated species and historically the main vector of Trypanosoma cruzi , is the target of an insecticide-based elimination program in the southern cone countries of South America since 1991 .", "Only limited success has been achieved in the Gran Chaco region due to repeated rein...	2011
[ "Introduction", "Results", "Discussion", "Material and methods" ]	[ "bacteriology", "dimers (chemical physics)", "complement system", "medicine and health sciences", "immune physiology", "pathology and laboratory medicine", "viral transmission and infection", "hela cells", "molecular probe techniques", "pathogens", "biological cultures", "immunology", "micro...	Molecular basis for CesT recognition of type III secretion effectors in enteropathogenic Escherichia coli	journal.ppat.1007224	null	[ [ "Enteropathogenic and enterohemorrhagic Escherichia coli ( EPEC and EHEC ) cause acute gastroenteritis in humans and are a common source of outbreaks [1] .", "EPEC is a significant pathogen in the pediatric population , especially in areas with limited access to healthcare and clean water , whereas EHEC i...	[ "Enteropathogenic Escherichia coli ( EPEC ) use a needle-like injection apparatus known as the type III secretion system ( T3SS ) to deliver protein effectors into host cells .", "Effector translocation is highly stratified in EPEC with the translocated intimin receptor ( Tir ) being the first effector delivered ...	[ "Enteropathogenic Escherichia coli injects effector proteins into host cells using a type III secretion system ( T3SS ) .", "The translocated intimin receptor ( Tir ) is the first effector delivered into host cells and imparts efficient secretion of other effectors .", "However , the mechanism for Tir-dependent...	2018
[ "Introduction", "Materials and methods", "Results", "Discussion" ]	[ "medicine and health sciences", "pathology and laboratory medicine", "pathogens", "geographical locations", "microbiology", "sequence assembly tools", "genome analysis", "molecular biology techniques", "bacterial pathogens", "research and analysis methods", "sequence analysis", "artificial gen...	Human Treponema pallidum 11q/j isolate belongs to subsp. endemicum but contains two loci with a sequence in TP0548 and TP0488 similar to subsp. pertenue and subsp. pallidum, respectively	journal.pntd.0005434	null	[ [ "Treponema pallidum subsp .", "endemicum ( TEN ) is the causative agent of bejel ( endemic syphilis ) , a chronic human infection usually affecting children under 15 years of age .", "The primary stage of endemic syphilis is often localized to the mucosa of the oral cavity or nasopharynx and frequentl...	[ "Treponema pallidum subsp .", "endemicum ( TEN ) is the causative agent of endemic syphilis ( bejel ) .", "An unusual human TEN 11q/j isolate was obtained from a syphilis-like primary genital lesion from a patient that returned to France from Pakistan .", "The TEN 11q/j isolate was characterized using nested ...	[ "Treponema pallidum subsp .", "endemicum ( TEN ) is an uncultivable pathogenic treponeme that causes bejel ( endemic syphilis ) , a chronic human infection mostly affecting children under 15 years of age , occurring mainly in several African and Middle East countries .", "In this work , we characterized a TEN 1...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine", "infectious diseases", "gastroenterology and hepatology", "biology", "microbiology", "bacterial pathogens" ]	Inflammation and Disintegration of Intestinal Villi in an Experimental Model for Vibrio parahaemolyticus-Induced Diarrhea	journal.ppat.1002593	null	[ [ "Vibrio parahaemolyticus is a Gram-negative bacterium that resides in the marine environment , often in association with shellfish .", "It is a leading cause of gastroenteritis linked to consumption of raw or undercooked seafood throughout the world , and especially in Asia [1] .", "Infections caused ...	[ "Vibrio parahaemolyticus is a leading cause of seafood-borne gastroenteritis in many parts of the world , but there is limited knowledge of the pathogenesis of V . parahaemolyticus-induced diarrhea .", "The absence of an oral infection-based small animal model to study V . parahaemolyticus intestinal colonization...	[ "The marine bacterium Vibrio parahaemolyticus is a leading cause worldwide of gastroenteritis linked to the consumption of contaminated seafood .", "Despite the prevalence of V . parahaemolyticus-induced gastroenteritis , there is limited understanding of how this pathogen causes disease in the intestine .", "I...	2012
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "medicine and health sciences", "pathology and laboratory medicine", "fungal genetics", "gene regulation", "pathogens", "microbiology", "fungi", "model organisms", "experimental organism systems", "fungal pathogens", "saccharomyces", "research and analysis methods", "genome complexity", "m...	TPP riboswitch-dependent regulation of an ancient thiamin transporter in Candida	journal.pgen.1007429	null	[ [ "Riboswitches are RNA regulatory elements that are located within messenger RNA , and control gene expression [1] .", "The most common classes bind to small molecule ligands , ranging from coenzymes , S-adenosylmethionine ( SAM ) and amino acids to metal ions [2] .", "Other classes respond to temperat...	[ "Riboswitches are non-coding RNA molecules that regulate gene expression by binding to specific ligands .", "They are primarily found in bacteria .", "However , one riboswitch type , the thiamin pyrophosphate ( TPP ) riboswitch , has also been described in some plants , marine protists and fungi .", "We find ...	[ "Thiamin , or Vitamin B1 , is an essential requirement in all living organisms because it is a co-factor for many enzymes in metabolism .", "Unlike animals , many yeasts can synthesize thiamin , or they can import it from the environment .", "Expression of thiamin biosynthesis genes and of thiamin transporters ...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "invertebrates", "growth control", "evolutionary ecology", "ecology and environmental sciences", "animals", "animal models", "developmental biology", "drosophila melanogaster", "model organisms", "organism development", "evolutionary adaptation", "morphogenesis", "drosophila", "research an...	Drosophila Embryogenesis Scales Uniformly across Temperature in Developmentally Diverse Species	journal.pgen.1004293	null	[ [ "It has long been known that Drosophila , like most poikilotherms , develops faster at higher temperatures , with embryonic [1] , larval [1] , [2] , and pupal stages [3] , [4] , as well as total lifespan [5] , [6] showing similar logarithmic trends .", "While genetics , ecology , and evolution of this tra...	[ "Temperature affects both the timing and outcome of animal development , but the detailed effects of temperature on the progress of early development have been poorly characterized .", "To determine the impact of temperature on the order and timing of events during Drosophila melanogaster embryogenesis , we used ...	[ "Temperature profoundly impacts the rate of development of “cold-blooded” animals , which proceeds far faster when it is warm .", "There is , however , no universal relationship .", "Closely related species can develop at markedly different speeds at the same temperature .", "This creates a major challenge wh...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Calcium Regulation of Hemorrhagic Fever Virus Budding: Mechanistic Implications for Host-Oriented Therapeutic Intervention	journal.ppat.1005220	null	[ [ "There is an urgent and unmet need for safe and effective therapeutics against high priority pathogens , including filoviruses ( Ebola and Marburg ) and arenaviruses ( Lassa fever and Junín ) , which can cause fatal infections in humans .", "We and others have established that enveloped RNA viruses , incl...	[ "Hemorrhagic fever viruses , including the filoviruses ( Ebola and Marburg ) and arenaviruses ( Lassa and Junín viruses ) , are serious human pathogens for which there are currently no FDA approved therapeutics or vaccines .", "Importantly , transmission of these viruses , and specifically late steps of budding ,...	[ "Filoviruses ( Ebola and Marburg viruses ) and arenaviruses ( Lassa and Junín viruses ) are high-priority pathogens that hijack host proteins and pathways to complete their replication cycles and spread from cell to cell .", "Here we provide genetic and pharmacological evidence to demonstrate that the host calciu...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biogeography", "ecology and environmental sciences", "plant science", "model organisms", "plant genomics", "epigenetics", "theoretical ecology", "plant ecology", "dna methylation", "arabidopsis thaliana", "research and analysis methods", "gene expression", "plant genetics", "phylogeograph...	Century-scale Methylome Stability in a Recently Diverged Arabidopsis thaliana Lineage	journal.pgen.1004920	null	[ [ "Differences in DNA methylation and other epigenetic marks between individuals can be due to genetic variation , stochastic events or environmental factors .", "Epigenetic marks such as DNA methylation are dynamic; they can be turned over during mitosis and meiosis or altered by chromatin remodeling or up...	[ "There has been much excitement about the possibility that exposure to specific environments can induce an ecological memory in the form of whole-sale , genome-wide epigenetic changes that are maintained over many generations .", "In the model plant Arabidopsis thaliana , numerous heritable DNA methylation differ...	[ "It continues to be hotly debated to what extent environmentally induced epigenetic change is stably inherited and thereby contributes to short-term adaptation .", "It has been shown before that natural Arabidopsis thaliana lines differ substantially in their methylation profiles .", "How much of this is indepe...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "blood cells", "medicine and health sciences", "immune cells", "pathology and laboratory medicine", "vacuoles", "intracellular pathogens", "pathogens", "immunology", "microbiology", "animal models", "model organisms", "mitochondria", "bioenergetics", "cellular structures and organelles", ...	IFNs Modify the Proteome of Legionella-Containing Vacuoles and Restrict Infection Via IRG1-Derived Itaconic Acid	journal.ppat.1005408	null	[ [ "Intracellular bacteria are major causes of morbidity and mortality .", "Upon infection , many intracellular pathogens establish intracellular membrane-bound compartments , where they resist lysosomal degradation and humoral immune responses [1] .", "As a result of co-evolution , host cells have in tu...	[ "Macrophages can be niches for bacterial pathogens or antibacterial effector cells depending on the pathogen and signals from the immune system .", "Here we show that type I and II IFNs are master regulators of gene expression during Legionella pneumophila infection , and activators of an alveolar macrophage-intr...	[ "Numerous intracellular bacterial pathogens replicate in specialized vacuoles within macrophages .", "We systematically study the molecular mechanism and the impact of macrophage-intrinsic antibacterial defense .", "Using L . pneumophila , an important cause of pneumonia and model organism for intracellular bac...	2016
[ "Introduction", "Methods", "Results", "Discussion" ]	[]	Prevalence of Cryptosporidium parvum/hominis, Entamoeba histolytica and Giardia lamblia among Young Children with and without Diarrhea in Dar es Salaam, Tanzania	journal.pntd.0004125	null	[ [ "Diarrheal disease is a leading cause of mortality and morbidity in young children , estimated to cause more than 760 000 annual deaths among children < 5 years of age [1] , with 72% of these deaths occurring in children < 2 years of age [2] .", "Globally , diarrheal diseases take more lives than malaria ...	[ "Although enteroparasites are common causes of diarrheal illness , few studies have been performed among children in Tanzania .", "This study aimed to investigate the prevalence of Cryptosporidium parvum/hominis , Entamoeba histolytica and Giardia lamblia among young children in Dar es Salaam , Tanzania , and ide...	[ "Diarrheal diseases are a leading cause of disease and deaths among young children .", "In Africa they contribute to more than one tenth of childhood deaths .", "Parasites like Cryptosporidium , Entamoeba histolytica and Giardia lamblia are all common causes of diarrheal illness , but there are few studies on t...	2015
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "cell death", "invertebrates", "lysosomes", "autophagic cell death", "medicine and health sciences", "oxidative stress", "cell processes", "animals", "animal models", "drosophila melanogaster", "model organisms", "experimental organism systems", "eyes", "cellular structures and organelles"...	Pleiotropic role of Drosophila phosphoribosyl pyrophosphate synthetase in autophagy and lysosome homeostasis	journal.pgen.1008376	null	[ [ "Phosphoribosyl pyrophosphate synthetase ( PRPS ) is a rate-limiting enzyme in the biosynthesis of purine , pyrimidine , and , pyridine nucleotides ( Fig 1A ) .", "Purine and pyrimidine nucleotides are the building blocks of RNA and DNA while pyridine nucleotides , such as NAD+ and NADP , are important co...	[ "Phosphoribosyl pyrophosphate synthetase ( PRPS ) is a rate-limiting enzyme whose function is important for the biosynthesis of purines , pyrimidines , and pyridines .", "Importantly , while missense mutations of PRPS1 have been identified in neurological disorders such as Arts syndrome , how they contribute to n...	[ "Phosphoribosyl pyrophosphate synthetase ( PRPS ) is an important enzyme in nucleotide synthesis: the building blocks of DNA and RNA and other important metabolites .", "Importantly , while PRPS is mutated in neurological disorders such as Arts syndrome , Charcot-Marie-Tooth disease , and nonsyndromic sensorineur...	2019
[ "Introduction", "Results and discussion", "Materials and methods" ]	[ "cell physiology", "rna-binding proteins", "messenger rna", "parasitic protozoans", "organisms", "trypanosoma brucei", "fractional precipitation", "protozoans", "translation initiation", "research and analysis methods", "proteins", "gene expression", "precipitation techniques", "biochemist...	Comparative proteomics of the two T. brucei PABPs suggests that PABP2 controls bulk mRNA	journal.pntd.0006679	null	[ [ "Gene expression is regulated by multiple transcriptional and post-transcriptional mechanisms .", "At the post-transcriptional level , regulation of protein synthesis by modulation of translation initiation is a major contributor .", "The first step in mRNA cap-dependent translation initiation is asse...	[ "Poly ( A ) -binding proteins ( PABPs ) regulate mRNA fate by controlling stability and translation through interactions with both the poly ( A ) tail and eIF4F complex .", "Many organisms have several paralogs of PABPs and eIF4F complex components and it is likely that different eIF4F/PABP complex combinations r...	[ "Poly ( A ) -binding proteins ( PABPs ) bind to the poly ( A ) tails of eukaryotic mRNAs and function in regulating mRNA fate .", "Many eukaryotes have several PABP paralogs and the current view is that each PABP binds a specific subset of mRNAs .", "Trypanosoma brucei has two PABPs , and to understand the diff...	2018
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[]	Experimental and Natural Infections of Goats with Severe Fever with Thrombocytopenia Syndrome Virus: Evidence for Ticks as Viral Vector	journal.pntd.0004092	null	[ [ "Severe fever with thrombocytopenia syndrome ( SFTS ) is an emerging infectious disease caused by SFTS bunyavirus ( SFTSV ) [1] .", "This virus was originally identified in 6 provinces of central and northeastern China [1] .", "Later on , 10 more provinces have been added to the list of endemic region...	[ "Severe fever with thrombocytopenia syndrome virus ( SFTSV ) , the causative agent for the fatal life-threatening infectious disease , severe fever with thrombocytopenia syndrome ( SFTS ) , was first identified in the central and eastern regions of China .", "Although the viral RNA was detected in free-living and...	[ "Severe fever with thrombocytopenia syndrome virus ( SFTSV ) , a newly identified bunyavirus , has been found to circulate in mainland China , South Korea , and Japan since 2009 .", "This virus is the etiologic agent for an emerging fatal hemorrhagic fever , severe fever with thrombocytopenia syndrome ( SFTS ) wi...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biotechnology", "animal models of infection", "antivirals", "viral evolution", "mechanisms of resistance and susceptibility", "viral immune evasion", "virology", "immunology", "biology", "microbiology", "drug discovery", "immunoglobulins" ]	Human Monoclonal Antibody HCV1 Effectively Prevents and Treats HCV Infection in Chimpanzees	journal.ppat.1002895	null	[ [ "More than 180 million people worldwide are infected with hepatitis C virus ( HCV ) [1] , [2] with over 80% developing chronic disease marked by progressive hepatitis , fibrosis and cirrhosis that often results in liver failure [3] , [4] , requiring transplantation .", "Unfortunately nearly all donor allo...	[ "Hepatitis C virus ( HCV ) infection is a leading cause of liver transplantation and there is an urgent need to develop therapies to reduce rates of HCV infection of transplanted livers .", "Approved therapeutics for HCV are poorly tolerated and are of limited efficacy in this patient population .", "Human mono...	[ "The majority of individuals infected with hepatitis C virus ( HCV ) become chronically infected and many go on to develop liver failure requiring liver transplantation .", "Unfortunately , the transplanted liver becomes infected with HCV in nearly 100% of transplant patients .", "Current treatments for HCV are...	2012
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "infectious diseases/helminth infections", "developmental biology/embryology", "cell biology/developmental molecular mechanisms" ]	Correlative and Dynamic Imaging of the Hatching Biology of Schistosoma japonicum from Eggs Prepared by High Pressure Freezing	journal.pntd.0000334	null	[ [ "The pathology associated with chronic schistosomiasis is related to host responsiveness to antigens released by schistosome eggs entrapped in tissues [1] , [2] .", "The primary source of the secreted antigens in developing eggs is a distinct extra-embryonal layer that surrounds the differentiating embryo...	[ "Schistosome eggs must traverse tissues of the intestine or bladder to escape the human host and further the life cycle .", "Escape from host tissues is facilitated by secretion of immuno-reactive molecules by eggs and the formation of an intense strong granulomatous response by the host which acts to exclude the...	[ "Adult schistosomes live within portal veins of their human hosts .", "Their offspring , laid as eggs within the venous system , escape by traversing the tissues between the blood vessel and the gut or bladder lumen .", "Eggs voided into the external environment hatch spontaneously on contact with freshwater , ...	2008
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "computational neuroscience", "audio signal processing", "signal processing", "biology", "computational biology", "sensory systems", "neuroscience", "engineering", "coding mechanisms" ]	Sustained Firing of Model Central Auditory Neurons Yields a Discriminative Spectro-temporal Representation for Natural Sounds	journal.pcbi.1002982	null	[ [ "It is widely believed that sensory representations are optimized to process the stimuli to which they are exposed in natural environments [1] .", "Of particular interest is understanding the computational principles that underlie the generation of observed neural firing patterns .", "A popular hypoth...	[ "The processing characteristics of neurons in the central auditory system are directly shaped by and reflect the statistics of natural acoustic environments , but the principles that govern the relationship between natural sound ensembles and observed responses in neurophysiological studies remain unclear .", "In...	[ "We explore a fundamental question with regard to the representation of sound in the auditory system , namely: what are the coding strategies that underlie observed neurophysiological responses in central auditory areas ?", "There has been debate in recent years as to whether neural ensembles explicitly minimize ...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "sequencing techniques", "rna extraction", "mutation", "epigenetics", "molecular biology techniques", "plants", "flowering plants", "extraction techniques", "chromatin", "research and analysis methods", "sequence analysis", "genome complexity", "sequence alignment", "chromosome biology", ...	BRR2a Affects Flowering Time via FLC Splicing	journal.pgen.1005924	null	[ [ "The switch from the vegetative to the reproductive phase is an important developmental transition in flowering plants .", "The timing of this transition is regulated by several factors , including endogenous and environmental signals .", "In Arabidopsis , the photoperiod , vernalization and autonomou...	[ "Several pathways control time to flowering in Arabidopsis thaliana through transcriptional and posttranscriptional gene regulation .", "In recent years , mRNA processing has gained interest as a critical regulator of flowering time control in plants .", "However , the molecular mechanisms linking RNA splicing ...	[ "Timing of flowering has a great effect on reproductive success and fitness .", "It is controlled by many external signals and internal states involving a large set of genes .", "Here we report that the Arabidopsis thaliana BRR2a gene is needed for normal flowering .", "BRR2 proteins are components of the spl...	2016
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "stiffness", "mechanical properties", "medicine and health sciences", "diagnostic radiology", "engineering and technology", "cardiovascular anatomy", "signal processing", "osteoblasts", "microscopy", "pelvis", "connective tissue cells", "materials science", "research and analysis methods", ...	Creating High-Resolution Multiscale Maps of Human Tissue Using Multi-beam SEM	journal.pcbi.1005217	null	[ [ "Cells and cellular connectivity undoubtedly play a substantial role in tissue and organ scale behavior , yet mechanisms by which higher order system characteristics emerge from local cellular and molecular phenomena remain a conundrum .", "Recent advances in coupled , multiscale imaging and modeling of b...	[ "Multi-beam scanning electron microscopy ( mSEM ) enables high-throughput , nano-resolution imaging of macroscopic tissue samples , providing an unprecedented means for structure-function characterization of biological tissues and their cellular inhabitants , seamlessly across multiple length scales .", "Here we ...	[ "Until recently , the assessment of organ and tissue health relied on site-sampling ( biopsy ) of micro-scale regions and was fraught with sampling errors .", "Overcoming these limitations requires a means for seamless imaging of organs , from their cellular inhabitants to whole organs , akin to charting a map of...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genome sequencing", "genomics", "chromosome biology", "genetics", "epigenetics", "biology", "human genetics", "genetics and genomics" ]	Integrating 5-Hydroxymethylcytosine into the Epigenomic Landscape of Human Embryonic Stem Cells	journal.pgen.1002154	null	[ [ "The potency and fate of a cell can be influenced strongly by the covalent modification of cytosine methylation at carbon five .", "This critical epigenetic mark influences cellular potency and differentiation by modulating DNA-protein interactions , which direct epigenomic states and transcriptional proc...	[ "Covalent modification of DNA distinguishes cellular identities and is crucial for regulating the pluripotency and differentiation of embryonic stem ( ES ) cells .", "The recent demonstration that 5-methylcytosine ( 5-mC ) may be further modified to 5-hydroxymethylcytosine ( 5-hmC ) in ES cells has revealed a nov...	[ "Recent studies revealed the oxygenase-catalyzed production of 5-hydroxymethylcytosine ( 5-hmC ) as a modification to mammalian DNA .", "5-hmC is known to play important roles in self-renewal and cell lineage specification in embryonic stem ( ES ) cells , suggesting a potential role for 5-hmC–mediated epigenetic ...	2011
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "medicine", "neglected tropical diseases", "infectious diseases", "trachoma" ]	Field Evaluation of the Cepheid GeneXpert Chlamydia trachomatis Assay for Detection of Infection in a Trachoma Endemic Community in Tanzania	journal.pntd.0002265	null	[ [ "Trachoma , a chronic conjunctivitis caused by repeated infection with Chlamydia trachomatis ( CT ) , is currently the leading cause of infectious blindness [1] .", "In recognition of the public health problem of trachoma as a Neglected Tropical Disease ( NTD ) , the World Health Assembly passed a resolut...	[ "To determine the sensitivity , specificity , and field utility of the Cepheid GeneXpert Chlamydia trachomatis ( CT ) Assay ( GeneXpert ) for ocular chlamydia infection compared to Roche Amplicor CT assay ( Amplicor ) .", "In a trachoma-endemic community in Kongwa Tanzania , 144 children ages 0 to 9 were surveyed...	[ "Trachoma , an eye infection caused by C . trachomatis , is the leading cause of infectious blindness worldwide , affecting the developing world .", "The current standard for trachoma treatment involves mass drug administration ( MDA ) of an antibiotic that is given to a community to reduce transmission .", "A ...	2013
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "nucleases", "enzymes", "cell cycle and cell division", "cell processes", "dna-binding proteins", "enzymology", "fungi", "dna replication", "immunoprecipitation", "epigenetics", "dna", "synthesis phase", "co-immunoprecipitation", "chromatin", "research and analysis methods", "chromosom...	Identification of Elg1 interaction partners and effects on post-replication chromatin re-formation	journal.pgen.1007783	null	[ [ "The genetic material in eukaryotes is packaged into chromatin , composed mainly of DNA and nucleosomes .", "During DNA replication , DNA helicases separate the two parental strands of DNA and nucleosomes are removed from the DNA .", "Once the nascent DNA strands have been synthesized , the nucleosoma...	[ "Elg1 , the major subunit of a Replication Factor C-like complex , is critical to ensure genomic stability during DNA replication , and is implicated in controlling chromatin structure .", "We investigated the consequences of Elg1 loss for the dynamics of chromatin re-formation following DNA replication .", "Me...	[ "DNA replication is the central process that duplicates the genetic information during cell multiplication .", "Many cellular factors play important roles in the efficient and accurate duplication of DNA , critical for faithful transmission of genetic information .", "One such factor is Elg1 .", "Elg1 acts to...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine", "complement system", "clinical immunology", "genetic association studies", "lupus erythematosus", "genetics", "autoimmune diseases", "immunology", "biology", "human genetics", "genetics and genomics", "immune system" ]	Association of Genetic Variants in Complement Factor H and Factor H-Related Genes with Systemic Lupus Erythematosus Susceptibility	journal.pgen.1002079	null	[ [ "SLE ( OMIM 152700 ) is a debilitating autoimmune disease with strong genetic and environmental components , characterized by the production of autoantibodies resulting in tissue injury of multiple organs [1] .", "In SLE patients , aberrant complement activation leads to inflammatory injury [2] , and fluc...	[ "Systemic lupus erythematosus ( SLE ) , a complex polygenic autoimmune disease , is associated with increased complement activation .", "Variants of genes encoding complement regulator factor H ( CFH ) and five CFH-related proteins ( CFHR1-CFHR5 ) within the chromosome 1q32 locus linked to SLE , have been associa...	[ "Systemic lupus erythematosus ( SLE ) is a complex autoimmune disease , associated with increased complement activation .", "Previous studies have provided evidence for the presence of SLE susceptibility gene ( s ) in the chromosome 1q31-32 locus .", "Within 1q32 , genes encoding complement regulator factor H (...	2011
[ "Introduction", "Methods", "Results", "Discussion" ]	[]	Leprosy Reactions in Patients Coinfected with HIV: Clinical Aspects and Outcomes in Two Comparative Cohorts in the Amazon Region, Brazil	journal.pntd.0003818	null	[ [ "Leprosy , a chronic infectious disease caused by Mycobacterium leprae , can cause scars and deformities , especially if not treated quickly [1] .", "Brazil is currently responsible for approximately 92% of leprosy cases in the Americas , and is ranked second , behind India , in the number of global cases...	[ "Leprosy , caused by Mycobacterium leprae , can lead to scarring and deformities .", "Human immunodeficiency virus ( HIV ) , a lymphotropic virus with high rates of replication , leads to cell death in various stages of infection .", "These diseases have major social and quality of life costs , and although the...	[ "Leprosy and HIV infections , separately , are serious modern public health problems .", "Many studies have been conducted on these diseases , but knowledge gaps remain .", "This article provides the first account of important clinical information on a significant sample of patients with leprosy , as well as pa...	2015
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "coronary artery disease", "medicine and health sciences", "parasite evolution", "tropical diseases", "parasitic diseases", "parasitology", "electrocardiography", "bioassays and physiological analysis", "neglected tropical diseases", "immunologic techniques", "cardiology", "research and analys...	Evaluation of Parasiticide Treatment with Benznidazol in the Electrocardiographic, Clinical, and Serological Evolution of Chagas Disease	journal.pntd.0004508	null	[ [ "Chagas’ disease ( CD ) , described by Carlos Chagas in 1909[1] , and caused by a parasite–Trypanosoma cruzi , is one of the most important endemic diseases in Latin America , where there are 10 million people infected ( about two million in Brazil ) .", "The vectorial transmission has historically been t...	[ "Chagas disease is one of the most important endemic parasitic diseases in Latin America .", "In its chronic phase , progression to cardiomyopathy has high morbidity and mortality .", "The persistence of a normal electrocardiogram ( ECG ) provides a similar prognosis to that of a non-diseased population .", "...	[ "Twenty years of follow-up of patients with Chagas disease treated with benznidazole is presented in this paper .", "The persistence of a normal electrocardiogram ( ECG ) provides a similar prognosis to that of a non-diseased population .", "Benznidazole ( BNZ ) is the only drug with trypanocidal action availab...	2016

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