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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", "Model", "Results", "Discussion" ]	[ "nonlinear dynamics", "computer and information sciences", "systems science", "mathematics", "neural homeostasis", "computational neuroscience", "single neuron function", "physiology", "biology and life sciences", "brain electrophysiology", "computational biology", "electrophysiology", "phys...	Dynamics from Seconds to Hours in Hodgkin-Huxley Model with Time-Dependent Ion Concentrations and Buffer Reservoirs	journal.pcbi.1003941	null	[ [ "In this paper we study ion dynamics in ion-based neuron models .", "In comparison to classical HH type membrane models this introduces dynamics on much slower time scales .", "While spiking activity is in the order of milliseconds , the time scales of ion dynamics range from seconds to minutes and ev...	[ "The classical Hodgkin-Huxley ( HH ) model neglects the time-dependence of ion concentrations in spiking dynamics .", "The dynamics is therefore limited to a time scale of milliseconds , which is determined by the membrane capacitance multiplied by the resistance of the ion channels , and by the gating time const...	[ "The classical theory by Hodgkin and Huxley ( HH ) describes nerve impulses ( spikes ) that manifest communication between nerve cells .", "The underlying mechanism of a single spike is excitability , i . e . , a small disturbance triggers a large excursion that reverts without further input to the original state...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genetics and genomics/population genetics", "infectious diseases", "genetics and genomics/comparative genomics", "evolutionary biology/genomics" ]	Long- and Short-Term Selective Forces on Malaria Parasite Genomes	journal.pgen.1001099	null	[ [ "Half of the world's population is at risk of contracting malaria from Plasmodium species [1] , so an understanding of their biology has considerable potential to influence human health .", "An understanding of evolution and natural selection are particularly important , because malaria control is limited...	[ "Plasmodium parasites , the causal agents of malaria , result in more than 1 million deaths annually .", "Plasmodium are unicellular eukaryotes with small ∼23 Mb genomes encoding ∼5200 protein-coding genes .", "The protein-coding genes comprise about half of these genomes .", "Although evolutionary processes ...	[ "Malaria causes debilitating ill-health in millions of people and kills about one million people annually , mostly young children .", "It is caused by a single-cell Plasmodium parasite transmitted to humans via mosquito bites .", "It is difficult to control this parasite because variable genetic make-up enables...	2010
[ "Introduction", "Results", "Discussion", "Methods" ]	[]	Emergence of Metastable State Dynamics in Interconnected Cortical Networks with Propagation Delays	journal.pcbi.1003304	null	[ [ "Cognition emerges from the organized temporal structure of electric activity in large , interconnected cortical networks [1]–[3] .", "The network topology is a key determinant of the types of macroscopic activity patterns a network can generate [4]–[11] .", "Understanding this structure-function rela...	[ "The importance of the large number of thin-diameter and unmyelinated axons that connect different cortical areas is unknown .", "The pronounced propagation delays in these axons may prevent synchronization of cortical networks and therefore hinder efficient information integration and processing .", "Yet , suc...	[ "The brain mediates behavior by orchestrating the activity of billions of neurons that communicate with each other through electric impulses .", "The transmission of these action potentials is surprisingly slow for a large fraction of these connections .", "Given the importance of precise timing of neuronal act...	2013
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "biochemistry", "proteins", "protein structure", "biology and life sciences", "computational biology", "biophysics", "molecular biology", "macromolecular structure analysis", "biophysical simulations" ]	A Coarse-Grained Elastic Network Atom Contact Model and Its Use in the Simulation of Protein Dynamics and the Prediction of the Effect of Mutations	journal.pcbi.1003569	null	[ [ "Biological macromolecules are dynamic objects .", "In the case of proteins , such movements form a continuum ranging from bond and angle vibrations , sub-rotameric and rotameric side-chain rearrangements [1] , loop or domain movements through to folding .", "Such movements are closely related to func...	[ "Normal mode analysis ( NMA ) methods are widely used to study dynamic aspects of protein structures .", "Two critical components of NMA methods are coarse-graining in the level of simplification used to represent protein structures and the choice of potential energy functional form .", "There is a trade-off be...	[ "Normal mode analysis ( NMA ) methods can be used to explore potential movements around an equilibrium conformation by mean of calculating the eigenvectors and eigenvalues associated to different normal modes .", "Each normal mode represents a global collective , correlated and complex , form of motion of the ent...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "immunology/antigen processing and recognition", "immunology/immune response", "infectious diseases/viral infections", "immunology/immunity to infections" ]	Genetic and Structural Basis for Selection of a Ubiquitous T Cell Receptor Deployed in Epstein-Barr Virus Infection	journal.ppat.1001198	null	[ [ "Epstein-Barr virus ( EBV ) , also called human herpesvirus 4 ( HHV-4 ) , is a genetically stable agent that has slowly co-evolved with our species and its antecedents for millions of years .", "EBV is typically transmitted orally during childhood , propagates in B cells and epithelia , and is shed for th...	[ "Despite the ∼1018 αβ T cell receptor ( TCR ) structures that can be randomly manufactured by the human thymus , some surface more frequently than others .", "The pinnacles of this distortion are public TCRs , which exhibit amino acid-identical structures across different individuals .", "Public TCRs are though...	[ "The human immune recombination machinery can generate approximately 1018 unique αβ T cell receptor structures .", "The recombination event , once thought to be random , has now been shown to involve enzymatic biases during chromosomal rearrangement; additional biases occur during thymic selection and antigen-dri...	2010
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "cell biology/cell growth and division", "microbiology/parasitology", "cell biology/cytoskeleton" ]	Functional Characterisation and Drug Target Validation of a Mitotic Kinesin-13 in Trypanosoma brucei	journal.ppat.1001050	null	[ [ "Although molecular evolutionary analysis places the branching point of kinetoplastids near the root of the eukaryotic tree , many aspects of their cellular architecture and complexity are nevertheless not hugely divergent from metazoan organisms [1] .", "One of the most conserved elements between kinetop...	[ "Mitotic kinesins are essential for faithful chromosome segregation and cell proliferation .", "Therefore , in humans , kinesin motor proteins have been identified as anti-cancer drug targets and small molecule inhibitors are now tested in clinical studies .", "Phylogenetic analyses have assigned five of the ap...	[ "Kinesins represent a class of mechanochemical enzymes that are able to move along microtubule filaments and transport cargo in a directional manner within the cell .", "Of particular importance are mitotic kinesins , as they ensure the accurate segregation of chromosomes and therefore cell survival .", "Such k...	2010
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "cell physiology", "gene regulation", "vertebrates", "animals", "mammals", "cell differentiation", "muscle regeneration", "animal models", "developmental biology", "model organisms", "organism development", "stem cells", "bioassays and physiological analysis", "morphogenesis", "research ...	Genetic Evidence That Captured Retroviral Envelope syncytins Contribute to Myoblast Fusion and Muscle Sexual Dimorphism in Mice	journal.pgen.1006289	null	[ [ "Syncytins are “captured” genes of retroviral origin that correspond to the envelope gene of ancestrally endogenized retroviruses ( reviewed in [1] ) .", "These genes encode fusogenic proteins that are involved in the formation by cell-cell fusion of the placental syncytiotrophoblast in eutherian mammals ...	[ "Syncytins are envelope genes from endogenous retroviruses , “captured” for a role in placentation .", "They mediate cell-cell fusion , resulting in the formation of a syncytium ( the syncytiotrophoblast ) at the fetomaternal interface .", "These genes have been found in all placental mammals in which they have...	[ "Syncytins are “captured” genes of retroviral origin , corresponding to the fusogenic envelope gene of endogenized retroviruses .", "They are present in all placental mammals in which they have been searched for , where they play an essential role in placentation via their cell-cell fusion activity .", "Here we...	2016
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "sequencing techniques", "medicine and health sciences", "protein interactions", "applied mathematics", "enzymology", "simulation and modeling", "algorithms", "mathematics", "forecasting", "statistics (mathematics)", "artificial intelligence", "pharmacology", "molecular biology techniques", ...	Computational-experimental approach to drug-target interaction mapping: A case study on kinase inhibitors	journal.pcbi.1005678	null	[ [ "Deregulated kinase activity plays a role in many diseases , hence calling for therapeutic compounds that could effectively inhibit specific members of the protein kinome .", "Although kinase inhibitors form the largest group of new drugs approved for cancer treatment [1] , a majority of them are ATP-comp...	[ "Due to relatively high costs and labor required for experimental profiling of the full target space of chemical compounds , various machine learning models have been proposed as cost-effective means to advance this process in terms of predicting the most potent compound-target interactions for subsequent verificat...	[ "Significant efforts have been devoted in recent years to the development of machine learning models to support different stages of drug development process .", "Given the enormous size of the chemical universe , such models could offer a complementary and cost-effective means to experimental determination of dru...	2017
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "visual system", "mathematics", "computational neuroscience", "biology", "computational biology", "sensory systems", "neuroscience", "nonlinear dynamics" ]	A Model for the Origin and Properties of Flicker-Induced Geometric Phosphenes	journal.pcbi.1002158	null	[ [ "Ever since they were first described by Jan Purkinje in 1819 , the swirling geometric visual patterns brought on by diffuse flickering light have fascinated both scientists and artists .", "Helmholtz described the patterns at the turn of the twentieth century .", "The invention of the stroboscope ena...	[ "We present a model for flicker phosphenes , the spontaneous appearance of geometric patterns in the visual field when a subject is exposed to diffuse flickering light .", "We suggest that the phenomenon results from interaction of cortical lateral inhibition with resonant periodic stimuli .", "We find that the...	[ "When the human visual system is subjected to diffuse flickering light in the range of 5-25 Hz , many subjects report beautiful swirling colorful geometric patterns .", "In the years since Jan Purkinje first described them , there have been many qualitative and quantitative analyses of the conditions in which the...	2011
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "medicine and health sciences", "cancers and neoplasms", "vertebrates", "animals", "oncology", "animal models", "osteichthyes", "developmental biology", "negative staining", "model organisms", "experimental organism systems", "epigenetics", "embryos", "eyes", "chromatin", "research and...	Loss of the chromatin modifier Kdm2aa causes BrafV600E-independent spontaneous melanoma in zebrafish	journal.pgen.1006959	null	[ [ "The World Health Organisation ( WHO ) reports that 132 , 000 melanoma skin cancers occur each year across the globe , with increasing incidence rates .", "Melanomas are cancers of the melanocytes , which are neural crest-derived pigment-producing cells in vertebrates .", "Accumulation of mutations , ...	[ "KDM2A is a histone demethylase associated with transcriptional silencing , however very little is known about its in vivo role in development and disease .", "Here we demonstrate that loss of the orthologue kdm2aa in zebrafish causes widespread transcriptional disruption and leads to spontaneous melanomas at a h...	[ "Epigenetic modifications of DNA and histones , the major components of chromatin , play a central role in transcriptional regulation .", "KDM2A is a histone demethylase that integrates DNA and histone modification signatures and is involved in transcriptional silencing through heterochromatin maintenance .", "...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "invertebrates", "rna interference", "chemical compounds", "enzymes", "enzymology", "animals", "organic compounds", "animal models", "drosophila melanogaster", "model organisms", "basic amino acids", "amino acids", "epigenetics", "genetic interactions", "ligases", "mapk signaling casca...	The Deubiquitinase USP47 Stabilizes MAPK by Counteracting the Function of the N-end Rule ligase POE/UBR4 in Drosophila	journal.pbio.1002539	In Drosophila, steady-state levels of the regulatory protein MAPK are found to be governed by the opposing actions of the deubiquitinase USP47 and components of the N-end rule pathway.	[ [ "The RAS-MAPK pathway is one of the principal signaling conduits controlling proliferation and differentiation in metazoans .", "Perturbations in pathway activity are closely associated to oncogenesis and developmental disorders [1 , 2] .", "Signaling through the small GTPase RAS is typically initiate...	[ "RAS-induced MAPK signaling is a central driver of the cell proliferation apparatus .", "Disruption of this pathway is widely observed in cancer and other pathologies .", "Consequently , considerable effort has been devoted to understanding the mechanistic aspects of RAS-MAPK signal transmission and regulation ...	[ "The RAS-MAPK pathway plays a central role in the development of multicellular organisms , predominantly by regulating cell proliferation and differentiation .", "At its core , the pathway includes the RAS GTPase and three kinases ( RAF , MEK , and MAPK ) that transmit RAS signals through a phosphorylation cascad...	2016
[ "Introduction", "Materials and methods", "Results", "Discussion", "Conclusions" ]	[ "medicine and health sciences", "ecology and environmental sciences", "surface water", "tropical diseases", "geographical locations", "uganda", "health care", "bacterial diseases", "aquatic environments", "bodies of water", "neglected tropical diseases", "sanitation", "africa", "hydrology"...	Epidemiology of cholera outbreaks and socio-economic characteristics of the communities in the fishing villages of Uganda: 2011-2015	journal.pntd.0005407	null	[ [ "Cholera remains a major public health problem in many countries in sub-Saharan Africa .", "In 2014 , 190 , 549 cases and 2 , 231 deaths were reported to the World Health Organization ( WHO ) .", "Among 2 , 231 deaths , 1 , 882 ( 84 . 3% ) were from Africa [1] .", "Some authors estimate that the r...	[ "The communities in fishing villages in the Great Lakes Region of Africa and particularly in Uganda experience recurrent cholera outbreaks that lead to considerable mortality and morbidity .", "We evaluated cholera epidemiology and population characteristics in the fishing villages of Uganda to better target prev...	[ "Cholera , though a preventable and treatable disease , remains a major cause of morbidity and mortality in the Great Lakes Region of Africa , including Uganda .", "The communities in the fishing villages constitute 5–10% of the total Ugandan population .", "Most fishing villages are located along Lakes Victori...	2017
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "chemistry", "biology" ]	Common Host-Derived Chemicals Increase Catches of Disease-Transmitting Mosquitoes and Can Improve Early Warning Systems for Rift Valley Fever Virus	journal.pntd.0002007	null	[ [ "Rift Valley fever ( RVF ) is a mosquito-borne zoonosis which is of major public health and veterinary concern in sub-Saharan Africa ( SSA ) .", "In the last 20 years , epidemics of the disease have occurred at irregular intervals with hundreds of thousands of infections in humans and livestock .", "T...	[ "Rift Valley fever ( RVF ) , a mosquito-borne zoonosis , is a major public health and veterinary problem in sub-Saharan Africa .", "Surveillance to monitor mosquito populations during the inter-epidemic period ( IEP ) and viral activity in these vectors is critical to informing public health decisions for early w...	[ "Enzootic transmission of arboviral diseases such as Rift Valley Fever ( RVF ) continues to occur at a low intensity among mosquito vectors in Kenya , which may remain undetected by most monitoring programs unless very sensitive tools are employed to detect virus activity before an outbreak occurs .", "Here , we ...	2013
[ "Introduction", "Methods", "Results", "Discussion", "Conclusions" ]	[ "schistosoma", "invertebrates", "schistosoma mansoni", "parasite groups", "medicine and health sciences", "plasmodium", "helminths", "tropical diseases", "microbiology", "plasmodium falciparum", "parasitic diseases", "animals", "parasitic protozoans", "parasitology", "pediatrics", "api...	Plasmodium falciparum Infection Status among Children with Schistosoma in Sub-Saharan Africa: A Systematic Review and Meta-analysis	journal.pntd.0005193	null	[ [ "Malaria and schistosomiasis are common in tropical and sub-tropical areas , causing high burden of morbidity and mortality , particularly in children [1 , 2] .", "In 2015 , about 214 million people were infected and 438 , 000 estimated to have died globally due to malaria [1] .", "Additionally , more...	[ "It has been suggested that Schistosoma infection may be associated with Plasmodium falciparum infection or related reduction in haemoglobin level , but the nature of this interaction remains unclear .", "This systematic review synthesized evidence on the relationship of S . haematobium or S . mansoni infection w...	[ "A clear understanding of the epidemiology of malaria during Schistosoma co-infection is essential to inform decisions on appropriate control strategies for schistosomiasis and malaria in SSA .", "In this systematic review and meta-analysis , we synthesized evidence on the nature of relationship of S . haematobiu...	2016
[ "Introduction", "Results", "Discussion" ]	[ "medicine and health sciences", "neural networks", "engineering and technology", "nervous system", "applied mathematics", "brain electrophysiology", "electrophysiology", "neuroscience", "simulation and modeling", "algorithms", "mathematics", "brain mapping", "network analysis", "bioassays ...	Modeling of Large-Scale Functional Brain Networks Based on Structural Connectivity from DTI: Comparison with EEG Derived Phase Coupling Networks and Evaluation of Alternative Methods along the Modeling Path	journal.pcbi.1005025	null	[ [ "In this study we probed this assumption of a strong structure-function relationship by simulating local node dynamics based on SC and comparing the phase relationships emerging from the simulated neural activity with empirically measured phase relationships .", "To this end , we combined SC from DTI data...	[ "In this study , we investigate if phase-locking of fast oscillatory activity relies on the anatomical skeleton and if simple computational models informed by structural connectivity can help further to explain missing links in the structure-function relationship .", "We use diffusion tensor imaging data and alph...	[ "Brain imaging techniques are broadly divided into the two categories of structural and functional imaging .", "Structural imaging provides information about the static physical connectivity within the brain , while functional imaging provides data about the dynamic ongoing activation of brain areas .", "Comput...	2016
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "medicine and health sciences", "engineering and technology", "nervous system", "signal processing", "electrical circuits", "membrane potential", "electrophysiology", "neuroscience", "signal filtering", "simulation and modeling", "probability distribution", "mathematics", "population biology...	The Computational Properties of a Simplified Cortical Column Model	journal.pcbi.1005045	null	[ [ "For more than a century , neuroscientists have worked to refine descriptions of cortical anatomy , either differentiating or consolidating models of cortical circuits [1] .", "The notion that a fundamental neuronal circuit performs a canonical computation in neocortex , that can be generalized across spe...	[ "The mammalian neocortex has a repetitious , laminar structure and performs functions integral to higher cognitive processes , including sensory perception , memory , and coordinated motor output .", "What computations does this circuitry subserve that link these unique structural elements to their function ?", ...	[ "What computations do existing biophysically-plausible models of cortex perform on their inputs , and how do these computations relate to theories of cortical processing ?", "We begin with a computational model of cortical tissue and seek to understand its input/output transformations .", "Our approach limits c...	2016
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "infectious diseases/bacterial infections" ]	Detection of Mycolactone A/B in Mycobacterium ulcerans–Infected Human Tissue	journal.pntd.0000577	null	[ [ "Mycobacterium ulcerans ( Mu ) disease ( Buruli ulcer ) is common in humid rural tropical areas mainly in West Africa and predominantly affects children between 5 and 15 years of age [1] .", "The classic lesion is a painless nodule which breaks down centrally to form an ulcer with undermined edges .", ...	[ "Mycobacterium ulcerans disease ( Buruli ulcer ) is a neglected tropical disease common amongst children in rural West Africa .", "Animal experiments have shown that tissue destruction is caused by a toxin called mycolactone .", "A molecule was identified among acetone-soluble lipid extracts from M . ulcerans (...	[ "Skin infection with bacteria called Mycobacterium ulcerans causes Buruli ulcer , a disease common in West Africa and mainly affecting children .", "M . ulcerans is the only mycobacterium to cause disease by production of a toxin .", "This lipid molecule called mycolactone diffuses from the site of infection , ...	2010
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "parasite groups", "nuclear staining", "parasite replication", "plasmodium", "parasitic protozoans", "parasitology", "plasmid construction", "apicomplexa", "protozoans", "dna construction", "molecular biology techniques", "research and analysis methods", "specimen preparation and treatment",...	Plasmodium falciparum dipeptidyl aminopeptidase 3 activity is important for efficient erythrocyte invasion by the malaria parasite	journal.ppat.1007031	null	[ [ "Malaria is a devastating infectious disease caused by Apicomplexan parasites of the Plasmodium genus and is transmitted by Anopheles mosquitoes during a blood meal .", "After an initial asymptomatic liver infection , parasites are released into the blood stream where they replicate within red blood cells...	[ "Parasite egress from infected erythrocytes and invasion of new red blood cells are essential processes for the exponential asexual replication of the malaria parasite .", "These two tightly coordinated events take place in less than a minute and are in part regulated and mediated by proteases .", "Dipeptidyl a...	[ "Malaria remains one of the most devastating infectious diseases and its clinical manifestation is caused by the exponential multiplication of parasites in patients .", "This asexual replication cycle consists of red blood cell invasion , intracellular parasite multiplication , and release ( also known as egress ...	2018
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "cell death", "cellular stress responses", "forkhead box", "evolutionary biology", "gene regulation", "cell processes", "hormones", "developmental biology", "small interfering rnas", "proteins", "gene expression", "biochemistry", "rna", "cell biology", "nucleic acids", "apoptosis", "...	The mammalian decidual cell evolved from a cellular stress response	journal.pbio.2005594	null	[ [ "Multicellular organisms consist of numerous specialized cells , or cell types , that play an important role in the structural and functional diversity of organisms .", "Evolutionary diversification of cell types in metazoans has been a significant source of novelty and was essential to the elaboration of...	[ "Among animal species , cell types vary greatly in terms of number and kind .", "The number of cell types found within an organism differs considerably between species , and cell type diversity is a significant contributor to differences in organismal structure and function .", "These observations suggest that ...	[ "Animals consist of a wide variety of cells that serve different functions depending on their location in the body .", "Cells with similar functions , or cell types , in different animal species are related both by an evolutionary line of descent—similar to the relatedness of species themselves—and by a developme...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	A Genetic Selection for dinB Mutants Reveals an Interaction between DNA Polymerase IV and the Replicative Polymerase That Is Required for Translesion Synthesis	journal.pgen.1005507	null	[ [ "Despite the actions of several DNA repair pathways , lesions capable of blocking progression of the replicative DNA polymerase ( Pol ) persist in the DNA template .", "Translesion DNA synthesis ( TLS ) represents one evolutionarily conserved mechanism by which organisms cope with these replication-blocki...	[ "Translesion DNA synthesis ( TLS ) by specialized DNA polymerases ( Pols ) is a conserved mechanism for tolerating replication blocking DNA lesions .", "The actions of TLS Pols are managed in part by ring-shaped sliding clamp proteins .", "In addition to catalyzing TLS , altered expression of TLS Pols impedes c...	[ "Bacterial DNA polymerase IV ( Pol IV ) is capable of replicating damaged DNA via a process termed translesion DNA synthesis ( TLS ) .", "Pol IV-mediated TLS can be accurate or error-prone , depending on the type of DNA damage .", "Errors made by Pol IV contribute to antibiotic resistance and adaptation of bact...	2015
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "invertebrates", "plant anatomy", "trichomes", "medicine and health sciences", "legs", "limbs (anatomy)", "animals", "animal models", "developmental biology", "plant science", "model organisms", "drosophila melanogaster", "experimental organism systems", "skeleton", "drosophila", "rese...	Gene regulatory network architecture in different developmental contexts influences the genetic basis of morphological evolution	journal.pgen.1007375	null	[ [ "A major challenge in biology is to understand the relationship between genotype and phenotype , and how genetic changes modify development to generate phenotypic diversification .", "The genetic basis of many phenotypic differences within and among species have been identified [e . g . 1–15] , and these ...	[ "Convergent phenotypic evolution is often caused by recurrent changes at particular nodes in the underlying gene regulatory networks ( GRNs ) .", "The genes at such evolutionary ‘hotspots’ are thought to maximally affect the phenotype with minimal pleiotropic consequences .", "This has led to the suggestion tha...	[ "A major goal of biology is to identify the genetic causes of organismal diversity .", "Convergent evolution of traits is often caused by changes in the same genes–evolutionary ‘hotspots’ .", "shavenbaby is a ‘hotspot’ for larval trichome loss in Drosophila , but microRNA-92a underlies the gain of leg trichomes...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "microbiology/immunity to infections", "microbiology/innate immunity", "immunology/innate immunity", "infectious diseases/bacterial infections", "immunology/immunity to infections" ]	XIAP Regulates Cytosol-Specific Innate Immunity to Listeria Infection	journal.ppat.1000142	null	[ [ "The inhibitor of apoptosis ( IAP ) family of proteins plays a key role in cellular signaling , such as apoptosis , by binding to pro-apoptotic proteins , interrupting the intrinsic programmed cell death pathway and activating anti-apoptotic mechanisms [1]–[3] .", "In addition to modulating apoptosis , re...	[ "The inhibitor of apoptosis protein ( IAP ) family has been implicated in immune regulation , but the mechanisms by which IAP proteins contribute to immunity are incompletely understood .", "We show here that X-linked IAP ( XIAP ) is required for innate immune control of Listeria monocytogenes infection .", "Mi...	[ "During a bacterial infection , the innate immune response plays two critical roles: controlling early bacterial replication and stimulating the adaptive immune response to clear infection .", "Host recognition of bacterial components occurs through pathogen sensors at the cell surface or within the host cell cyt...	2008
[ "Introduction", "Results", "Discussion", "Methods" ]	[]	Robust Demographic Inference from Genomic and SNP Data	journal.pgen.1003905	null	[ [ "Reconstructing the past history of a given species is important not only for its own sake , but for disentangling demographic from selective effects [1] , [2] .", "Demography is indeed often estimated on a set of markers and the best neutral model is used as a null for evidencing markers under selection ...	[ "We introduce a flexible and robust simulation-based framework to infer demographic parameters from the site frequency spectrum ( SFS ) computed on large genomic datasets .", "We show that our composite-likelihood approach allows one to study evolutionary models of arbitrary complexity , which cannot be tackled b...	[ "We present a new likelihood-based method to infer the past demography of a set of populations from large genomic datasets .", "Our method can be applied to arbitrarily complex models as the likelihood is estimated by coalescent simulations .", "Under simple scenarios , our method behaves similarly to a widely ...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "chitin", "invertebrates", "animals", "animal models", "drosophila melanogaster", "animal anatomy", "model organisms", "microscopy", "materials science", "zoology", "macromolecules", "drosophila", "materials by structure", "research and analysis methods", "polymers", "polymer chemistry...	The Gene Expression Program for the Formation of Wing Cuticle in Drosophila	journal.pgen.1006100	null	[ [ "The cuticular exoskeleton of insects provides multiple functions for the animal .", "It provides shape , protects the animal from the environment , limits water loss and provides the skeletal elements needed for locomotion .", "In different tissues of an individual animal the cuticle will have very d...	[ "The cuticular exoskeleton of insects and other arthropods is a remarkably versatile material with a complex multilayer structure .", "We made use of the ability to isolate cuticle synthesizing cells in relatively pure form by dissecting pupal wings and we used RNAseq to identify genes expressed during the format...	[ "Insects and other arthropods are an extremely successful group of animals .", "A unique and key feature of their lifestyle is their chitin containing cuticular exoskeleton , a complex layered material , which remains rather poorly understood for so prominent of a biological material .", "We have characterized ...	2016
[ "Introduction", "Methods", "Results/Discussion" ]	[ "genetics and genomics/gene discovery", "genetics and genomics/comparative genomics", "evolutionary biology/evolutionary and comparative genetics", "infectious diseases/neglected tropical diseases", "evolutionary biology/genomics", "genetics and genomics/genome projects", "infectious diseases/protozoal ...	The Genome Sequence of Trypanosoma brucei gambiense, Causative Agent of Chronic Human African Trypanosomiasis	journal.pntd.0000658	null	[ [ "Trypanosoma brucei subsp .", "gambiense is the causative agent of Human African Trypanosomiasis ( HAT ) , or sleeping sickness , which is a vector-borne disease restricted to rural areas of sub-Saharan Africa .", "Trypanosomiasis in humans and livestock imposes substantial morbidity , representing a ...	[ "Trypanosoma brucei gambiense is the causative agent of chronic Human African Trypanosomiasis or sleeping sickness , a disease endemic across often poor and rural areas of Western and Central Africa .", "We have previously published the genome sequence of a T . b .", "brucei isolate , and have now employed a co...	[ "Sleeping sickness , or Human African Trypanosomiasis , is a disease affecting the health and productivity of poor people in many rural areas of sub-Saharan Africa .", "The disease is caused by a single-celled flagellate , Trypanosoma brucei , which evades the immune system by periodically switching the proteins ...	2010
[ "Introduction", "Results/Discussion", "Methods" ]	[ "infectious diseases/bacterial infections", "cell biology/cytoskeleton", "molecular biology", "cell biology/cell signaling" ]	Tyrosine-Phosphorylated Caveolin-1 Blocks Bacterial Uptake by Inducing Vav2-RhoA-Mediated Cytoskeletal Rearrangements	journal.pbio.1000457	During the early stages of infection, Neisseria gonorrhoeae triggers a phosphotyrosine-dependent Cav1-Vav2-RhoA signaling cascade that promotes the pathogen's extracellular state.	[ [ "The primarily extracellular obligate human pathogen Neisseria gonorrhoeae ( P+GC ) is the causative agent of the sexually transmitted disease gonorrhoea , affecting over 60 million people every year worldwide [1] .", "It is a type IV pili ( Tfp ) -producing bacteria that colonizes mucosal epithelia of th...	[ "Certain bacterial adhesins appear to promote a pathogen's extracellular lifestyle rather than its entry into host cells .", "However , little is known about the stimuli elicited upon such pathogen host-cell interactions .", "Here , we report that type IV pili ( Tfp ) -producing Neisseria gonorrhoeae ( P+GC ) i...	[ "Like many bacterial pathogens , successful attachment of Neisseria gonorrhoeae—the causative agent of the sexually transmitted disease gonorrhoea—to its host cells depends on specialized structures on the bacterial surface called type IV pili ( Tfp ) .", "Pathogen attachment induces changes within host cells tha...	2010
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genome-wide association studies", "genome expression analysis", "genomics", "functional genomics", "gene expression", "genetics", "molecular genetics", "biology", "human genetics", "population genetics", "genetics of disease", "genetics and genomics" ]	Use of Allele-Specific FAIRE to Determine Functional Regulatory Polymorphism Using Large-Scale Genotyping Arrays	journal.pgen.1002908	null	[ [ "The proliferation of genome-wide association studies ( GWAS ) has achieved considerable advances concerning the identification of novel genetic loci associated with phenotypic traits and diseases , and also confirmed many established genetic associations .", "Following GWAS , the next objective in geneti...	[ "Following the widespread use of genome-wide association studies ( GWAS ) , focus is turning towards identification of causal variants rather than simply genetic markers of diseases and traits .", "As a step towards a high-throughput method to identify genome-wide , non-coding , functional regulatory variants , w...	[ "The identification of genetic variants associated with complex diseases has rapidly grown through lowering costs of genome sequencing and the use of large-scale genotyping chips based on this sequencing data .", "There have not been corresponding advances in the identification of causal genetic variants compared...	2012
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "gastroenterology and hepatology", "medicine and health sciences" ]	Inhibition of cAMP-Activated Intestinal Chloride Secretion by Diclofenac: Cellular Mechanism and Potential Application in Cholera	journal.pntd.0003119	null	[ [ "Transepithelial Cl− secretion is an essential transport process in intestine and plays an important role in determining intestinal fluid secretion [1] .", "Chloride secretion creates a negative electrical potential , which in turn provides a driving force for transport of Na+ and water into intestinal lu...	[ "Cyclic AMP-activated intestinal Cl− secretion plays an important role in pathogenesis of cholera .", "This study aimed to investigate the effect of diclofenac on cAMP-activated Cl− secretion , its underlying mechanisms , and possible application in the treatment of cholera .", "Diclofenac inhibited cAMP-activa...	[ "Diarrhea in cholera results from stimulation of cAMP-mediated intestinal Cl− secretion by cholera toxin ( CT ) .", "This study demonstrates that diclofenac , a widely used non-steroidal anti-inflammatory drug ( NSAID ) , inhibited cAMP-activated Cl− secretion in human intestinal epithelial ( T84 ) cells by inhib...	2014
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "invertebrates", "medicine and health sciences", "chemical compounds", "carbamates", "tropical diseases", "parasitic diseases", "animals", "organic compounds", "infectious disease control", "insect vectors", "zoology", "public and occupational health", "agrochemicals", "infectious diseases...	Efficacy of novel indoor residual spraying methods targeting pyrethroid-resistant Aedes aegypti within experimental houses	journal.pntd.0007203	null	[ [ "Vector control is the principal approach for managing Aedes aegypti and reducing transmission of Aedes-borne diseases ( ABD; e . g . , dengue , chikungunya , Zika ) .", "Implementation of vector control targeting ABDs has primarily been in response to reports of virus transmission , using methods such as...	[ "Challenges in maintaining high effectiveness of classic vector control in urban areas has renewed the interest in indoor residual spraying ( IRS ) as a promising approach for Aedes-borne disease prevention .", "While IRS has many benefits , application time and intrusive indoor applications make its scalability ...	[ "Vector control is the primary strategy for managing Aedes aegypti and reducing transmission of Aedes-borne diseases; however , the indoor resting behavior of Ae .", "aegypti and the evolution of insecticide resistance reduces the effectiveness of many vector control tactics .", "Indoor residual spraying ( IRS ...	2019
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "sequencing techniques", "medicine and health sciences", "x chromosome inactivation", "gene regulation", "messenger rna", "dna transcription", "simulation and modeling", "molecular biology techniques", "epigenetics", "rna sequencing", "kidneys", "research and analysis methods", "gene express...	Allele-specific RNA imaging shows that allelic imbalances can arise in tissues through transcriptional bursting	journal.pgen.1007874	null	[ [ "Gene expression in genetically identical individual cells often deviates from that of the cell population average [1] , which in mammals can impact cell fate and development [2–5] , response to environmental stimuli [6–9] and disease [10–13] .", "Over the past few years , it has emerged that at least som...	[ "Extensive cell-to-cell variation exists even among putatively identical cells , and there is great interest in understanding how the properties of transcription relate to this heterogeneity .", "Differential expression from the two gene copies in diploid cells could potentially contribute , yet our ability to me...	[ "In mammals , most cells of the body contain two genetic datasets: one from the mother and one from the father , and—in theory—these two sets of information could contribute equally to produce the molecules in a given cell .", "In practice , however , this is not always the case , which can have dramatic implicat...	2019
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "medicine and health sciences", "prader-willi syndrome", "long non-coding rnas", "disorders of imprinting", "developmental biology", "epigenetics", "chromatin", "embryology", "genetic interference", "chromosome biology", "genomic imprinting", "gene expression", "genetic loci", "clinical ge...	The Airn lncRNA does not require any DNA elements within its locus to silence distant imprinted genes	journal.pgen.1008268	null	[ [ "Long non-coding ( lnc ) RNAs are a diverse and numerous group of non-protein-coding RNA species longer than 200 nucleotides , some of which have been shown to be involved in gene regulation [1 , 2] .", "A growing number of lncRNAs have been implicated in development and disease , sparking interest in how...	[ "Long non-coding ( lnc ) RNAs are numerous and found throughout the mammalian genome , and many are thought to be involved in the regulation of gene expression .", "However , the majority remain relatively uncharacterised and of uncertain function making the use of model systems to uncover their mode of action va...	[ "Long non-coding ( lnc ) RNAs are numerous in the mammalian genome and many have been implicated in gene regulation .", "However , the vast majority are uncharacterised and of uncertain function making known functional lncRNAs valuable models for understanding their mechanism of action .", "One mode of lncRNA a...	2019
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	A Human Type 5 Adenovirus-Based Trypanosoma cruzi Therapeutic Vaccine Re-programs Immune Response and Reverses Chronic Cardiomyopathy	journal.ppat.1004594	null	[ [ "Chagas disease ( CD ) is a neglected tropical illness caused by the protozoan parasite Trypanosoma cruzi , which is transmitted by blood-sucking triatomines .", "The disease afflicts 8 to 15 million people in Latin America; more than 40 , 000 new cases occur every year and the rate of congenital transmis...	[ "Chagas disease ( CD ) , caused by the protozoan Trypanosoma cruzi , is a prototypical neglected tropical disease .", "Specific immunity promotes acute phase survival .", "Nevertheless , one-third of CD patients develop chronic chagasic cardiomyopathy ( CCC ) associated with parasite persistence and immunologic...	[ "The idea that Chagas disease ( CD ) has an important autoimmune involvement contributed to delay the development of therapies and vaccines .", "CD is a parasitic neglected disease which afflicts millions of people mostly in Latin America .", "The cardiac form is the main clinical manifestation of CD .", "Cur...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "auditory system", "natural language processing", "cognitive neuroscience", "computational neuroscience", "sensory systems", "biology", "computational biology", "neuroscience", "neuroimaging" ]	Speech Rhythms and Multiplexed Oscillatory Sensory Coding in the Human Brain	journal.pbio.1001752	A neuroimaging study reveals how coupled brain oscillations at different frequencies align with quasi-rhythmic features of continuous speech such as prosody, syllables, and phonemes.	[ [ "A large number of invasive and non-invasive neurophysiological studies provide converging evidence that cortical oscillations play an important role in gating information flow in the human brain , thereby supporting a variety of cognitive processes including attention , working memory , and decision-making [...	[ "Cortical oscillations are likely candidates for segmentation and coding of continuous speech .", "Here , we monitored continuous speech processing with magnetoencephalography ( MEG ) to unravel the principles of speech segmentation and coding .", "We demonstrate that speech entrains the phase of low-frequency ...	[ "Continuous speech is organized into a nested hierarchy of quasi-rhythmic components ( prosody , syllables , phonemes ) with different time scales .", "Interestingly , neural activity in the human auditory cortex shows rhythmic modulations with frequencies that match these speech rhythms .", "Here , we use magn...	2013
[ "Introduction", "Materials and methods", "Results", "Discussion" ]	[ "invertebrates", "innate immune system", "medicine and health sciences", "reproductive system", "immune physiology", "cytokines", "body fluids", "maternal health", "obstetrics and gynecology", "helminths", "immunology", "tropical diseases", "hookworms", "parasitic diseases", "animals", ...	Maternal, placental and cord blood cytokines and the risk of adverse birth outcomes among pregnant women infected with Schistosoma japonicum in the Philippines	journal.pntd.0007371	null	[ [ "Adverse perinatal outcomes account for a substantial proportion of the global burden of disease [1] and lay the foundation for health in later childhood , adolescence , and adulthood [2–5] .", "Low birthweight ( LBW ) , fetal growth restriction ( FGR ) and preterm births together account for more than 80...	[ "The objectives of this study were to", "1 ) evaluate the influence of treatment with praziquantel on the inflammatory milieu in maternal , placental , and cord blood ,", "2 ) assess the extent to which proinflammatory signatures in placental and cord blood impacts birth outcomes , and", "3 ) evaluate the imp...	[ "Schistosomiasis is one of the most prevalent parasitic tropical diseases , and it is primarily treated with the drug praziquantel .", "This study examined the effects of praziquantel treatment for schistosomiasis and the presence of geohelminth infections during pregnancy on cytokines in maternal , placental , a...	2019
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "virology/viral replication and gene regulation", "virology/viruses and cancer", "virology/host antiviral responses" ]	Mechanism of Genomic Instability in Cells Infected with the High-Risk Human Papillomaviruses	journal.ppat.1000397	null	[ [ "Papillomaviruses are small dsDNA viruses that infect the basal cells of differentiating epithelium in variety of animals , including humans [1] .", "Initial infection is followed by the transient nuclear amplification of the HPV circular genomes via the viral pre-replication complex ( pre-RC ) , which is...	[ "In HPV–related cancers , the “high-risk” human papillomaviruses ( HPVs ) are frequently found integrated into the cellular genome .", "The integrated subgenomic HPV fragments express viral oncoproteins and carry an origin of DNA replication that is capable of initiating bidirectional DNA re-replication in the pr...	[ "High-risk human papillomavirus infection can cause several types of cancers .", "During the normal virus life cycle , these viruses maintain their genomes as multicopy nuclear plasmids in infected cells .", "However , in cancer cells , the viral plasmids are lost , which leaves one of the HPV genomes to be int...	2009
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[]	A Horizontal Alignment Tool for Numerical Trend Discovery in Sequence Data: Application to Protein Hydropathy	journal.pcbi.1003247	null	[ [ "Determining the evolutionary relatedness of two protein sequences is most successfully performed by amino acid sequence comparison [1]–[5] .", "However , it is well known that structure can be preserved even when sequence has diverged past the point of amino acid similarity recognition [6] , suggesting t...	[ "An algorithm is presented that returns the optimal pairwise gapped alignment of two sets of signed numerical sequence values .", "One distinguishing feature of this algorithm is a flexible comparison engine ( based on both relative shape and absolute similarity measures ) that does not rely on explicit gap penal...	[ "Trend discovery is an important way to generate understanding from large amounts of data .", "We have developed a novel tool that discovers significantly similar trends shared between two numerical data sets .", "Since the tool's algorithmic method compares both the relative shapes of the “peaks” and “valleys”...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Sleep-Dependent Reactivation of Ensembles in Motor Cortex Promotes Skill Consolidation	journal.pbio.1002263	During non-REM sleep in rats, consolidation and offline improvements of a recently learned motor skill are linked to synchronous reactivation of task-related neural ensembles.	[ [ "The cardinal features of motor skill learning are enhanced speed and automaticity of motor execution with preserved accuracy [1–3] .", "Motor learning is known to progress through a series of stages: an early stage accompanied by rapid improvements in accuracy with continued variability of movement kinem...	[ "Despite many prior studies demonstrating offline behavioral gains in motor skills after sleep , the underlying neural mechanisms remain poorly understood .", "To investigate the neurophysiological basis for offline gains , we performed single-unit recordings in motor cortex as rats learned a skilled upper-limb t...	[ "Sleep has been shown to help in consolidating learned motor tasks .", "In other words , sleep can induce “offline” gains in a new motor skill even in the absence of further training .", "However , how sleep induces this change has not been clearly identified .", "One hypothesis is that consolidation of memor...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine and health sciences", "pathology and laboratory medicine", "chemical compounds", "manganese", "engineering and technology", "pathogens", "microbiology", "carbohydrates", "staphylococcus aureus", "organic compounds", "glucose", "organisms", "bacterial diseases", "nutrition", "ca...	The Two-Component System ArlRS and Alterations in Metabolism Enable Staphylococcus aureus to Resist Calprotectin-Induced Manganese Starvation	journal.ppat.1006040	null	[ [ "Staphylococcus aureus is a ubiquitous pathogen that colonizes 30% of the population at any given time and can infect virtually every human tissue [1] .", "These facts and the continued spread of antibiotic resistance have led both the Centers for Disease Control and the World Health Organization to state...	[ "During infection the host imposes manganese and zinc starvation on invading pathogens .", "Despite this , Staphylococcus aureus and other successful pathogens remain capable of causing devastating disease .", "However , how these invaders adapt to host-imposed metal starvation and overcome nutritional immunity...	[ "The ubiquitous pathogen Staphylococcus aureus is a serious threat to human health due to the continued spread of antibiotic resistance .", "This spread has made it challenging to treat staphylococcal infections and led to the call for new approaches to treat this devastating pathogen .", "One approach is to di...	2016
[ "Introduction", "Results", "Discussion", "Methods" ]	[]	The Neonatal Fc Receptor (FcRn) Enhances Human Immunodeficiency Virus Type 1 (HIV-1) Transcytosis across Epithelial Cells	journal.ppat.1003776	null	[ [ "Sexual transmission of HIV-1 requires that virus establish infection across genital tract or intestinal tissue .", "Sexually transmitted infections , other causes of inflammation , and localized trauma may allow susceptible CD4+ target cells at skin or mucosal surfaces to become directly exposed to secre...	[ "The mechanisms by which human immunodeficiency virus type 1 ( HIV-1 ) crosses mucosal surfaces to establish infection are unknown .", "Acidic genital secretions of HIV-1-infected women contain HIV-1 likely coated by antibody .", "We found that the combination of acidic pH and Env-specific IgG , including that ...	[ "HIV-1 causes a sexually transmitted disease .", "However , the mechanisms employed by the virus to cross genital tract tissue and establish infection are uncertain .", "Since cervicovaginal fluid is acidic and HIV-1 in cervicovaginal fluid is likely coated with antibodies , we explored the effect of low pH and...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genetics and genomics", "evolutionary biology" ]	Cryptic Variation in the Human Mutation Rate	journal.pbio.1000027	Substantial variation is seen in the rate of mutation among different sites in the human genome, which is not associated with mutable CpG sites or due to simple context effects.	[ [ "The mutation rate is thought to vary across the human genome on several different scales .", "At the chromosomal level , the Y chromosome evolves faster than the autosomes , which evolve faster than the X chromosome [1 , 2] .", "This is thought to be due to males having a higher mutation rate than fe...	[ "The mutation rate is known to vary between adjacent sites within the human genome as a consequence of context , the most well-studied example being the influence of CpG dinucelotides .", "We investigated whether there is additional variation by testing whether there is an excess of sites at which both humans and...	[ "Understanding the process of mutation is important , not only mechanistically , but also because it has implications for the analysis of sequence evolution and population genetic inference .", "The mutation rate is known to differ between sites within the human genome .", "The most dramatic example of this is ...	2009
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "fluorescence imaging", "medicine and health sciences", "pathology and laboratory medicine", "cell division analysis", "cell cycle and cell division", "pathogens", "cell processes", "bacillus", "microbiology", "light microscopy", "parasitic protozoans", "balantidium coli", "prokaryotic model...	The Replisomes Remain Spatially Proximal throughout the Cell Cycle in Bacteria	journal.pgen.1006582	null	[ [ "Rapid and faithful replication of the chromosome is essential for the proliferation of all living cells .", "Many bacteria possess a single circular chromosome .", "Replication is initiated at a single origin and two multicomponent protein complexes ( replisomes ) replicate bidirectionally around the...	[ "The positioning of the DNA replication machinery ( replisome ) has been the subject of several studies .", "Two conflicting models for replisome localization have been proposed: In the Factory Model , sister replisomes remain spatially co-localized as the replicating DNA is translocated through a stationary repl...	[ "Cell proliferation depends on efficient replication of the genome .", "Bacteria typically have a single origin of replication on a circular chromosome .", "After replication initiation , two replisomes assemble at the origin and each copy one of the two arms of the chromosome until they reach the terminus .", ...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "immunology/antigen processing and recognition", "virology/viral replication and gene regulation", "immunology/immune response", "virology/immune evasion", "immunology/immunity to infections" ]	Stage-Specific Inhibition of MHC Class I Presentation by the Epstein-Barr Virus BNLF2a Protein during Virus Lytic Cycle	journal.ppat.1000490	null	[ [ "The detection and elimination of virally infected cells by the host immune system relies heavily upon CD8+ T cells recognizing peptides endogenously processed and presented by HLA class I molecules .", "Proteasomal degradation of endogenously synthesized proteins provides a source of peptides which are d...	[ "The gamma-herpesvirus Epstein-Barr virus ( EBV ) persists for life in infected individuals despite the presence of a strong immune response .", "During the lytic cycle of EBV many viral proteins are expressed , potentially allowing virally infected cells to be recognized and eliminated by CD8+ T cells .", "We ...	[ "Epstein-Barr virus ( EBV ) is carried by approximately 90% of the world's population , where it persists and is chronically shed despite a vigorous specific immune response , a key component of which are CD8+ T cells that recognize and kill infected cells .", "The mechanisms the virus uses to evade these respons...	2009
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "cell biology", "computational biology", "molecular biology" ]	BEAF Regulates Cell-Cycle Genes through the Controlled Deposition of H3K9 Methylation Marks into Its Conserved Dual-Core Binding Sites	journal.pbio.0060327	Chromatin Dual-Cores define new potent nucleosome-associatedcis-regulatory elements that regulate the accessibility of promoters of genes controlling chromosome organization/segregation and the cell cycle.	[ [ "Chromatin insulators/boundary elements ( BEs ) [1 , 2] are defined as sequences able to insulate a transgene from its chromosomal context and to block promiscuous enhancer–promoter interactions or heterochromatin spreading [1 , 3–5] .", "These elements are thought to subdivide the genome into functional ...	[ "Chromatin insulators/boundary elements share the ability to insulate a transgene from its chromosomal context by blocking promiscuous enhancer–promoter interactions and heterochromatin spreading .", "Several insulating factors target different DNA consensus sequences , defining distinct subfamilies of insulators...	[ "The genome of eukaryotes is packaged in chromatin , which consists of DNA , histones , and accessory proteins .", "This leads to a general repression of genes , particularly for those exposed to mostly condensed , heterochromatin regions .", "DNA sequences called chromatin insulators/boundary elements are able...	2008
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "statistical noise", "decision making", "statistics", "social sciences", "vertebrates", "neuroscience", "animals", "mammals", "primates", "probability distribution", "mathematics", "cognitive psychology", "cognition", "skewness", "gaussian noise", "statistical distributions", "monkey...	Human representation of multimodal distributions as clusters of samples	journal.pcbi.1007047	null	[ [ "As Horace Barlow wrote , “the brain has to decide upon actions in a competitive , chance-driven world , and to do this well it must know about and exploit the non-random probabilities and interdependences of objects and events” [1] .", "In general , the probabilistic information the cognitive system need...	[ "Behavioral and neuroimaging evidence shows that human decisions are sensitive to the statistical regularities ( mean , variance , skewness , etc . ) of reward distributions .", "However , it is unclear what representations human observers form to approximate reward distributions , or probability distributions in...	[ "Life is full of uncertainties: An action may yield multiple possible consequences and a percept may imply multiple possible causes .", "To survive , humans and animals must compensate for the uncertainty in the environment and in their own perceptual and motor systems .", "However , how humans represent probab...	2019
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biology", "computational biology" ]	Rampant Exchange of the Structure and Function of Extramembrane Domains between Membrane and Water Soluble Proteins	journal.pcbi.1002997	null	[ [ "The structural space of soluble proteins has been extensively explored .", "Indeed , most single-domain soluble proteins now appear to have at least one structural homolog in the current PDB database [1] , [2] .", "In contrast , the exploration of membrane protein fold space lags far behind [3]–[5] ....	[ "Of the membrane proteins of known structure , we found that a remarkable 67% of the water soluble domains are structurally similar to water soluble proteins of known structure .", "Moreover , 41% of known water soluble protein structures share a domain with an already known membrane protein structure .", "We a...	[ "Membrane proteins play important roles in cellular communication and molecular transport .", "However , experimental difficulties and lack of structural information have limited the functional characterization of membrane proteins .", "In this study , we find that over 60% of the extramembrane domains were str...	2013
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "biotechnology", "public and occupational health", "infectious diseases", "medicine and health sciences", "biology and life sciences" ]	Preclinical Detection of Variant CJD and BSE Prions in Blood	journal.ppat.1004202	null	[ [ "The emergence of variant Creutzfeldt Jakob Disease ( vCJD ) is considered a likely consequence of human dietary exposure to the Bovine Spongiform Encephalopathy ( BSE ) agent [1] .", "Both primate and sheep experimental models rapidly indicated that vCJD/BSE could be transmitted by blood transfusion [2] ...	[ "The emergence of variant Creutzfeldt Jakob Disease ( vCJD ) is considered a likely consequence of human dietary exposure to Bovine Spongiform Encephalopathy ( BSE ) agent .", "More recently , secondary vCJD cases were identified in patients transfused with blood products prepared from apparently healthy donors w...	[ "Variant Creutzfeldt Jakob Disease ( vCJD ) cases were identified in patients who received blood products that had been prepared from donors who later developed the disease .", "The blood borne transmission of vCJD is a major concern for blood transfusion banks , plasma derived products manufacturers and public h...	2014
[ "Introduction", "Methods", "Results" ]	[]	Larval Breeding Sites of Lutzomyia longipalpis (Diptera: Psychodidae) in Visceral Leishmaniasis Endemic Urban Areas in Southeastern Brazil	journal.pntd.0002443	null	[ [ "Members of the Lutzomyia longipalpis ( Lutz & Neiva ) species complex are the main vector of Leishmania ( Leishmania ) infantum chagasi ( Cunha & Chagas ) , the causative agent of the visceral leishmaniasis ( VL ) in Brazil and Latin America [1]–[3] .", "Its recent introduction and adaptation to domicili...	[ "The scarcity of information on the immature stages of sand flies and their preferred breeding sites has resulted in the focus of vectorial control on the adult stage using residual insecticide house-spraying .", "This strategy , along with the treatment of human cases and the euthanasia of infected dogs , has pr...	[ "Sand flies are the vectors of a number of pathogens that infect man , especially cutaneous and visceral leishmaniasis .", "The control of sand flies through residual house-spraying insecticide has proven inefficient in preventing the spread of these diseases in several areas of the globe .", "Sand flies have a...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Adhesive Fiber Stratification in Uropathogenic Escherichia coli Biofilms Unveils Oxygen-Mediated Control of Type 1 Pili	journal.ppat.1004697	null	[ [ "In nature , bacteria predominantly exist in a biofilm state [1] forming mutualistic or parasitic associations with other living organisms [2 , 3] .", "Within vertebrate hosts , the resident microbiota are essentially multi-species biofilms that play a key role in preventing colonization by pathogens [4] ...	[ "Bacterial biofilms account for a significant number of hospital-acquired infections and complicate treatment options , because bacteria within biofilms are generally more tolerant to antibiotic treatment .", "This resilience is attributed to transient bacterial subpopulations that arise in response to variations...	[ "Bacteria are commonly found in multicellular communities known as biofilms .", "Biofilms can form on a variety of surfaces , both outside and within living things , and can have detrimental effects on human health .", "The characteristics of bacteria occupying different areas within biofilms are not well under...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biochemistry", "functional genomics", "protein interactions", "proteins", "genetics", "biology", "genomics", "gene networks", "genetics and genomics" ]	Widespread Cotranslational Formation of Protein Complexes	journal.pgen.1002398	null	[ [ "The majority of cellular proteins function as subunits in larger protein complexes .", "However , very little is known about how protein complexes form in vivo .", "One possibility is that proteins are fully translated and released into the cytoplasm before finding their interacting partners ( posttr...	[ "Most cellular processes are conducted by multi-protein complexes .", "However , little is known about how these complexes are assembled .", "In particular , it is not known if they are formed while one or more members of the complexes are being translated ( cotranslational assembly ) .", "We took a genomic a...	[ "Most proteins do not function in isolation .", "Instead , they associate with other proteins to form complexes .", "Little is known about the assembly of protein complexes within cells .", "One possibility is that proteins are completely synthesised before they bind to each other .", "An alternative is tha...	2011
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine and health sciences", "pathology and laboratory medicine", "molecular probe techniques", "293t cells", "pathogens", "biological cultures", "microbiology", "vertebrates", "marmosets", "immunoblotting", "animals", "mammals", "retroviruses", "primates", "immunodeficiency viruses",...	Non-human Primate Schlafen11 Inhibits Production of Both Host and Viral Proteins	journal.ppat.1006066	null	[ [ "RNA viruses pose a major threat to public health because of their potential to rapidly adapt to the human host after transmission from animal reservoirs [1] .", "In general , the genetic barriers to cross-species transmission of viruses are poorly understood .", "A notable exception exists in the cas...	[ "Schlafen11 ( encoded by the SLFN11 gene ) has been shown to inhibit the accumulation of HIV-1 proteins .", "We show that the SLFN11 gene is under positive selection in simian primates and is species-specific in its activity against HIV-1 .", "The activity of human Schlafen11 is relatively weak compared to that...	[ "Schlafen11 was recently identified as a human antiviral protein with activity against HIV-1 .", "Here we show that some nonhuman primate versions of Schlafen11 are much stronger at blocking the accumulation of viral proteins than is human Schlafen11 .", "These relatively larger phenotypes of nonhuman primate S...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "chitin", "cell walls", "plant anatomy", "plant cell biology", "fungal structure", "plant cell walls", "cereal crops", "fungi", "plant science", "rice", "model organisms", "developmental biology", "materials science", "crops", "appressoria", "plant pathology", "plants", "macromolec...	Chitosan Mediates Germling Adhesion in Magnaporthe oryzae and Is Required for Surface Sensing and Germling Morphogenesis	journal.ppat.1005703	null	[ [ "All fungal cells are encased within a cell wall .", "This complex and dynamic structural barrier is composed of interwoven polysaccharides and proteins .", "Indeed , the polysaccharide moiety makes up the majority of the fungal wall , being comprised of chitin ( a polymer of β1 , 4-N-acetylglucosamin...	[ "The fungal cell wall not only plays a critical role in maintaining cellular integrity , but also forms the interface between fungi and their environment .", "The composition of the cell wall can therefore influence the interactions of fungi with their physical and biological environments .", "Chitin , one of t...	[ "Magnaporthe oryzae is a filamentous fungal pathogen which causes devastating crop losses in rice .", "Successful invasion of the host is dependent upon the ability of the fungus to remain undetected by the innate immune system of the plant , which recognizes conserved components of the fungal cell wall , such as...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "developmental biology/cell differentiation", "immunology/leukocyte development", "immunology/immunity to infections", "immunology/innate immunity" ]	EBV Promotes Human CD8+ NKT Cell Development	journal.ppat.1000915	null	[ [ "NKT cells are unconventional T cells that bridge the innate and adaptive immune systems [1]–[4] .", "Unlike conventional T cells , which recognize MHC-molecule-presented peptide antigens via their αβTCR , NKT cells recognize CD1d-presented glycolipids .", "Two subsets of functionally distinct CD1d-de...	[ "The reports on the origin of human CD8+ Vα24+ T-cell receptor ( TCR ) natural killer T ( NKT ) cells are controversial .", "The underlying mechanism that controls human CD4 versus CD8 NKT cell development is not well-characterized .", "In the present study , we have studied total 177 eligible patients and subj...	[ "We show that the average frequency of total and CD8+ NKT cells in PBMCs from 128 healthy latent EBV-infected subjects is significantly higher than in 17 patients with acute lytic EBV infection , 16 EBV-associated HL patients , and 16 EBV-negative normal subjects .", "The frequency of total and CD8+ NKT cells is ...	2010
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "infectious diseases/protozoal infections", "immunology/immunity to infections" ]	The Role of B-cells and IgM Antibodies in Parasitemia, Anemia, and VSG Switching in Trypanosoma brucei–Infected Mice	journal.ppat.1000122	null	[ [ "African trypanosomes are extracellular protozoa that cause chronic infections in humans and livestock and are predominantly transmitted by the bite of the haematophagic tsetse fly [1] .", "Trypanosoma brucei gambiense and Trypanosoma brucei rhodesiense are the causative agents of West/Central- and East-A...	[ "African trypanosomes are extracellular parasitic protozoa , predominantly transmitted by the bite of the haematophagic tsetse fly .", "The main mechanism considered to mediate parasitemia control in a mammalian host is the continuous interaction between antibodies and the parasite surface , covered by variant-sp...	[ "African trypanosomiasis is a disease caused by different species of extracellular flagellated protozoan trypanosome parasites .", "Trypanosomes have developed a mechanism of regular antigenic variation of their variant-specific surface glycoprotein ( VSG ) coat which allows chronic infection .", "Replacement o...	2008
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "biochemistry", "rna", "nucleic acids", "biology and life sciences", "dna", "biophysics", "biophysical simulations" ]	Blind Predictions of DNA and RNA Tweezers Experiments with Force and Torque	journal.pcbi.1003756	null	[ [ "Nucleic acids play central roles in biological processes including transcription , translation , catalysis and regulation of gene expression [1] , [2] .", "Double-stranded RNA and DNA ( dsRNA and dsDNA ) stretch and twist when interacting with proteins [3] , [4] and when forming compact structures such a...	[ "Single-molecule tweezers measurements of double-stranded nucleic acids ( dsDNA and dsRNA ) provide unprecedented opportunities to dissect how these fundamental molecules respond to forces and torques analogous to those applied by topoisomerases , viral capsids , and other biological partners .", "However , tweez...	[ "DNA and RNA are fundamental molecules in the central dogma of molecular biology .", "Many biological behaviors of double-stranded DNA and RNA – including transcription/translation by proteins and packaging into compact structures – depend on their ability to flex and twist .", "Single-molecule tweezers now pro...	2014
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "paneth cells", "antimicrobials", "medicine and health sciences", "immune physiology", "viral transmission and infection", "drugs", "immunology", "microbiology", "vertebrates", "mice", "animals", "mammals", "epithelial cells", "animal models", "model organisms", "antibiotics", "pharm...	Defensins Potentiate a Neutralizing Antibody Response to Enteric Viral Infection	journal.ppat.1005474	null	[ [ "In addition to a sophisticated adaptive immune system , mammals retain more primitive immune effectors , such as antimicrobial peptides , as components of the innate response to microbial infection .", "In humans , one of the most abundant classes of antimicrobial peptides is α-defensins [1 , 2] .", ...	[ "α-defensins are abundant antimicrobial peptides with broad , potent antibacterial , antifungal , and antiviral activities in vitro .", "Although their contribution to host defense against bacteria in vivo has been demonstrated , comparable studies of their antiviral activity in vivo are lacking .", "Using a mo...	[ "Mammals express abundant antimicrobial peptides , including α-defensins , to protect their epithelial surfaces from microbes .", "α-defensins are potently antibacterial and antiviral ex vivo; however , their contribution to host defense from viral infection in vivo has not been demonstrated .", "We show that m...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "circadian rhythms", "biochemistry", "molecular neuroscience", "behavioral neuroscience", "animal genetics", "cellular neuroscience", "genetics", "chronobiology", "biology and life sciences", "neuroscience", "circadian oscillators" ]	Differentially Timed Extracellular Signals Synchronize Pacemaker Neuron Clocks	journal.pbio.1001959	Circadian pacemaker neurons in Drosophila are regulated by two synchronizing signals that are released at opposite times of day, generating a rhythm in intracellular cyclic AMP.	[ [ "Coordinated neuronal activity is vital for neural networks to regulate complex processes such as behavior .", "Synchrony can be studied at the microsecond level by measuring neuronal activity , with synchronous activity often achieved via gap junctions that electrically couple neurons [1] .", "The ci...	[ "Synchronized neuronal activity is vital for complex processes like behavior .", "Circadian pacemaker neurons offer an unusual opportunity to study synchrony as their molecular clocks oscillate in phase over an extended timeframe ( 24 h ) .", "To identify where , when , and how synchronizing signals are perceiv...	[ "Circadian molecular clocks are essential for daily cycles in animal behavior and we have a good understanding of how these clocks work in individual pacemaker neurons .", "However , the accuracy of these individual clocks is meaningless unless they are synchronized with one another .", "In this study we show t...	2014
[ "Introduction", "Methods", "Results", "Discussion" ]	[]	The Diterpenoid 7-Keto-Sempervirol, Derived from Lycium chinense, Displays Anthelmintic Activity against both Schistosoma mansoni and Fasciola hepatica	journal.pntd.0003604	null	[ [ "Schistosomiasis and fascioliasis are Neglected Tropical Diseases ( NTDs ) caused by related parasitic blood ( Schistosoma sp . including Schistosoma mansoni ) and liver ( Fasciola sp including Fasciola hepatica ) flukes found within the phylum Platyhelminthes .", "These NTDs are responsible for chronic c...	[ "Two platyhelminths of biomedical and commercial significance are Schistosoma mansoni ( blood fluke ) and Fasciola hepatica ( liver fluke ) .", "These related trematodes are responsible for the chronic neglected tropical diseases schistosomiasis and fascioliasis , respectively .", "As no vaccine is currently av...	[ "Schistosomiasis and fascioliasis are caused by two related trematodes found within the phylum Platyhelminthes ( flatworms ) , and are classified as neglected diseases of poverty due to their effects on people living in the most underprivileged areas of the world .", "With no vaccine currently near development , ...	2015
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "medicine and health sciences", "pathology and laboratory medicine", "infectious disease epidemiology", "pathogens", "tropical diseases", "ebola hemorrhagic fever", "probability distribution", "mathematics", "forecasting", "statistics (mathematics)", "neglected tropical diseases", "infectious ...	Detecting Presymptomatic Infection Is Necessary to Forecast Major Epidemics in the Earliest Stages of Infectious Disease Outbreaks	journal.pcbi.1004836	null	[ [ "As an example of a disease for which initial cases are frequently not followed by major outbreaks , and with a significant delay between infection and emergence of symptoms , we consider Ebola virus disease .", "All five strains of the genus Ebolavirus cause severe acute illness , with early non-specific...	[ "We assess how presymptomatic infection affects predictability of infectious disease epidemics .", "We focus on whether or not a major outbreak ( i . e . an epidemic that will go on to infect a large number of individuals ) can be predicted reliably soon after initial cases of disease have appeared within a popul...	[ "Emerging epidemics pose a significant challenge to human health worldwide .", "Accurate real-time forecasts of whether or not initial reports will be followed by a major outbreak are necessary for efficient deployment of control .", "For all infectious diseases , there is a delay between infection and the appe...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "infectious diseases/protozoal infections", "microbiology/cellular microbiology and pathogenesis", "cell biology/cytoskeleton" ]	Concerted Action of Two Formins in Gliding Motility and Host Cell Invasion by Toxoplasma gondii	journal.ppat.1001132	null	[ [ "The phylum Apicomplexa encompasses pathogens of significant medical relevance including those responsible for malaria and toxoplasmosis .", "These parasites cross biological barriers and enter cells by an active process that depends on a unique form of gliding motility [1] .", "In Toxoplasma gondii ,...	[ "The invasive forms of apicomplexan parasites share a conserved form of gliding motility that powers parasite migration across biological barriers , host cell invasion and egress from infected cells .", "Previous studies have established that the duration and direction of gliding motility are determined by actin ...	[ "Gliding motility is a unique property of the Apicomplexa .", "Members of this phylum include important human and animal pathogens .", "An actomyosin-based machine powers parasite motility and is crucial for parasite migration across biological barriers , host cell invasion and egress from infected cells .", ...	2010
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "algorithms", "systems biology", "developmental biology", "computer science", "genomics", "mathematics", "physiology", "genetics", "biology", "anatomy and physiology", "evolutionary biology", "population biology", "computational biology", "genetics and genomics" ]	Cell Lineage Analysis of the Mammalian Female Germline	journal.pgen.1002477	null	[ [ "Understanding the complex processes of embryonic development and post-natal maintenance in multi-cellular organisms requires advanced methods for cell lineage reconstruction .", "The mammalian female germline is a prominent example , in which fundamental aspects of these processes remain debatable .", ...	[ "Fundamental aspects of embryonic and post-natal development , including maintenance of the mammalian female germline , are largely unknown .", "Here we employ a retrospective , phylogenetic-based method for reconstructing cell lineage trees utilizing somatic mutations accumulated in microsatellites , to study fe...	[ "Many aspects of mammalian female germline development during embryogenesis and throughout adulthood are either unknown or under debate .", "In this study we applied a novel method for the reconstruction of cell lineage trees utilizing microsatellite mutations , accumulated during mouse life , in oocytes and othe...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "sequencing techniques", "database searching", "social sciences", "neuroscience", "molecular biology techniques", "sequence similarity searching", "research and analysis methods", "sequence analysis", "sequence alignment", "proteins", "prokaryotic cells", "biological databases", "sensory rec...	Cache Domains That are Homologous to, but Different from PAS Domains Comprise the Largest Superfamily of Extracellular Sensors in Prokaryotes	journal.pcbi.1004862	null	[ [ "Signal transduction is a universal feature of all living cells .", "It is initiated by specialized receptors that detect various extracellular and/or intracellular signals , such as nutrients , and transmit information to regulators of different cellular functions [1 , 2] .", "Receptors are usually c...	[ "Cellular receptors usually contain a designated sensory domain that recognizes the signal .", "Per/Arnt/Sim ( PAS ) domains are ubiquitous sensors in thousands of species ranging from bacteria to humans .", "Although PAS domains were described as intracellular sensors , recent structural studies revealed PAS-l...	[ "Cell-surface receptors control multiple cellular functions and are attractive targets for drug design .", "These receptors often have dedicated extracellular domains that bind signaling molecules , such as hormones and nutrients .", "Computational identification of these ligand-binding domains in genomic seque...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "introgression", "biology", "evolutionary biology", "hybridization", "evolutionary processes" ]	Adaptive Introgression across Species Boundaries in Heliconius Butterflies	journal.pgen.1002752	null	[ [ "Closely related species often hybridise through incomplete barriers to gene flow , but the evolutionary consequences of such genetic interchange remain a matter of debate [1] , [2] , [3] , [4] , [5] , [6] .", "This is primarily because hybridisation is considered unlikely to introduce useful genetic vari...	[ "It is widely documented that hybridisation occurs between many closely related species , but the importance of introgression in adaptive evolution remains unclear , especially in animals .", "Here , we have examined the role of introgressive hybridisation in transferring adaptations between mimetic Heliconius bu...	[ "Hybridisation occurs between many animal species , however its evolutionary relevance is still a matter of great debate .", "While some argue that hybridisation leads to maladaptive gene combinations , and therefore to an evolutionary dead end , others consider interspecific hybridisation as a process with great...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "virology/viral replication and gene regulation", "virology/animal models of infection", "infectious diseases/viral infections", "virology/effects of virus infection on host gene expression", "virology/host antiviral responses" ]	HCV Induces Oxidative and ER Stress, and Sensitizes Infected Cells to Apoptosis in SCID/Alb-uPA Mice	journal.ppat.1000291	null	[ [ "Hepatitis C virus ( HCV ) is a positive strand RNA virus that belongs to the family Flaviviradae .", "HCV is a blood borne pathogen which is a major cause of liver disease worldwide , with an estimated 200 million people infected .", "It is estimated that 30% of chronically infected patients eventual...	[ "Hepatitis C virus ( HCV ) is a blood-borne pathogen and a major cause of liver disease worldwide .", "Gene expression profiling was used to characterize the transcriptional response to HCV H77c infection .", "Evidence is presented for activation of innate antiviral signaling pathways as well as induction of li...	[ "Hepatitis C virus is a common cause of liver disease worldwide .", "The details of how HCV causes liver disease are not well understood .", "It has been thought that HCV infection does not kill liver cells directly , but indirectly by stimulating the immune system to kill HCV-infected liver cells .", "In thi...	2009
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine and health sciences", "body fluids", "parasite replication", "immunology", "tropical diseases", "parasitic diseases", "parasitic protozoans", "parasitology", "vaccines", "preventive medicine", "protozoans", "mathematics", "statistics (mathematics)", "infectious disease control", ...	The Power of Malaria Vaccine Trials Using Controlled Human Malaria Infection	journal.pcbi.1005255	null	[ [ "In 2015 , malaria caused an estimated 438 , 000 deaths ( 236 , 000–635 , 000 ) [1] , most of which were associated with Plasmodium falciparum ( Pf ) infections .", "Hypothetically , a malaria vaccine targeting the sporozoite parasite stage ( pre-hepatic vaccine ) , hepatic parasite stage ( hepatic vaccin...	[ "Controlled human malaria infection ( CHMI ) in healthy human volunteers is an important and powerful tool in clinical malaria vaccine development .", "However , power calculations are essential to obtain meaningful estimates of protective efficacy , while minimizing the risk of adverse events .", "To optimize ...	[ "Controlled human malaria infection ( CHMI ) in healthy human volunteers is an important and powerful tool in clinical malaria vaccine development .", "However , to obtain meaningful estimates of protective efficacy , it is important to include an appropriate minimum number of participants , while minimizing the ...	2017
[ "Introduction", "Results", "Discussion", "Methods" ]	[]	Modelling Circulating Tumour Cells for Personalised Survival Prediction in Metastatic Breast Cancer	journal.pcbi.1004199	null	[ [ "Breast cancer is characterised by multi-year survival from the first diagnosis of bone metastases .", "It is a leading cause of cancer death among women , and if detected at an early stage , its prognosis is favourable , with 5-year survival—for death from the cancer—in more than 90% of the patients .", ...	[ "Ductal carcinoma is one of the most common cancers among women , and the main cause of death is the formation of metastases .", "The development of metastases is caused by cancer cells that migrate from the primary tumour site ( the mammary duct ) through the blood vessels and extravasating they initiate metasta...	[ "Breast cancer is caused by genetic mutations leading to uncontrollable cell reproduction .", "During successive proliferations , the progenies of tumour cells acquire further mutations increasing their heterogeneity .", "Among the tumoural mutated cells , there are some which present specific markers of increa...	2015
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "medicine and health sciences", "vesicular stomatitis virus", "pathology and laboratory medicine", "gene regulation", "pathogens", "microbiology", "light microscopy", "viruses", "rna viruses", "microscopy", "adp-ribosylation", "research and analysis methods", "small interfering rnas", "pro...	The coronavirus macrodomain is required to prevent PARP-mediated inhibition of virus replication and enhancement of IFN expression	journal.ppat.1007756	null	[ [ "ADP-ribosylation is the post-translational covalent addition of a single ( mono-ADP-ribosylation or MARylation ) or multiple ( poly-ADP-ribosylation or PARylation ) subunits of ADP-ribose from NAD+ to a protein .", "This process is catalyzed by intracellular poly ( ADP-ribose ) polymerases ( PARPs ) also...	[ "ADP-ribosylation is a ubiquitous post-translational addition of either monomers or polymers of ADP-ribose to target proteins by ADP-ribosyltransferases , usually by interferon-inducible diphtheria toxin-like enzymes known as PARPs .", "While several PARPs have known antiviral activities , these activities are mo...	[ "ADP-ribosylation , an understudied post-translational modification , facilitates the host response to virus infection .", "Several viruses , including all members of the coronavirus family , encode a macrodomain to reverse ADP-ribosylation and combat this immune response .", "As such , viruses with mutations i...	2019
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "protein interactions", "microbiology", "gene function", "developmental biology", "model organisms", "molecular development", "molecular genetics", "microbial growth and development", "gene expression", "biology", "proteomics", "molecular biology", "biochemistry", "signal transduction", ...	The Aspergillus nidulans MAPK Module AnSte11-Ste50-Ste7-Fus3 Controls Development and Secondary Metabolism	journal.pgen.1002816	null	[ [ "Eukaryotic organisms communicate between cell surface and nucleus to respond to environmental signals .", "The mitogen-activated protein kinase ( MAPK ) module consisting of a cascade of three protein kinases represents a highly conserved eukaryotic signal transduction system present from yeast to man ."...	[ "The sexual Fus3 MAP kinase module of yeast is highly conserved in eukaryotes and transmits external signals from the plasma membrane to the nucleus .", "We show here that the module of the filamentous fungus Aspergillus nidulans ( An ) consists of the AnFus3 MAP kinase , the upstream kinases AnSte7 and AnSte11 ,...	[ "Mitogen activated protein ( MAP ) kinase cascades are conserved from yeast to man to transmit an external signal to the nucleus and induce an appropriate cellular response .", "The yeast Fus3 MAP kinase module represents a textbook paradigm for signal transduction .", "The pathway is activated by external sexu...	2012
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "biotechnology", "medicine", "anatomy and physiology", "cardiovascular", "biomedical engineering", "biological systems engineering", "bone", "bioengineering", "musculoskeletal system", "theoretical biology", "biology", "cardiovascular system", "systems biology", "physiology", "vascular b...	MOSAIC: A Multiscale Model of Osteogenesis and Sprouting Angiogenesis with Lateral Inhibition of Endothelial Cells	journal.pcbi.1002724	null	[ [ "The biological process of fracture healing comprises three main stages:", "( i ) the “inflammation phase” , where the trauma site becomes hypoxic and is invaded by inflammatory cells , fibroblasts , endothelial cells and mesenchymal stem cells [1];", "( ii ) the “reparative phase” , which starts with...	[ "The healing of a fracture depends largely on the development of a new blood vessel network ( angiogenesis ) in the callus .", "During angiogenesis tip cells lead the developing sprout in response to extracellular signals , amongst which vascular endothelial growth factor ( VEGF ) is critical .", "In order to e...	[ "The healing of a fracture largely depends on the development of a new blood vessel network ( angiogenesis ) , which can be investigated and simulated with mathematical models .", "The current mathematical models of angiogenesis during fracture healing do not , however , implement all relevant biological scales (...	2012
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "infectious diseases/infectious diseases of the nervous system", "infectious diseases/viral infections", "pathology/neuropathology", "virology/emerging viral diseases" ]	Rabies Post-Exposure Prophylaxis in the Philippines: Health Status of Patients Having Received Purified Equine F(ab')2 Fragment Rabies Immunoglobulin (Favirab)	journal.pntd.0000243	null	[ [ "Rabies is a zoonotic disease characterized by progressive and incurable viral encephalitis , invariably fatal if untreated and usually transmitted by the bite ( s ) or scratches of an infected animal .", "Data from the Department of Health show that every year , over 100 , 000 people at risk in the Phili...	[ "Recommended treatment for severe rabies exposure in unvaccinated individuals includes wound cleaning , administration of rabies immunoglobulins ( RIG ) , and rabies vaccination .", "We conducted a survey of rabies treatment outcomes in the Philippines .", "This was a case series involving 7 , 660 patients ( 4 ...	[ "Infection from a bite by a rabid animal is fatal unless rapid treatment ( thorough cleaning of the wound , administration of rabies immunoglobulins ( RIG ) , and a full anti-rabies vaccination course ) is provided .", "Ideally human RIG should be used , but cheaper , more readily available purified horse RIG ( p...	2008
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "infectious diseases", "infectious disease immunology", "veterinary diseases", "zoonoses", "medicine and health sciences", "clinical immunology", "leishmaniasis", "biology and life sciences", "immunology", "vector-borne diseases", "veterinary science", "parasitology" ]	Meta-analysis of the Effects of Insect Vector Saliva on Host Immune Responses and Infection of Vector-Transmitted Pathogens: A Focus on Leishmaniasis	journal.pntd.0003197	null	[ [ "Vector-borne diseases are a major cause of morbidity and mortality in many areas of the world .", "In addition to their cost to human health , vector-borne diseases can have a high economic cost primarily affecting impoverished nations and the people with the least resources .", "While there have bee...	[ "A meta-analysis of the effects of vector saliva on the immune response and progression of vector-transmitted disease , specifically with regard to pathology , infection level , and host cytokine levels was conducted .", "Infection in the absence or presence of saliva in naïve mice was compared .", "In addition...	[ "Arthropod vectors transmit a wide variety of diseases resulting in substantial human morbidity and economic costs worldwide .", "When hematophagous arthropods blood feed , they release saliva into the host .", "This saliva elicits a strong immune response and has recently been a focus for vaccine research .", ...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "invertebrates", "medicine and health sciences", "abdomen", "gene regulation", "cell cycle and cell division", "cell processes", "neuroscience", "animals", "notch signaling", "animal models", "drosophila melanogaster", "model organisms", "genome analysis", "drosophila", "research and ana...	Control of Neural Daughter Cell Proliferation by Multi-level Notch/Su(H)/E(spl)-HLH Signaling	journal.pgen.1005984	null	[ [ "The Notch signal transduction pathway plays a central role during animal development , and is also critical for tissue homeostasis during adulthood [1] .", "Notch signaling typically acts as a short-range , cell-cell communication system , which can trigger a multitude of cellular responses , including p...	[ "The Notch pathway controls proliferation during development and in adulthood , and is frequently affected in many disorders .", "However , the genetic sensitivity and multi-layered transcriptional properties of the Notch pathway has made its molecular decoding challenging .", "Here , we address the complexity ...	[ "Communication between cells is critical for controlling proliferation , and the Notch signal transduction pathway plays a well-established and evolutionary conserved role during these processes .", "However , in spite of numerous studies of this pathway over the years , the genetic sensitivity of the pathway , c...	2016
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "neonatology", "hiv infections", "medicine and health sciences", "maternal health", "geographical locations", "parasitic diseases", "parasitology", "pediatrics", "health care", "age groups", "nutrition", "women's health", "tanzania", "infants", "sanitation", "cryptosporidiosis", "afr...	Cryptosporidium Prevalence and Risk Factors among Mothers and Infants 0 to 6 Months in Rural and Semi-Rural Northwest Tanzania: A Prospective Cohort Study	journal.pntd.0003072	null	[ [ "The World Health Organization reports that the most common diarrhea-causing protozoan parasite worldwide is Cryptosporidium [1] , and a recent , large , multi-country investigation reported Cryptosporidium as the second most common pathogen indentified among care-seeking African and Asian infants 0 to 11 mon...	[ "Cryptosporidium epidemiology is poorly understood , but infection is suspected of contributing to childhood malnutrition and diarrhea-related mortality worldwide .", "A prospective cohort of 108 women and their infants in rural/semi-rural Tanzania were followed from delivery through six months .", "Cryptospori...	[ "Early infancy and childhood Cryptosporidium infection is associated with poor nutritional status , stunted growth , and cognitive deficits , yet minimal research is available regarding the burden and risk factors worldwide .", "Since there is no vaccine available , and because diagnostic challenges exist and tre...	2014
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "blood cells", "medicine and health sciences", "body fluids", "classical mechanics", "fluid mechanics", "cardiovascular anatomy", "oxygen", "blood counts", "capillaries", "red blood cells", "arterioles", "blood vessels", "animal cells", "flow field", "chemistry", "fluid dynamics", "h...	Red blood cells stabilize flow in brain microvascular networks	journal.pcbi.1007231	null	[ [ "Tissues depend on a continuous supply of oxygen and energy substrates delivered via the bloodstream .", "This is particularly evident in the brain , which contains limited energy reserves and undergoes rapid and substantial increases in blood flow during neuronal activation ( neurovascular coupling ) [1]...	[ "Capillaries are the prime location for oxygen and nutrient exchange in all tissues .", "Despite their fundamental role , our knowledge of perfusion and flow regulation in cortical capillary beds is still limited .", "Here , we use in vivo measurements and blood flow simulations in anatomically accurate microva...	[ "Glucose and oxygen are key energy sources of the brain .", "As energy storage capabilities are limited in the brain , a continuous supply of oxygen and glucose via the bloodstream is crucial for the brain’s functioning .", "The bulk of discharge occurs at the level of capillaries , which are the smallest and m...	2019
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genome expression analysis", "microbial metabolism", "gene regulation", "population genetics", "microbiology", "parallel evolution", "microbial evolution", "molecular genetics", "forms of evolution", "microbial physiology", "metabolic pathways", "biology", "evolutionary genetics", "bioche...	Evolution after Introduction of a Novel Metabolic Pathway Consistently Leads to Restoration of Wild-Type Physiology	journal.pgen.1003427	null	[ [ "Physiological stressors affect organisms across individual and evolutionary timescales: they invoke in individuals processes that work to restore homeostasis , and become over evolutionary timescales the selective pressures that drive adaptation in populations .", "How organisms generate innate and evolv...	[ "Organisms cope with physiological stressors through acclimatizing mechanisms in the short-term and adaptive mechanisms over evolutionary timescales .", "During adaptation to an environmental or genetic perturbation , beneficial mutations can generate numerous physiological changes: some will be novel with respec...	[ "Acclimatizing and adaptive ( evolutionary ) processes allow organisms to thrive despite cellular and environmental perturbations .", "Our work examined whether adaptation restores stress responses towards wild-type ( pre-stressed ) versus novel physiological states during adaptation by studying a bacterium ( Met...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "developmental biology", "homo (human)", "computational biology", "neuroscience" ]	Alternative Splicing Events Identified in Human Embryonic Stem Cells and Neural Progenitors	journal.pcbi.0030196	null	[ [ "The human central nervous system is composed of thousands of neuronal subtypes originating from neural stem cells ( NSCs ) that migrate from the developing neural tube .", "Such neuronal complexity is generated by a vast repertoire of molecular , genetic , and epigenetic mechanisms , such as the active r...	[ "Human embryonic stem cells ( hESCs ) and neural progenitor ( NP ) cells are excellent models for recapitulating early neuronal development in vitro , and are key to establishing strategies for the treatment of degenerative disorders .", "While much effort had been undertaken to analyze transcriptional and epigen...	[ "Deriving neural progenitors ( NP ) from human embryonic stem cells ( hESC ) is the first step in creating homogeneous populations of cells that will differentiate into myriad neuronal subtypes necessary to form a human brain .", "During alternative RNA splicing ( AS ) , noncoding sequences ( introns ) in a pre-m...	2007
[ "Introduction", "Materials and Methods", "Results/Discussion" ]	[ "infectious diseases", "immunology/immunomodulation", "infectious diseases/fungal infections", "immunology", "immunology/immunity to infections" ]	T Helper 1–Inducing Adjuvant Protects against Experimental Paracoccidioidomycosis	journal.pntd.0000183	null	[ [ "Paracoccidioides brasiliensis is a thermally dimorphic human pathogenic fungus that causes paracoccidioidomycosis ( PCM ) , the most prevalent human systemic mycosis in Latin America , being endemic in Brazil , Argentina , Venezuela and Colombia .", "This infection is acquired by inhalation of airborne p...	[ "Immunostimulatory therapy is a promising approach to improving the treatment of systemic fungal infections such as paracoccidioidomycosis ( PCM ) , whose drug therapy is usually prolonged and associated with toxic side effects and relapses .", "The current study was undertaken to determine if the injection of a ...	[ "P . brasiliensis is a thermally dimorphic human pathogenic fungus that causes paracoccidioidomycosis ( PCM ) , the most prevalent human systemic mycosis in Latin America , whose drug therapy is usually prolonged and associated with toxic side effects and relapses .", "Although immunostimulatory therapy is a prom...	2008
[ "Introduction", "Methods", "Results", "What is the Nature of the Queueing?", "Mixtures of Multiple mRNA Species", "Discussion" ]	[ "physics", "rna", "rna processing", "statistical mechanics", "nucleic acids", "biophysic al simulations", "biology", "computational biology", "biophysics simulations", "biophysics" ]	The Dynamics of Supply and Demand in mRNA Translation	journal.pcbi.1002203	null	[ [ "The translation of mRNAs by ribosomes is one of the steps in protein synthesis , and as such underpins all cellular processes .", "Control pathways at the transcriptional level are a long studied phenomenon , but it is becoming clear that control of protein production could also be exercised at the level...	[ "We study the elongation stage of mRNA translation in eukaryotes and find that , in contrast to the assumptions of previous models , both the supply and the demand for tRNA resources are important for determining elongation rates .", "We find that increasing the initiation rate of translation can lead to the depl...	[ "In this paper we show that the rate at which proteins are produced can be controlled at the elongation stage of mRNA translation .", "Regulation of translation initiation has been a focus of much study , but the subsequent effect of changes in the initiation rate on the overall translation rate , and the role of...	2011
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "medicine", "infectious diseases", "veterinary diseases", "immunology", "biology", "microbiology", "veterinary science" ]	Development of a Fluorescent Based Immunosensor for the Serodiagnosis of Canine Leishmaniasis Combining Immunomagnetic Separation and Flow Cytometry	journal.pntd.0002371	null	[ [ "Efficient diagnostic tests capable of providing early and accurate diagnosis are essential in determining the choice of treatment and in the epidemiological surveillance of infectious diseases .", "Classically , the microscopic observation or isolation of the infectious agent was considered as the gold s...	[ "An accurate diagnosis is essential for the control of infectious diseases .", "In the search for effective and efficient tests , biosensors have increasingly been exploited for the development of new and highly sensitive diagnostic methods .", "Here , we describe a new fluorescent based immunosensor comprising...	[ "Dogs are the most important domestic reservoirs of the parasite Leishmania infantum .", "Some infected animals develop a subclinical infection , without the classical symptoms characteristics of this disease .", "One of the major challenges in the serodiagnosis of canine leishmaniasis is the detection of activ...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "viruses", "infectious diseases", "immunology", "homo (human)" ]	Identification of a CCR5-Expressing T Cell Subset That Is Resistant to R5-Tropic HIV Infection	journal.ppat.0030058	null	[ [ "Chronic immune activation and homeostatic disturbance of T cell subsets that accompany viral replication are hallmarks of HIV-1 infection [1–4] .", "The cause and implications of these profound quantitative and qualitative changes in CD4+ memory T cell subsets during HIV-1 infection are still not well un...	[ "Infection with HIV-1 perturbs homeostasis of human T cell subsets , leading to accelerated immunologic deterioration .", "While studying changes in CD4+ memory and naïve T cells during HIV-1 infection , we found that a subset of CD4+ effector memory T cells that are CCR7−CD45RO−CD45RA+ ( referred to as TEMRA cel...	[ "HIV-1 infection profoundly perturbs the immune system and is characterized by depletion of CD4+ T cells and chronic immune activation , which lead to AIDS .", "Although HIV-1 targets CD4+ T cells , it also requires a second receptor in order to infect the target cells .", "The majority of HIV-1 strains that ar...	2007
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "model organisms", "theoretical biology", "ecology", "genetics", "biology", "microbiology", "evolutionary biology", "population biology", "genetics and genomics" ]	The Population and Evolutionary Dynamics of Phage and Bacteria with CRISPR–Mediated Immunity	journal.pgen.1003312	null	[ [ "The experimental demonstrations , in 2007 and 2008 , that the Clustered Regularly Interspaced Short Palindromic Repeats that abound in the genomes of the vast majority of archaea and nearly half of bacteria can serve as part of an adaptive immune system ( CRISPR–cas ) that protects these prokaryotes against ...	[ "Clustered Regularly Interspaced Short Palindromic Repeats ( CRISPR ) , together with associated genes ( cas ) , form the CRISPR–cas adaptive immune system , which can provide resistance to viruses and plasmids in bacteria and archaea .", "Here , we use mathematical models , population dynamic experiments , and D...	[ "The evidence that the CRISPR regions of the genomes of archaea and bacteria play a role in the ecology and ( co ) evolution of these microbes and their viruses is overwhelming:", "( i ) the spacers ( variable sequences of 26–72 bp of DNA between the repeats of this region ) of these prokaryotes are homologous to...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "molecular biology/dna replication", "virology/viral replication and gene regulation", "virology/viruses and cancer", "virology" ]	A Subset of Replication Proteins Enhances Origin Recognition and Lytic Replication by the Epstein-Barr Virus ZEBRA Protein	journal.ppat.1001054	null	[ [ "There are many gaps in our understanding of the process by which the Epstein-Barr virus ( EBV ) lytic replication machinery assemble on DNA sites present in the viral genome .", "EBV encodes an essential bZIP protein known as ZEBRA ( aka Zta , Z and BZLF1 ) that functions as a transcription activator of ...	[ "ZEBRA is a site-specific DNA binding protein that functions as a transcriptional activator and as an origin binding protein .", "Both activities require that ZEBRA recognizes DNA motifs that are scattered along the viral genome .", "The mechanism by which ZEBRA discriminates between the origin of lytic replica...	[ "Epstein-Barr virus encodes a protein , ZEBRA , which plays an essential role in the switch between viral latency and the viral lytic cycle .", "ZEBRA activates transcription of early viral genes and also promotes lytic viral DNA replication .", "It is not understood how these two functions are discriminated ."...	2010
[ "Introduction", "Materials and Methods", "Results", "Discussion", "Mutation Rates at Equilibrium", "Effect of Initial Values and Parameters on the Simulation Results" ]	[ "computational biology", "evolutionary biology", "saccharomyces" ]	Phenotypic Mutation Rates and the Abundance of Abnormal Proteins in Yeast	journal.pcbi.0030203	null	[ [ "Every biological organism is built according to information stored in its genome .", "Genomes composed of billions of base pairs are not unusual .", "This information has to be duplicated during cell replication .", "Since replication errors can have devastating effects , DNA replication needs to...	[ "Phenotypic mutations are errors that occur during protein synthesis .", "These errors lead to amino acid substitutions that give rise to abnormal proteins .", "Experiments suggest that such errors are quite common .", "We present a model to study the effect of phenotypic mutation rates on the amount of abnor...	[ "A functional protein machinery , built from genetic information , is central to every living organism .", "Surprisingly , the decoding of genes into amino acid sequences is fairly inaccurate .", "Errors in this process ( phenotypic mutations ) are several orders of magnitude more frequent than errors during DN...	2007
[ "Introduction", "Results and discussion", "Materials and methods" ]	[ "phosphorylation", "parasite groups", "medicine and health sciences", "body fluids", "plasmodium", "enzymes", "enzymology", "plasmodium falciparum", "parasitic protozoans", "parasitology", "apicomplexa", "protozoans", "sequence motif analysis", "research and analysis methods", "sequence ...	Phosphodiesterase beta is the master regulator of cAMP signalling during malaria parasite invasion	journal.pbio.3000154	Phosphodiesterase β (PDEβ) is essential for blood stage development of the malaria parasite. In its absence, phosphorylation of over 200 proteins is adversely affected, revealing PDEβ to be a central regulator that could be targeted with new antimalarial drugs.	[ [ "The malaria parasite life cycle comprises extended phases in both a human host and a mosquito vector , but little is known of the control mechanisms that orchestrate progression of parasite development and transmission .", "Asexually replicating blood stage forms cause all the symptoms and pathology asso...	[ "Cyclic nucleotide signalling is a major regulator of malaria parasite differentiation .", "Phosphodiesterase ( PDE ) enzymes are known to control cyclic GMP ( cGMP ) levels in the parasite , but the mechanisms by which cyclic AMP ( cAMP ) is regulated remain enigmatic .", "Here , we demonstrate that Plasmodium...	[ "Cyclic nucleotide signalling pathways are ubiquitous in eukaryotes and regulate a plethora of cellular processes .", "Pathway components include cyclases and phosphodiesterases that synthesise and break down the intracellular second messengers cyclic AMP ( cAMP ) and cyclic GMP ( cGMP ) ; the signal is translate...	2019
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "medicine and health sciences", "legs", "feet", "decision making", "tropical diseases", "social sciences", "parasitic diseases", "neuroscience", "cognitive psychology", "ectoparasitic infections", "sexually transmitted diseases", "cognition", "neglected tropical diseases", "body limbs", ...	Exploration of a simplified clinical examination for scabies to support public health decision-making	journal.pntd.0006996	null	[ [ "Scabies , a skin condition due to the microscopic mite Sarcoptes scabiei [1] , is a major public health problem worldwide , particularly in low and middle income tropical settings , and has recently been adopted as a neglected tropical disease by the World Health Organization ( WHO ) [2] .", "This design...	[ "In most settings , the diagnosis of scabies is reliant on time-consuming and potentially intrusive clinical examination of all accesible regions of skin .", "With the recent recognition of scabies as a neglected tropical disease by the World Health Organization there is a need for standardised approaches to dise...	[ "Scabies , caused by infestation with the microscopic mite Sarcoptes scabiei , is a major public health problem worldwide , particularly in low- and middle-income tropical settings .", "The diagnosis of scabies is reliant on detection of characteristic signs on clinical examination .", "Examination of the whole...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biotechnology", "medicine and health sciences", "viral transmission and infection", "virology", "epidemiology", "vector biology", "biology and life sciences", "microbiology", "disease vectors", "genetic engineering", "viral vectors" ]	High-Efficiency Targeted Editing of Large Viral Genomes by RNA-Guided Nucleases	journal.ppat.1004090	null	[ [ "With the rapid development of biotechnology , site-specific genome editing approaches allow researchers to target any gene within any organism .", "Two well-known genome-editing technologies include zinc-finger nucleases ( ZFNs ) and transcription activator-like effector nucleases ( TALENs ) .", "The...	[ "A facile and efficient method for the precise editing of large viral genomes is required for the selection of attenuated vaccine strains and the construction of gene therapy vectors .", "The type II prokaryotic CRISPR-Cas ( clustered regularly interspaced short palindromic repeats ( CRISPR ) -associated ( Cas ) ...	[ "The clustered regularly interspaced short palindromic repeats ( CRISPR ) -associated ( Cas ) system was discovered as a component of the bacterial acquired immune system that cleaves foreign DNA .", "This system is now used for site-specific genome editing in a wide range of organisms , including bacteria , yeas...	2014
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "helminth infections", "infectious diseases", "medicine and health sciences", "neglected tropical diseases", "tropical diseases", "infectious disease control", "onchocerciasis", "parasitic diseases" ]	Reproductive Status of Onchocerca volvulus after Ivermectin Treatment in an Ivermectin-Naïve and a Frequently Treated Population from Cameroon	journal.pntd.0002824	null	[ [ "The macrocyclic lactone drug ivermectin ( IVM ) has a broad spectrum of applications against arthropods and nematodes .", "In human medicine , one of the major indications for IVM is the treatment of onchocerciasis or river blindness [1] .", "IVM targets both the microfilariae ( mf ) and adult stages...	[ "For two decades , onchocerciasis control has been based on mass treatment with ivermectin ( IVM ) , repeated annually or six-monthly .", "This drug kills Onchocerca volvulus microfilariae ( mf ) present in the skin and the eyes ( microfilaricidal effect ) and prevents for 3–4 months the release of new mf by adul...	[ "Onchocerciasis , also known as river blindness , is a parasitic disease due to the filarial nematode Onchocerca volvulus .", "It affects more than 37 million people worldwide , most of them ( 99% ) living in Africa .", "The control of river blindness is , up to now , based on annual or six-monthly mass treatme...	2014
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "blood cells", "sequencing techniques", "pseudogenes", "medicine and health sciences", "immune cells", "immunology", "variant genotypes", "alleles", "genetic mapping", "gene types", "molecular biology techniques", "dna", "gene conversion", "neutrophils", "research and analysis methods", ...	Heterogeneity of Human Neutrophil CD177 Expression Results from CD177P1 Pseudogene Conversion	journal.pgen.1006067	null	[ [ "CD177 ( also known as neutrophil specific antigen B1 [NB1] , human neutrophil antigen 2a [HNA-2a] , and polycythemia rubra vera 1 [PRV1] ) is a 56–64 kDa protein belonging to the Ly-6 family [1 , 2] , and is expressed exclusively on neutrophils by glycosylphosphatidylinositol ( GPI ) -linkage [3 , 4] .", ...	[ "Most humans harbor both CD177neg and CD177pos neutrophils but 1–10% of people are CD177null , placing them at risk for formation of anti-neutrophil antibodies that can cause transfusion-related acute lung injury and neonatal alloimmune neutropenia .", "By deep sequencing the CD177 locus , we catalogued CD177 sin...	[ "Expression of the neutrophil-specific antigen CD177 varies across the population .", "1–10% of humans are CD177null .", "CD177pos neonates born to CD177null mothers are susceptible to alloimmune neutropenia .", "Interestingly , CD177pos and CD177neg populations of neutrophils often exist together within indi...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine", "biology" ]	Mycobacterium tuberculosis ClpP1 and ClpP2 Function Together in Protein Degradation and Are Required for Viability in vitro and During Infection	journal.ppat.1002511	null	[ [ "Intracellular protein degradation is critical for maintaining cellular homeostasis through protein quality control and regulation of numerous biological pathways [1] , [2] .", "In eukaryotes , the ubiquitin-proteasome pathway constitutes the predominant degradation pathway [3] .", "Most prokaryotes ,...	[ "In most bacteria , Clp protease is a conserved , non-essential serine protease that regulates the response to various stresses .", "Mycobacteria , including Mycobacterium tuberculosis ( Mtb ) and Mycobacterium smegmatis , unlike most well studied prokaryotes , encode two ClpP homologs , ClpP1 and ClpP2 , in a si...	[ "Due to the significant and rapid rise in multidrug resistant Mycobacterium tuberculosis ( Mtb ) , there is an urgent need to validate novel drug targets for the treatment of tuberculosis .", "Here , we show that Clp protease is an ideal potential target .", "Mtb encodes two ClpP genes , ClpP1 and ClpP2 , which...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "molecular biology/transcription initiation and activation", "genetics and genomics/gene expression", "cell biology/cell signaling", "cell biology/developmental molecular mechanisms", "genetics and genomics/gene function", "developmental biology/developmental molecular mechanisms" ]	A Novel Ecdysone Receptor Mediates Steroid-Regulated Developmental Events during the Mid-Third Instar of Drosophila	journal.pgen.1000102	null	[ [ "During metamorphosis in Drosophila melanogaster , pulses of the 20E steroid hormone , stimulate diverse tissue-specific responses such as the histolysis of many larval tissues and the simultaneous differentiation of adult structures from imaginal discs [reviewed in 1] .", "In addition , multiple pulses o...	[ "The larval salivary gland of Drosophila melanogaster synthesizes and secretes glue glycoproteins that cement developing animals to a solid surface during metamorphosis .", "The steroid hormone 20-hydroxyecdysone ( 20E ) is an essential signaling molecule that modulates most of the physiological functions of the ...	[ "During animal development the physiological response of individual tissues is often “reprogrammed” in response to signaling molecules .", "One important example is the activity of nuclear-hormone receptors that are controlled by small lipid compounds such as steroids and retinoids .", "Thus , understanding how...	2008
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "cell binding", "cell physiology", "medicine and health sciences", "nuclear staining", "pathology and laboratory medicine", "pathogens", "endothelial cells", "permeability", "microbiology", "light microscopy", "epithelial cells", "viruses", "physiological processes", "rna viruses", "micr...	Dengue Virus NS1 Disrupts the Endothelial Glycocalyx, Leading to Hyperpermeability	journal.ppat.1005738	null	[ [ "The four dengue virus serotypes ( DENV1-4 ) are mosquito-borne flaviviruses that are responsible for ~390 million infections per year worldwide [1] .", "Of these , up to 96 million manifest in clinical disease .", "The majority of these cases are dengue fever ( DF ) , the uncomplicated form of diseas...	[ "Dengue is the most prevalent arboviral disease in humans and a major public health problem worldwide .", "Systemic plasma leakage , leading to hypovolemic shock and potentially fatal complications , is a critical determinant of dengue severity .", "Recently , we and others described a novel pathogenic effect o...	[ "Dengue is the most prevalent mosquito-borne disease in humans and represents a major public health problem worldwide .", "Leakage of fluids and molecules from the bloodstream into tissues can lead to shock and potentially death and is a critical determinant of dengue disease severity .", "Recently , we showed ...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biomacromolecule-ligand interactions", "biochemistry", "proteins", "virology", "protein structure", "biology", "microbiology", "host-pathogen interaction", "biophysics" ]	The GM2 Glycan Serves as a Functional Coreceptor for Serotype 1 Reovirus	journal.ppat.1003078	null	[ [ "Virus infections are initiated by attachment of the virus to target cells of susceptible hosts .", "Receptors facilitate attachment , determine host range , and govern susceptibility of particular cells to infection .", "While viral attachment can be a monophasic event , this process frequently invol...	[ "Viral attachment to target cells is the first step in infection and also serves as a determinant of tropism .", "Like many viruses , mammalian reoviruses bind with low affinity to cell-surface carbohydrate receptors to initiate the infectious process .", "Reoviruses disseminate with serotype-specific tropism i...	[ "Receptor utilization plays an important role in viral disease .", "Viruses must recognize a receptor or sometimes multiple receptors to infect a cell .", "Mammalian orthoreoviruses ( reoviruses ) serve as useful models for studies of viral receptor binding and pathogenesis .", "The reovirus experimental syst...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "developmental biology", "molecular development", "genetics", "gene expression", "epigenetics", "biology", "molecular genetics", "gene regulation", "chromatin", "genetics and genomics", "dna transcription", "gene function" ]	New Partners in Regulation of Gene Expression: The Enhancer of Trithorax and Polycomb Corto Interacts with Methylated Ribosomal Protein L12 Via Its Chromodomain	journal.pgen.1003006	null	[ [ "Chromatin structure strongly impacts on regulation of gene expression .", "Indeed , post-translational histone modifications ( methylations , acetylations , phosphorylations etc… ) called epigenetic marks , are recognized by protein complexes that shape chromatin ( reviewed in [1] ) .", "A number of ...	[ "Chromodomains are found in many regulators of chromatin structure , and most of them recognize methylated lysines on histones .", "Here , we investigate the role of the Drosophila melanogaster protein Corto's chromodomain .", "The Enhancer of Trithorax and Polycomb Corto is involved in both silencing and activ...	[ "Chromatin , the combination of DNA and histones , strongly impacts transcriptional regulation of genes .", "This is achieved thanks to various protein complexes that bind chromatin and remodel its structure .", "These complexes bind specific motifs , also called epigenetic marks , through specific protein doma...	2012
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "developmental biology/stem cells", "cell biology/cell signaling", "genetics and genomics/gene expression", "cell biology/developmental molecular mechanisms", "developmental biology/cell differentiation", "cell biology/gene expression" ]	Functional Heterogeneity of Embryonic Stem Cells Revealed through Translational Amplification of an Early Endodermal Transcript	journal.pbio.1000379	Detection of low-level, lineage-specific transcription aids in the identification of lineage-primed populations of ES cells provides a new framework for pluripotency.	[ [ "ES cells are an in vitro cell line derived from the inner cell mass ( ICM ) of the early mammalian blastocyst [1] , [2] .", "In mouse they are defined functionally as a karyotypically normal immortal cell line that can give rise to all the future lineages of the conceptus [3] .", "Thus they can self-...	[ "ES cells are defined as self-renewing , pluripotent cell lines derived from early embryos .", "Cultures of ES cells are also characterized by the expression of certain markers thought to represent the pluripotent state .", "However , despite the widespread expression of key markers such as Oct4 and the appeara...	[ "Embryonic stem ( ES ) cells are karyotypically normal , embryo-derived cell lines that are pluripotent , i . e . capable of generating all the cell types of the future organism , but not the extra-embryonic lineages .", "What gives ES cells this unique capacity ?", "Here , we use a fluorescent reporter cell li...	2010
[ "Introduction", "Results and discussion", "Materials and methods" ]	[ "chemical bonding", "chemical compounds", "oxides", "enzymes", "enzymology", "dismutases", "organisms", "fungi", "crystals", "materials science", "sequence motif analysis", "oligomers", "hydrogen bonding", "physical chemistry", "research and analysis methods", "sequence analysis", "p...	Molecular recognition and maturation of SOD1 by its evolutionarily destabilised cognate chaperone hCCS	journal.pbio.3000141	null	[ [ "Copper binding and disulphide bond formation are strongly discouraged in the eukaryotic cytoplasm despite widespread use within extracellular spaces and organelles .", "In the latter case , the preponderance of reduced glutathione and the thioredoxin system almost completely prevent their existence .", ...	[ "Superoxide dismutase-1 ( SOD1 ) maturation comprises a string of posttranslational modifications which transform the nascent peptide into a stable and active enzyme .", "The successive folding , metal ion binding , and disulphide acquisition steps in this pathway can be catalysed through a direct interaction wit...	[ "Cellular complexity necessitates an equally complex network of courier proteins to internalise , sort , and deliver biologically useful metals like copper .", "These relay systems negotiate a landscape of metal-binding sites through handshake–handoff interactions , but the mechanisms that impart a necessary tran...	2019
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[]	The B Cell Adaptor Molecule Bam32 Is Critically Important for Optimal Antibody Response and Resistance to Trypanosoma congolense Infection in Mice	journal.pntd.0003716	null	[ [ "African trypanosomiasis , also called sleeping sickness in man , is a deadly disease of humans and livestock caused by blood parasites belonging to the genus Trypanosoma .", "In human , the disease is caused by Trypanosoma brucei gambiense and Trypanosoma brucei rhodesiense; whereas the animal form of th...	[ "Bam32 , a 32 kDa adaptor molecule , plays important role in B cell receptor signalling , T cell receptor signalling and antibody affinity maturation in germinal centres .", "Since antibodies against trypanosome variant surface glycoproteins ( VSG ) are critically important for control of parasitemia , we hypothe...	[ "African trypanosomiasis continues to be a major threat to human health and economic development in sub-Saharan Africa .", "Despite intense studies , the immunopathogenesis of the disease remains poorly understood .", "Understanding the factors that regulate disease pathogenesis would be important in designing ...	2015
[ "Introduction", "Materials and Methods", "Results", "Discussion", "Supporting Information" ]	[ "drosophila", "cell biology" ]	Motility Screen Identifies Drosophila IGF-II mRNA-Binding Protein—Zipcode-Binding Protein Acting in Oogenesis and Synaptogenesis	journal.pgen.0040036	null	[ [ "The subcellular localization of mRNAs is a conserved means of localizing protein concentration gradients that underlie the establishment of cellular asymmetries and specialized cell functions [1 , 2] .", "For example , the localization of β-actin mRNA to the leading edge of neurite growth cones and embry...	[ "The localization of specific mRNAs can establish local protein gradients that generate and control the development of cellular asymmetries .", "While all evidence underscores the importance of the cytoskeleton in the transport and localization of RNAs , we have limited knowledge of how these events are regulated...	[ "The localization of messenger RNA is a major mechanism to generate local asymmetries in protein activities and is utilized in a diverse array of biological functions .", "mRNA localization and the resultant protein gradients are critical for the establishment of embryonic axes , the polarized motility of cells a...	2008
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Simple Plans or Sophisticated Habits? State, Transition and Learning Interactions in the Two-Step Task	journal.pcbi.1004648	null	[ [ "Humans and other animals are thought to use a mixture of different strategies to learn to choose actions that lead to positive outcomes and prevent negative outcomes [1 , 2] .", "Much interest is currently focused on the distinction between control systems which employ model-based and ( value-based ) mod...	[ "The recently developed ‘two-step’ behavioural task promises to differentiate model-based from model-free reinforcement learning , while generating neurophysiologically-friendly decision datasets with parametric variation of decision variables .", "These desirable features have prompted its widespread adoption ."...	[ "Planning is the use of a predictive model of the consequences of actions to guide decision making .", "Planning plays a critical role in human behaviour , but isolating its contribution is challenging because it is complemented by control systems which learn values of actions directly from the history of reinfor...	2015
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "medicine and health sciences", "immune physiology", "gene regulation", "immunology", "microbiology", "signal inhibition", "immunoprecipitation", "antibodies", "research and analysis methods", "erk signaling cascade", "small interfering rnas", "immune system proteins", "infectious diseases",...	Activation of PI3K, Akt, and ERK during early rotavirus infection leads to V-ATPase-dependent endosomal acidification required for uncoating	journal.ppat.1006820	null	[ [ "Group A rotavirus ( RVA ) , a species of the Rotavirus genus in the Reoviridae family , is recognized as a major pathogen that causes severe acute dehydrating diarrhea in young children and in a wide variety of young animals [1 , 2] .", "RVA infections are responsible for approximately 200 , 000 deaths e...	[ "The cellular PI3K/Akt and/or MEK/ERK signaling pathways mediate the entry process or endosomal acidification during infection of many viruses .", "However , their roles in the early infection events of group A rotaviruses ( RVAs ) have remained elusive .", "Here , we show that late-penetration ( L-P ) human DS...	[ "Viral particles must transport their genome into the cytoplasm or the nucleus of host cells to initiate successful infection .", "Knowledge of how viruses may pirate host cell signaling cascades or molecules to promote their own replication can facilitate the development of antiviral drugs .", "Group A rotavir...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine", "biochemistry", "public health and epidemiology", "immunology", "biology", "molecular cell biology", "public health" ]	Identification of a Novel Splice Variant Form of the Influenza A Virus M2 Ion Channel with an Antigenically Distinct Ectodomain	journal.ppat.1002998	null	[ [ "Influenza A virus ( IAV ) is a genetically diverse pathogen of global significance , responsible for seasonal epidemics and sporadic pandemics in humans , as well as outbreaks in domestic animals .", "Its primary reservoir is wild birds , but it can infect a wide range of vertebrate species .", "For ...	[ "Segment 7 of influenza A virus produces up to four mRNAs .", "Unspliced transcripts encode M1 , spliced mRNA2 encodes the M2 ion channel , while protein products from spliced mRNAs 3 and 4 have not previously been identified .", "The M2 protein plays important roles in virus entry and assembly , and is a targe...	[ "Influenza A virus is a pathogen capable of infecting a wide range of avian and mammalian hosts , causing seasonal epidemics and pandemics in humans .", "In recent years , the unexpected coding capacity of the virus has begun to be unravelled , with the identification of three more protein products ( PB1-F2 , PB1...	2012
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "organismal evolution", "medicine and health sciences", "infectious disease epidemiology", "microbiology", "bacterial diseases", "emerging infectious diseases", "population modeling", "microbial evolution", "population biology", "infectious disease control", "bacterial pathogens", "infectious ...	Cycling Empirical Antibiotic Therapy in Hospitals: Meta-Analysis and Models	journal.ppat.1004225	null	[ [ "The emergence and spread of antibiotic resistance threatens our ability to treat bacterial infections and is a substantial danger for public health world-wide [1] .", "Resistant strains are especially prevalent in hospitals , where the high usage of antibiotics facilitates emergence and spread of resista...	[ "The rise of resistance together with the shortage of new broad-spectrum antibiotics underlines the urgency of optimizing the use of available drugs to minimize disease burden .", "Theoretical studies suggest that coordinating empirical usage of antibiotics in a hospital ward can contain the spread of resistance ...	[ "The rise of antibiotic resistance is a major concern for public health .", "In hospitals , frequent usage of antibiotics leads to high resistance levels; at the same time the patients are especially vulnerable .", "We therefore urgently need treatment strategies that limit resistance without compromising patie...	2014

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