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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", "Materials and Methods", "Results", "Discussion" ]	[ "mathematics", "statistics", "genetics", "biology", "computational biology", "genetics and genomics" ]	A Bayesian Approach to Analyse Genetic Variation within RNA Viral Populations	journal.pcbi.1002027	null	[ [ "Reverse transcription-polymerase chain reaction ( RT-PCR ) is a common tool to generate", "copy DNA ( cDNA ) from RNA .", "All publicly available sequences of RNA viruses have been", "generated using this technique .", "The method consists of two steps: the first is an", "in vitro synthes...	[ "The development of modern and affordable sequencing technologies has allowed the", "study of viral populations to an unprecedented depth .", "This is of particular", "interest for the study of within-host RNA viral populations , where variation due", "to error-prone polymerases can lead to immune escape , ...	[ "Characterising genetic variation in viral populations can have important", "implications in terms of understanding how viruses evolve within infected hosts .", "Modern sequencing technologies allow genetic information to be obtained faster ,", "more affordably , and in much greater quantities than before .",...	2011
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "blood cells", "innate immune system", "medicine and health sciences", "immune physiology", "cytokines", "body fluids", "clinical research design", "immune cells", "pathology and laboratory medicine", "immunology", "wolbachia", "research design", "developmental biology", "molecular develop...	Systems analysis-based assessment of post-treatment adverse events in lymphatic filariasis	journal.pntd.0007697	null	[ [ "Lymphatic filariasis ( LF ) is a disabling neglected tropical disease that is caused by the mosquito-borne filarial parasites Wuchereria bancrofti , Brugia malayi and B . timori .", "Adult worms live in the human host’s lymphatic system and release larval parasites ( microfilariae or Mf ) that circulate ...	[ "Lymphatic filariasis ( LF ) is a neglected tropical disease , and the Global Program to Eliminate LF delivers mass drug administration ( MDA ) to 500 million people every year .", "Adverse events ( AEs ) are common after LF treatment .", "To better understand the pathogenesis of AEs , we studied LF-patients fr...	[ "Lymphatic filariasis ( LF ) is a disabling parasitic disease that affects millions of people in the developing world .", "The Global Programme to Eliminate Lymphatic Filariasis ( coordinated by the World Health Organization ) uses mass administration of antifilarial medications to cure infections , prevent disea...	2019
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genome sequencing", "mycology", "genomics", "fungal evolution", "microbial evolution", "microbial pathogens", "biology", "evolutionary biology", "genomic evolution", "microbiology", "host-pathogen interaction", "genetics and genomics" ]	Global Analysis of the Evolution and Mechanism of Echinocandin Resistance in Candida glabrata	journal.ppat.1002718	null	[ [ "The emergence of drug resistance is an evolutionary process with a profound impact on human health .", "The widespread deployment of antimicrobial agents in medicine and agriculture exerts strong selection for organisms with enhanced capacity to survive and reproduce in the presence of drug , which has l...	[ "The evolution of drug resistance has a profound impact on human health .", "Candida glabrata is a leading human fungal pathogen that can rapidly evolve resistance to echinocandins , which target cell wall biosynthesis and are front-line therapeutics for Candida infections .", "Here , we provide the first globa...	[ "The evolution of drug resistance poses a severe threat to human health .", "Candida glabrata is a leading cause of mortality due to fungal infections worldwide .", "It can rapidly evolve resistance to drugs such as echinocandins , which target the fungal cell wall and are front-line therapeutics for Candida in...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "systems biology", "developmental biology", "gene expression", "genetics", "regulatory networks", "biology", "computational biology", "pattern formation", "genetics and genomics", "evolutionary developmental biology" ]	A Conserved Developmental Patterning Network Produces Quantitatively Different Output in Multiple Species of Drosophila	journal.pgen.1002346	null	[ [ "Transcriptional programs specify and elaborate cell identity during animal development , as a single cell gives rise to the hundreds of cell types that comprise the adult animal .", "Accordingly , variation in the timing , spatial location , and level of transcription is thought to be a major source of m...	[ "Differences in the level , timing , or location of gene expression can contribute to alternative phenotypes at the molecular and organismal level .", "Understanding the origins of expression differences is complicated by the fact that organismal morphology and gene regulatory networks could potentially vary even...	[ "For a gene to function properly , it must be active in the right place , at the right time , and in the right amount .", "Changes in any of these features can lead to observable differences between individuals and species and in some cases can lead to disease .", "We do not currently understand how the positio...	2011
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "immunology/cellular microbiology and pathogenesis", "molecular biology/histone modification", "cell biology/leukocyte signaling and gene expression", "immunology/innate immunity", "infectious diseases/respiratory infections", "infectious diseases/bacterial infections" ]	Anthrax Lethal Toxin Impairs IL-8 Expression in Epithelial Cells through Inhibition of Histone H3 Modification	journal.ppat.1000359	null	[ [ "Pulmonary infection by B . anthracis , the etiologic agent of anthrax disease [1] , has been shown to be the most life-threatening form of the disease as compared to gastrointestinal and cutaneous forms of anthrax .", "Whatever the infection route used by this bacterium , spores are taken up by macrophag...	[ "Lethal toxin ( LT ) is a critical virulence factor of Bacillus anthracis , the etiological agent of anthrax , whose pulmonary form is fatal in the absence of treatment .", "Inflammatory response is a key process of host defense against invading pathogens .", "We report here that intranasal instillation of a B ...	[ "Bacillus anthracis , the etiological agent of anthrax , can infect mammals either accidentally or as a potential consequence of a terrorism threat .", "Pulmonary infection is a life-threatening form of the disease , causing a near 100% mortality rate in the absence of appropriate therapy .", "Thus , it is impo...	2009
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "infectious diseases/neglected tropical diseases", "cardiovascular disorders/myopathies" ]	Testing the Efficacy of a Multi-Component DNA-Prime/DNA-Boost Vaccine against Trypanosoma cruzi Infection in Dogs	journal.pntd.0001050	null	[ [ "American trypanosomiasis ( Chagas disease ) is a disease of humans and caused by the", "protozoan Trypanosoma cruzi of the family trypanosomatidae [1] .", "Approximately", "30–40% of the infected patients develop a chronic debilitating illness", "of the cardiac system , characterized by clini...	[ "Trypanosoma cruzi , the etiologic agent of Chagas Disease , is", "a major vector borne health problem in Latin America and an emerging", "infectious disease in the United States .", "We tested the efficacy of a multi-component DNA-prime/DNA-boost vaccine", "( TcVac1 ) against experimental T . cruzi infecti...	[ "Immunization of dogs with DNA-prime/DNA-boost vaccine ( TcVac1 ) enhanced the", "Trypanosoma cruzi-specific type 1 antibody and", "CD8+ T cell responses that resulted in an early control of", "acute parasitemia and a moderate decline in pathological symptoms during chronic", "phase .", "Further improveme...	2011
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[]	Serological Evidence of Chikungunya Virus among Acute Febrile Patients in Southern Mozambique	journal.pntd.0004146	null	[ [ "Chikungunya virus ( CHIKV ) is an arthropod borne virus ( arbovirus ) transmitted by Aedes mosquitoes and belonging to the Togaviridae family and alphavirus genus .", "Clinical presentation of CHIKV disease ranges from a self-limiting and undifferentiated febrile illness accompanied by exanthema , myalgi...	[ "In the last two decades , chikungunya virus ( CHIKV ) has rapidly expanded to several geographical areas , causing frequent outbreaks in sub-Saharan Africa , South East Asia , South America , and Europe .", "Therefore , the disease remains heavily neglected in Mozambique , and no recent study has been conducted ...	[ "Chikungunya virus ( CHIKV ) is an emerging arbovirus that remains heavily neglected in Mozambique , and no recent study has been conducted .", "Between January and September 2013 , four hundred acute febrile patients with no other evident cause of fever and attending a health center in a suburban area of Maputo ...	2015
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "blood cells", "flow cytometry", "graduates", "medicine and health sciences", "immune physiology", "enzyme-linked immunoassays", "pathology and laboratory medicine", "immune cells", "pathogens", "immunology", "microbiology", "alumni", "vaccines", "animal models", "fungi", "model organi...	The NDV-3A vaccine protects mice from multidrug resistant Candida auris infection	journal.ppat.1007460	null	[ [ "The fungus Candida auris was first detected in 2009 from an ear canal infection in Japan [1] .", "However , the earliest known strain of C . auris dates back to 1996 isolated in a retrospective analysis of previously misdiagnosed samples from Korea [2] .", "Since then , C . auris has been reported in...	[ "Candida auris is an emerging , multi-drug resistant , health care-associated fungal pathogen .", "Its predominant prevalence in hospitals and nursing homes indicates its ability to adhere to and colonize the skin , or persist in an environment outside the host—a trait unique from other Candida species .", "Bes...	[ "Candida auris has emerged as a major health concern to hospitalized patients and nursing home subjects .", "C . auris strains display multidrug resistance to current antifungal therapy and cause lethal infections .", "We have determined that C . auris harbors homologs of C . albicans Als cell surface proteins ...	2019
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "molecular neuroscience", "developmental neuroscience", "cellular neuroscience", "biology", "sensory systems", "neuroscience" ]	Eps8 Regulates Hair Bundle Length and Functional Maturation of Mammalian Auditory Hair Cells	journal.pbio.1001048	null	[ [ "The mechanoelectrical transduction of sound information is made possible by sensory hair cells ( inner and outer hair cells ) in the cochlea [1] .", "The initial step in the sound transduction cascade is performed by mechanically gated ion channels positioned near the tips of hair cell stereocilia .", ...	[ "Hair cells of the mammalian cochlea are specialized for the dynamic coding of sound stimuli .", "The transduction of sound waves into electrical signals depends upon mechanosensitive hair bundles that project from the cell's apical surface .", "Each stereocilium within a hair bundle is composed of uniformly po...	[ "Mammalian hearing depends on mechanosensory inner and outer hair cells within the inner ear that convert sound vibrations into electrical signals .", "While inner hair cells are the primary sensory receptors , outer hair cells improve auditory sensitivity .", "Although we know that sensory cells of the auditor...	2011
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "phosphorylation", "immunofluorescence staining", "hela cells", "biological cultures", "neuroscience", "cytoplasmic staining", "cell cultures", "cellular structures and organelles", "research and analysis methods", "specimen preparation and treatment", "staining", "animal cells", "proteins",...	TDP-43 proteinopathy in Theiler’s murine encephalomyelitis virus infection	journal.ppat.1007574	null	[ [ "Trans-activation response ( TAR ) DNA-binding protein of 43 kDa ( TDP-43 ) is an RNA-binding protein ( as well as DNA-binding protein ) primarily present in the nucleus and important in RNA processing , mRNA transport/stability , and mRNA translation [2–4] .", "A variety of cellular stresses normally tri...	[ "TDP-43 , an RNA-binding protein that is primarily nuclear and important in splicing and RNA metabolism , is mislocalized from the nucleus to the cytoplasm of neural cells in amyotrophic lateral sclerosis ( ALS ) , and contributes to disease .", "We sought to investigate whether TDP-43 is mislocalized in infectio...	[ "TDP-43 is a widely expressed nuclear protein that shuttles between the nucleus and cytoplasm , and regulates many aspects of RNA processing , such as splicing , trafficking , stabilization , and miRNA production .", "In almost all cases of ALS , neuronal and glial TDP-43 is phosphorylated , cleaved , and misloca...	2019
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "blood cells", "cell death", "medicine and health sciences", "immune cells", "vesicles", "pathology and laboratory medicine", "pathogens", "cell processes", "immunology", "microbiology", "staphylococcus aureus", "bacterial diseases", "physiological processes", "homeostasis", "phagosomes"...	The Drosophila CD36 Homologue croquemort Is Required to Maintain Immune and Gut Homeostasis during Development and Aging	journal.ppat.1005961	null	[ [ "Mounting appropriate immune responses against pathogens is critical for the survival of all animals .", "Mechanisms to both eliminate microbes and resolve infection by returning the immune system to basal activity are necessary to maintain an adequate and balanced immune response [1 , 2] .", "Alterat...	[ "Phagocytosis is an ancient mechanism central to both tissue homeostasis and immune defense .", "Both the identity of the receptors that mediate bacterial phagocytosis and the nature of the interactions between phagocytosis and other defense mechanisms remain elusive .", "Here , we report that Croquemort ( Crq ...	[ "Phagocytosis is a first-line host defense mechanism against microbes .", "Interactions between phagocytosis and other immune mechanisms , such as the humoral response , however , remain elusive .", "Defective phagocytosis can lead to immune deficiencies and chronic auto-inflammation .", "Here , we show that ...	2016
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "genome-wide association studies", "medicine and health sciences", "tropical diseases", "alleles", "long non-coding rnas", "ethnicities", "vietnamese people", "bacterial diseases", "mathematics", "statistics (mathematics)", "gastroenterology and hepatology", "genome analysis", "neglected tro...	A genome wide association study identifies a lncRna as risk factor for pathological inflammatory responses in leprosy	journal.pgen.1006637	null	[ [ "A clear temporal separation from the different stages of leprosy pathogenesis identifies the endophenotype Type-1 Reactions ( T1Rs ) as a well-delineated example for host pathological inflammatory responses in humans .", "An endophenotype , as defined by John and Lewis in 1966 , is a microscopic and inte...	[ "Leprosy Type-1 Reactions ( T1Rs ) are pathological inflammatory responses that afflict a sub-group of leprosy patients and result in peripheral nerve damage .", "Here , we employed a family-based GWAS in 221 families with 229 T1R-affect offspring with stepwise replication to identify risk factors for T1R .", "...	[ "Leprosy still affects approximately 200 , 000 new victims each year .", "A major challenge of leprosy control is the prevention of permanent disability due to nerve damage .", "Nerve damage occurs if leprosy remains undiagnosed for extended periods or when patients undergo pathological inflammatory responses t...	2017
[ "Introduction", "Results", "Discussions", "Methods and materials" ]	[ "cell physiology", "cryptococcus neoformans", "medicine and health sciences", "cryptococcus", "pathology and laboratory medicine", "pathogens", "rna extraction", "microbiology", "sexual reproduction", "developmental biology", "fungi", "regulator genes", "gene types", "fungal pathogens", ...	Pheromone independent unisexual development in Cryptococcus neoformans	journal.pgen.1006772	null	[ [ "Sexual reproduction is generally considered bisexual , involving partners of the opposite sex .", "However , unisexual development ( self-fertile or inbreeding ) occurs in some eukaryotes without the need for an opposite mating partner [1–4] .", "Each reproduction mode has its own costs and benefits ...	[ "The fungus Cryptococcus neoformans can undergo a-α bisexual and unisexual reproduction .", "Completion of both sexual reproduction modes requires similar cellular differentiation processes and meiosis .", "Although bisexual reproduction generates equal number of a and α progeny and is far more efficient than u...	[ "Like many higher eukaryotes , the fungus Cryptococcus neoformans is known to undergo bisexual mating that involves α and a partners .", "Surprisingly , the α mating type is dominant in nature ( >99% ) .", "Unisexual reproduction was previously discovered in Cryptococcus and the mating type α allele enhances th...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biotechnology", "marker-assisted selection", "agricultural biotechnology", "agriculture" ]	Genetic Architecture of Aluminum Tolerance in Rice (Oryza sativa) Determined through Genome-Wide Association Analysis and QTL Mapping	journal.pgen.1002221	null	[ [ "Aluminum ( Al ) toxicity is the major constraint to crop productivity on acid soils , which comprise over 50% of the world's arable land [1] .", "Under highly acidic soil conditions ( pH<5 . 0 ) , Al is solubilized into the soil solution as Al3+ , which is highly phytotoxic , causing a rapid inhibition o...	[ "Aluminum ( Al ) toxicity is a primary limitation to crop productivity on acid soils , and rice has been demonstrated to be significantly more Al tolerant than other cereal crops .", "However , the mechanisms of rice Al tolerance are largely unknown , and no genes underlying natural variation have been reported ....	[ "While rice ( Oryza sativa ) is significantly more Al tolerant than other cereals , no genes underlying Al tolerance in rice have been reported .", "Using genome-wide association ( GWA ) and bi-parental QTL mapping , we investigated the genetic architecture of Al tolerance in rice .", "Japonica varieties were t...	2011
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "pharmacology/personalized medicine", "pharmacology", "computational biology/systems biology" ]	Search Algorithms as a Framework for the Optimization of Drug Combinations	journal.pcbi.1000249	null	[ [ "To understand the motivation for our work it is important to consider that , even", "if simulations might play a role , the intended use of the algorithms is not", "entirely in silico , but partially in vivo or", "in vitro , using high-throughput biological measurements in", "organisms or iso...	[ "Combination therapies are often needed for effective clinical outcomes in the", "management of complex diseases , but presently they are generally based on", "empirical clinical experience .", "Here we suggest a novel application of search", "algorithms—originally developed for digital", "communication—m...	[ "This work describes methods that identify drug combinations that might alleviate", "the suffering caused by complex diseases .", "Our biological model systems are:", "physiological decline associated with aging , and selective killing of cancer", "cells .", "The novelty of this approach is based on a new...	2008
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "neuroscience/behavioral neuroscience", "genetics and genomics/animal genetics", "biochemistry/rna structure", "genetics and genomics/gene expression", "developmental biology/cell differentiation", "genetics and genomics/disease models", "genetics and genomics/gene function", "developmental biology/ne...	Defects in tRNA Modification Associated with Neurological and Developmental Dysfunctions in Caenorhabditis elegans Elongator Mutants	journal.pgen.1000561	null	[ [ "Regulation at the level of translation is one important way in which gene activity is controlled in metazoans .", "Several different mechanisms have previously been identified by which translation can be regulated during development or memory formation [reviewed in 1] .", "During anterior-posterior p...	[ "Elongator is a six subunit protein complex , conserved from yeast to humans .", "Mutations in the human Elongator homologue , hELP1 , are associated with the neurological disease familial dysautonomia .", "However , how Elongator functions in metazoans , and how the human mutations affect neural functions is i...	[ "The efficiency of protein synthesis can be modulated by alterations of various components of the translation machinery .", "In translation , transfer RNAs act as adapter molecules that decode mRNA into protein and thereby play a central role in gene expression .", "In the tRNA maturation process , a subset of ...	2009
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "public health and epidemiology" ]	Comparing Diagnostic Accuracy of Kato-Katz, Koga Agar Plate, Ether-Concentration, and FLOTAC for Schistosoma mansoni and Soil-Transmitted Helminths	journal.pntd.0000754	null	[ [ "Schistosomiasis and soil-transmitted helminthiasis are widespread in many parts of the developing world where they negatively impact on human health and wellbeing , and thus exacerbate poverty [1]–[4] .", "Schistosomiasis is caused by blood flukes of the genus Schistosoma; in Africa both S . mansoni and ...	[ "Infections with schistosomes and soil-transmitted helminths exert a considerable yet underappreciated economic and public health burden on afflicted populations .", "Accurate diagnosis is crucial for patient management , drug efficacy evaluations , and monitoring of large-scale community-based control programs ....	[ "Infections with parasitic worms ( e . g . , Schistosoma mansoni , hookworm , roundworm , whipworm , and threadworm ) are still widespread in the developing world .", "Accurate diagnosis is important for better patient management and for monitoring of deworming programs .", "Unfortunately , methods to detect pa...	2010
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "computational biology/protein structure prediction", "computational biology/macromolecular structure analysis", "pharmacology/drug development", "biotechnology/small molecule chemistry" ]	A Kernel for Open Source Drug Discovery in Tropical Diseases	journal.pntd.0000418	null	[ [ "There is a lack of high-quality protein drug targets and drug leads for neglected diseases [1] , [2] .", "Fortunately , many genomes of organisms that cause tropical diseases have already been sequenced and published .", "Therefore , we are now in a position to leverage this information by identifyin...	[ "Conventional patent-based drug development incentives work badly for the developing world , where commercial markets are usually small to non-existent .", "For this reason , the past decade has seen extensive experimentation with alternative R&D institutions ranging from private–public partnerships to developmen...	[ "Open source drug discovery , a promising alternative avenue to conventional patent-based drug development , has so far remained elusive with few exceptions .", "A major stumbling block has been the absence of a critical mass of preexisting work that volunteers can improve through a series of granular contributio...	2009
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "cell physiology", "colorimetric assays", "medicine and health sciences", "cell viability testing", "pathology and laboratory medicine", "pathogens", "microbiology", "cell metabolism", "biochemical analysis", "viruses", "enzyme assays", "immunoprecipitation", "dna viruses", "bioassays and ...	The KSHV K1 Protein Modulates AMPK Function to Enhance Cell Survival	journal.ppat.1005985	null	[ [ "Kaposi’s sarcoma-associated herpesvirus ( KSHV ) is the causative agent of the endothelial cancer , Kaposi’s sarcoma ( KS ) , and two B-cell lymphomas including primary effusion lymphoma ( PEL ) and multicentric Castleman’s disease ( MCD ) [1–3] .", "KSHV-related malignancies primarily arise in immune-su...	[ "Kaposi’s sarcoma herpesvirus ( KSHV ) is the etiologic agent of Kaposi’s sarcoma ( KS ) as well as two lymphoproliferative diseases , primary effusion lymphoma and multicentric Castleman’s disease .", "KSHV encodes viral proteins , such as K1 , that alter signaling pathways involved in cell survival .", "Expre...	[ "Infectious agents such as Kaposi’s sarcoma associated herpesvirus ( KSHV ) are etiologic agents of human cancer .", "KSHV-infected cells must survive various environmental stresses .", "Cells infected with KSHV express viral proteins that alter normal cellular processes to promote cell survival and viral persi...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "signal transduction", "virology", "host-pathogen interaction", "biology", "microbiology", "molecular cell biology" ]	Human Cytomegalovirus Gene UL76 Induces IL-8 Expression through Activation of the DNA Damage Response	journal.ppat.1003609	null	[ [ "Human cytomegalovirus ( HCMV ) is a β-herpesvirus that infects healthy individuals , usually asymptomatically , but can cause severe or fatal disease in immunocompromised individuals .", "Primary HCMV infection , as with other herpesviruses , is followed by establishment of lifelong latency with periodic...	[ "Human cytomegalovirus ( HCMV ) , a β-herpesvirus , has evolved many strategies to subvert both innate and adaptive host immunity in order to ensure its survival and propagation within the host .", "Induction of IL-8 is particularly important during HCMV infection as neutrophils , primarily attracted by IL-8 , pl...	[ "The importance of herpesviruses is evident by their prevalence in the human population and the diverse range of diseases that they provoke .", "Their ability to establish latency provides a compelling example of how herpesviruses successfully evade the immune system and manipulate cellular biology .", "One pro...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "computational biology/protein structure prediction", "computational biology" ]	Influence of Sequence Changes and Environment on Intrinsically Disordered Proteins	journal.pcbi.1000497	null	[ [ "In the past decade , significant progress has been achieved in our understanding of the ubiquity and function of intrinsically disordered proteins [1]–[8] .", "What once seemed to be a set of exceptions to the traditional structure-to-function paradigm , where every protein was believed to have unique an...	[ "Many large-scale studies on intrinsically disordered proteins are implicitly based on the structural models deposited in the Protein Data Bank .", "Yet , the static nature of deposited models supplies little insight into variation of protein structure and function under diverse cellular and environmental conditi...	[ "Intrinsically disordered proteins , proteins that exist as conformational ensembles without time-invariant residue positions , have emerged as an important and common class of proteins in all kingdoms of life .", "Disordered proteins are characterized by distinct amino acid preferences , distinct mechanisms of b...	2009
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genome-wide association studies", "medicine and health sciences", "sleep", "diabetes mellitus", "physiological processes", "endocrine disorders", "mathematics", "statistics (mathematics)", "genome analysis", "chronobiology", "type 2 diabetes", "research and analysis methods", "endocrinology...	Genome-Wide Association Analyses in 128,266 Individuals Identifies New Morningness and Sleep Duration Loci	journal.pgen.1006125	null	[ [ "There are strong epidemiological associations between disrupted circadian rhythms , sleep duration and disease .", "A circadian rhythm refers to an underlying 24-hour physiological cycle that occurs in most living organisms .", "In humans , there are clear daily cyclical patterns in core body tempera...	[ "Disrupted circadian rhythms and reduced sleep duration are associated with several human diseases , particularly obesity and type 2 diabetes , but until recently , little was known about the genetic factors influencing these heritable traits .", "We performed genome-wide association studies of self-reported chro...	[ "Numerous studies have identified links between too little or too much sleep and circadian misalignment with metabolic disorders such as obesity and type 2 diabetes .", "However , cause-and-effect is not easily determined , because of multiple confounding factors affecting both sleep patterns and disease risk .",...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine", "biochemistry", "infectious diseases", "medicinal chemistry", "chemistry", "biology", "chemical biology", "biophysics" ]	The Molecular Basis of Drug Resistance against Hepatitis C Virus NS3/4A Protease Inhibitors	journal.ppat.1002832	null	[ [ "Hepatitis C virus ( HCV ) is a genetically diverse positive-stranded RNA virus of the Flaviviridae family infecting an estimated 170 million people worldwide [1] , [2] .", "Based on genetic diversity , HCV is divided into six major genotypes ( genotypes 1–6 ) and numerous subtypes with different geograph...	[ "Hepatitis C virus ( HCV ) infects over 170 million people worldwide and is the leading cause of chronic liver diseases , including cirrhosis , liver failure , and liver cancer .", "Available antiviral therapies cause severe side effects and are effective only for a subset of patients , though treatment outcomes ...	[ "Hepatitis C virus ( HCV ) infects over 170 million people worldwide and is the leading cause of chronic liver diseases , including cirrhosis , liver failure , and liver cancer .", "New classes of directly-acting antiviral agents that target various HCV enzymes are being developed .", "Two such drugs that targe...	2012
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "invertebrates", "signaling networks", "animals", "animal models", "drosophila melanogaster", "model organisms", "systems science", "mathematics", "network analysis", "experimental organism systems", "sequence motif analysis", "drosophila", "research and analysis methods", "sequence analys...	Identifying (un)controllable dynamical behavior in complex networks	journal.pcbi.1006630	null	[ [ "A key goal in the study of complex dynamical systems is to extract important qualitative information from models of varying specificity ( e . g . , [1 , 2] ) .", "This has been approached via the construction and analysis of qualitative models ( e . g . , discrete models [3–7] ) and also by analytic tech...	[ "We present a technique applicable in any dynamical framework to identify control-robust subsets of an interacting system .", "These robust subsystems , which we call stable modules , are characterized by constraints on the variables that make up the subsystem .", "They are robust in the sense that if the defin...	[ "We show how to uncover the causal relationships between qualitative statements about the values of variables in ODE systems .", "We then show how these relationships can be used to identify subsystem behaviors that are robust to outside interventions .", "This informs potential system control strategies ( e . ...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "phosphorylation", "medicine and health sciences", "luciferase", "poxviruses", "pathology and laboratory medicine", "viral transmission and infection", "enzymes", "pathogens", "messenger rna", "microbiology", "enzymology", "viruses", "rna viruses", "immunoprecipitation", "dna viruses", ...	PKR Transduces MDA5-Dependent Signals for Type I IFN Induction	journal.ppat.1005489	null	[ [ "The innate immune response allows for the rapid production of type I interferons ( IFNs ) and other proinflammatory cytokines to counteract invading viral pathogens .", "This response relies , in part , on a group of molecules collectively referred to as pattern recognition receptors ( PRRs ) , which rec...	[ "Sensing invading pathogens early in infection is critical for establishing host defense .", "Two cytosolic RIG-like RNA helicases , RIG-I and MDA5 , are key to type I interferon ( IFN ) induction in response to viral infection .", "Mounting evidence suggests that another viral RNA sensor , protein kinase R ( P...	[ "Induction of type I interferon ( IFN ) during viral infection is a key step in the activation of innate host defense .", "Critical to this response is the ability to recognize viral nucleic acids in the host cell cytoplasm .", "Detection of viral RNA is mediated by RNA helicases , including RIG-I and MDA5 , wh...	2016
[ "Introduction", "Results", "Discussion", "Methods" ]	[]	Protein Sectors: Statistical Coupling Analysis versus Conservation	journal.pcbi.1004091	null	[ [ "A fundamental question in biology is the relation between the amino acid sequence of a protein and its function and three-dimensional structure .", "Given the rapid growth in the sequence data available from many organisms , it has become possible to use statistical sequence analysis to approach this que...	[ "Statistical coupling analysis ( SCA ) is a method for analyzing multiple sequence alignments that was used to identify groups of coevolving residues termed “sectors” .", "The method applies spectral analysis to a matrix obtained by combining correlation information with sequence conservation .", "It has been a...	[ "Statistical analyses of alignments of evolutionarily related protein sequences have been proposed as a method for obtaining information about protein structure and function .", "One such method , called statistical coupling analysis , identifies patterns of correlated mutations and uses them to find groups of co...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "gram negative", "inflammation", "immune cells", "monocytes", "immunity", "innate immunity", "immune activation", "immune defense", "immunology", "immunity to infections", "biology", "microbiology", "host-pathogen interaction", "bacterial pathogens", "pathogenesis" ]	Caspase-11 Activation in Response to Bacterial Secretion Systems that Access the Host Cytosol	journal.ppat.1003400	null	[ [ "Antibacterial defense is initiated by germline-encoded pattern recognition receptors ( PRRs ) , which detect conserved pathogen-associated molecular patterns ( PAMPs ) [1]–[3] .", "Plasma membrane-bound PRRs , such as the Toll-like receptors ( TLRs ) , detect PAMPs present in the extracellular space and ...	[ "Inflammasome activation is important for antimicrobial defense because it induces cell death and regulates the secretion of IL-1 family cytokines , which play a critical role in inflammatory responses .", "The inflammasome activates caspase-1 to process and secrete IL-1β .", "However , the mechanisms governing...	[ "The inflammasome , a multiprotein complex , is critical for host defense against bacterial infection .", "The inflammasome activates the host protease caspase-1 to process and secrete IL-1β .", "Another caspase , caspase-11 , can cause cell death and IL-1α release .", "The bacterial signals that trigger casp...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biology" ]	Synchronized Retrovirus Fusion in Cells Expressing Alternative Receptor Isoforms Releases the Viral Core into Distinct Sub-cellular Compartments	journal.ppat.1002694	null	[ [ "A large number of enveloped and non-enveloped viruses enter cells through endocytosis [1] .", "Depending on the nature of cellular receptors and replication strategies , viruses have evolved to utilize alternative entry routes and fuse with distinct intracellular compartments .", "Preferential entry ...	[ "Disparate enveloped viruses initiate infection by fusing with endosomes .", "However , the highly diverse and dynamic nature of endosomes impairs mechanistic studies of fusion and identification of sub-cellular sites supporting the nucleocapsid release .", "We took advantage of the extreme stability of avian r...	[ "Endosomal trafficking and regulation of retrovirus fusion is poorly understood , due in part to heterogeneity of viral particles and their asynchronous entry into an endocytic pathway .", "Here , we used an avian retrovirus that enters host cells in a receptor- and low pH-dependent manner .", "This feature all...	2012
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "model organisms", "cell biology", "genetics", "biology and life sciences", "genomics", "molecular cell biology", "research and analysis methods" ]	Genome-Wide Profiling of Yeast DNA:RNA Hybrid Prone Sites with DRIP-Chip	journal.pgen.1004288	null	[ [ "Elevated DNA:RNA hybrid formation due to defects in RNA processing pathways leads to genome instability and replication stress across species [1]–[7] .", "R loops threaten genome stability and often form under abnormal conditions where nascent mRNA is improperly processed or RNA half-life is increased , ...	[ "DNA:RNA hybrid formation is emerging as a significant cause of genome instability in biological systems ranging from bacteria to mammals .", "Here we describe the genome-wide distribution of DNA:RNA hybrid prone loci in Saccharomyces cerevisiae by DNA:RNA immunoprecipitation ( DRIP ) followed by hybridization on...	[ "RNA processing factors are mutated in human cancers , inherited developmental disorders and neurodegenerative syndromes .", "Defects in RNA processing have been associated with increased levels of mutations and DNA damage in part via the formation of DNA:RNA hybrids .", "Although it is likely that specific reg...	2014
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "antimicrobials", "transfer rna", "medicine and health sciences", "toxins", "pathology and laboratory medicine", "drugs", "microbiology", "toxicology", "toxic agents", "protein synthesis", "antibiotics", "mitochondria", "pharmacology", "bioenergetics", "cellular structures and organelles...	Efficiency of protein synthesis inhibition depends on tRNA and codon compositions	journal.pcbi.1006979	null	[ [ "Ribosomes and elongation factors EF-Tu are the most important targets of antibiotics inhibiting bacterial protein synthesis because of the crucial roles they play in this vital process [1 , 2] .", "Ribosomes are molecular machines that use the genetic information stored in messenger RNAs ( mRNAs ) to syn...	[ "Regulation and maintenance of protein synthesis are vital to all organisms and are thus key targets of attack and defense at the cellular level .", "Here , we mathematically analyze protein synthesis for its sensitivity to the inhibition of elongation factor EF-Tu and/or ribosomes in dependence of the system’s t...	[ "We predict and analyze the response of differently composed protein synthesis systems to the inhibition of elongation factor EF-Tu and/or ribosomes .", "The study reveals a strong interdependency of a protein synthesis system’s composition and its susceptibility to inhibition .", "This interdependency defines ...	2019
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "plant anatomy", "stem anatomy", "guard cells", "enzymes", "plant cell biology", "ions", "enzymology", "signaling networks", "anions", "stomata", "phosphatases", "plant science", "network analysis", "physical chemistry", "computer and information sciences", "network motifs", "protein...	A new discrete dynamic model of ABA-induced stomatal closure predicts key feedback loops	journal.pbio.2003451	null	[ [ "The epidermes of leaves and other aerial plant parts have natural openings known as stomata .", "Stomata are the entry and exit points where gas exchange , particularly CO2 uptake for photosynthesis and O2 and water vapor diffusion from the leaf interior to the atmosphere , takes place .", "Each stom...	[ "Stomata , microscopic pores in leaf surfaces through which water loss and carbon dioxide uptake occur , are closed in response to drought by the phytohormone abscisic acid ( ABA ) .", "This process is vital for drought tolerance and has been the topic of extensive experimental investigation in the last decades ....	[ "Guard cells , located in pairs on the surface of plant leaves , circumscribe microscopic pores called stomata , through which plants take up gaseous carbon dioxide that will be fixed by photosynthesis into sugars .", "However , plants also inevitably lose water vapor to the atmosphere through open stomata .", ...	2017
[ "Introduction", "Results/Discussion", "Materials and Methods" ]	[]	Reverse PCA, a Systematic Approach for Identifying Genes Important for the Physical Interaction between Protein Pairs	journal.pgen.1003838	null	[ [ "Protein-protein interactions ( PPIs ) are critical to virtually all biological processes , from the formation of cellular macromolecular structures and enzymatic complexes to the regulation of signal transduction pathways .", "Hence , detailed analysis of these interactions is essential for understanding...	[ "Protein-protein interactions ( PPIs ) are of central importance for many areas of biological research .", "Several complementary high-throughput technologies have been developed to study PPIs .", "The wealth of information that emerged from these technologies led to the first maps of the protein interactomes o...	[ "Protein–protein interactions ( PPI ) occur when two or more proteins bind together to form large molecular machines .", "The importance of PPIs led to the development of multitude technologies to detect them , and to the first maps of the protein interactomes .", "One important challenge in biology is to under...	2013
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "genetics and genomics/genetics of disease", "neurological disorders" ]	Genetic Modifiers of MeCP2 Function in Drosophila	journal.pgen.1000179	null	[ [ "Research in the last decade has linked the methyl-CpG-binding protein 2 ( MeCP2 ) with a variety of related neurological disorders [1] .", "Loss of MeCP2 function causes classic Rett syndrome ( RTT ) , but can also lead to related neurological conditions with symptoms that include autism , mild or severe...	[ "The levels of methyl-CpG–binding protein 2 ( MeCP2 ) are critical for normal post-natal development and function of the nervous system .", "Loss of function of MeCP2 , a transcriptional regulator involved in chromatin remodeling , causes classic Rett syndrome ( RTT ) as well as other related conditions character...	[ "Rett syndrome ( RTT ) is a progressive neurodevelopmental disorder that affects girls early in childhood and is caused by mutations in the MECP2 gene .", "Loss of MeCP2 function can also lead to clinically distinct conditions characterized by autism , learning disability , and mental retardation .", "Remarkabl...	2008
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "medicine and health sciences", "influenza", "seasons", "probability distribution", "mathematics", "forecasting", "statistics (mathematics)", "discrete mathematics", "combinatorics", "research and analysis methods", "public and occupational health", "infectious diseases", "epidemiology", "...	Prediction of infectious disease epidemics via weighted density ensembles	journal.pcbi.1005910	null	[ [ "The practice of combining predictions from different models has been used for decades by climatologists and geophysical scientists .", "These methods have subsequently been adapted and extended by statisticians and computer scientists in diverse areas of scientific inquiry .", "In recent years , thes...	[ "Accurate and reliable predictions of infectious disease dynamics can be valuable to public health organizations that plan interventions to decrease or prevent disease transmission .", "A great variety of models have been developed for this task , using different model structures , covariates , and targets for pr...	[ "Public health agencies such as the US Centers for Disease Control and Prevention would like to have as much information as possible when planning interventions intended to reduce and prevent the spread of infectious disease .", "For instance , accurate and reliable predictions of the timing and severity of the i...	2018
[ "Introduction", "Results", "Discussion", "Materials and methods", "DNA and RNA isolation and analysis" ]	[ "medicine and health sciences", "functional genomics", "pathology and laboratory medicine", "pathogens", "microbiology", "dna transcription", "viruses", "dna replication", "dna viruses", "dna", "epigenetics", "dna methylation", "chromatin", "herpesviruses", "chromosome biology", "medic...	Continuous DNA replication is required for late gene transcription and maintenance of replication compartments in gammaherpesviruses	journal.ppat.1007070	null	[ [ "The human gammaherpesviruses Kaposi's sarcoma-associated herpesvirus ( KSHV ) and Epstein-Barr virus ( EBV ) establish lifelong persistent infection in B lymphocytes and intermittently reactivate , producing infectious virions transmitted by the oral route [1 , 2] .", "KSHV is associated with Kaposi’s sa...	[ "Late gene transcription in herpesviruses is dependent on viral DNA replication in cis but the mechanistic basis for this linkage remains unknown .", "DNA replication results in demethylated DNA , topological changes , removal of proteins and recruitment of proteins to promoters .", "One or more of these effect...	[ "Herpesviruses exhibit both latent and lytic replication cycles .", "Gammaherpesviruses such as Kaposi’s sarcoma-associated herpesvirus and Epstein Barr virus undergo lytic replication when they reactivate from latency .", "During this process , when infectious virions are produced , an orderly cascade of gene ...	2018
[ "Introduction", "Results", "Discussion", "Methods" ]	[]	Exploring Fold Space Preferences of New-born and Ancient Protein Superfamilies	journal.pcbi.1003325	null	[ [ "The current wealth of freely available genetic sequences offers the potential to uncover the evolutionary history of genes and their products , proteins .", "While there exist no remains of primitive proteins , extant protein information can be used to estimate a protein family's history .", "This ap...	[ "The evolution of proteins is one of the fundamental processes that has delivered the diversity and complexity of life we see around ourselves today .", "While we tend to define protein evolution in terms of sequence level mutations , insertions and deletions , it is hard to translate these processes to a more co...	[ "Proteins are the molecular workers of the cell .", "They are formed from a string of amino acids which folds into an elaborate three-dimensional structure .", "While there is a relationship between a protein's sequence and its structure this relationship is highly complex and not fully understood .", "Protei...	2013
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "medicine", "infectious diseases", "immune cells", "clinical immunology", "immunity", "t cells", "immunity to infections", "immunology", "viral diseases", "immune response" ]	HTLV-1 Tax Specific CD8+ T Cells Express Low Levels of Tim-3 in HTLV-1 Infection: Implications for Progression to Neurological Complications	journal.pntd.0001030	null	[ [ "The vast majority of HTLV-1-infected individuals with low and stable HTLV-1 proviral", "load levels are clinically asymptomatic for life [1] .", "However , 1–3% of", "subjects develop progressive neurological complications related to HTLV-1 infection ,", "classically denominated as HTLV-1 ass...	[ "The T cell immunoglobulin mucin 3 ( Tim-3 ) receptor is highly expressed on", "HIV-1-specific T cells , rendering them partially “exhausted” and", "unable to contribute to the effective immune mediated control of viral", "replication .", "To elucidate novel mechanisms contributing to the HTLV-1", "neurol...	[ "The retrovirus , Human T lymphotropic virus type 1 ( HTLV-1 ) infects 10–20", "million people worldwide .", "The majority of infected individuals are asymptomatic;", "however , approximately 3% develop the debilitating neurological disease ,", "HTLV-1-associated myelopathy/tropical spastic paraparesis ( HA...	2011
[ "Introduction", "Results and Discussion", "Materials and Methods" ]	[ "biomacromolecule-ligand interactions", "invertebrates", "animal genetics", "molecular complexes", "neuroscience", "animals", "animal models", "developmental biology", "drosophila melanogaster", "model organisms", "molecular genetics", "drosophila", "research and analysis methods", "molecu...	SMA-Causing Missense Mutations in Survival motor neuron (Smn) Display a Wide Range of Phenotypes When Modeled in Drosophila	journal.pgen.1004489	null	[ [ "Proximal spinal muscular atrophy ( SMA ) is a common neuromuscular disorder , recognized as the most prevalent genetic cause of early childhood mortality [1] .", "SMA is characterized by degeneration of motor neurons in the anterior horn of the lower spinal cord , and progressive symmetrical paralysis ."...	[ "Mutations in the human survival motor neuron 1 ( SMN ) gene are the primary cause of spinal muscular atrophy ( SMA ) , a devastating neuromuscular disorder .", "SMN protein has a well-characterized role in the biogenesis of small nuclear ribonucleoproteins ( snRNPs ) , core components of the spliceosome .", "A...	[ "Spinal Muscular Atrophy ( SMA ) is a prevalent childhood neuromuscular disease , which in its most common form causes death by the age of two .", "One in fifty Americans is a carrier for SMA , making this genetic disease a serious health concern .", "SMA is caused by loss of function mutations in the survival ...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "blood cells", "sequencing techniques", "cell motility", "medicine and health sciences", "immune cells", "body fluids", "immunology", "vertebrates", "animals", "mammals", "membrane proteins", "sequence motif analysis", "molecular biology techniques", "cellular structures and organelles", ...	Allelic Variation in CXCL16 Determines CD3+ T Lymphocyte Susceptibility to Equine Arteritis Virus Infection and Establishment of Long-Term Carrier State in the Stallion	journal.pgen.1006467	null	[ [ "Equine arteritis virus ( EAV ) is a single-stranded , positive-sense RNA virus that belongs to the family Arteriviridae in the order Nidovirales [1–3] .", "It is the causative agent of equine viral arteritis ( EVA ) a respiratory , systemic , and reproductive disease of horses [2 , 4 , 5] .", "While ...	[ "Equine arteritis virus ( EAV ) is the causative agent of equine viral arteritis ( EVA ) , a respiratory , systemic , and reproductive disease of horses and other equid species .", "Following natural infection , 10–70% of the infected stallions can become persistently infected and continue to shed EAV in their se...	[ "A variable proportion of EAV infected stallions ( 10–70% ) may become persistently infected and continuously shed the virus exclusively in their semen after recovery from acute infection .", "Previous studies in our laboratory have shown that stallions with the CD3+ T lymphocyte susceptibility phenotype to in vi...	2016
[ "Introduction", "Results", "Discussion", "Methods" ]	[]	Sex-specific Trans-regulatory Variation on the Drosophila melanogaster X Chromosome	journal.pgen.1005015	null	[ [ "When the X chromosome stops recombining with the Y chromosome , a unique genomic environment is formed .", "Several important population genetic parameters are presumably affected , and collectively this sets the scene for different patterns of evolution on the X chromosome [1–3] .", "In particular ,...	[ "The X chromosome constitutes a unique genomic environment because it is present in one copy in males , but two copies in females .", "This simple fact has motivated several theoretical predictions with respect to how standing genetic variation on the X chromosome should differ from the autosomes .", "Unmasked ...	[ "Theory provides contrasting predictions with respect to the relative magnitude of standing genetic variation on the X chromosome and the autosomes .", "While most classic population genetics theory suggests a dearth of variation on the X chromosome , theory which concerns selection operating differently in males...	2015
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "neuroscience", "neuroscience/sensory systems" ]	Brief Bursts Self-Inhibit and Correlate the Pyramidal Network	journal.pbio.1000473	A multi-cell patch clamp study reveals the summation properties of frequency-dependent disynaptic inhibition between neocortical pyramidal cells and shows how brief bursts of activity in a few cells can synchronize the entire microcircuit.	[ [ "The mammalian neocortex consists of neurons that form an intricate network of recurrent circuits [1]–[3] .", "The synaptic wiring between cells follows a number of stereotypic rules including targeting specific domains of neurons , specific connection probabilities , target neuron preferences , and speci...	[ "Inhibitory pathways are an essential component in the function of the neocortical microcircuitry .", "Despite the relatively small fraction of inhibitory neurons in the neocortex , these neurons are strongly activated due to their high connectivity rate and the intricate manner in which they interconnect with py...	[ "The neocortex of the mammalian brain contains many more excitatory neurons than inhibitory neurons , yet inhibitory neurons are essential components of neocortical circuitry .", "Inhibitory neurons form dense and intricate connections with excitatory neurons , which are mainly pyramidal cells .", "One prominen...	2010
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "computational biology/protein structure prediction", "biophysics/biomacromolecule-ligand interactions", "computational biology/macromolecular sequence analysis", "computational biology/protein homology detection" ]	A Threading-Based Method for the Prediction of DNA-Binding Proteins with Application to the Human Genome	journal.pcbi.1000567	null	[ [ "The past decade has witnessed tremendous progress in genome sequencing [1]–[5] .", "According to the Genomes On Line Database , the complete sequenced genomes of almost 1 , 000 cellular organisms have been released , and about 5 , 000 active genome sequencing projects are on the way [6] .", "The unpr...	[ "Diverse mechanisms for DNA-protein recognition have been elucidated in numerous atomic complex structures from various protein families .", "These structural data provide an invaluable knowledge base not only for understanding DNA-protein interactions , but also for developing specialized methods that predict th...	[ "DNA-binding proteins represent only a small fraction of proteins encoded in genomes , yet they play a critical role in a variety of biological activities .", "Identifying these proteins and understanding how they function are important issues .", "The structures of solved DNA protein complexes of different pro...	2009
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "sequencing techniques", "invertebrates", "animals", "necator americanus", "ascaris", "ascaris lumbricoides", "molecular biology techniques", "strongyloides stercoralis", "research and analysis methods", "ancylostoma", "sequence analysis", "strongyloides", "trichuris", "artificial gene amp...	Improved PCR-Based Detection of Soil Transmitted Helminth Infections Using a Next-Generation Sequencing Approach to Assay Design	journal.pntd.0004578	null	[ [ "Estimated to infect more than one quarter of the world’s total population , the soil transmitted helminths ( STH ) are responsible for profound morbidity and nutritional insufficiency [1] .", "Concentrated in the world’s most impoverished locations , the results of widespread infection on economic capaci...	[ "The soil transmitted helminths are a group of parasitic worms responsible for extensive morbidity in many of the world’s most economically depressed locations .", "With growing emphasis on disease mapping and eradication , the availability of accurate and cost-effective diagnostic measures is of paramount import...	[ "With a growing emphasis on the mapping and elimination of soil transmitted helminth ( STH ) infections , the need for optimal and specific diagnostic methods is increasing .", "While PCR-based diagnostic methods for the detection of these parasitic organisms exist , these assays make use of sub-optimal target se...	2016
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "statistical mechanics", "nervous system", "applied mathematics", "neuroscience", "systems science", "mathematics", "statistics (mathematics)", "computational neuroscience", "neuroimaging", "complex systems", "computer and information sciences", "connectomics", "systems biology", "physics"...	Resolving Structural Variability in Network Models and the Brain	journal.pcbi.1003491	null	[ [ "Increasing resolution of noninvasive neuroimaging methods for quantifying structural brain organization in humans has inspired a great deal of theoretical activity [1]–[4] , aimed at developing methods to understand , diagnose , and predict aspects of human development and behavior based on underlying organi...	[ "Large-scale white matter pathways crisscrossing the cortex create a complex pattern of connectivity that underlies human cognitive function .", "Generative mechanisms for this architecture have been difficult to identify in part because little is known in general about mechanistic drivers of structured networks ...	[ "White matter tracts crisscrossing the human cortex are linked in a complex pattern that constrains human thought and behavior .", "Why the human brain displays the complex pattern that it does is a fascinating open question .", "Progress in uncovering generative mechanisms for this architecture requires greate...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "cell biology/cellular death and stress responses", "cell biology/microbial physiology and metabolism", "cell biology/gene expression", "cell biology/cell signaling" ]	Pro-Aging Effects of Glucose Signaling through a G Protein-Coupled Glucose Receptor in Fission Yeast	journal.pgen.1000408	null	[ [ "Glucose is the major carbon source entering the metabolic pathways .", "Glucose ultimately generates ATP to supply the energy necessary for the cell biosynthetic and functional demands .", "Substantial evidences support the idea that excess glucose acts as a pro-aging and pathogenic factor [1] , [2] ...	[ "Glucose is the preferred carbon and energy source in prokaryotes , unicellular eukaryotes , and metazoans .", "However , excess of glucose has been associated with several diseases , including diabetes and the less understood process of aging .", "On the contrary , limiting glucose ( i . e . , calorie restrict...	[ "Lowering caloric intake by limiting glucose ( the preferred carbon and energy source ) increases life span in various species .", "Excess glucose can have deleterious effects , but it is not clear whether this is due to the caloric contribution of glucose or to some other effect .", "Glucose sensed by the cell...	2009
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine and health sciences", "immune physiology", "nuclear staining", "pathology and laboratory medicine", "viral transmission and infection", "gene regulation", "pathogens", "messenger rna", "immunology", "microbiology", "viral structure", "viruses", "rna viruses", "antibodies", "res...	Rabies Virus Infection Induces the Formation of Stress Granules Closely Connected to the Viral Factories	journal.ppat.1005942	null	[ [ "Viral infections initiate a number of cellular stress responses that modulate gene expression by affecting the regulation of cellular mRNA translation , localization and degradation , while promoting viral transcription , replication and translation [1] .", "One of the stress responses is the assembly of...	[ "Stress granules ( SGs ) are membrane-less dynamic structures consisting of mRNA and protein aggregates that form rapidly in response to a wide range of environmental cellular stresses and viral infections .", "They act as storage sites for translationally silenced mRNAs under stress conditions .", "During vira...	[ "Exposure of cells to environmental stresses , such as heat shock and viral infection , induces a cellular response leading to the formation of Stress Granules ( SGs ) composed of stalled translation initiation complexes ( RNA-binding proteins and mRNA ) .", "The subsequent inhibition of host translation particip...	2016
[ "Introduction", "Results", "Discussion" ]	[ "neuroscience" ]	Electrical Neuroimaging Reveals Timing of Attentional Control Activity in Human Brain	journal.pbio.0060081	Localization of low-frequency brain rhythms reveals that within the frontal-parietal attentional control network, the parietal lobes provide the initial signal to shift attention in space.	[ [ "Shifting attention to the expected location of an impending visual stimulus will improve the perception of that stimulus once it occurs there [1] .", "This perceptual improvement is considered to be a consequence of attentional-control operations that are performed by frontal and parietal regions of the ...	[ "Voluntarily shifting attention to a location of the visual field improves the perception of events that occur there .", "Regions of frontal cortex are thought to provide the top-down control signal that initiates a shift of attention , but because of the temporal limitations of functional brain imaging , the tim...	[ "To extract important details about objects in the environment , people must focus their attention on a specific location in space at any given moment .", "Research using functional magnetic resonance imaging ( fMRI ) has suggested that regions of the frontal and parietal lobes work together to control our abilit...	2008
[ "Introduction", "Methods", "Results", "Discussion" ]	[]	An Open Label Non-inferiority Trial Assessing Vibriocidal Response of a Killed Bivalent Oral Cholera Vaccine Regimen following a Five Year Interval in Kolkata, India	journal.pntd.0003809	null	[ [ "Recent outbreaks in Haiti , Pakistan , and throughout the African continent , along with increased antimicrobial resistance and the heightening awareness of climate’s role upon the global burden have contributed to renewed interest in global cholera control .", "Though improved water and sanitation shoul...	[ "The bivalent killed oral cholera vaccine ( OCV ) provides 65% cumulative protection over five years .", "It remains unknown whether a boosting regimen can maintain protection in previously immunized populations .", "This study examines the immunogenicity and safety of an OCV regimen given five years following ...	[ "The five year efficacy results of the bivalent , killed whole cell oral cholera vaccine ( WC OCV ) was shown to offer 65% protection in cholera endemic Kolkata .", "Further search strategies focused on natural boosting of immunity , since this trial assessed protection in a population that has endemic cholera at...	2015
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "alkaloids", "chemical compounds", "formaldehyde", "molecular probe techniques", "carbohydrates", "galactose", "organic compounds", "fungi", "model organisms", "experimental organism systems", "copy number variation", "molecular biology techniques", "research and analysis methods", "saccha...	Environmental change drives accelerated adaptation through stimulated copy number variation	journal.pbio.2001333	null	[ [ "Copy number variation ( CNV ) is widespread in human populations , with 5%–10% of the human reference genome showing CNV between normal individuals [1–3] .", "CNV of protein-coding genes contributes to multiple disorders , and specific genetic syndromes have been directly attributed to CNV [4–6] .", ...	[ "Copy number variation ( CNV ) is rife in eukaryotic genomes and has been implicated in many human disorders , particularly cancer , in which CNV promotes both tumorigenesis and chemotherapy resistance .", "CNVs are considered random mutations but often arise through replication defects; transcription can interfe...	[ "Evolutionary theory asserts that adaptive mutations , which improve cellular fitness in challenging environments , occur at random and cannot be controlled by the cell .", "The mutation mechanisms involved are of widespread importance , governing diverse processes from the acquisition of resistance during chemot...	2017
[ "Introduction", "Results", "Discussion", "Methods and Materials" ]	[ "medicine and health sciences", "pathology and laboratory medicine", "nucleases", "enzymes", "pathogens", "messenger rna", "microbiology", "dna-binding proteins", "enzymology", "nucleotides", "fungi", "model organisms", "untranslated regions", "molecular biology techniques", "fungal path...	Dom34 Links Translation to Protein O-mannosylation	journal.pgen.1006395	null	[ [ "In eukaryotes , secretory proteins can get O-mannosylated at serine or threonine residues by protein mannosyltransferases ( Pmt proteins ) .", "This modification occurs during or shortly after translation , during transit across the secretory pore complex into the ER lumen .", "O-mannosylation initia...	[ "In eukaryotes , Dom34 upregulates translation by securing levels of activatable ribosomal subunits .", "We found that in the yeast Saccharomyces cerevisiae and the human fungal pathogen Candida albicans , Dom34 interacts genetically with Pmt1 , a major isoform of protein O-mannosyltransferase .", "In C . albic...	[ "Fungi respond to damages of their glycostructures in their cell wall by transcriptional upregulation of genes that specify compensatory activities .", "Upon block of protein N-glycosylation , the human fungal pathogen Candida albicans increases transcription of PMT1 encoding a major isoform of protein O-mannosyl...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biophysics/experimental biophysical methods", "biochemistry/macromolecular assemblies and machines", "biochemistry/experimental biophysical methods" ]	Kissing G Domains of MnmE Monitored by X-Ray Crystallography and Pulse Electron Paramagnetic Resonance Spectroscopy	journal.pbio.1000212	The authors of this research article demonstrate the nature of the conformational changes MnmE was previously suggested to undergo during its GTPase cycle, and show the nucleotide-dependent dynamic movements of the G domains around two swivel positions relative to the rest of the protein. These movements are of crucial...	[ [ "Cells devote substantial biosynthetic effort and resources to posttranscriptional modification of tRNAs [1] .", "A frequent feature of tRNAs in all domains of life are modified nucleosides in the anticodon region and especially at the wobble position ( position 34 ) [2] , which prestructure the anticodon...	[ "MnmE , which is involved in the modification of the wobble position of certain tRNAs , belongs to the expanding class of G proteins activated by nucleotide-dependent dimerization ( GADs ) .", "Previous models suggested the protein to be a multidomain protein whose G domains contact each other in a nucleotide dep...	[ "MnmE is an evolutionary conserved G protein that is involved in modification of the wobble U position of certain tRNAs to suppress translational wobbling .", "Despite high homology between its G domain and the small G protein Ras , MnmE displays entirely different regulatory properties to that of many molecular ...	2009
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "invertebrates", "medicine and health sciences", "geographical locations", "tropical diseases", "parasitic diseases", "animals", "filariasis", "neglected tropical diseases", "molecular biology techniques", "insect vectors", "zoology", "lymphatic filariasis", "bangladesh", "research and ana...	Molecular xenomonitoring for Wuchereria bancrofti in Culex quinquefasciatus in two districts in Bangladesh supports transmission assessment survey findings	journal.pntd.0006574	null	[ [ "Lymphatic filariasis ( LF ) , an important cause of acute and chronic morbidity worldwide , is caused by infection with the thread-like nematodes Wuchereria bancrofti , Brugia malayi and Brugia timori .", "The Global Programme to Eliminate Lymphatic Filariasis was established in 2000 by the World Health ...	[ "Careful monitoring for recrudescence of Wuchereria bancrofti infection is necessary in communities where mass drug administration ( MDA ) for the elimination of lymphatic filariasis ( LF ) as a public health problem has been stopped .", "During the post-MDA period , transmission assessment surveys ( TAS ) are re...	[ "To ensure elimination of lymphatic filariasis , efficient surveillance methods are needed .", "While some available methods rely on the detection of Wuchereria bancrofti microfilaria , antigen or antibody in human blood samples , molecular xenomonitoring can identify parasite DNA in vector mosquitoes .", "We c...	2018
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "haplotypes", "mathematics", "genetic polymorphism", "statistics", "statistical methods", "population genetics", "biology", "evolutionary biology", "gene flow", "evolutionary genetics" ]	The Date of Interbreeding between Neandertals and Modern Humans	journal.pgen.1002947	null	[ [ "A much-debated question in human evolution is the relationship between modern humans and Neandertals .", "Modern humans appear in the African fossil record about 200 , 000 years ago .", "Neandertals appear in the European fossil record about 230 , 000 years ago [1] and disappear about 30 , 000 year a...	[ "Comparisons of DNA sequences between Neandertals and present-day humans have shown that Neandertals share more genetic variants with non-Africans than with Africans .", "This could be due to interbreeding between Neandertals and modern humans when the two groups met subsequent to the emergence of modern humans o...	[ "One of the key discoveries from the analysis of the Neandertal genome is that Neandertals share more genetic variants with non-Africans than with Africans .", "This observation is consistent with two hypotheses: interbreeding between Neandertals and modern humans after modern humans emerged out of Africa or popu...	2012
[ "Introduction", "Results/Discussion", "Materials and Methods" ]	[ "algorithms", "computer science", "biology", "computational biology", "molecular cell biology" ]	Prediction of Cell Penetrating Peptides by Support Vector Machines	journal.pcbi.1002101	null	[ [ "Cell penetrating peptides ( CPPs ) , also referred to as “Trojan” peptides , protein transduction domains , or membrane translocation sequences , are typically hydrophobic linear arrangements of 8–24 amino acids able to cross the lipid bi-layer membrane that serves as the cell’s outer barrier and gain access...	[ "Cell penetrating peptides ( CPPs ) are those peptides that can transverse cell membranes to enter cells .", "Once inside the cell , different CPPs can localize to different cellular components and perform different roles .", "Some generate pore-forming complexes resulting in the destruction of cells while othe...	[ "Cell penetrating peptides ( CPPs ) are peptides that can potentially transport other functional molecules across cellular membranes and therefore serve a role as drug delivery vehicles .", "The properties of a given peptide that make it cell penetrating are unclear , and the rapid screening of potential CPPs aid...	2011
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	The Nuclear Receptor DAF-12 Regulates Nutrient Metabolism and Reproductive Growth in Nematodes	journal.pgen.1005027	null	[ [ "The evolutionary success of nematodes is derived from their ability to adapt different developmental pathways depending on environmental conditions .", "The best studied of these pathways exists in the free-living nematode Caenorhabditis elegans ( C . elegans ) .", "After hatching from eggs when envi...	[ "Appropriate nutrient response is essential for growth and reproduction .", "Under favorable nutrient conditions , the C . elegans nuclear receptor DAF-12 is activated by dafachronic acids , hormones that commit larvae to reproductive growth .", "Here , we report that in addition to its well-studied role in con...	[ "Animals adjust their internal biological processes in response to their environments .", "In this study , we report that in a nutrient rich environment the free-living nematode , Caenorhabditis elegans , induces an energy-generating metabolic pathway to govern its reproductive growth by activating the nuclear re...	2015
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "schistosoma", "invertebrates", "schistosoma mansoni", "medicine and health sciences", "diagnostic radiology", "ultrasound imaging", "helminths", "cardiovascular anatomy", "tropical diseases", "fibrosis", "parasitic diseases", "animals", "liver diseases", "surgical and invasive medical pro...	Pulmonary shunts in severe hepatosplenic schistosomiasis: Diagnosis by contrast echocardiography and their relationship with abdominal ultrasound findings	journal.pntd.0005417	null	[ [ "It is estimated that more than 200 million people in the world are infected with Schistosoma and more than 700 million remain at risk of infection , according to World Health Organiztion reports [1 , 2] .", "Of the species of Schistosoma that infect humans , the two that most frequently cause illness are...	[ "Schistosomiasis is endemic to several parts of the world .", "Among the species that affect humans , Schistosoma mansoni is one of the most common causes of illness .", "In regions where schistosomiasis mansoni is endemic , reinfection is responsible for the emergence of hepatosplenic schistosomiasis ( HSS ) w...	[ "Among the species of Schistosoma that infect humans Schistosoma mansoni is one of the most common causes of illness .", "In the areas where schistosomiasis mansoni is endemic , around 10% of infected individuals develop hepatosplenic schistosomiasis ( HSS ) with portal hypertension .", "Portal hypertension may...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "plant science", "plant evolution", "plant genetics", "biology", "plant physiology" ]	Local Evolution of Seed Flotation in Arabidopsis	journal.pgen.1004221	null	[ [ "Polysaccharides released from the seed coat on imbibition form a sticky , gelatinous halo called mucilage around the seed .", "This property , termed myxospermy , was observed in cress ( Lepidium sativum ) by Darwin [1] and is found in the model plant Arabidopsis .", "In addition to the Brassicaceae ...	[ "Arabidopsis seeds rapidly release hydrophilic polysaccharides from the seed coat on imbibition .", "These form a heavy mucilage layer around the seed that makes it sink in water .", "Fourteen natural Arabidopsis variants from central Asia and Scandinavia were identified with seeds that have modified mucilage r...	[ "Seeds of the model plant Arabidopsis release sticky mucilage on imbibition that is constituted of complex polysaccharides .", "In this study , we have identified and characterised natural Arabidopsis variants that do not release mucilage and found that their seeds float .", "The accumulation of unreleased poly...	2014
[ "Introduction", "Results and Discussion", "Materials and Methods" ]	[ "mycology", "zoology", "immunity", "immunology", "biology", "evolutionary biology", "microbiology" ]	Social Transfer of Pathogenic Fungus Promotes Active Immunisation in Ant Colonies	journal.pbio.1001300	Social contact with fungus-exposed ants leads to pathogen transfer to healthy nest-mates, causing low-level infections. These micro-infections promote pathogen-specific immune gene expression and protective immunization of nest-mates.	[ [ "The first encounter of a host with a particular pathogen often leads to the outbreak of the disease , yet a secondary exposure rarely causes illness , due to the immunological memory of the host .", "Whereas immune memory in vertebrates is well appreciated [1] , the phenomenon of an individual developing...	[ "Due to the omnipresent risk of epidemics , insect societies have evolved sophisticated disease defences at the individual and colony level .", "An intriguing yet little understood phenomenon is that social contact to pathogen-exposed individuals reduces susceptibility of previously naive nestmates to this pathog...	[ "Close social contact facilitates pathogen transmission in societies , often causing epidemics .", "In contrast to this , we show that limited transmission of a fungal pathogen in ant colonies can be beneficial for the host , because it promotes “social immunisation” of healthy group members .", "We found that ...	2012
[ "Introduction", "Materials and methods", "Results", "Discussion" ]	[ "carbohydrate metabolism", "medicine and health sciences", "pathology and laboratory medicine", "pathogens", "cancers and neoplasms", "microbiology", "glucose metabolism", "retroviruses", "oncology", "immunodeficiency viruses", "viruses", "regulator genes", "signs and symptoms", "rna virus...	RNA-Seq of Kaposi’s sarcoma reveals alterations in glucose and lipid metabolism	journal.ppat.1006844	null	[ [ "Kaposi’s sarcoma ( KS ) is a multi-focal pleomorphic , highly vascularized tumor that is one of the AIDS defining illnesses .", "KS mostly manifest as cutaneous lesions , but it can also be detected in the oral mucosa , lymph nodes and all visceral organ systems .", "There are four types of KS: iatro...	[ "Kaposi’s sarcoma-associated herpesvirus ( KSHV ) is the etiologic agent of Kaposi’s sarcoma ( KS ) .", "It is endemic in a number of sub-Saharan African countries with infection rate of >50% .", "The high prevalence of HIV-1 coupled with late presentation of advanced cancer staging make KS the leading cancer i...	[ "Kaposi’s sarcoma-associated herpesvirus ( KSHV ) is endemic in sub-Saharan Africa and cause Kaposi’s sarcoma ( KS ) .", "KS is one of the most common cancer among HIV-1 patients in this region .", "Despite anti-retroviral treatment , prognosis for KS is poor with high mortality often due to presentation of lat...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods", "Supporting Information" ]	[ "biochemistry", "infectious diseases", "pharmacology", "microbiology", "paramecium etc)", "ciliates (tetrahymena" ]	Nitroimidazole Action in Entamoeba histolytica: A Central Role for Thioredoxin Reductase	journal.pbio.0050211	Metronidazole is used for treatment of infections with microaerophilic protist parasites. Here, a new model of metronidazole activation is proposed, with a central role for thioredoxin reductase.	[ [ "Entamoeba histolytica is a microaerophilic protozoan parasite and the causative agent of amoebiasis , a disease that affects millions of people worldwide and claims up to 100 , 000 casualties per annum [1] .", "As is the case with other microaerophilic parasitic infections , such as giardiasis ( caused b...	[ "Metronidazole , a 5-nitroimidazole drug , has been the gold standard for several decades in the treatment of infections with microaerophilic protist parasites , including Entamoeba histolytica .", "For activation , the drug must be chemically reduced , but little is known about the targets of the active metaboli...	[ "The protist parasites Entamoeba histolytica , Trichomonas vaginalis , and Giardia intestinalis grow in environments with low oxygen concentration .", "Infections with these parasites are commonly treated with metronidazole , a nitroimidazole drug that must be reduced for activation , resulting in several toxic m...	2007
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "bacteriology", "medicine and health sciences", "toxins", "pathology and laboratory medicine", "pathogens", "immunology", "microbiology", "enterotoxins", "pili and fimbriae", "toxic agents", "toxicology", "vaccines", "diarrhea", "preventive medicine", "signs and symptoms", "gastroenter...	Colonization factors among enterotoxigenic Escherichia coli isolates from children with moderate-to-severe diarrhea and from matched controls in the Global Enteric Multicenter Study (GEMS)	journal.pntd.0007037	null	[ [ "Enterotoxigenic Escherichia coli ( ETEC ) cause diarrheal disease in children <5 years of age in developing countries and travelers’ diarrhea among persons from industrialized countries who visit developing countries [1 , 2] .", "Human ETEC strains can produce a heat-labile enterotoxin ( LT ) that resemb...	[ "Enterotoxigenic Escherichia coli ( ETEC ) encoding heat-stable enterotoxin ( ST ) alone or with heat-labile enterotoxin ( LT ) cause moderate-to-severe diarrhea ( MSD ) in developing country children .", "The Global Enteric Multicenter Study ( GEMS ) identified ETEC encoding ST among the top four enteropathogens...	[ "Enterotoxigenic Escherichia coli ( “ETEC” ) were found to be one of the four most consistently important agents that cause moderate-to-severe diarrhea among children <5 years of age in a large case-control study , the Global Enteric Multicenter Study , performed in four countries in sub-Saharan Africa and three in...	2019
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Comprehensive Profiling of Amino Acid Response Uncovers Unique Methionine-Deprived Response Dependent on Intact Creatine Biosynthesis	journal.pgen.1005158	null	[ [ "While amino acids are the building blocks of proteins , different amino acids also participate in a wide variety of biological processes .", "For example , amino acids supply carbon and nitrogen molecules for biosynthesis , feed substrates to maintain TCA cycle activity for ATP generation , and provide r...	[ "Besides being building blocks for protein synthesis , amino acids serve a wide variety of cellular functions , including acting as metabolic intermediates for ATP generation and for redox homeostasis .", "Upon amino acid deprivation , free uncharged tRNAs trigger GCN2-ATF4 to mediate the well-characterized trans...	[ "In order for mammalian cells to live and function , amino acids are required for protein synthesis and the generation of metabolic intermediates .", "An imbalance or deficiency of amino acids often triggers an “amino acid response” ( AAR ) to allow cells to adapt to their environment .", "However , it remains ...	2015
[ "Introduction", "Materials and methods", "Results", "Discussion" ]	[ "medicine and health sciences", "european union", "pathology and laboratory medicine", "statistics", "influenza", "geographical locations", "ireland", "mathematics", "forecasting", "signs and symptoms", "infectious disease control", "research and analysis methods", "infectious diseases", "...	Unsupervised extraction of epidemic syndromes from participatory influenza surveillance self-reported symptoms	journal.pcbi.1006173	null	[ [ "Seasonal influenza is an acute contagious respiratory illness caused by viruses that can be easily transmitted from person to person .", "Influenza viruses circulate worldwide causing annual epidemics with the highest activity during winter seasons in temperate regions and produce an estimated annual att...	[ "Seasonal influenza surveillance is usually carried out by sentinel general practitioners ( GPs ) who compile weekly reports based on the number of influenza-like illness ( ILI ) clinical cases observed among visited patients .", "This traditional practice for surveillance generally presents several issues , such...	[ "This study suggests how web-based surveillance data can provide an epidemiological signal capable of detecting the temporal trends of influenza-like illness without relying on a specific case definition .", "The proposed framework was able to forecast quite accurately the ILI trend of the forthcoming influenza s...	2019
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biochemistry", "infectious diseases", "microbiology" ]	Bacillus anthracis Secretes Proteins That Mediate Heme Acquisition from Hemoglobin	journal.ppat.1000132	null	[ [ "Vegetative forms of Bacillus anthracis replicate in vertebrate tissues and form spores once their host has succumbed to anthrax infection [1] .", "Spore contamination of food sources for vertebrates ensures pathogen dissemination to new hosts and reiterative replication cycles [2] .", "A hallmark of ...	[ "Acquisition of iron is necessary for the replication of nearly all bacterial pathogens; however , iron of vertebrate hosts is mostly sequestered by heme and bound to hemoglobin within red blood cells .", "In Bacillus anthracis , the spore-forming agent of anthrax , the mechanisms of iron scavenging from hemoglob...	[ "Iron is an essential nutrient used by almost all organisms .", "Bacterial pathogens must acquire iron in order to grow inside mammalian hosts .", "The host , however , limits the availability of free iron , thereby providing an effective defense strategy against infection .", "In response , bacteria have evo...	2008
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "pseudogenes", "human genomics", "genome analysis", "gene types", "energy-producing organelles", "mitochondria", "bioenergetics", "cell nucleus", "cellular structures and organelles", "nucleolus", "genome complexity", "proteins", "gene expression", "gene ontologies", "ribosomes", "home...	The long-range interaction map of ribosomal DNA arrays	journal.pgen.1007258	null	[ [ "Ribosomal RNAs ( rRNAs ) are essential components of the cell , and are encoded in the 5S and 45S ribosomal DNA ( rDNA ) arrays of higher eukaryotes [1–4] .", "The 5S rDNA array resides on chromosome 1 and encodes the 5S rRNA , whereas the 45S rDNA array resides on five human acrocentric chromosomes and ...	[ "The repeated rDNA array gives rise to the nucleolus , an organelle that is central to cellular processes as varied as stress response , cell cycle regulation , RNA modification , cell metabolism , and genome stability .", "The rDNA array is also responsible for the production of more than 70% of all cellular RNA...	[ "The repeated ribosomal DNA ( rDNA ) array gives rise to the nucleolus , an organelle that is involved in key cellular processes such as stress response , cell cycle regulation , RNA modification , and production of more than 70% of all cellular RNAs ( the ribosomal RNAs ) .", "This critical genome element has re...	2018
[ "Introduction", "Methods", "Results", "Discussion" ]	[]	Membrane Mechanics of Endocytosis in Cells with Turgor	journal.pcbi.1004538	null	[ [ "Endocytosis enables cells to internalize extracellular material and to recycle membrane components [1] .", "During this process , the plasma membrane is deformed into an invagination progressing inwards , which is severed and eventually released in the cytoplasm as a vesicle .", "Key endocytic compon...	[ "Endocytosis is an essential process by which cells internalize a piece of plasma membrane and material from the outside .", "In cells with turgor , pressure opposes membrane deformations , and increases the amount of force that has to be generated by the endocytic machinery .", "To determine this force , and c...	[ "Cells use endocytosis to intake molecules and to recycle components of their membrane .", "Even in its simplest form , endocytosis involves a large number of proteins with often redundant functions that are organized into a microscopic force-producing “machine” .", "Knowing how much force is needed to induce a...	2015
[ "Introduction", "Materials and Methods", "Results" ]	[]	International External Quality Assessment Study for Molecular Detection of Lassa Virus	journal.pntd.0003793	null	[ [ "Lassa fever was first described in 1969 as the cause of a nosocomial outbreak of hemorrhagic fever in Nigeria [1] .", "Lassa fever is an acute viral infection associated with a wide spectrum of disease manifestations , which range from mild courses to multiorgan failure [1–3] .", "The etiologic agent...	[ "Lassa virus ( LASV ) is a causative agent of hemorrhagic fever in West Africa .", "In recent years , it has been imported several times to Europe and North America .", "The method of choice for early detection of LASV in blood is RT-PCR .", "Therefore , the European Network for Diagnostics of ‘Imported’ Vira...	[ "A proficiency test panel for molecular diagnostic of Lassa virus provides objective evidence of testing quality of International diagnostic laboratories .", "Since there are no commercial assays available , it is very important to assess the quality of diagnostic test used as well as evaluate detection sensitivi...	2015
[ "Introduction", "Results/Discussion", "Materials and Methods", "Supporting Information" ]	[ "mus (mouse)", "molecular biology", "genetics and genomics", "neurological disorders" ]	CTG Trinucleotide Repeat “Big Jumps”: Large Expansions, Small Mice	journal.pgen.0030052	null	[ [ "Trinucleotide DNA repeat expansion is the mutational cause of at least 14 neurological , neurodegenerative , and neuromuscular diseases in humans , including Huntington disease , many spinocerebellar ataxias , fragile X syndrome , and myotonic dystrophy type 1 ( DM1 ) .", "While expansion of other repeat...	[ "Trinucleotide repeat expansions are the genetic cause of numerous human diseases , including fragile X mental retardation , Huntington disease , and myotonic dystrophy type 1 .", "Disease severity and age of onset are critically linked to expansion size .", "Previous mouse models of repeat instability have not...	[ "Many neurological and/or neuromuscular diseases , such as myotonic dystrophy , Huntington disease , and fragile X mental retardation are caused by an increase in the size of a repeated DNA sequence within a specific gene .", "These repetitive DNA sequences are prone to expansion , increasing in size when transmi...	2007
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Synaptic Scaling Enables Dynamically Distinct Short- and Long-Term Memory Formation	journal.pcbi.1003307	null	[ [ "Memory function consists of different , temporally overlapping stages , roughly divided into working memory , short-term and long-term memory , which are distinguishable by their increasing capacity and storage duration [1] , [2] .", "Especially long-term memory requires lasting changes which involve syn...	[ "Memory storage in the brain relies on mechanisms acting on time scales from minutes , for long-term synaptic potentiation , to days , for memory consolidation .", "During such processes , neural circuits distinguish synapses relevant for forming a long-term storage , which are consolidated , from synapses of sho...	[ "The ability to form memories of the past is a main feature of the brain .", "Memories are formed by learning .", "However , the biological mechanisms for learning , which change the synaptic weights by synaptic plasticity , act on a different time scale ( minutes ) than those that lead to memory consolidation ...	2013
[ "Introduction", "Results", "Discussion", "Models and Methods" ]	[ "physics", "interdisciplinary physics", "biology", "computational biology", "molecular cell biology", "biophysics" ]	Connection between Oligomeric State and Gating Characteristics of Mechanosensitive Ion Channels	journal.pcbi.1003055	null	[ [ "The biological function of membrane proteins is determined by a complex interplay between protein structure and the properties of the surrounding lipid bilayer [1]–[6] .", "In particular , the bilayer hydrophobic core couples to the hydrophobic regions of membrane proteins [7]–[10] .", "The resulting...	[ "The mechanosensitive channel of large conductance ( MscL ) is capable of transducing mechanical stimuli such as membrane tension into an electrochemical response .", "MscL provides a widely-studied model system for mechanotransduction and , more generally , for how bilayer mechanical properties regulate protein ...	[ "A fundamental property of living cells is their ability to detect mechanical stimuli .", "Microbes , in particular , often transition between different chemical environments , leading to osmotic shock and concurrent changes in membrane tension .", "The tension of microbial cell membranes is detected and contro...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Rational Design and Adaptive Management of Combination Therapies for Hepatitis C Virus Infection	journal.pcbi.1004040	null	[ [ "Hepatitis C virus ( HCV ) affects approximately 170 million people and chronic infections can lead to cirrhosis and hepatocellular carcinoma [1 , 2] .", "Recently , development of direct acting antivirals ( DAAs ) against HCV infection has revolutionized the field of HCV treatment , because of their high...	[ "Recent discoveries of direct acting antivirals against Hepatitis C virus ( HCV ) have raised hopes of effective treatment via combination therapies .", "Yet rapid evolution and high diversity of HCV populations , combined with the reality of suboptimal treatment adherence , make drug resistance a clinical and pu...	[ "Hepatitis C virus ( HCV ) affects approximately 170 million people world-wide and chronic infections can lead to cirrhosis and liver cancer .", "New combination therapies of direct acting antivirals have achieved remarkably high cure rates in clinical trials .", "However , high mutation rates and high diversit...	2015
[ "Introduction", "Results", "Discussion", "Conclusions", "Materials and Methods" ]	[ "biophysics/theory and simulation", "cell biology/cytoskeleton" ]	In Silico Reconstitution of Actin-Based Symmetry Breaking and Motility	journal.pbio.1000201	Computational modeling and experimentation in a model system for actin-based force generation explain how actin networks initiate and maintain directional movement.	[ [ "The directed assembly of actin networks drives the motility of most eukaryotic cells [1] .", "Specialized cellular factors assemble actin into different network types , each with a unique architecture and cellular function [2] .", "One of the most well-studied actin assembly factors is the Arp2/3 com...	[ "Eukaryotic cells assemble viscoelastic networks of crosslinked actin filaments to control their shape , mechanical properties , and motility .", "One important class of actin network is nucleated by the Arp2/3 complex and drives both membrane protrusion at the leading edge of motile cells and intracellular motil...	[ "Networks of actin filaments provide the force that drives eukaryotic cell movement .", "In a model system for this kind of force generation , a spherical bead coated with an actin nucleating protein builds and rockets around on an actin “comet tail , ” much like the tails observed in some cellular systems .", ...	2009
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "phosphorylation", "medicine and health sciences", "pathology and laboratory medicine", "vacuoles", "intracellular pathogens", "gene regulation", "pathogens", "microbiology", "immunoprecipitation", "cellular structures and organelles", "bacterial pathogens", "research and analysis methods", ...	Vasodilator-Stimulated Phosphoprotein Activity Is Required for Coxiella burnetii Growth in Human Macrophages	journal.ppat.1005915	null	[ [ "Coxiella burnetii is an intracellular bacterial pathogen that causes the zoonosis human Q fever .", "C . burnetii infects domestic mammals and livestock , which serve as the primary reservoir for the pathogen in nature .", "C . burnetii is shed from infected animals in body fluids , particularly duri...	[ "Coxiella burnetii is an intracellular bacterial pathogen that causes human Q fever , an acute flu-like illness that can progress to chronic endocarditis and liver and bone infections .", "Humans are typically infected by aerosol-mediated transmission , and C . burnetii initially targets alveolar macrophages wher...	[ "Q fever , caused by the intracellular bacterial pathogen Coxiella burnetii , is an aerosol-transmitted infection that can develop into life-threatening chronic infections such as endocarditis .", "The pathogen preferentially grows within alveolar macrophages in a phagolysosome-like compartment termed the parasit...	2016
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "developmental biology/stem cells", "cell biology/cell signaling", "physiology/pattern formation", "developmental biology/pattern formation", "physiology/neurodevelopment", "physiology/cell signaling", "pharmacology" ]	A Novel Biological Activity of Praziquantel Requiring Voltage-Operated Ca2+ Channel β Subunits: Subversion of Flatworm Regenerative Polarity	journal.pntd.0000464	null	[ [ "Flatworms ( ‘platyhelminths’ ) comprise a diverse grouping of ∼25 , 000 species representing some of the simplest organisms that are triploblastic and bilaterally symmetric .", "The majority of flatworms are parasitic ( tapeworms , flukes and skin/gill ectoparasites ) and several are associated with infe...	[ "Approximately 200 million people worldwide harbour parasitic flatworm infections that cause schistosomiasis .", "A single drug—praziquantel ( PZQ ) —has served as the mainstay pharmacotherapy for schistosome infections since the 1980s .", "However , the relevant in vivo target ( s ) of praziquantel remain unde...	[ "Praziquantel is the major drug used to treat people infected with parasitic worms that cause the neglected tropical disease schistosomiasis .", "Despite being in widespread clinical use , it is surprising that scientists have not identified how praziquantel works to kill pathogenic schistosomes .", "This lack ...	2009
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "molecular biology", "oncology/breast cancer", "cell biology/cell signaling" ]	Regulation of Mammary Stem/Progenitor Cells by PTEN/Akt/β-Catenin Signaling	journal.pbio.1000121	The PTEN/Akt/β-catenin pathway is important for maintaining stem or progenitor cells in normal and cancerous breast tissue and may be a promising target for effective, long-lasting cancer treatment.	[ [ "There is increasing evidence that a variety of cancers , including those of the breast , may be driven by a component of tumor-initiating cells that retain stem cell-like properties .", "These properties include self-renewal , which drives carcinogenesis , as well as differentiation , which contributes t...	[ "Recent evidence suggests that many malignancies , including breast cancer , are driven by a cellular subcomponent that displays stem cell-like properties .", "The protein phosphatase and tensin homolog ( PTEN ) is inactivated in a wide range of human cancers , an alteration that is associated with a poor prognos...	[ "Healthy adult tissues are maintained through the regulated proliferation of a subset of cells known as tissue stem and progenitor cells .", "Many cancers , including breast cancer , also are thought to arise from and be maintained by a small population of cells that display stem cell-like properties .", "These...	2009
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Regulation of Clostridium difficile Spore Formation by the SpoIIQ and SpoIIIA Proteins	journal.pgen.1005562	null	[ [ "A small subset of bacteria can survive adverse environmental conditions by forming a metabolically dormant cell-type known as an endospore ( referred to as a “spore” hereafter ) [1–3] .", "Spore formation allows bacteria to survive harsh environmental conditions , such as heat , desiccation , oxygen-rich...	[ "Sporulation is an ancient developmental process that involves the formation of a highly resistant endospore within a larger mother cell .", "In the model organism Bacillus subtilis , sporulation-specific sigma factors activate compartment-specific transcriptional programs that drive spore morphogenesis .", "σG...	[ "The bacterial spore-forming pathogen Clostridium difficile is a leading cause of nosocomial infections in the United States and represents a significant threat to healthcare systems around the world .", "As an obligate anaerobe , C . difficile must form spores in order to survive exit from the gastrointestinal t...	2015
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "medicine and health sciences", "pathology and laboratory medicine", "enzymes", "enzymology", "neuroscience", "developmental biology", "signs and symptoms", "immunoprecipitation", "nerve fibers", "embryos", "research and analysis methods", "embryology", "developmental neuroscience", "anima...	Post-guidance signaling by extracellular matrix-associated Slit/Slit-N maintains fasciculation and position of axon tracts in the nerve cord	journal.pgen.1007094	null	[ [ "In the Drosophila embryonic ventral nerve cord , about 20 longitudinal axon tracts traverse up and down the nerve cord to connect all hemisegments on either side of the midline .", "These tracts are inter-connected across the midline by the commissural tracts , which cross the midline only once and never...	[ "Axon-guidance by Slit-Roundabout ( Robo ) signaling at the midline initially guides growth cones to synaptic targets and positions longitudinal axon tracts in discrete bundles on either side of the midline .", "Following the formation of commissural tracts , Slit is found also in tracts of the commissures and lo...	[ "Early during embryogenesis , the Slit ligand is present only at the midline of the nerve cord .", "It binds its receptor Robo on growth cones of axons and guides axons such that they form a series of axon tracts called longitudinal tracts on either side of the midline .", "It has been proposed that Slit regula...	2017
[ "Introduction", "Results", "Discussion", "Material and Methods" ]	[ "genetics", "immunology", "biology", "microbiology" ]	IL-22 and IDO1 Affect Immunity and Tolerance to Murine and Human Vaginal Candidiasis	journal.ppat.1003486	null	[ [ "Candida species are the causative agents of vulvovaginal candidiasis ( VVC ) and recurrent VVC ( RVVC ) , two forms of disease that affect a large number of otherwise healthy women [1] , [2] .", "Uncomplicated VVC is associated with several predisposing factors , including antibiotic and oral contracepti...	[ "The ability to tolerate Candida albicans , a human commensal of the gastrointestinal tract and vagina , implicates that host defense mechanisms of resistance and tolerance cooperate to limit fungal burden and inflammation at the different body sites .", "We evaluated resistance and tolerance to the fungus in exp...	[ "This study disentangles resistance and tolerance components of murine and human C . albicans vaginal infection and introduces the challenging notion of a disease due to a defective tolerance mechanism .", "Vulvovaginal candidiasis ( VVC ) and recurrent VVC ( RVVC ) are two forms of disease that affect a large nu...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "virology/vaccines", "virology", "virology/host antiviral responses", "virology/immune evasion", "virology/host invasion and cell entry" ]	Rabies Virus Infection Induces Type I Interferon Production in an IPS-1 Dependent Manner While Dendritic Cell Activation Relies on IFNAR Signaling	journal.ppat.1001016	null	[ [ "Type I interferon ( IFN ) was first identified as a “factor” that rendered cells resistant to viral infection [1] .", "It is now known that following viral infection , cells induce type I IFN , which in turn upregulates the expression of numerous antiviral proteins [2] .", "This class of cytokines is...	[ "As with many viruses , rabies virus ( RABV ) infection induces type I interferon ( IFN ) production within the infected host cells .", "However , RABV has evolved mechanisms by which to inhibit IFN production in order to sustain infection .", "Here we show that RABV infection of dendritic cells ( DC ) induces ...	[ "Rabies virus ( RABV ) is a neurotropic RNA virus responsible for the deaths of the at least 40 , 000 to 70 , 000 individuals globally each year .", "However , the innate immune response induced by both wildtype and vaccine strains of RABV is not well understood .", "In this study , we assessed the pattern reco...	2010
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "medicine and health sciences", "liver", "variant genotypes", "genetic mapping", "oncology", "mutation", "developmental biology", "epigenetics", "dna", "chromatin", "dna methylation", "chromosome biology", "gene expression", "chromatin modification", "dna modification", "mutant genotyp...	Distinctive types of postzygotic single-nucleotide mosaicisms in healthy individuals revealed by genome-wide profiling of multiple organs	journal.pgen.1007395	null	[ [ "Postzygotic mutations refer to DNA changes arising after the formation of the zygote that lead to genomic mosaicisms in a single individual [1 , 2] .", "Unlike de novo or inherited germline mutations , postzygotic mutations only affect a fraction of cells in multicellular organisms , and individuals carr...	[ "Postzygotic single-nucleotide mosaicisms ( pSNMs ) have been extensively studied in tumors and are known to play critical roles in tumorigenesis .", "However , the patterns and origin of pSNMs in normal organs of healthy humans remain largely unknown .", "Using whole-genome sequencing and ultra-deep amplicon r...	[ "Genomic mosaicism led by postzygotic mutation is the major cause of cancers and many non-cancer developmental disorders .", "Theoretically , postzygotic mutations should be accumulated during the developmental process of healthy individuals , but the genome-wide characterization of postzygotic mosaicisms across ...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "computational biology/alternative splicing", "genetics and genomics/gene expression", "evolutionary biology/genomics" ]	Diverse Splicing Patterns of Exonized Alu Elements in Human Tissues	journal.pgen.1000225	null	[ [ "Alu is a class of primate-specific transposable elements that belongs to the short interspersed nuclear elements ( SINE ) family [1] .", "The rapid expansion of Alu during primate evolution has produced over one million copies of Alu elements in the human genome [2] .", "Until recently , Alu elements...	[ "Exonization of Alu elements is a major mechanism for birth of new exons in primate genomes .", "Prior analyses of expressed sequence tags show that almost all Alu-derived exons are alternatively spliced , and the vast majority of these exons have low transcript inclusion levels .", "In this work , we provide g...	[ "New exons have been created and added to existing functional genes during eukaryotic genome evolution .", "Alu elements , a class of primate-specific retrotransposons , are a major source of new exons in primates .", "However , recent analyses of expressed sequence tags suggest that the vast majority of Alu-de...	2008
[ "Introduction", "Materials and methods", "Results", "Discussion" ]	[ "medicine and health sciences", "influenza", "applied mathematics", "immunology", "social sciences", "human mobility", "simulation and modeling", "vaccines", "preventive medicine", "algorithms", "mathematics", "infectious disease control", "vaccination and immunization", "human geography",...	Optimizing spatial allocation of seasonal influenza vaccine under temporal constraints	journal.pcbi.1007111	null	[ [ "There is an abundance of literature on the modeling , analysis , and control of epidemics .", "We briefly mention three areas that are closely related to our paper , namely , mobility modeling , disease modeling , and designing interventions to control the spread of epidemics .", "We refer to [11] [1...	[ "Prophylactic interventions such as vaccine allocation are some of the most effective public health policy planning tools .", "The supply of vaccines , however , is limited and an important challenge is to optimally allocate the vaccines to minimize epidemic impact .", "This resource allocation question ( which...	[ "Annual vaccination campaigns continue to be one of the prime measures which help alleviate the burden of seasonal influenza .", "Due to production and logistic constraints , there is a need for prioritization policies associated with vaccine deployment .", "While there is general consensus on age-based or risk...	2019
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	The Molecular Mechanism of a Cis-Regulatory Adaptation in Yeast	journal.pgen.1003813	null	[ [ "Evolutionary adaptation is the process that has given rise to the ubiquitous , yet remarkable , fit between all living organisms and their environments [1] .", "The origins of these adaptations at the molecular level have been a subject of great interest , with active debate surrounding the relative role...	[ "Despite recent advances in our ability to detect adaptive evolution involving the cis-regulation of gene expression , our knowledge of the molecular mechanisms underlying these adaptations has lagged far behind .", "Across all model organisms , the causal mutations have been discovered for only a handful of gene...	[ "Evolutionary adaptation is the process that has given rise to the ubiquitous , yet remarkable , fit between all living organisms and their environments .", "The molecular mechanisms of these adaptations have been a subject of great interest , but we still know very little about their mechanisms , particularly in...	2013
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "cell death", "autophagic cell death", "medicine and health sciences", "pathology and laboratory medicine", "molecular probe techniques", "hela cells", "pathogens", "cell processes", "biological cultures", "microbiology", "immunoblotting", "viruses", "protein expression", "rna viruses", ...	A new mechanism of interferon’s antiviral action: Induction of autophagy, essential for paramyxovirus replication, is inhibited by the interferon stimulated gene, TDRD7	journal.ppat.1006877	null	[ [ "Interferon ( IFN ) system provides the first line of immune defense against viral infections in vertebrates [1–3] .", "It is designed to inhibit viral infection by blocking virus replication and eliminating the virus-infected cells .", "The Pattern Recognition Receptors ( PRRs ) , e . g . Toll Like R...	[ "The interferon ( IFN ) system represents the first line of defense against a wide range of viruses .", "Virus infection rapidly triggers the transcriptional induction of IFN-β and IFN Stimulated Genes ( ISGs ) , whose protein products act as viral restriction factors by interfering with specific stages of virus ...	[ "The antiviral functions of interferons ( IFNs ) are mediated by the IFN-induced proteins , encoded by the IFN Stimulated Genes ( ISGs ) .", "Because ISGs are virus-specific , we performed a high throughput genetic screen to identify novel antiviral ISGs against Sendai virus ( SeV ) , a respirovirus of the Paramy...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	How Obstacles Perturb Population Fronts and Alter Their Genetic Structure	journal.pcbi.1004615	null	[ [ "Populations expand into new territory on all length and time scales .", "Examples include the migration of humans out of Africa [1] , the recent invasion of cane toads in Australia [2] , and the growth of colonies of microbes .", "Although populations often persist long after invading [3] , events du...	[ "As populations spread into new territory , environmental heterogeneities can shape the population front and genetic composition .", "We focus here on the effects of an important building block of heterogeneous environments , isolated obstacles .", "With a combination of experiments , theory , and simulation , ...	[ "Geographical structure influences the dynamics of the expansion of populations into new habitats and the relative importance of the evolutionary forces of mutation , selection , genetic drift , and gene flow .", "While populations often spread and evolve in highly complex environments , simplified scenarios allo...	2015
[ "Introduction", "Material and methods", "Results", "Discussion" ]	[ "mycobacterium leprae", "medicine and health sciences", "variant genotypes", "tropical diseases", "alleles", "genetic mapping", "bacterial diseases", "neglected tropical diseases", "molecular biology techniques", "bacteria", "research and analysis methods", "infectious diseases", "genome com...	Association of a new FCN3 haplotype with high ficolin-3 levels in leprosy	journal.pntd.0005409	null	[ [ "Leprosy is a chronic infectious disease caused by Mycobacterium leprae that mainly affects the skin and peripheral nerves [1] and can cause progressive and permanent damage , if untreated .", "Despite the disease elimination in 119 of the 122 countries where it was considered a public health problem , Br...	[ "Leprosy is a chronic inflammatory disease caused by Mycobacterium leprae that mainly affects the skin and peripheral nervous system , leading to a high disability rate and social stigma .", "Previous studies have shown a contribution of genes encoding products of the lectin pathway of complement in the modulatio...	[ "Leprosy is considered a neglected disease and still a public health problem in many countries where it was not yet eliminated , leading to a high disability rate and social stigma .", "The molecular mechanisms of M . leprae infection and immune evasion are still poorly known , raising the need for studies that m...	2017
[ "Introduction", "Methodology", "Results", "Discussion" ]	[ "invertebrates", "medicine and health sciences", "geographical locations", "randomized controlled trials", "animals", "north america", "clinical medicine", "pharmacology", "infectious disease control", "caribbean", "insect vectors", "zoology", "research and analysis methods", "infectious d...	The additional benefit of residual spraying and insecticide-treated curtains for dengue control over current best practice in Cuba: Evaluation of disease incidence in a cluster randomized trial in a low burden setting with intensive routine control	journal.pntd.0006031	null	[ [ "Dengue is a growing problem worldwide , and it is currently present in more than 100 countries [1] .", "Recently , chikungunya and Zika , two other Aedes-borne diseases , have also been spreading geographically , and they represent a growing public health threat [2 , 3] .", "The recent co-circulation...	[ "Aedes control interventions are considered the cornerstone of dengue control programmes , but there is scarce evidence on their effect on disease .", "We set-up a cluster randomized controlled trial in Santiago de Cuba to evaluate the entomological and epidemiological effectiveness of periodical intra- and peri-...	[ "This is the first cluster randomized controlled trial providing evidence on the effect of applying residual insecticide treatment and deploying insecticide treated curtains on clinical dengue case incidence .", "In a context of intensive routine control activities , low Aedes infestation and moderate transmissio...	2017
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "medicine and health sciences", "classical mechanics", "cell cycle and cell division", "cell processes", "mechanical stress", "epithelial cells", "damage mechanics", "digestive system", "dentition", "animal cells", "deformation", "biological tissue", "head", "physics", "teeth", "anatom...	Differential tissue growth and cell adhesion alone drive early tooth morphogenesis: An ex vivo and in silico study	journal.pcbi.1005981	null	[ [ "From gastrulation to late organogenesis , animal development involves many examples of reciprocal genetic and biomechanical interactions between epithelial and mesenchymal tissues [1] .", "Ectodermal organs , such as hairs , feathers , teeth and mammary glands are easily accessible examples of organs who...	[ "From gastrulation to late organogenesis animal development involves many genetic and bio-mechanical interactions between epithelial and mesenchymal tissues .", "Ectodermal organs , such as hairs , feathers and teeth are well studied examples of organs whose development is based on epithelial-mesenchymal interact...	[ "The genes and signalling pathways involved in ectodermal organ development ( teeth , hair , mammary glands , etc . ) are relatively well studied .", "However , the bio-mechanical processes by which these organs grow and change shape from an early primordium ( an epithelial bud similar among different organs ) is...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "arthropoda", "invertebrates", "developmental biology", "genomics", "genome evolution", "moths and butterflies", "genetics", "biology and life sciences", "comparative genomics", "molecular evolution", "computational biology", "evolutionary biology", "gene duplication", "animals", "insect...	Ancient Expansion of the Hox Cluster in Lepidoptera Generated Four Homeobox Genes Implicated in Extra-Embryonic Tissue Formation	journal.pgen.1004698	null	[ [ "The characterization of Hox genes in the 1980s awakened the idea that there may be similar processes controlling body patterning in divergent animals and gave the first opportunity to compare the control of developmental processes between taxa at a molecular level .", "In animals as evolutionarily diverg...	[ "Gene duplications within the conserved Hox cluster are rare in animal evolution , but in Lepidoptera an array of divergent Hox-related genes ( Shx genes ) has been reported between pb and zen .", "Here , we use genome sequencing of five lepidopteran species ( Polygonia c-album , Pararge aegeria , Callimorpha dom...	[ "We have examined gene duplication in a set of ancient genes used in patterning of animal embryos: the Hox genes .", "These genes code for proteins that bind DNA and switch on or off other genes , and they are very similar between distantly related animal species .", "Butterflies and moths , however , have addi...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "virology", "biology", "microbiology" ]	PKR-Like Endoplasmic Reticulum Kinase Is Necessary for Lipogenic Activation during HCMV Infection	journal.ppat.1003266	null	[ [ "Viruses rely on the host cells to make viral proteins , replicate viral genomes and produce infectious virions .", "All the building blocks and energy required for these biosynthetic activities are derived from intermediary metabolism in the host cells .", "It is important to understand how viral inf...	[ "PKR-like endoplasmic reticulum ( ER ) kinase ( PERK ) is an ER-associated stress sensor protein which phosphorylates eukaryotic initiation factor 2α ( eIF2α ) to induce translation attenuation in response to ER stress .", "PERK is also a regulator of lipogenesis during adipocyte differentiation through activatio...	[ "HCMV , a β-herpesvirus , is a significant pathogen which infects most of the human population by puberty .", "Primary HCMV infection can be unnoticed in healthy people , but can be life threatening for the immunocompromised and it is the most important cause of congenital infection in the developed world , frequ...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "immunodeficiency viruses", "virology", "biology", "microbiology" ]	Extreme Genetic Fragility of the HIV-1 Capsid	journal.ppat.1003461	null	[ [ "Genetic robustness is defined as the ability of a biological entity ( e . g . a protein or organism ) to maintain function in the face of mutations [1] , [2] .", "More robust proteins or organisms tolerate higher mutation rates while less robust ( more ‘brittle’ or ‘fragile’ ) proteins or organisms are i...	[ "Genetic robustness , or fragility , is defined as the ability , or lack thereof , of a biological entity to maintain function in the face of mutations .", "Viruses that replicate via RNA intermediates exhibit high mutation rates , and robustness should be particularly advantageous to them .", "The capsid ( CA ...	[ "The HIV-1 capsid protein ( CA ) is absolutely essential for viral replication and there is , therefore , intense evolutionary pressure for HIV-1 CA to conserve its functions .", "However , HIV-1 CA is also a key target of the host immune response , which should provide evolutionary pressure to diversify CA seque...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine", "infectious diseases", "virology", "biology", "microbiology", "viral diseases" ]	The Nuclear Chaperone Nucleophosmin Escorts an Epstein-Barr Virus Nuclear Antigen to Establish Transcriptional Cascades for Latent Infection in Human B Cells	journal.ppat.1003084	null	[ [ "EBV is a human γ-herpesvirus that infects both epithelial cells and B lymphocytes , and it has been implicated in several human malignancies , including Burkitt's lymphoma ( BL ) , Hodgkin's lymphoma , lymphoproliferative disease in immune-suppressed patients , nasopharyngeal carcinoma ( NPC ) , and some cas...	[ "Epstein-Barr Virus ( EBV ) is an oncogenic γ-herpesvirus that capably establishes both latent and lytic modes of infection in host cells and causes malignant diseases in humans .", "Nuclear antigen 2 ( EBNA2 ) -mediated transcription of both cellular and viral genes is essential for the establishment and mainten...	[ "Epstein-Barr Virus ( EBV ) infects human B cells to establish a permanent infection in hosts , which can cause diseases ranging from infectious mononucleosis to a broad spectrum of human malignancies .", "The conversion of human primary B cells into indefinitely proliferating lymphoblastoid cell lines ( LCLs ) b...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "systems biology", "genome-wide association studies", "genomics", "functional genomics", "genetics", "biology", "computational biology", "metabolic networks", "signaling networks", "genetics and genomics" ]	Identification of Novel Type 2 Diabetes Candidate Genes Involved in the Crosstalk between the Mitochondrial and the Insulin Signaling Systems	journal.pgen.1003046	null	[ [ "Insulin resistance is a common trait present in complex disorders such as type 2 diabetes ( T2D ) , obesity or metabolic syndrome ( MetS ) .", "Around 340 million people suffer from diabetes worldwide , 90% of whom have T2D ( http://www . who . int/diabetes/facts/en ) .", "Unlike type 1 diabetes , ov...	[ "Type 2 Diabetes ( T2D ) is a highly prevalent chronic metabolic disease with strong co-morbidity with obesity and cardiovascular diseases .", "There is growing evidence supporting the notion that a crosstalk between mitochondria and the insulin signaling cascade could be involved in the etiology of T2D and insul...	[ "It has been shown that the crosstalk between insulin signaling and the mitochondria may be involved in the etiology of type 2 diabetes .", "In order to characterize the molecular basis of this crosstalk , we mined and filtered several interaction databases of different natures , including protein–protein interac...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "gram negative", "emerging infectious diseases", "immunity", "innate immunity", "microbial pathogens", "immune defense", "host-pathogen interaction", "biology", "microbiology", "bacterial pathogens" ]	Early Apoptosis of Macrophages Modulated by Injection of Yersinia pestis YopK Promotes Progression of Primary Pneumonic Plague	journal.ppat.1003324	null	[ [ "Acute bacterial pneumonia is the result of active colonization of the airspace in the lungs combined with host inflammation that is unable to resolve due to host-pathogen interactions as well as progressing host- and microbial- induced injury .", "Resident macrophages in the lungs play an important role ...	[ "Yersinia pestis causes pneumonic plague , a disease characterized by inflammation , necrosis and rapid bacterial growth which together cause acute lung congestion and lethality .", "The bacterial type III secretion system ( T3SS ) injects 7 effector proteins into host cells and their combined activities are nece...	[ "In this work , we studied the mechanism whereby bacteria manipulate innate immune responses by controlling host cell death .", "Yersinia pestis , the causative agent of plague , requires effector Yops of the Type III Secretion System ( T3SS ) to evade the innate immune system during infection .", "We show that...	2013
[ "Introduction", "Materials and Methods", "Results", "Discussion", "Supporting Information" ]	[ "mus (mouse)", "infectious diseases", "microbiology", "eubacteria" ]	Primary Involvement of Pharynx and Peyer's Patch in Inhalational and Intestinal Anthrax	journal.ppat.0030076	null	[ [ "Bacillus anthracis is a sporulating Gram-positive bacterium that causes the disease anthrax .", "The three forms of anthrax reflect the route by which the infection is initiated: cutaneous , gastrointestinal , and inhalational [1 , 2] .", "Anthrax is characterized by both toxemia , which is caused by...	[ "Bacillus anthracis causes three forms of anthrax: inhalational , gastrointestinal , and cutaneous .", "Anthrax is characterized by both toxemia , which is caused by secretion of immunomodulating toxins ( lethal toxin and edema toxin ) , and septicemia , which is associated with bacterial encapsulation .", "Her...	[ "Anthrax is caused by Bacillus anthracis , a bacterial pathogen that forms spores , dormant bacteria that are highly resistant to destruction .", "Infections initiate from the introduction of spores into airways or damaged skin , or from the consumption of contaminated food .", "Within the host , spores germina...	2007
[ "Introduction", "Results", "Discussion", "Material and Methods" ]	[ "virology/virion structure, assembly, and egress", "virology/immunodeficiency viruses", "virology/viral replication and gene regulation", "virology/antivirals, including modes of action and resistance" ]	HIV Capsid is a Tractable Target for Small Molecule Therapeutic Intervention	journal.ppat.1001220	null	[ [ "Highly active antiretroviral therapies ( HAART ) against human immunodeficiency virus type 1 ( HIV-1 ) have proven in recent years to be extremely effective at reducing viral load and significantly delaying disease progression [1] .", "However , there remains a pressing need to discover and develop new c...	[ "Despite a high current standard of care in antiretroviral therapy for HIV , multidrug-resistant strains continue to emerge , underscoring the need for additional novel mechanism inhibitors that will offer expanded therapeutic options in the clinic .", "We report a new class of small molecule antiretroviral compo...	[ "Although the current standard of care for Human Immunodeficiency Virus ( HIV ) is high , viral resistance has emerged to every drug currently in the clinic , in some cases rendering the entire class ineffective for patients .", "A new class of antiretroviral drugs would be effective against strains of HIV-1 that...	2010
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "medicine", "biology" ]	Antidiarrheal Efficacy and Cellular Mechanisms of a Thai Herbal Remedy	journal.pntd.0002674	null	[ [ "Secretory diarrhea is a major health challenge in developing countries , representing the second leading cause of mortality globally in children under age 5 [1] .", "Repeated episodes of hypovolemia from diarrhea can produce malnutrition and impaired development [2] .", "The mainstay of diarrhea ther...	[ "Screening of herbal remedies for Cl− channel inhibition identified Krisanaklan , a herbal extract used in Thailand for treatment of diarrhea , as an effective antidiarrheal in mouse models of secretory diarrheas with inhibition activity against three Cl− channel targets .", "Krisanaklan fully inhibited cholera t...	[ "Secretory diarrhea is a major health challenge in developing countries .", "Causative agents include bacteria , as in cholera , and viruses , as in childhood rotaviral diarrhea .", "Though oral rehydration solution ( ORS ) has reduced mortality from diarrhea four-fold in the last three decades , its efficacy i...	2014
[ "Introduction", "Results", "Discussion", "Material and Methods" ]	[ "sequence analysis", "genome expression analysis", "plant science", "genomics", "genome evolution", "evolutionary biology", "plant evolution", "plant biology", "plant genomics", "biology", "computational biology", "comparative genomics", "genetics and genomics" ]	Rapid De Novo Evolution of X Chromosome Dosage Compensation in Silene latifolia, a Plant with Young Sex Chromosomes	journal.pbio.1001308	Evidence for dosage compensation in Silene latifolia, a plant with 10-million-year-old sex chromosomes, reveals that dosage compensation can evolve rapidly in young XY systems and is not an animal-specific phenomenon.	[ [ "In humans , where the evolution of sex chromosomes is probably best known , the XY chromosome pair was originally a recombining pair of autosomes that progressively stopped recombining , most likely because of a series of inversions on the Y chromosome [1]–[4] .", "This started ∼150 million years ago [5]...	[ "Silene latifolia is a dioecious plant with heteromorphic sex chromosomes that have originated only ∼10 million years ago and is a promising model organism to study sex chromosome evolution in plants .", "Previous work suggests that S . latifolia XY chromosomes have gradually stopped recombining and the Y chromos...	[ "The mammalian sex chromosomes originated from an ancestral pair of autosomes about 150 million years ago and the Y chromosome subsequently degenerated , losing most of its genes .", "During this process , a phenomenon called dosage compensation evolved to compensate for the gene loss on the Y chromosome and to e...	2012
[ "Introduction", "Materials and methods", "Results", "Discussion" ]	[ "schistosoma", "invertebrates", "biogeography", "medicine and health sciences", "ecology and environmental sciences", "pathology and laboratory medicine", "helminths", "population genetics", "parasitic diseases", "animals", "microsatellite loci", "gastropods", "gene types", "population bio...	Geographic strain differentiation of Schistosoma japonicum in the Philippines using microsatellite markers	journal.pntd.0005749	null	[ [ "Schistosomiasis is one of the most important neglected tropical diseases affecting almost 240 million people throughout the world with more than 700 million considered to be at risk of infection [1] .", "Five species of schistosomes are known to cause human infection: Schistosoma haematobium , S . manson...	[ "Microsatellites have been found to be useful in determining genetic diversities of various medically-important parasites which can be used as basis for an effective disease management and control program .", "In Asia and Africa , the identification of different geographical strains of Schistosoma japonicum , S ....	[ "Schistosomiasis is one of the important neglected tropical diseases endemic in 78 countries throughout the world .", "The disease is caused by the parasitic worms known as schistosomes .", "In the Philippines , S . japonicum is the causative agent of the disease .", "The prevalence of the disease varies in e...	2017
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "genome-wide association studies", "medicine and health sciences", "genetic networks", "protein interactions", "pathology and laboratory medicine", "neurodegenerative diseases", "protein interaction networks", "immunology", "signs and symptoms", "network analysis", "genome analysis", "alzheime...	One for all and all for One: Improving replication of genetic studies through network diffusion	journal.pgen.1007306	null	[ [ "The discovery of disease-associated genomic variation has numerous clinical and scientific applications , including earlier disease prognosis , improved understanding of disease pathophysiology , and development of personalized treatment therapies [1] .", "A commonly used technique for identifying these ...	[ "Improving accuracy in genetic studies would greatly accelerate understanding the genetic basis of complex diseases .", "One approach to achieve such an improvement for risk variants identified by the genome wide association study ( GWAS ) approach is to incorporate previously known biology when screening variant...	[ "Integrating multiple types of -omics data is a rapidly growing research area due in part to the increasing amount of diverse and publicly accessible data .", "In this study , we demonstrated that integration of genetic association and protein interaction data using a network diffusion approach measurably improve...	2018

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