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headings list	keywords list	title stringlengths 20 281	id stringlengths 20 20	toc stringlengths 57 522 ⌀	sections list	abstract list	summary list	year stringclasses 13 values
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biology" ]	HIV/SIV Infection Primes Monocytes and Dendritic Cells for Apoptosis	journal.ppat.1002087	null	[ [ "Monocytes originating from the bone marrow are released into peripheral blood , where they circulate for several days before entering tissues , and replenish tissue macrophage populations in the steady state .", "Monocytes constitute a considerable systemic reservoir of myeloid precursors .", "Monocy...	[ "Subversion or exacerbation of antigen-presenting cells ( APC ) death modulates host/pathogen equilibrium .", "We demonstrated during in vitro differentiation of monocyte-derived macrophages and monocyte-derived dendritic cells ( DCs ) that HIV sensitizes the cells to undergo apoptosis in response to TRAIL and Fa...	[ "Antigen-presenting cells ( APCs ) are critical for both innate and adaptive immunity .", "They have a profound impact on the hosts' ability to combat microbes .", "Dysfunction and premature death by apoptosis of APCs may contribute to an abnormal immune response unable to clear pathogens .", "Circulating blo...	2011
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "learning", "medicine and health sciences", "neurochemistry", "chemical compounds", "classical conditioning", "vertebrates", "social sciences", "conditioned response", "neuroscience", "animals", "mammals", "learning and memory", "organic compounds", "hormones", "animal models", "surgic...	Manipulating the revision of reward value during the intertrial interval increases sign tracking and dopamine release	journal.pbio.2004015	null	[ [ "Lesaint and colleagues [1] recently proposed a new computational model—the “STGT model” ( for sign tracking and goal tracking ) —which accounts for a large set of behavioral , physiological , and pharmacological data obtained from studies investigating individual variation in Pavlovian conditioned approach b...	[ "Recent computational models of sign tracking ( ST ) and goal tracking ( GT ) have accounted for observations that dopamine ( DA ) is not necessary for all forms of learning and have provided a set of predictions to further their validity .", "Among these , a central prediction is that manipulating the intertrial...	[ "In classical or Pavlovian conditioning , subjects learn to associate a previously neutral stimulus ( called “conditioned” stimulus; for example , a bell ) with a biologically potent stimulus ( called “unconditioned” stimulus; for example , a food reward ) .", "In some animals , the incentive salience of the cond...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genetic networks", "rna extraction", "cell differentiation", "multivariate analysis", "developmental biology", "mathematics", "statistics (mathematics)", "network analysis", "forms of dna", "dna", "thermodynamics", "extraction techniques", "research and analysis methods", "computer and in...	Single-Cell-Based Analysis Highlights a Surge in Cell-to-Cell Molecular Variability Preceding Irreversible Commitment in a Differentiation Process	journal.pbio.1002585	A single-cell transcriptomics analysis offers a new dynamical view of the differentiation process, involving an increase in between-cell variability prior to commitment.	[ [ "The classical view of a linear differentiation process driven by the sequential activation of master regulators [1] has been increasingly challenged in the last few years both by experimental findings and theoretical considerations .", "Thanks to the recent development in single-cell profiling technologi...	[ "In some recent studies , a view emerged that stochastic dynamics governing the switching of cells from one differentiation state to another could be characterized by a peak in gene expression variability at the point of fate commitment .", "We have tested this hypothesis at the single-cell level by analyzing pri...	[ "The differentiation process has classically been seen as a stereotyped program leading from one progenitor toward a functional cell .", "This vision was based upon cell population-based analyses averaged over millions of cells .", "However , new methods have recently emerged that allow interrogation of the mol...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine and health sciences", "oxidative stress", "neurodegenerative diseases", "microglial cells", "animal models", "model organisms", "veterinary science", "research and analysis methods", "veterinary diseases", "zoonoses", "animal cells", "mouse models", "glial cells", "cell biology",...	The Role of the NADPH Oxidase NOX2 in Prion Pathogenesis	journal.ppat.1004531	null	[ [ "Prion infections cause the deposition of misfolded , aggregated prion protein ( PrPSc ) in the brain , and lead to progressive , lethal neurodegeneration .", "These diseases are also known as transmissible spongiform encephalopathies because their main neuropathological hallmark is the presence of vacuol...	[ "Prion infections cause neurodegeneration , which often goes along with oxidative stress .", "However , the cellular source of reactive oxygen species ( ROS ) and their pathogenetic significance are unclear .", "Here we analyzed the contribution of NOX2 , a prominent NADPH oxidase , to prion diseases .", "We ...	[ "The deposition of misfolded , aggregated prion protein in the brain causes transmissible spongiform encephalopathies ( TSE ) , a group of disorders including Creutzfeldt–Jakob disease and mad cow disease .", "TSE are characterized by neurodegeneration and progressive , lethal neurological dysfunction .", "Sign...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine", "infectious diseases", "drugs and devices", "immunology", "biology", "microbiology", "molecular cell biology" ]	HSV-2 Infection of Dendritic Cells Amplifies a Highly Susceptible HIV-1 Cell Target	journal.ppat.1002109	null	[ [ "Herpes Simplex Virus Type 2 ( HSV-2 ) infects genital and perianal mucosa and its infection is associated with a three-fold increased risk of HIV-1 acquisition among both men and women [1] .", "Although active HSV-2 shedding , inflammation and ulcers during primary infections and virus reactivation certa...	[ "Herpes simplex virus type 2 ( HSV-2 ) increases the risk of HIV-1 infection and , although several reports describe the interaction between these two viruses , the exact mechanism for this increased susceptibility remains unclear .", "Dendritic cells ( DCs ) at the site of entry of HSV-2 and HIV-1 contribute to ...	[ "The vast majority of HIV-1 infections occur through genital and rectal mucosa .", "A better understanding of the characteristics of the mucosal microenvironment that help HIV-1 replication is critical to developing strategies for prevention of HIV-1 transmission .", "HSV-2 infects genital and rectal mucosa and...	2011
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biotechnology", "oncology", "developmental biology", "cell biology", "immunology", "evolutionary biology", "molecular biology" ]	Senescence-Associated Secretory Phenotypes Reveal Cell-Nonautonomous Functions of Oncogenic RAS and the p53 Tumor Suppressor	journal.pbio.0060301	By controlling how damaged cells modify their surrounding tissue environment, a tumor suppressor gene can restrain, and an oncogene can promote, the development of cancer.	[ [ "Cancer is a multistep disease in which cells acquire increasingly malignant phenotypes .", "These phenotypes are acquired in part by somatic mutations , which derange normal controls over cell proliferation ( growth ) , survival , invasion , and other processes important for malignant tumorigenesis [1] ....	[ "Cellular senescence suppresses cancer by arresting cell proliferation , essentially permanently , in response to oncogenic stimuli , including genotoxic stress .", "We modified the use of antibody arrays to provide a quantitative assessment of factors secreted by senescent cells .", "We show that human cells i...	[ "Cells with damaged DNA are at risk of becoming cancerous tumors .", "Although “cellular senescence” can suppress tumor formation from damaged cells by blocking the cell division that underlies cancer growth , it has also been implicated in promoting cancer and other age-related diseases .", "To understand how ...	2008
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Revealing Pathway Dynamics in Heart Diseases by Analyzing Multiple Differential Networks	journal.pcbi.1004332	null	[ [ "Many heart diseases are attributable to both genetic and environmental factors [1] .", "These factors can perturb gene transcript levels , protein levels , and metabolite levels , which in turn perturbs the interactions among the molecules .", "Perturbation of the molecular network ultimately leads t...	[ "Development of heart diseases is driven by dynamic changes in both the activity and connectivity of gene pathways .", "Understanding these dynamic events is critical for understanding pathogenic mechanisms and development of effective treatment .", "Currently , there is a lack of computational methods that ena...	[ "Recent advances in systems biology have revealed that changes in the structure and activity of gene network play a critical role in the disease progression .", "Heart failure is a complex disease involving multiple molecular pathways .", "Yet little is known regarding the dynamic changes in the gene network of...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "infectious diseases/viral infections", "virology/host invasion and cell entry", "immunology/innate immunity" ]	A Differential Role for Macropinocytosis in Mediating Entry of the Two Forms of Vaccinia Virus into Dendritic Cells	journal.ppat.1000866	null	[ [ "Vaccinia virus ( VACV ) is best known for its role as a vaccine in the global eradication of smallpox .", "Research on VACV has been pursued with renewed fervour in recent years in light of its potential use as an effective vaccine vector for viral and parasitic infections as well as cancer .", "Expl...	[ "Vaccinia virus ( VACV ) is being developed as a recombinant viral vaccine vector for several key pathogens .", "Dendritic cells ( DCs ) are specialised antigen presenting cells that are crucial for the initiation of primary immune responses; however , the mechanisms of uptake of VACV by these cells are unclear ....	[ "Vaccinia virus ( VACV ) is a relative of the smallpox virus and was used for many decades as a successful vaccine that contributed to the eradication of smallpox .", "Today , through genetic recombination technology , VACV shows potential as a modern vaccine for many unconquered diseases including HIV and cancer...	2010
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biotechnology", "plant genomes", "quantitative traits", "genetic complementation", "genome analysis", "speciation", "trait locus analysis", "plant genomics", "genetic interactions", "genomics", "plant genetics", "evolutionary theory", "evolutionary genetics", "macroevolution", "phenotyp...	Interspecific Tests of Allelism Reveal the Evolutionary Timing and Pattern of Accumulation of Reproductive Isolation Mutations	journal.pgen.1004623	null	[ [ "New species evolve via the accumulation of genetic changes that confer ecological differences and , in sexually reproducing organisms , reproductive isolating barriers .", "Of these barriers , hybrid sterility and inviability are thought to be due to deleterious interactions between mutations , at two or...	[ "Despite extensive theory , little is known about the empirical accumulation and evolutionary timing of mutations that contribute to speciation .", "Here we combined QTL ( Quantitative Trait Loci ) analyses of reproductive isolation , with information on species evolutionary relationships , to reconstruct the ord...	[ "The evolution of reproductive barriers between species , like inviability and sterility in hybrids , continues to fascinate and puzzle evolutionary biologists .", "However , very few studies have successfully identified the genes responsible for these barriers , or when the underlying mutations appeared during s...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biophysics", "microbiology" ]	Quantifying the Integration of Quorum-Sensing Signals with Single-Cell Resolution	journal.pbio.1000068	How do bacteria integrate multiple cell-to-cell communication signals? Information from two signaling molecules is combined in a strictly additive way with equal weight from each signal.	[ [ "In a process called quorum sensing , bacteria communicate with one another using extracellular signaling molecules called autoinducers .", "Quorum sensing allows groups of bacteria to track their cell numbers , synchronize gene expression on a population-wide scale , and thereby carry out collective acti...	[ "Cell-to-cell communication in bacteria is a process known as quorum sensing that relies on the production , detection , and response to the extracellular accumulation of signaling molecules called autoinducers .", "Often , bacteria use multiple autoinducers to obtain information about the vicinal cell density ."...	[ "Although bacteria are unicellular , the individual cells communicate with each other via small diffusible molecules .", "This communication process , known as quorum sensing , allows groups of bacteria to track the density of the population they are in , synchronize gene expression across the population , and th...	2009
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "cell physiology", "vesicles", "enzymes", "brassica", "enzymology", "hormones", "model organisms", "immunoprecipitation", "experimental organism systems", "seedlings", "co-immunoprecipitation", "plants", "cellular structures and organelles", "estradiol", "arabidopsis thaliana", "resear...	A single class of ARF GTPase activated by several pathway-specific ARF-GEFs regulates essential membrane traffic in Arabidopsis	journal.pgen.1007795	null	[ [ "ARF GTPases and their guanine-nucleotide exchange factors ( ARF-GEFs ) play essential roles in the formation of membrane vesicles that transport cargo proteins from donor to acceptor compartments within the endomembrane system .", "Sometimes called molecular switches , ARF proteins cycle between an inact...	[ "In eukaryotes , GTP-bound ARF GTPases promote intracellular membrane traffic by mediating the recruitment of coat proteins , which in turn sort cargo proteins into the forming membrane vesicles .", "Mammals employ several classes of ARF GTPases which are activated by different ARF guanine-nucleotide exchange fac...	[ "Membrane traffic plays an important role in cellular homeostasis , cell-cell communication , nutrient uptake and organismal interaction , delivering membrane proteins as well as secreted proteins to their sites of action and degradation .", "This requires sorting of proteins into forming membrane vesicles , whic...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine", "infectious hepatitis", "hepatitis b", "immunity", "gastroenterology and hepatology", "virology", "innate immunity", "host-pathogen interaction", "biology", "microbiology", "liver diseases" ]	Inhibition of Hepatitis B Virus Replication by the Host Zinc Finger Antiviral Protein	journal.ppat.1003494	null	[ [ "Hepatitis B virus ( HBV ) is the etiological agent of human hepatitis B . Despite the fact that most adulthood HBV infections are transient , approximately 5–10% of infected adults and more than 90% of infected neonates develop a life-long chronic infection , constituting a substantial public health burden a...	[ "The zinc finger antiviral protein ( ZAP ) is a mammalian host restriction factor that inhibits the replication of a variety of RNA viruses , including retroviruses , alphaviruses and filoviruses , through interaction with the ZAP-responsive elements ( ZRE ) in viral RNA , and recruiting the exosome to degrade RNA ...	[ "The dynamics of virus and host interaction greatly influence viral pathogenesis , and host cells have evolved multiple mechanisms to inhibit viral replication .", "Since it was first discovered as a cellular restriction factor for retroviruses , the host-encoded zinc finger antiviral protein ( ZAP ) has been sho...	2013
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "cell physiology", "medicine and health sciences", "oxygen", "cancers and neoplasms", "cell metabolism", "oncology", "physiological processes", "oxygen metabolism", "metabolomics", "metabolites", "pharmacology", "drug metabolism", "melanomas", "chemistry", "pharmacokinetics", "biochemi...	A systems approach reveals distinct metabolic strategies among the NCI-60 cancer cell lines	journal.pcbi.1005698	null	[ [ "Aerobic glycolysis indicates the incomplete oxidation of glucose to lactate under normoxic conditions [1] and has been a focus of cancer research in recent decades [2] .", "However , cancer cells are increasingly thought to employ heterogeneous metabolic strategies beyond aerobic glycolysis [3–6] .", ...	[ "The metabolic phenotype of cancer cells is reflected by the metabolites they consume and by the byproducts they release .", "Here , we use quantitative , extracellular metabolomic data of the NCI-60 panel and a novel computational method to generate 120 condition-specific cancer cell line metabolic models .", ...	[ "Altered metabolism is characteristic for many human diseases including cancer .", "Disease progression and treatment efficacy vary between patients .", "Hence , we need personalized approaches to define metabolic disease phenotypes .", "This definition will enable us to unravel the underlying disease mechani...	2017
[ "Introduction", "Models", "Results", "Discussion" ]	[ "meiosis", "cell motility", "cell cycle and cell division", "cell processes", "condensed matter physics", "vertebrates", "animals", "xenopus", "germ cells", "animal models", "oocytes", "model organisms", "amphibians", "dyneins", "molecular motors", "nucleation", "epigenetics", "chr...	A Motor-Gradient and Clustering Model of the Centripetal Motility of MTOCs in Meiosis I of Mouse Oocytes	journal.pcbi.1005102	null	[ [ "Spindle assembly in higher eukaryotic cells involves the self-organization of microtubules ( MT ) into a bipolar structure .", "During mitosis in animal cells , spindle poles are defined by a pair of centrosomes .", "However bipolar structures emerge even in the absence of centrosomes during meiosis ...	[ "Asters nucleated by Microtubule ( MT ) organizing centers ( MTOCs ) converge on chromosomes during spindle assembly in mouse oocytes undergoing meiosis I . Time-lapse imaging suggests that this centripetal motion is driven by a biased ‘search-and-capture’ mechanism .", "Here , we develop a model of a random walk...	[ "Recent microscopy based time-lapse measurements of spindle assembly in the absence of pre-existing centrosomes , have improved our understanding of the principles of self-organization at a cellular scale .", "Mouse oocytes meiosis is one such example , where radial microtubule ( MT ) arrays , or asters , nucleat...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "plant science", "plant microbiology", "viral transmission and infection", "virology", "plant biology", "biology", "microbiology", "viral structure" ]	Structural Insights into Viral Determinants of Nematode Mediated Grapevine fanleaf virus Transmission	journal.ppat.1002034	null	[ [ "Efficient transmission from host to host by vectors is an important biological", "feature shared by many animal and plant viruses .", "Arthropods transmit many viruses to", "mammals and plants .", "Examples include highly pathogenic viruses such as Rift", "Valley fever virus , Dengue viru...	[ "Many animal and plant viruses rely on vectors for their transmission from host to", "host .", "Grapevine fanleaf virus ( GFLV ) , a picorna-like virus from", "plants , is transmitted specifically by the ectoparasitic nematode", "Xiphinema index .", "The icosahedral capsid of GFLV , which", "consists of...	[ "Numerous pathogenic viruses from animals and plants rely on vectors such as", "insects , worms or other organisms for their transmission from host to host .", "The", "reasons why certain vectors transmit some viruses but not others remain poorly", "understood .", "In plants , Grapevine fanleaf virus ( GF...	2011
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "medicine and health sciences", "pathology and laboratory medicine", "clinical research design", "tropical diseases", "geographical locations", "north america", "treponematoses", "bacterial diseases", "research design", "age groups", "case series", "jamaica", "neglected tropical diseases", ...	Epidemiological situation of yaws in the Americas: A systematic review in the context of a regional elimination goal	journal.pntd.0007125	null	[ [ "Yaws is a poverty-related chronic disease characterized by a primary skin lesion ( “mother yaws” ) followed by a secondary skin lesion , latent infection , and a chronic stage which may include a destructive process of bones and joints .", "[1 , 2] The disease is a contagious non-venereal treponematosis ...	[ "Yaws is targeted for eradication by 2020 in the WHA66 . 12 resolution of the World Health Assembly .", "The objective of this study was to describe the occurrence of yaws in the Americas and to contribute to the compilation of evidence based on published data to undertake the certification of yaws eradication ."...	[ "Yaws is a contagious non-venereal treponematosis caused by the bacterium Treponema pallidum subspecies pertenue , transmitted by skin contact .", "It is a poverty-related chronic disease characterized by primary and secondary skin lesions , with latent infection and a chronic stage , which could include a destru...	2019
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "virology/host antiviral responses", "virology/animal models of infection", "immunology/innate immunity" ]	IFN-Lambda (IFN-λ) Is Expressed in a Tissue-Dependent Fashion and Primarily Acts on Epithelial Cells In Vivo	journal.ppat.1000017	null	[ [ "Type I interferon ( IFN ) , also called IFN-α/β , was originally discovered owing to its potent antiviral activity [1] .", "Type I IFN was later shown to display pleiotropic activities .", "It modulates innate and acquired immune responses , cell growth and apoptosis [2] .", "Type I IFN forms a v...	[ "Interferons ( IFN ) exert antiviral , immunomodulatory and cytostatic activities .", "IFN-α/β ( type I IFN ) and IFN-λ ( type III IFN ) bind distinct receptors , but regulate similar sets of genes and exhibit strikingly similar biological activities .", "We analyzed to what extent the IFN-α/β and IFN-λ systems...	[ "Virus-infected cells can secrete interferons ( IFNs ) , cytokines that induce an infection-resistant state in neighboring cells .", "IFNs are critical to slow down early multiplication of pathogens in the body .", "Two IFN families exhibiting strikingly similar properties were described: type I IFNs ( or IFN-α...	2008
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "cell biology", "neurological disorders", "neuroscience" ]	Gamma-Secretase Represents a Therapeutic Target for the Treatment of Invasive Glioma Mediated by the p75 Neurotrophin Receptor	journal.pbio.0060289	Gamma-secretase inhibitors in clinical trials for patients with Alzheimer disease can be used to block the highly invasive behavior of malignant glioma and prolong survival.	[ [ "Human malignant glioma ( MG ) is one of the most common primary central nervous system tumors in adults .", "These tumors are diffuse , highly invasive , with dismal prognosis , and long-term survivors are rare [1 , 2] .", "MG extend tendrils of tumor several centimeters away from the main tumor mass...	[ "The multifunctional signaling protein p75 neurotrophin receptor ( p75NTR ) is a central regulator and major contributor to the highly invasive nature of malignant gliomas .", "Here , we show that neurotrophin-dependent regulated intramembrane proteolysis ( RIP ) of p75NTR is required for p75NTR-mediated glioma i...	[ "Despite technical advances , clinical prognosis of patients with malignant glioma , with an average survival of less than one year , has not changed .", "The highly invasive nature of these tumors , together with the recently identified brain tumor-initiating cells , provide disease reservoirs that render these ...	2008
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "ecology/evolutionary ecology", "infectious diseases/fungal infections", "ecology/spatial and landscape ecology", "infectious diseases/sexually transmitted diseases", "ecology/population ecology", "genetics and genomics/population genetics" ]	Glacial Refugia in Pathogens: European Genetic Structure of Anther Smut Pathogens on Silene latifolia and Silene dioica	journal.ppat.1001229	null	[ [ "Understanding the dynamics of emerging infectious diseases and their routes to colonize new geographic regions is a major challenge for ecologists in an effort to prevent negative impacts upon human , domestic , and natural populations .", "Because pathogens causing emerging diseases have not coevolved w...	[ "Climate warming is predicted to increase the frequency of invasions by pathogens and to cause the large-scale redistribution of native host species , with dramatic consequences on the health of domesticated and wild populations of plants and animals .", "The study of historic range shifts in response to climate ...	[ "Global change is expected to cause the large-scale redistribution of species , including pathogens that threaten the health of domestic populations and natural ecosystems .", "Predicting the dynamics of invasive pathogens is therefore a major challenge for the 21st century ecologists and epidemiologists .", "B...	2010
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "signal transduction", "plant science", "model organisms", "plant and algal models", "molecular cell biology", "membrane receptor signaling", "mechanisms of signal transduction", "plant biology", "plant genetics", "signaling pathways", "biology", "molecular biology", "arabidopsis thaliana" ]	Genetic Evidence for an Indispensable Role of Somatic Embryogenesis Receptor Kinases in Brassinosteroid Signaling	journal.pgen.1002452	null	[ [ "Brassinosteroids ( BRs ) are naturally produced plant hormones regulating many developmental processes from seed germination to flowering and senescence [1] .", "BR deficiency or response mutants show typical phenotypic defects including decreased rate of seed germination , rounded and epinastic rosette ...	[ "The Arabidopsis thaliana Somatic Embryogenesis Receptor Kinases ( SERKs ) consist of five members , SERK1 to SERK5 , of the leucine-rich repeat receptor-like kinase subfamily II ( LRR-RLK II ) .", "SERK3 was named BRI1-Associated Receptor Kinase 1 ( BAK1 ) due to its direct interaction with the brassinosteroid (...	[ "Brassinosteroids ( BRs ) are a group of plant hormones critical for plant growth and development .", "BRs are perceived by a cell-surface receptor complex including two distinctive receptor kinases , BRI1 and BAK1 .", "Whereas BRI1 is a true BR-binding receptor , BAK1 does not appear to have BR-binding activit...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods", "Supporting Information" ]	[ "toxoplasma", "genetics and genomics" ]	Epigenomic Modifications Predict Active Promoters and Gene Structure in Toxoplasma gondii	journal.ppat.0030077	null	[ [ "Toxoplasma gondii is an obligate intracellular apicomplexan parasite responsible for encephalitis in immunocompromised individuals and birth defects when a fetus is exposed in utero [1 , 2] .", "The life cycle of T . gondii is complex , with multiple differentiation steps that are critical to survival of...	[ "Mechanisms of gene regulation are poorly understood in Apicomplexa , a phylum that encompasses deadly human pathogens like Plasmodium and Toxoplasma .", "Initial studies suggest that epigenetic phenomena , including histone modifications and chromatin remodeling , have a profound effect upon gene expression and ...	[ "Apicomplexan parasites , including Toxoplasma gondii , are responsible for a variety of deadly infections , but little is understood about how these important pathogens regulate gene expression .", "Initial studies suggest that alterations in chromatin structure regulate expression of virulence traits .", "To ...	2007
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "medicine", "infectious disease epidemiology", "epidemiology", "biology", "microbiology", "parasitology" ]	A Scoping Review and Prevalence Analysis of Soil-Transmitted Helminth Infections in Honduras	journal.pntd.0002653	null	[ [ "Intestinal parasites including soil-transmitted helminths ( STH ) have been long recognized as public health problems in much of the developing world [1] .", "Soil-transmitted helminthiases are caused by four species of intestinal worms , namely , Ascaris lumbricoides , Trichuris trichiura , and the two ...	[ "Honduras is endemic for soil-transmitted helminth ( STH ) infections , but critical information gaps still remain on the prevalence and intensity of these infections as well as on their spatial distribution at subnational levels .", "Firstly , to review the research activity on STH infections in Honduras and sec...	[ "Soil-transmitted helminthiases are infections of public health importance in Honduras .", "Although research data on this topic in the country is somewhat inconsistent and scattered , a wealth of information has been produced by Honduran researchers and practitioners over the years .", "The vast majority of th...	2014
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "evolutionary biology/evolutionary and comparative genetics", "computational biology/molecular genetics", "evolutionary biology/genomics", "computational biology/evolutionary modeling", "evolutionary biology/bioinformatics", "computational biology/genomics" ]	Sm/Lsm Genes Provide a Glimpse into the Early Evolution of the Spliceosome	journal.pcbi.1000315	null	[ [ "The modern spliceosome is a sophisticated molecular machine consisting of over 200 protein and 5 RNA components .", "The appearance of the spliceosome was abrupt; it is absent in prokaryotic cells , yet simple eukaryotic organisms have a rather complex spliceosome containing at least 78 proteins [1] .", ...	[ "The spliceosome , a sophisticated molecular machine involved in the removal of intervening sequences from the coding sections of eukaryotic genes , appeared and subsequently evolved rapidly during the early stages of eukaryotic evolution .", "The last eukaryotic common ancestor ( LECA ) had both complex spliceos...	[ "The spliceosome is a complex molecular machine that removes intervening sequences ( introns ) from mRNAs .", "It is unique to eukaryotes .", "Although prokaryotes have self-splicing introns , they completely lack spliceosomal introns and the spliceosome itself .", "Yet even the simplest eukaryotic organisms ...	2009
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "animal types", "genetics", "biology", "genomics", "population biology", "genetics and genomics", "veterinary science", "agriculture" ]	A High Density SNP Array for the Domestic Horse and Extant Perissodactyla: Utility for Association Mapping, Genetic Diversity, and Phylogeny Studies	journal.pgen.1002451	null	[ [ "Horses have held a valued place in human civilization for over 5 , 000 years through service in war , agriculture , sport and companionship [1] .", "Over the last several centuries , more than 400 distinct horse breeds have been established by genetic selection for a wide number of desirable phenotypic t...	[ "An equine SNP genotyping array was developed and evaluated on a panel of samples representing 14 domestic horse breeds and 18 evolutionarily related species .", "More than 54 , 000 polymorphic SNPs provided an average inter-SNP spacing of ∼43 kb .", "The mean minor allele frequency across domestic horse breeds...	[ "We utilized the previously generated horse genome sequence and a large SNP database to design an ∼54 , 000 SNP assay for use in the domestic horse and related species .", "The utility of this SNP array was demonstrated through genome-wide linkage disequilibrium , inbreeding and genetic distance measurements with...	2012
[ "Introduction", "Results", "Materials and Methods" ]	[ "biology and life sciences", "immunology", "microbiology" ]	Distinct Lipid A Moieties Contribute to Pathogen-Induced Site-Specific Vascular Inflammation	journal.ppat.1004215	null	[ [ "Host recognition of Gram-negative bacteria occurs via detection of LPS expressed on the bacterial membrane by the innate immune receptor , TLR4 [1] .", "This initial recognition is critical for instructing host immunity and promoting an inflammatory response that eradicates the pathogen from the host [1]...	[ "Several successful pathogens have evolved mechanisms to evade host defense , resulting in the establishment of persistent and chronic infections .", "One such pathogen , Porphyromonas gingivalis , induces chronic low-grade inflammation associated with local inflammatory bone loss and systemic inflammation manife...	[ "Several human pathogens express structurally divergent forms of lipid A , the endotoxic portion of lipopolysaccharide ( LPS ) , as a strategy to evade host innate immune detection and establish persistent infection .", "Expression of modified lipid A species promotes pathogen evasion of host recognition by Toll-...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "skin", "flow cytometry", "cell death", "keratinocytes", "medicine and health sciences", "integumentary system", "immunofluorescence staining", "cell processes", "epithelial cells", "dna damage", "epidermis", "dna", "research and analysis methods", "specimen preparation and treatment", "...	A Glutathione-Nrf2-Thioredoxin Cross-Talk Ensures Keratinocyte Survival and Efficient Wound Repair	journal.pgen.1005800	null	[ [ "Maintenance of the cellular redox balance is essential for appropriate cellular function .", "This balance is frequently challenged , particularly in response to infections or tissue damage inflicted by mechanical , chemical or physical insults .", "Under these conditions cells produce an excess of r...	[ "The tripeptide glutathione is the most abundant cellular antioxidant with high medical relevance , and it is also required as a co-factor for various enzymes involved in the detoxification of reactive oxygen species and toxic compounds .", "However , its cell-type specific functions and its interaction with othe...	[ "The skin is frequently exposed to various challenges that cause oxidative stress , such as UV irradiation , exposure to toxic chemicals or mechanical injury .", "Therefore , keratinocytes -the major cell type of the outermost layer of our skin—need sophisticated antioxidant defense systems .", "However , the r...	2016
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "medicine and health sciences", "gene regulation", "regulatory proteins", "blastomas", "cancers and neoplasms", "vertebrates", "dna-binding proteins", "animals", "oncology", "animal models", "osteichthyes", "developmental biology", "model organisms", "experimental organism systems", "tra...	Regulation of Gli ciliary localization and Hedgehog signaling by the PY-NLS/karyopherin-β2 nuclear import system	journal.pbio.2002063	null	[ [ "Cell–cell signaling often occurs in specialized subcellular compartments .", "One such cell signaling center is the primary cilium , which is a microtubule-based plasma membrane protrusion [1] .", "Primary cilia regulate many essential cellular processes , and their malfunction is attributed to numer...	[ "Hedgehog ( Hh ) signaling in vertebrates depends on primary cilia .", "Upon stimulation , Hh pathway components , including Gli transcription factors , accumulate at primary cilia to transduce the Hh signal , but the mechanisms underlying their ciliary targeting remains largely unknown .", "Here , we show that...	[ "The secreted Hedgehog ( Hh ) protein plays an evolutionarily conserved role in both embryonic development and adult tissue homeostasis .", "Malfunction of Hh signaling activity contributes to a wide range of human diseases , including birth defects and cancer .", "Hh signaling in vertebrates critically depends...	2017
[ "Introduction", "Methods", "Results", "Discussion", "Conclusion" ]	[ "dermatology", "medicine and health sciences", "pathology and laboratory medicine", "pathogens", "tropical diseases", "microbiology", "parasitic diseases", "streptococcus pyogenes", "skin infections", "signs and symptoms", "ectoparasitic infections", "sexually transmitted diseases", "neglect...	Are scabies and impetigo “normalised”? A cross-sectional comparative study of hospitalised children in northern Australia assessing clinical recognition and treatment of skin infections	journal.pntd.0005726	null	[ [ "Skin infections including scabies , impetigo , tinea and pediculosis are common in children , with high prevalence in developing countries and marginalised populations within developed countries[1–4] .", "It is estimated that 162 million children in low and low-middle income countries have active impetig...	[ "Complications of scabies and impetigo such as glomerulonephritis and invasive bacterial infection in Australian Aboriginal children remain significant problems and the overall global burden of disease attributable to these skin infections remains high despite the availability of effective treatment .", "We hypot...	[ "Scabies and impetigo are common skin infections in children across the developing world as well as in disadvantaged populations living in developed countries .", "In previous studies including Australian Aboriginal and Pacific Islander children the rates of impetigo and scabies were amongst the highest described...	2017
[ "Introduction", "Results and Discussion", "Materials and Methods" ]	[ "biotechnology", "cell biology", "biology and life sciences", "molecular biology" ]	Sensors at Centrosomes Reveal Determinants of Local Separase Activity	journal.pgen.1004672	null	[ [ "Centrosomes are the main microtubule organizing centers of animal cells that consist of the organizing centrioles and pericentriolar material .", "Centrosomes , like DNA , duplicate exactly once per cell cycle .", "From S phase to the end of mitosis centrosomes are composed of a pair of centrioles , ...	[ "Separase is best known for its function in sister chromatid separation at the metaphase-anaphase transition .", "It also has a role in centriole disengagement in late mitosis/G1 .", "To gain insight into the activity of separase at centrosomes , we developed two separase activity sensors: mCherry-Scc1 ( 142-46...	[ "Centriole disengagement in telophase/G1 is the licensing step for centrosome duplication in the subsequent S phase .", "Recent data suggest that separase , together with polo-like kinase Plk1 , is essential for the centriole disengagement and individual depletion of either separase or Plk1 alone fails to suppres...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "neurological disorders", "eukaryotes", "vertebrates", "mus (mouse)", "animals" ]	In Vitro and In Vivo Neurotoxicity of Prion Protein Oligomers	journal.ppat.0030125	null	[ [ "Transmissible spongiform encephalopathies are infectious neurodegenerative diseases .", "They are characterized by the accumulation in the brain , and sometimes the lymphoid tissues [1 , 2] , of an abnormally structured form ( PrPsc ) of the host prion protein ( PrP ) [3] .", "PrPsc may constitute th...	[ "The mechanisms underlying prion-linked neurodegeneration remain to be elucidated , despite several recent advances in this field .", "Herein , we show that soluble , low molecular weight oligomers of the full-length prion protein ( PrP ) , which possess characteristics of PrP to PrPsc conversion intermediates su...	[ "Prion diseases are transmissible neurodegenerative diseases caused by an infectious agent thought to be composed mainly of a host protein , the prion protein ( PrP ) .", "The mechanisms of neurodegeneration prevailing in these diseases are not well understood .", "In the present study , we demonstrate that sma...	2007
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "schistosoma", "invertebrates", "medicine and health sciences", "body fluids", "education", "helminths", "sociology", "tropical diseases", "geographical locations", "social sciences", "parasitic diseases", "animals", "arithmetic", "urine", "mathematics", "pharmaceutics", "neglected t...	Assessing the benefits of five years of different approaches to treatment of urogenital schistosomiasis: A SCORE project in Northern Mozambique	journal.pntd.0006061	null	[ [ "Schistosomiasis is a major yet neglected public health problem , second only to malaria in terms of parasite-induced human morbidity and mortality worldwide [1] .", "Estimates show that globally at least 218 million people required preventive treatment in 2015 [2–4] , and at least 20 million suffer from ...	[ "In Mozambique , schistosomiasis is highly endemic across the whole country .", "The Schistosomiasis Consortium for Operational Research and Evaluation ( SCORE ) coordinates a five-year study that has been implemented in various African countries , including Mozambique .", "The overall goal of SCORE was to bett...	[ "Urogenital schistosomiasis is highly endemic in Mozambique .", "This study was part of a multi-country trial , including Mozambique , designed to understand the impact of different schistosomiasis treatment strategies involving community-wide treatment ( CWT ) , school-based ( SBT ) , and treatment holidays over...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "infectious diseases/hiv infection and aids", "virology/immunodeficiency viruses", "molecular biology" ]	Episomal Viral cDNAs Identify a Reservoir That Fuels Viral Rebound after Treatment Interruption and That Contributes to Treatment Failure	journal.ppat.1001303	null	[ [ "Despite great advances in the treatment of HIV infection and disease , therapeutic eradication of viral infection is currently not possible .", "Individuals who respond well to ART and maximally suppress virus replication based on standard assays , harbor viral reservoirs that fuel a rapid rebound in vir...	[ "Viral reservoirs that persist in HIV-1 infected individuals on antiretroviral therapy ( ART ) are the major obstacle to viral eradication .", "The identification and definition of viral reservoirs in patients on ART is needed in order to understand viral persistence and achieve the goal of viral eradication .", ...	[ "Infection by HIV-1 and the related effects on human health continue to be a major problem throughout the world .", "Since the early 1980's , more than 25 million people have died from AIDS and the only treatment option for infected individuals is likely to be life-long treatment with a combination of antiviral d...	2011
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "cell biology/cell signaling", "biophysics/theory and simulation", "cell biology/membranes and sorting", "biophysics/membrane proteins and energy transduction", "computational biology/systems biology", "cell biology/cytoskeleton" ]	The Mechanochemistry of Endocytosis	journal.pbio.1000204	An integrated theoretical model reveals how the chemical and the mechanical aspects of endocytosis are coordinated coherently in yeast cells, driving progression through the endocytic pathway and ensuring efficient vesicle scission in vivo.	[ [ "During clathrin-mediated endocytosis , cells regulate plasma membrane molecular composition and internalize essential nutrients .", "This process involves coordination of biochemical activities with membrane shape changes [1] , [2] .", "Multicolor real-time fluorescence microscopy studies in mammalia...	[ "Endocytic vesicle formation is a complex process that couples sequential protein recruitment and lipid modifications with dramatic shape transformations of the plasma membrane .", "Although individual molecular players have been studied intensively , how they all fit into a coherent picture of endocytosis remain...	[ "Endocytosis is a complex and efficient process that cells utilize to take up nutrients and communicate with other cells .", "Eukaryotes have diverse endocytic pathways with two common features , mechanical and chemical .", "Proper mechanical forces are necessary to deform the plasma membrane and , eventually ,...	2009
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "cell biology/nuclear structure and function", "computational biology/transcriptional regulation", "cell biology/cell signaling", "physiology/neuronal signaling mechanisms", "biophysics/theory and simulation", "cell biology/neuronal signaling mechanisms", "physiology/cell signaling", "neuroscience/neu...	Electrotonic Signals along Intracellular Membranes May Interconnect Dendritic Spines and Nucleus	journal.pcbi.1000036	null	[ [ "Glutamatergic synaptic inputs onto dendritic spines of pyramidal neurons induce phosphorylation of the transcription factor CREB ( cAMP-Responsive-Element Binding protein ) in the nucleus [1]–[3] .", "CREB phosphorylation is important for converting specific synaptic inputs into long-term memory in sever...	[ "Synapses on dendritic spines of pyramidal neurons show a remarkable ability to induce phosphorylation of transcription factors at the nuclear level with a short latency , incompatible with a diffusion process from the dendritic spines to the nucleus .", "To account for these findings , we formulated a novel exte...	[ "Our study incorporates the fact that the endoplasmic reticulum ( ER ) forms a complete continuum from the spine head to the nuclear envelope and suggests that electrical current flow in a neuron may be better described by a cable-within-a-cable system , where synaptic current flows simultaneously in the medium bet...	2008
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genomics", "functional genomics", "genetics", "epigenetics", "biology", "dna modification", "genetics and genomics" ]	In Vivo Control of CpG and Non-CpG DNA Methylation by DNA Methyltransferases	journal.pgen.1002750	null	[ [ "DNA methylation at the C-5 positions of cytosine ( 5mC ) is a key epigenetic modification in mammals essential for normal development [1] , [2] .", "Cytosine methylation is predominantly found in CpG dinucleotide context and about 70 to 80% of all CpGs are methylated .", "These methylated CpGs are us...	[ "The enzymatic control of the setting and maintenance of symmetric and non-symmetric DNA methylation patterns in a particular genome context is not well understood .", "Here , we describe a comprehensive analysis of DNA methylation patterns generated by high resolution sequencing of hairpin-bisulfite amplicons of...	[ "DNA methylation is a stable covalent epigenetic modification of cytosines mostly confined to CpG-dinucleotides in mammals .", "In general , it is associated with silencing of genomic DNA regions .", "Three catalytically active DNA methyltransferases ( Dnmts ) set and maintain CpG methylation in cooperation wit...	2012
[ "Introduction", "Results", "Discussion" ]	[ "genetics and genomics/genomics", "genetics and genomics/comparative genomics", "evolutionary biology/evolutionary and comparative genetics", "evolutionary biology/human evolution", "genetics and genomics/gene expression", "evolutionary biology/genomics", "evolutionary biology/bioinformatics", "comput...	Clustering of Codons with Rare Cognate tRNAs in Human Genes Suggests an Extra Level of Expression Regulation	journal.pgen.1000548	null	[ [ "Codon usage bias is abundant in every sequenced genome and several theories have been put forward to explain it , depending on the genome or the gene .", "In many organisms , including bacteria , yeast and Drosophila species , the strongest factor determining codon bias is selection for maximizing transl...	[ "In species with large effective population sizes , highly expressed genes tend to be encoded by codons with highly abundant cognate tRNAs to maximize translation rate .", "However , there has been little evidence for a similar bias of synonymous codons in highly expressed human genes .", "Here , we ask instead...	[ "The degeneracy of the genetic code means that many amino acids are encoded by not one , but a range of codons .", "In bacteria and yeast , it is known that the choice of codons used can be beneficial ( or detrimental ) to the gene function .", "As humans have a relatively small effective population size , and ...	2009
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "biochemistry", "infectious diseases" ]	Metabolic Profiling of an Echinostoma caproni Infection in the Mouse for Biomarker Discovery	journal.pntd.0000254	null	[ [ "An estimated 40 million individuals are infected with food-borne trematodes and , in many parts of the world , the diseases caused by these infections are emerging [1] .", "Yet , food-borne trematodiases are so-called neglected tropical diseases [2] .", "An infection with food-borne trematodes is acq...	[ "Metabolic profiling holds promise with regard to deepening our understanding of infection biology and disease states .", "The objectives of our study were to assess the global metabolic responses to an Echinostoma caproni infection in the mouse , and to compare the biomarkers extracted from different biofluids (...	[ "Consumption of raw fish and other freshwater products can lead to unpleasant worm infections .", "Indeed , such worm infections are of growing public health and veterinary concern , but they are often neglected , partially explained by the difficulty of accurate diagnosis .", "In the present study we infected ...	2008
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "plant science", "virulence factors and mechanisms", "virology", "plant pathogens", "plant pathology", "biology", "microbiology" ]	The Hypervariable Amino-Terminus of P1 Protease Modulates Potyviral Replication and Host Defense Responses	journal.ppat.1003985	null	[ [ "Viruses are obligate parasite pathogens that hijack host factors to assure their own survival and propagation .", "Due to the limited coding capacity of their genome , viruses undertake distinct translational strategies [1]; one of most widely employed by RNA viruses involves polyprotein synthesis [2] ."...	[ "The replication of many RNA viruses involves the translation of polyproteins , whose processing by endopeptidases is a critical step for the release of functional subunits .", "P1 is the first protease encoded in plant potyvirus genomes; once activated by an as-yet-unknown host factor , it acts in cis on its own...	[ "RNA viruses are ideal systems for the study of population dynamics , relationships among pathogen traits such as fitness and virulence , and of host immune responses to pathogen attacks .", "Based on experimental evolution studies , early models equated parasite virulence with fitness .", "Some reports showed ...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genetics and genomics/microbial evolution and genomics", "genetics and genomics/genetics of the immune system", "genetics and genomics/complex traits", "public health and epidemiology/epidemiology", "genetics and genomics/genetics of disease", "public health and epidemiology/infectious diseases", "infe...	Leprosy and the Adaptation of Human Toll-Like Receptor 1	journal.ppat.1000979	null	[ [ "Leprosy is a chronic granulomatous disease affecting the skin and peripheral nerves and caused by Mycobacterium leprae .", "Despite its being the first identified pathogen in humans , leprosy remains endemic in central Africa , Southeast Asia and South America with more than 200 , 000 new cases per year ...	[ "Leprosy is an infectious disease caused by the obligate intracellular pathogen Mycobacterium leprae and remains endemic in many parts of the world .", "Despite several major studies on susceptibility to leprosy , few genomic loci have been replicated independently .", "We have conducted an association analysis...	[ "Mycobacterium leprae is an obligate intracellular pathogen that causes leprosy , a disease that shares a long history with the human population but which remains endemic in many parts of the world .", "Despite the fact that the genome of M . leprae has been sequenced , our understanding of its pathogenesis and i...	2010
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genomics", "reproductive system", "signatures of natural selection", "anatomy", "genome scans", "natural selection", "genome analysis", "genetics", "biology and life sciences", "population genetics", "computational biology", "evolutionary biology", "ecological selection", "evolutionary pr...	Genetic Control of Contagious Asexuality in the Pea Aphid	journal.pgen.1004838	null	[ [ "While sexuality is the dominant reproductive mode in metazoans , parthenogenesis - the development of an embryo from an unfertilized egg - occurs in most branches of the animal kingdom ( e . g . molluscs , insects , crustaceans , nematodes , fish , reptiles ) [e . g . 1 , 2 , 3] .", "Cyclical parthenogen...	[ "Although evolutionary transitions from sexual to asexual reproduction are frequent in eukaryotes , the genetic bases of such shifts toward asexuality remain largely unknown .", "We addressed this issue in an aphid species where both sexual and obligate asexual lineages coexist in natural populations .", "These...	[ "Asexual lineages occur in most groups of organisms and arise from loss of sex in sexual species .", "Yet , the genomic bases of these transitions remain largely unknown .", "Here , we combined quantitative genetic and population genomic approaches to unravel the genetic control of shifts towards permanent asex...	2014
[ "Introduction", "Materials and methods", "Results", "Discussion", "Conclusion" ]	[ "medicine and health sciences", "body fluids", "pathology and laboratory medicine", "pathogens", "geographical locations", "microbiology", "salmonella typhi", "salmonellosis", "bacterial diseases", "antibiotic resistance", "signs and symptoms", "enterobacteriaceae", "pharmacology", "bacter...	The clinical and microbiological characteristics of enteric fever in Cambodia, 2008-2015	journal.pntd.0005964	null	[ [ "Salmonella enterica serovar Typhi ( Salmonella Typhi ) and Salmonella enterica serovars Paratyphi ( Salmonella Paratyphi ) A , B , and C are Gram-negative bacteria which can invade the bloodstream and cause typhoid and paratyphoid fever respectively ( also jointly known as ‘enteric fever’ ) .", "They are...	[ "Enteric fever remains a major public health problem in low resource settings and antibiotic resistance is increasing .", "In Asia , an increasing proportion of infections is caused by Salmonella enterica serovar Paratyphi A , which for a long time was assumed to cause a milder clinical syndrome compared to Salmo...	[ "Enteric fever is a bloodstream infection caused by the bacteria Salmonella Typhi or Salmonella Paratyphi A , B , or C . It is common in low resource settings and linked to poor water quality and sanitation .", "The disease is also endemic in Cambodia and since 2013 there has been a sharp increase in the number o...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine and health sciences", "brain", "time series analysis", "circadian oscillators", "mathematics", "statistics (mathematics)", "genome analysis", "chronobiology", "dna", "dna methylation", "discrete mathematics", "combinatorics", "research and analysis methods", "genomics", "neocor...	24-Hour Rhythms of DNA Methylation and Their Relation with Rhythms of RNA Expression in the Human Dorsolateral Prefrontal Cortex	journal.pgen.1004792	null	[ [ "Circadian rhythms—intrinsic 24-hour biological rhythms—have a major impact on the molecular biology , physiology , and function of many human tissues , including the human brain , where they have an important influence on neurological diseases like dementia , epilepsy , and stroke .", "In model organisms...	[ "Circadian rhythms modulate the biology of many human tissues , including brain tissues , and are driven by a near 24-hour transcriptional feedback loop .", "These rhythms are paralleled by 24-hour rhythms of large portions of the transcriptome .", "The role of dynamic DNA methylation in influencing these rhyth...	[ "Circadian rhythms are intrinsic 24-hour biological rhythms that influence many aspects of human biology , including normal and abnormal human brain functions such as cognition and seizures .", "Circadian rhythms are maintained by a near 24-hour feedback loop mediated by a series of “clock” genes that are similar...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine", "antibody-producing cells", "infectious diseases", "immune cells", "cytokines", "b cells", "immunoglobulins", "hiv", "t cells", "retrovirology and hiv immunopathogenesis", "immunology", "biology", "viral diseases", "immune system" ]	Loss of Circulating CD4 T Cells with B Cell Helper Function during Chronic HIV Infection	journal.ppat.1003853	null	[ [ "Follicular helper CD4 T cells ( TFH ) are crucial for the development of antigen-specific B cells within germinal centers ( GC ) .", "TFH cells interact through co-stimulatory receptors and provide essential soluble factors ( i . e . IL-4 , IL-21 ) to promote the survival , isotype switching and selectio...	[ "The interaction between follicular T helper cells ( TFH ) and B cells in the lymph nodes and spleen has a major impact on the development of antigen-specific B cell responses during infection or vaccination .", "Recent studies described a functional equivalent of these cells among circulating CD4 T cells , refer...	[ "Follicular T helper cells ( TFH ) interact with B cells within germinal centers of lymphoid tissue to promote the survival , isotype switching and generation of high affinity memory B cells and plasma cells .", "Recently , a population of circulating CD4 T cells that shares phenotypic and functional characterist...	2014
[ "Introduction", "Methods", "Results and Discussion" ]	[ "medicine", "public health and epidemiology", "biomarker epidemiology", "molecular epidemiology", "epidemiology", "infectious disease epidemiology", "global health" ]	Prevalence of Human African Trypanosomiasis in the Democratic Republic of the Congo	journal.pntd.0001246	null	[ [ "Human African trypanosomiasis ( HAT ) has been reported in most of sub-Saharan Africa as well as in travelers to the region [1] .", "Currently , the global prevalence of the disease is uncertain .", "From 2006 to 2008 , there were 7200–8200 reported cases of HAT per year [2] .", "However , since ...	[ "Human African Trypanosomiasis ( HAT ) is a major public health problem in the Democratic Republic of the Congo ( DRC ) .", "Active and passive surveillance for HAT is conducted but may underestimate the true prevalence of the disease .", "We used ELISA to screen 7 , 769 leftover dried blood spots from a nation...	[ "Because of weak health surveillance infrastructures in poor countries , estimates of the burdens ( numbers of infections ) of many tropical diseases may be inaccurate .", "In particular , current estimates for the global burden of Human African Trypanosomiasis ( Sleeping Sickness , HAT ) vary widely .", "Most ...	2011
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "cell physiology", "carbohydrate metabolism", "medicine and health sciences", "metabolic networks", "enzymology", "cell metabolism", "glucose metabolism", "physiological processes", "metabolomics", "metabolites", "warburg effect", "network analysis", "enzyme metabolism", "energy metabolism...	Flux balance analysis predicts Warburg-like effects of mouse hepatocyte deficient in miR-122a	journal.pcbi.1005618	null	[ [ "Cancer cell metabolism is an exciting field of biology that provides a novel approach for treating cancer [1–8] .", "For almost a century , researchers have known that cancer cells have an abnormal metabolism and utilize glucose differently than normal cells do .", "However , glucose uptake may revea...	[ "The liver is a vital organ involving in various major metabolic functions in human body .", "MicroRNA-122 ( miR-122 ) plays an important role in the regulation of liver metabolism , but its intrinsic physiological functions require further clarification .", "This study integrated the genome-scale metabolic mod...	[ "For almost a century , researchers have known that cancer cells have an abnormal metabolism and utilize glucose differently than normal cells do .", "Aerobic glycolysis or the Warburg effect in cancer cells involves elevated glucose uptake with lactic acid production in the presence of oxygen .", "MicroRNAs ha...	2017
[ "Introduction", "Methods", "Results", "Discussion" ]	[]	Nucleosides Present on Phlebotomine Saliva Induce Immunossuppression and Promote the Infection Establishment	journal.pntd.0003600	null	[ [ "Leishmaniasis is a vector-borne disease transmitted exclusively by sand fly bites in which the host is inoculated with saliva and regurgitated parasites during the blood meal [1] .", "There is evidence that Phlebotomine saliva enhances the infectivity of many different Leishmania species [2–5] .", "T...	[ "Sand fly saliva plays a crucial role in establishing Leishmania infection .", "We identified adenosine ( ADO ) and adenosine monophosphate ( AMP ) as active pharmacologic compounds present in Phlebotomus papatasi saliva that inhibit dendritic cell ( DC ) functions through a PGE2/IL 10-dependent mechanism .", "...	[ "Leishmania parasites are transmitted to their vertebrate hosts by infected Phlebotomine sand flies during the blood meal of the flies .", "During the Leishmania transmission , the saliva is inoculated together with parasites and exhibit several pharmacological compounds that facilitate blood feeding , interferin...	2015
[ "Introduction", "Methods", "Results", "Discussion" ]	[]	Socio-Environmental Factors Associated with the Risk of Contracting Buruli Ulcer in Tiassalé, South Côte d’Ivoire: A Case-Control Study	journal.pntd.0004327	null	[ [ "Buruli ulcer ( BU ) is an infectious skin disease caused by the environmental mycobacterium , Mycobacterium ulcerans .", "It is the third most common mycobacterial disease in the world in immunocompetent individuals , after tuberculosis and leprosy [1–3] and the second one in Côte d’Ivoire after tubercul...	[ "Buruli ulcer ( BU ) is a cutaneous infectious disease caused by Mycobacterium ulcerans .", "The exact mode of transmission remains elusive; yet , some studies identified environmental , socio-sanitary , and behavioral risk factors .", "The purpose of this study was to assess the association of such factors to ...	[ "In Côte d’Ivoire , West Africa , Buruli ulcer ( BU ) is the second leading cause of mycobacterial infection after tuberculosis .", "Moreover , Côte d’Ivoire is one of the most affected countries worldwide by BU .", "Studies suggest that the reservoir of this mycobacterial infection is environmental , but the e...	2016
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "livestock", "medicine and health sciences", "ruminants", "immunology", "tropical diseases", "geographical locations", "vertebrates", "dogs", "animals", "mammals", "vaccines", "preventive medicine", "rabies", "neglected tropical diseases", "vaccination and immunization", "veterinary sc...	Rabies in Kazakhstan	journal.pntd.0004889	null	[ [ "Rabies is a fatal viral zoonotic disease largely transmitted to humans from bites by infected animals .", "Rabies is currently registered in over 100 countries in all continents except Australia and Antarctica .", "The disease is characterized by neuroencephalitis with 100% case fatality ratio once c...	[ "Rabies is a neglected zoonotic disease .", "There is a sparsity of data on this disease with regard to the incidence of human and animal disease in many low and middle income countries .", "Furthermore , rabies results in a large economic impact and a high human burden of disease .", "Kazakhstan is a large l...	[ "Kazakhstan is a large central Asian country that was part of the Soviet Union until 1991 .", "The country is endemic for rabies .", "This study shows that there are areas of Kazakhstan such as the north and south east of the country where outbreaks of animal rabies are concentrated .", "Cattle , dogs and fox...	2016
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "public and occupational health", "infectious diseases", "medicine and health sciences", "epidemiology", "biology and life sciences", "immunology", "microbiology", "tropical diseases", "parasitic diseases" ]	A Sero-epidemiological Study of Arboviral Fevers in Djibouti, Horn of Africa	journal.pntd.0003299	null	[ [ "Arboviral fevers are a threat to the global population and warrant a continuous surveillance and monitoring , especially in tropical and subtropical regions , where most of the low income countries are located [1] .", "Viruses from families of Togaviridae and Bunyaviridae , and from genus Flavivirus are ...	[ "Arboviral infections have repeatedly been reported in the republic of Djibouti , consistent with the fact that essential vectors for arboviral diseases are endemic in the region .", "However , there is a limited recent information regarding arbovirus circulation , and the associated risk predictors to human expo...	[ "The arboviruses are a group of viruses transmitted by arthropods such as mosquitoes , ticks , or sandflies .", "These pathogens have complex life cycles and depend on both arthropods and vertebrate hosts for survival and transmission .", "Recent global increase in cases confirms that they are of great public h...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "molecular cell biology", "neuroscience", "developmental biology", "biology" ]	Functional Interrogation of an Odorant Receptor Locus Reveals Multiple Axes of Transcriptional Regulation	journal.pbio.1001568	A transgenic approach in mice allows the functional interrogation of an odorant receptor locus in vivo and reveals characteristics of its monogenic and monoallelic expression.	[ [ "Olfactory sensory neurons are activated by odors in the periphery and transmit neural signals centrally to produce the perception of smell .", "On a molecular level , the diversity of odorous molecules is accommodated by a large number of G-protein-coupled odorant receptors ( ORs ) , which form the large...	[ "The odorant receptor ( OR ) genes constitute the largest mammalian gene family and are expressed in a monogenic and monoallelic fashion , through an unknown mechanism that likely exploits positive and negative regulation .", "We devised a genetic strategy in mice to examine OR selection by determining the transc...	[ "Odorant receptor ( OR ) gene choice is a paradigmatic example of transcriptional regulation in which each olfactory sensory neuron selects a single OR from a repertoire of over 1 , 000 genes .", "Two mechanistic models of OR choice have been proposed .", "One postulates the existence of a specialized transcrip...	2013
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[]	Assessment of Inhibitors of Pathogenic Crimean-Congo Hemorrhagic Fever Virus Strains Using Virus-Like Particles	journal.pntd.0004259	null	[ [ "Crimean-Congo hemorrhagic fever ( CCHF ) is a rapidly progressing inflammatory illness with high case fatality rates and a vast endemic area [1–6] .", "The etiological agent , CCHF virus ( CCHFV ) , is a tri-segmented virus belonging to the Nairovirus genus of the Bunyaviridae family; it is primarily mai...	[ "Crimean-Congo hemorrhagic fever ( CCHF ) is an often lethal , acute inflammatory illness that affects a large geographic area .", "The disease is caused by infection with CCHF virus ( CCHFV ) , a nairovirus from the Bunyaviridae family .", "Basic research on CCHFV has been severely hampered by biosafety requir...	[ "The tick-borne Crimean-Congo hemorrhagic fever virus ( CCHFV ) is the causative agent of a frequently life-threatening disease .", "CCHFV is present in a wide geographic area with potential for expansion .", "Moreover , CCHFV segmented genome reassortment leads to new strains with potentially different virulen...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "ecology", "plant biology" ]	Invasive Mutualists Erode Native Pollination Webs	journal.pbio.0060031	Alien mutualists can alter the structure of native pollination networks by usurping interaction links, thereby becoming central nodes of highly invaded webs.	[ [ "Plant–animal mutualisms are highly asymmetric , such that if a plant species depends strongly on an animal species , the animal typically depends weakly on the plant , and vice versa [1 , 2] .", "Thus , the resulting mutualistic webs have a nested structure—a robust property of this type of networks [3] ...	[ "Plant–animal mutualisms are characterized by weak or asymmetric mutual dependences between interacting species , a feature that could increase community stability .", "If invasive species integrate into mutualistic webs , they may alter web structure , with consequences for species persistence .", "However , t...	[ "Plant–animal mutualisms are characterized by weak or asymmetric mutual dependences between interacting species , such that if a plant species depends strongly on an animal species , the animal typically depends weakly on the plant , and vice versa .", "This limited reciprocal dependency , or “mutualism strength ...	2008
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "developmental biology", "population genetics", "biology", "evolutionary biology", "population biology", "genetics and genomics", "evolutionary developmental biology" ]	An Excess of Gene Expression Divergence on the X Chromosome in Drosophila Embryos: Implications for the Faster-X Hypothesis	journal.pgen.1003200	null	[ [ "It has long been suspected that the distinct properties of the X chromosome might in turn produce distinct patterns of evolution on the X relative to the autosomes [1] , [2] .", "In particular , the hemizygoisty of the X could be responsible for increased adaptive or non-adaptive evolution on this chromo...	[ "The X chromosome is present as a single copy in the heterogametic sex , and this hemizygosity is expected to drive unusual patterns of evolution on the X relative to the autosomes .", "For example , the hemizgosity of the X may lead to a lower chromosomal effective population size compared to the autosomes , sug...	[ "There is a single copy of the X chromosome in males , yet two copies in females .", "This unique inheritance pattern has long been predicted to influence how the X chromosome evolves .", "In particular , the theory suggests that the single copy of the X in males could facilitate faster evolution of the X , alt...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genetics", "biology" ]	Combinatorial Regulation of Meiotic Holliday Junction Resolution in C. elegans by HIM-6 (BLM) Helicase, SLX-4, and the SLX-1, MUS-81 and XPF-1 Nucleases	journal.pgen.1003591	null	[ [ "Homologous recombination is important for error-free DNA double-strand break ( DSB ) repair and for meiotic crossover ( CO ) formation .", "Meiosis is a specialized series of two sequential cell divisions that ensures the reduction of the diploid genome and results in the production of haploid gametes ."...	[ "Holliday junctions ( HJs ) are cruciform DNA structures that are created during recombination events .", "It is a matter of considerable importance to determine the resolvase ( s ) that promote resolution of these structures .", "We previously reported that C . elegans GEN-1 is a symmetrically cleaving HJ reso...	[ "Meiosis is a specialized cell division , where a single S-phase is followed by two rounds of cell divisions to ensure the production of haploid gametes .", "Meiotic crossover ( CO ) recombination is required for genetic diversity and for the proper segregation of chromosomes during the first meiotic division .",...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "cancer detection and diagnosis", "medicine and health sciences", "body fluids", "nervous system", "blood-brain barrier", "cancers and neoplasms", "biomarkers", "oncology", "dna libraries", "molecular biology techniques", "dna", "densitometry", "research and analysis methods", "spectrum an...	Fragment Length of Circulating Tumor DNA	journal.pgen.1006162	null	[ [ "Increased quantity of cell-free DNA in the circulation has been associated with malignant solid tumors [1] .", "Longitudinal studies have reported reductions in cell-free DNA quantity in response to therapy and elevations associated with recurrence suggesting quantification of cell-free DNA may be useful...	[ "Malignant tumors shed DNA into the circulation .", "The transient half-life of circulating tumor DNA ( ctDNA ) may afford the opportunity to diagnose , monitor recurrence , and evaluate response to therapy solely through a non-invasive blood draw .", "However , detecting ctDNA against the normally occurring ba...	[ "During cell death , DNA that is not contained within a membrane ( i . e . , cell-free DNA ) enters the circulation .", "Detecting cell-free DNA originating from solid tumors ( i . e . , circulating tumor DNA , ctDNA ) , particularly solid tumors that have not metastasized , has proven challenging due to the rela...	2016
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "invertebrates", "medicine and health sciences", "helminths", "tropical diseases", "hookworms", "parasitic diseases", "animals", "anemia", "research design", "nutrition", "ferritin", "neglected tropical diseases", "surveys", "research and analysis methods", "proteins", "iron deficiency...	Sustained effectiveness of weekly iron-folic acid supplementation and regular deworming over 6 years in women in rural Vietnam	journal.pntd.0005446	null	[ [ "Anaemia ( haemoglobin < 120g/L ) is estimated to affect 29 . 0% of non-pregnant women world-wide .", "[1] Iron deficiency anaemia ( IDA ) is the most common form of anaemia in many resource-poor settings .", "Nutritional anaemia can also be caused by vitamin deficiencies ( A , B2 , B6 , folate , B12 ...	[ "Weekly iron-folic acid ( IFA ) supplementation and regular deworming is effective for the prevention of iron deficiency and anaemia in women of child-bearing age .", "Between 2006 and 2013 , a program of weekly IFA and biannual deworming was implemented in Yen Bai province , Vietnam .", "In this study we aimed...	[ "Weekly iron-folic acid ( IFA ) supplementation combined with regular deworming for women of child bearing age is effective in the prevention of iron deficiency and anaemia .", "Following a baseline survey , a weekly IFA and regular deworming project was implemented in Yen Bai province , Vietnam in 2006 , and aft...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "mutation", "genetic polymorphism", "natural selection", "gene expression", "genetics", "population genetics", "biology", "evolutionary biology" ]	Strong Purifying Selection at Synonymous Sites in D. melanogaster	journal.pgen.1003527	null	[ [ "As there are 64 codons and only 20 amino acids , most amino acids can be encoded by more than a single codon .", "Mutations that alter coding sequences ( CDS ) , but do not alter amino acid sequences are referred to as synonymous mutations .", "Synonymous sites are then the collection of potential sy...	[ "Synonymous sites are generally assumed to be subject to weak selective constraint .", "For this reason , they are often neglected as a possible source of important functional variation .", "We use site frequency spectra from deep population sequencing data to show that , contrary to this expectation , 22% of f...	[ "Synonymous mutations do not alter the sequence of amino acids encoded by the gene in which they occur .", "These synonymous mutations were thus long thought to have no effect on the function of the ensuing protein or the fitness of the organism .", "At four-fold degenerate sites , every possible mutation is sy...	2013
[ "Introduction", "Design and implementation", "Results", "Availability and future directions" ]	[ "data acquisition", "engineering and technology", "rna analysis", "molecular biology techniques", "research and analysis methods", "computer and information sciences", "gene expression", "molecular biology", "molecular biology assays and analysis techniques", "programming languages", "data visua...	Exploring the single-cell RNA-seq analysis landscape with the scRNA-tools database	journal.pcbi.1006245	null	[ [ "Single-cell RNA-sequencing ( scRNA-seq ) has rapidly gained traction as an effective tool for interrogating the transcriptome at the resolution of individual cells .", "Since the first protocols were published in 2009 [1] the number of cells profiled in individual scRNA-seq experiments has increased expo...	[ "As single-cell RNA-sequencing ( scRNA-seq ) datasets have become more widespread the number of tools designed to analyse these data has dramatically increased .", "Navigating the vast sea of tools now available is becoming increasingly challenging for researchers .", "In order to better facilitate selection of...	[ "In recent years single-cell RNA-sequencing technologies have emerged that allow scientists to measure the activity of genes in thousands of individual cells simultaneously .", "This means we can start to look at what each cell in a sample is doing instead of considering an average across all cells in a sample , ...	2018
[ "Introduction", "Models and methods", "Results", "Discussion" ]	[ "epidemiological statistics", "population metrics", "infectious diseases", "medicine and health sciences", "simulation and modeling", "infectious disease epidemiology", "epidemiology", "biology and life sciences", "population biology", "spatial epidemiology", "population density", "infectious ...	A mechanistic spatio-temporal framework for modelling individual-to-individual transmission—With an application to the 2014-2015 West Africa Ebola outbreak	journal.pcbi.1005798	null	[ [ "Epidemiological data collected by traditional public health surveillance often contain relatively coarse spatial and temporal information on infected individuals .", "In recent years , the amount and resolution of the spatio-temporal data have increased vastly due to the advent of ‘digital epidemiology’ ...	[ "In recent years there has been growing availability of individual-level spatio-temporal disease data , particularly due to the use of modern communicating devices with GPS tracking functionality .", "These detailed data have been proven useful for inferring disease transmission to a more refined level than previ...	[ "Availability of individual-level , spatio-temporal disease data ( e . g . GPS locations of infected individuals ) has been increasing in recent years , primarily due to the increased use of modern communication devices such as mobile phones .", "Such data create invaluable opportunities for researchers to study ...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biochemistry", "virology/viral replication and gene regulation", "virology/virulence factors and mechanisms", "microbiology/immunity to infections", "virology/virion structure, assembly, and egress", "virology/immunodeficiency viruses", "cell biology", "microbiology/innate immunity", "immunology/in...	HIV-1 Vpu Neutralizes the Antiviral Factor Tetherin/BST-2 by Binding It and Directing Its Beta-TrCP2-Dependent Degradation	journal.ppat.1000574	null	[ [ "In order to successfully infect human cells , HIV-1 has to neutralize cellular restriction factors that impede its replication at multiple steps .", "HIV-1 Vpu serves this goal by counteracting a blockade imposed by the newly identified protein tetherin [1]–[4] .", "Under basal conditions , tetherin ...	[ "Host cells impose a broad range of obstacles to the replication of retroviruses .", "Tetherin ( also known as CD317 , BST-2 or HM1 . 24 ) impedes viral release by retaining newly budded HIV-1 virions on the surface of cells .", "HIV-1 Vpu efficiently counteracts this restriction .", "Here , we show that HIV-...	[ "To efficiently replicate in cells , HIV-1 needs to inactivate a number of intracellular host defenses .", "One such antiviral mechanism is provided by the newly identified tetherin protein .", "This factor blocks viral production by impeding the release of newly generated HIV-1 particles from the surface of ce...	2009
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "microbiology/environmental microbiology" ]	Distribution of Mycobacterium ulcerans in Buruli Ulcer Endemic and Non-Endemic Aquatic Sites in Ghana	journal.pntd.0000205	null	[ [ "Mycobacterium ulcerans is the cause of Buruli ulcer , a severe necrotizing skin infection ( Figure 1 ) .", "Although Buruli ulcer is globally distributed , it is an emerging infection primarily in Australia and West Africa [1] .", "The disease begins as a painless nodule or papule that , if left untr...	[ "Mycobacterium ulcerans , the causative agent of Buruli ulcer , is an emerging environmental bacterium in Australia and West Africa .", "The primary risk factor associated with Buruli ulcer is proximity to slow moving water .", "Environmental constraints for disease are shown by the absence of infection in arid...	[ "Buruli ulcer is an ulcerative skin disease caused by Mycobacterium ulcerans .", "Though usually not fatal , ulceration can cover up to 15% of the body , with treatment being costly and sometimes painful .", "Primary risk for Buruli ulcer in Africa is exposure to stagnant water , but the route of transmission i...	2008
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "medicine", "immune physiology", "immune cells", "cytokines", "clinical research design", "immune activation", "animal models of disease", "immunology", "anatomy and physiology", "preclinical models", "adaptive immunity", "genetics and genomics", "immunoregulation", "immunomodulation", "...	An Integrated Disease/Pharmacokinetic/Pharmacodynamic Model Suggests Improved Interleukin-21 Regimens Validated Prospectively for Mouse Solid Cancers	journal.pcbi.1002206	null	[ [ "Cancer is a multi-faceted disease , involving complex interactions between neoplastic cells and the surrounding microenvironment [1] .", "The prospect of immunotherapy , i . e . stimulating endogenous immune responses by various molecular and cellular factors , is emerging as a promising approach against...	[ "Interleukin ( IL ) -21 is an attractive antitumor agent with potent immunomodulatory functions .", "Yet thus far , the cytokine has yielded only partial responses in solid cancer patients , and conditions for beneficial IL-21 immunotherapy remain elusive .", "The current work aims to identify clinically-releva...	[ "Among the many potential drugs explored within the scope of cancer immunotherapy are selected cytokines which possess promising immune-boosting properties .", "Yet , the natural involvement of these proteins in multiple , often contradicting biological processes can complicate their use in the clinic .", "The ...	2011
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "blood cells", "medicine and health sciences", "enzyme-linked immunoassays", "immune physiology", "immune cells", "epitope mapping", "immunology", "tropical diseases", "vertebrates", "parasitic diseases", "dogs", "animals", "mammals", "neglected tropical diseases", "molecular biology tec...	Epitope mapping of recombinant Leishmania donovani virulence factor A2 (recLdVFA2) and canine leishmaniasis diagnosis using a derived synthetic bi-epitope	journal.pntd.0005562	null	[ [ "Visceral leishmaniasis ( VL ) is an infection caused by various species of Leishmania , an intracellular protozoan parasite .", "Currently , VL is among the six endemic prioritized diseases in the world [1] .", "In humans , infection with Leishmania can cause a broad spectrum of symptoms ranging from...	[ "Leishmaniasis is one of the most important zoonotic diseases spread in Latin America .", "Since many species are involved in dog infection with different clinical manifestations , the development of specific diagnostic tests is mandatory for more accurate disease control and vaccine strategies .", "Seventy-fiv...	[ "Leishmaniasis is a neglected tropical disease being among the six endemic prioritized diseases in the world .", "Visceral leishmaniasis ( VL ) is caused by Leishmania infantum and represents a serious public health problem in Brazil .", "Dogs are the main source of infection in the urban area and , in Brazil ,...	2017
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "medicine and health sciences", "ecology and environmental sciences", "water resources", "pathology and laboratory medicine", "giardia", "pathogens", "cryptosporidium", "parasitic diseases", "parasitic protozoans", "diarrhea", "protozoans", "signs and symptoms", "gastroenterology and hepatol...	Estimating Cryptosporidium and Giardia disease burdens for children drinking untreated groundwater in a rural population in India	journal.pntd.0006231	null	[ [ "Untreated groundwater is the primary source of drinking water for nearly a quarter of the world’s population and in low-income settings groundwater tubewells are widely used for drinking [1] .", "Although tubewells have been classified as an improved source of drinking water , they are susceptible to fec...	[ "In many low-income settings , despite improvements in sanitation and hygiene , groundwater sources used for drinking may be contaminated with enteric pathogens such as Cryptosporidium and Giardia , which remain important causes of childhood morbidity .", "In this study , we examined the contribution of diarrhea ...	[ "Water , sanitation , and hygiene ( WASH ) interventions aimed at reducing exposure to enteric pathogens have produced mixed health impacts , with some interventions finding no significant difference in health outcomes between intervention and control groups .", "While there are many explanations why individual W...	2018
[ "Introduction", "Methods", "Results/Discussion" ]	[ "invertebrates", "livestock", "medicine and health sciences", "pathology and laboratory medicine", "tropical diseases", "geographical locations", "fascioliasis", "parasitic diseases", "animals", "peru", "trematodes", "signs and symptoms", "pharmaceutics", "neglected tropical diseases", "...	Treatment Failure after Multiple Courses of Triclabendazole among Patients with Fascioliasis in Cusco, Peru: A Case Series	journal.pntd.0004361	null	[ [ "Fascioliasis is a worldwide zoonotic infection caused by the trematode parasite Fasciola hepatica .", "Livestock infection causes large economic losses in developed and developing countries . [1]", "Even in some wealthy countries , up to 50% of the dairy and meat herds may be infected; but data from ...	[ "Triclabendazole is reported to be highly effective in treatment of human fascioliasis .", "We present 7 of 19 selected cases of human fascioliasis referred to our center in the Cusco region of Peru that failed to respond to triclabendazole .", "These were mostly symptomatic adults of both sexes that continued ...	[ "Fascioliasis is a zoonotic food borne trematode infection with a wide distribution .", "The complex epidemiology of this infection makes control efforts difficult .", "The paucity of drugs available for treatment may further hinder their success .", "Triclabendazole , the only first line drug for Fasciola , ...	2016
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "infectious diseases/neglected tropical diseases", "public health and epidemiology/preventive medicine", "public health and epidemiology/infectious diseases", "infectious diseases/epidemiology and control of infectious diseases" ]	Evaluation of the Effectiveness of Insecticide Treated Materials for Household Level Dengue Vector Control	journal.pntd.0000994	null	[ [ "An estimated forty percent of the world's population lives at risk of contracting dengue , which currently is the most important mosquito-borne viral disease worldwide , responsible for 24 , 000 deaths , 250 , 000–500 , 000 hemorrhagic fever cases and up to 50 million dengue infections annually [1] , [2] .",...	[ "To assess the operational effectiveness of long-lasting insecticide treated materials ( ITMs ) , when used at household level , for the control of Aedes aegypti in moderately infested urban and suburban areas .", "In an intervention study , ITMs consisting of curtains and water jar-covers ( made from PermaNet ) ...	[ "An estimated 40% of the world's population lives at risk of contracting dengue , and it inflicts a significant health , economic and social burden on the populations of endemic areas .", "In the absence of a vaccine , vector control is the only available strategy to prevent transmission .", "Some control metho...	2011
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	The Role of the Mammalian DNA End-processing Enzyme Polynucleotide Kinase 3’-Phosphatase in Spinocerebellar Ataxia Type 3 Pathogenesis	journal.pgen.1004749	null	[ [ "DNA strand breaks ( SBs ) , both single-stranded ( SSBs ) and double-stranded ( DSBs ) , with various “dirty” DNA ends are among the most toxic and mutagenic lesions in mammalian genomes , because such ends block the action of DNA polymerases and DNA ligases; the conventional 3’-OH ( hydroxyl ) and 5’-P ( ph...	[ "DNA strand-breaks ( SBs ) with non-ligatable ends are generated by ionizing radiation , oxidative stress , various chemotherapeutic agents , and also as base excision repair ( BER ) intermediates .", "Several neurological diseases have already been identified as being due to a deficiency in DNA end-processing ac...	[ "We report that human polynucleotide kinase 3’-phosphatase ( PNKP ) , a major DNA strand break repair enzyme , stably associates with Ataxin-3 ( ATXN3 ) .", "This protein contains repeats of the amino acid glutamine , and the expansion of these repeats from 14–41 to 55–82 glutamines leads to a neurological disord...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biochemistry", "signal transduction", "developmental biology", "model organisms", "cell biology", "nucleic acids", "genetics", "biology and life sciences", "molecular genetics", "wnt signaling cascade", "molecular cell biology", "cell signaling", "computational biology", "signaling cascad...	Bipartite Recognition of DNA by TCF/Pangolin Is Remarkably Flexible and Contributes to Transcriptional Responsiveness and Tissue Specificity of Wingless Signaling	journal.pgen.1004591	null	[ [ "During metazoan development , Wnt/β-catenin signaling , often called “canonical” Wnt signaling and hereafter referred to as “Wnt signaling” , is required to drive multiple stage and tissue specific events [1]–[4] .", "Wnt signaling is essential in such diverse events as specification of the anterior/post...	[ "The T-cell factor ( TCF ) family of transcription factors are major mediators of Wnt/β-catenin signaling in metazoans .", "All TCFs contain a High Mobility Group ( HMG ) domain that possesses specific DNA binding activity .", "In addition , many TCFs contain a second DNA binding domain , the C-clamp , which bi...	[ "Regulation of gene expression is controlled in large part by proteins known as transcription factors , which bind to specific DNA sequences in the genome .", "The DNA binding domains of transcription factors recognize short stretches ( 5–11 base pairs ) of DNA with considerable sequence degeneracy .", "This me...	2014
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "children", "medicine and health sciences", "respiratory infections", "pathology and laboratory medicine", "geographical locations", "pulmonology", "north america", "diarrhea", "age groups", "vaccines", "research design", "signs and symptoms", "gastroenterology and hepatology", "cohort stu...	Heterogeneous susceptibility to rotavirus infection and gastroenteritis in two birth cohort studies: Parameter estimation and epidemiological implications	journal.pcbi.1007014	null	[ [ "Rotavirus is the leading source of gastrointestinal disease burden in children globally , with nearly 10 million severe cases and 193 , 000 fatalities estimated to occur annually [1] .", "One decade after their rollout in high-income settings , live oral rotavirus vaccines are currently being introduced ...	[ "Cohort studies , randomized trials , and post-licensure studies have reported reduced natural and vaccine-derived protection against rotavirus gastroenteritis ( RVGE ) in low- and middle-income countries .", "While susceptibility of children to rotavirus is known to vary within and between settings , implication...	[ "Differences in susceptibility can help explain why some individuals , and not others , acquire infection and exhibit symptoms when exposed to infectious disease agents .", "However , it is difficult to distinguish between differences in susceptibility versus exposure in epidemiological studies .", "We develope...	2019
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "developmental biology/embryology", "infectious diseases/neglected tropical diseases", "developmental biology/microbial growth and development", "cell biology/microbial growth and development", "infectious diseases/helminth infections" ]	Asymmetric Wolbachia Segregation during Early Brugia malayi Embryogenesis Determines Its Distribution in Adult Host Tissues	journal.pntd.0000758	null	[ [ "Filarial nematodes are the causative agents of human filariasis , affecting over 150 million individuals .", "The most pathogenic diseases , lymphatic filariasis and onchocerciasis , ( river blindness ) comprise a major cause of global morbidity in the tropics , with over 1 billion people at risk of thes...	[ "Wolbachia are required for filarial nematode survival and fertility and contribute to the immune responses associated with human filarial diseases .", "Here we developed whole-mount immunofluorescence techniques to characterize Wolbachia somatic and germline transmission patterns and tissue distribution in Brugi...	[ "Filarial diseases affect over 150 million people in tropical countries .", "They are caused by parasitic nematodes like Brugia malayi that rely on their endosymbiont Wolbachia for their survival and fertility .", "These bacteria are a recognized drug target in the search for treatments killing adult worms .", ...	2010
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genetics and genomics/disease models", "genetics and genomics/genetics of disease", "genetics and genomics/animal genetics" ]	A Novel Unstable Duplication Upstream of HAS2 Predisposes to a Breed-Defining Skin Phenotype and a Periodic Fever Syndrome in Chinese Shar-Pei Dogs	journal.pgen.1001332	null	[ [ "Shar-Pei dogs have been companion animals for centuries within China where they were commissioned to guard and hunt , and to sometimes serve as fighting animals .", "At the beginning of the communist era dog ownership was highly taxed and the breed was brought close to extinction .", "A few Chinese S...	[ "Hereditary periodic fever syndromes are characterized by recurrent episodes of fever and inflammation with no known pathogenic or autoimmune cause .", "In humans , several genes have been implicated in this group of diseases , but the majority of cases remain unexplained .", "A similar periodic fever syndrome ...	[ "Shar-Pei dogs have two unique features: a breed defining “wrinkled” skin phenotype and a genetic disorder called Familial Shar-Pei Fever ( FSF ) .", "The wrinkled phenotype is strongly selected for and is the result of excessive hyaluronan ( HA ) deposited in the skin .", "HA is a molecule that may behave in a...	2011
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "sequencing techniques", "sequence analysis", "mutation", "infectious diseases", "medicine and health sciences", "personalized medicine", "genetics", "biology and life sciences", "population genetics", "molecular biology techniques", "computational biology", "evolutionary biology", "viral di...	Analysis of Stop-Gain and Frameshift Variants in Human Innate Immunity Genes	journal.pcbi.1003757	null	[ [ "There is considerable variability in the human immune response to pathogens .", "The observation of genetic causes of a number of primary immunodeficiencies underscores the fundamental role of variants in immune genes - in many cases resulting in severe , pathogen-specific disorders [1] .", "A main c...	[ "Loss-of-function variants in innate immunity genes are associated with Mendelian disorders in the form of primary immunodeficiencies .", "Recent resequencing projects report that stop-gains and frameshifts are collectively prevalent in humans and could be responsible for some of the inter-individual variability ...	[ "There are well-characterized severe immunodeficiencies associated with loss-of-function variants in innate immunity genes .", "Genome sequencing projects identify rare stop-gain and frameshift variants in innate immunity genes whose phenotype is uncharacterized .", "Current methods to estimate the severity of ...	2014
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "genetics and genomics/microbial evolution and genomics", "genetics and genomics/gene discovery", "infectious diseases", "genetics and genomics/gene expression" ]	Identification of the Regulatory Logic Controlling Salmonella Pathoadaptation by the SsrA-SsrB Two-Component System	journal.pgen.1000875	null	[ [ "Precise gene regulation is crucial to the successful activation and execution of virulence programs for all pathogenic organisms .", "The acquisition of genes through horizontal gene transfer , a widespread means of bacterial evolution [1] , requires a process to integrate new coding sequence into pre-ex...	[ "Sequence data from the past decade has laid bare the significance of horizontal gene transfer in creating genetic diversity in the bacterial world .", "Regulatory evolution , in which non-coding DNA is mutated to create new regulatory nodes , also contributes to this diversity to allow niche adaptation and the e...	[ "All organisms have a means to control gene expression ensuring correct spatiotemporal deployment of gene products .", "In bacteria , gene control presents a challenge because one species can reside in multiple niches , requiring them to coordinate gene expression with environmental sensing .", "Also , widespre...	2010
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "kala-azar", "medicine and health sciences", "immune physiology", "pathology and laboratory medicine", "antiviral therapy", "pathogens", "spleen", "immunology", "tropical diseases", "microbiology", "parasitic diseases", "parasitology", "retroviruses", "viruses", "preventive medicine", ...	The initial effectiveness of liposomal amphotericin B (AmBisome) and miltefosine combination for treatment of visceral leishmaniasis in HIV co-infected patients in Ethiopia: A retrospective cohort study	journal.pntd.0006527	null	[ [ "Visceral leishmaniasis ( VL ) is a protozoan infection caused by the Leishmania donovani species complex [1] .", "In East Africa and the Indian subcontinent , it is caused by L . donovani , whereas in the Mediterranean region and South America , by L . infantum [2] .", "Ethiopia is among the top six ...	[ "North-west Ethiopia faces the highest burden world-wide of visceral leishmaniasis ( VL ) and HIV co-infection .", "VL-HIV co-infected patients have higher ( initial ) parasitological failure and relapse rates than HIV-negative VL patients .", "Whereas secondary prophylaxis reduces the relapse rate , parasitolo...	[ "North-west Ethiopia faces the highest burden world-wide of visceral leishmaniasis ( VL ) and HIV co-infection .", "VL treatment outcomes in HIV co-infected patients are associated with high initial treatment ( parasitological ) failure and recurrence rates after cure ( relapse ) .", "With secondary chemoprophy...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine and health sciences", "pathology and laboratory medicine", "gene regulation", "enzymes", "protein interaction networks", "rna extraction", "enzymology", "cloning", "immunoprecipitation", "network analysis", "molecular biology techniques", "ligases", "extraction techniques", "rese...	Comparative Proteomics Reveals Strain-Specific β-TrCP Degradation via Rotavirus NSP1 Hijacking a Host Cullin-3-Rbx1 Complex	journal.ppat.1005929	null	[ [ "β-transducin repeat-containing protein ( β-TrCP , encoded by BTRC ) is the core substrate recognition component of the Skp1-Cul1-F-box ( SCF ) β-TrCP E3 ubiquitin ligase complex , which plays essential roles in a variety of biological processes , including apoptosis , cell cycle , carcinogenesis and innate i...	[ "Rotaviruses ( RVs ) are the leading cause of severe gastroenteritis in young children , accounting for half a million deaths annually worldwide .", "RV encodes non-structural protein 1 ( NSP1 ) , a well-characterized interferon ( IFN ) antagonist , which facilitates virus replication by mediating the degradation...	[ "Rotaviruses ( RVs ) are the leading cause of diarrhea in young children and lead to over 215 , 000 deaths annually worldwide .", "For virtually every mammal , there are RV strains specifically adapted to replicate efficiently in that host species .", "The success of RV , to a large extent , derives from its ex...	2016
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "medicine", "immunology", "microbiology", "host-pathogen interaction", "parasitic diseases", "parastic protozoans", "leishmania", "global health", "neglected tropical diseases", "immunoregulation", "immunomodulation", "immunotherapy", "infectious diseases", "biology", "immune response", ...	Therapeutic Enhancement of Protective Immunity during Experimental Leishmaniasis	journal.pntd.0001316	null	[ [ "Protozoa of the genus Leishmania cause a wide spectrum of human disease [1] .", "At the severe end of the spectrum , visceral leishmaniasis ( kala azar ) , due to disseminated parasitism of macrophages and dendritic cells , causes an annual mortality of approximately 50 , 000 , largely in India and Sudan...	[ "Leishmaniasis remains a significant cause of morbidity and mortality in the tropics .", "Available therapies are problematic due to toxicity , treatment duration and emerging drug resistance .", "Mouse models of leishmaniasis have demonstrated that disease outcome depends critically on the balance between effe...	[ "Leishmaniasis is an infectious disease that causes a large burden of morbidity and mortality in the tropics .", "Caused by protozoan parasites of the genus Leishmania that are transmitted by sandflies , leishmaniasis causes a wide spectrum of human disease .", "The severe end of the spectrum , visceral leishma...	2011
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biochemistry", "proteins", "protein structure", "biology and life sciences", "dna-binding proteins", "computational biology", "biophysics", "biophysical simulations" ]	Communication Routes in ARID Domains between Distal Residues in Helix 5 and the DNA-Binding Loops	journal.pcbi.1003744	null	[ [ "ARID3A is a member of the ARID ( AT-rich interactive domain ) family of transcription factors and is also known as “dead ringer-like protein 1” ( Dril1 ) , “B-cell regulator of IgH transcription” ( Bright ) and “E2F-binding protein 1” ( E2FBP1 ) .", "The ARID family is a family of DNA-binding proteins wi...	[ "ARID is a DNA-binding domain involved in several transcriptional regulatory processes , including cell-cycle regulation and embryonic development .", "ARID domains are also targets of the Human Cancer Protein Interaction Network .", "Little is known about the molecular mechanisms related to conformational chan...	[ "Regulation of DNA transcription is a key element for the cell to finely regulate its physiological processes .", "This is acquired by the use of a special class of proteins that bind to DNA and function as transcriptional regulators .", "ARID domains are responsible for many of these DNA-protein interactions i...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "inflammation", "immunity", "virology", "innate immunity", "immunology", "biology", "microbiology" ]	Type I IFN Triggers RIG-I/TLR3/NLRP3-dependent Inflammasome Activation in Influenza A Virus Infected Cells	journal.ppat.1003256	null	[ [ "Influenza A virus ( IAV ) is the etiological agent of a contagious acute respiratory disease .", "Its seasonal and , more rarely , pandemic strains – such as the deadly 1918 H1N1 virus , are responsible for severe illness and considerable mortality worldwide [1] , [2] .", "The outcome of IAV infectio...	[ "Influenza A virus ( IAV ) triggers a contagious and potentially lethal respiratory disease .", "A protective IL-1β response is mediated by innate receptors in macrophages and lung epithelial cells .", "NLRP3 is crucial in macrophages; however , which sensors elicit IL-1β secretion in lung epithelial cells rema...	[ "Although epithelial cells lining our respiratory tract are both the primary targets of influenza A virus ( IAV ) infection and major players in the outcome of this infection , we still have an imperfect understanding of their response to the virus .", "Such knowledge is important to design proper anti-influenza ...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biochemistry/bioinformatics", "microbiology/cellular microbiology and pathogenesis", "microbiology/immunity to infections" ]	Fis Is Essential for Capsule Production in Pasteurella multocida and Regulates Expression of Other Important Virulence Factors	journal.ppat.1000750	null	[ [ "Pasteurella multocida is an important veterinary pathogen of worldwide economic significance; it is the causative agent of a range of diseases , including fowl cholera in poultry , hemorrhagic septicemia in ungulates and atrophic rhinitis in swine .", "P . multocida is a heterogeneous species , and is ge...	[ "P . multocida is the causative agent of a wide range of diseases of animals , including fowl cholera in poultry and wild birds .", "Fowl cholera isolates of P . multocida generally express a capsular polysaccharide composed of hyaluronic acid .", "There have been reports of spontaneous capsule loss in P . mult...	[ "Pasteurella multocida is an animal pathogen of worldwide economic significance .", "It causes fowl cholera in wild birds and poultry , hemorrhagic septicemia in ungulates , and atrophic rhinitis in swine .", "The major virulence factor in fowl cholera-causing isolates is the polysaccharide capsule , which is c...	2010
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "sequencing techniques", "medicine and health sciences", "pathology and laboratory medicine", "chromosome structure and function", "centromeres", "pathogens", "microbiology", "fungi", "model organisms", "molecular biology techniques", "fungal pathogens", "schizosaccharomyces", "research and ...	Repeat-Associated Fission Yeast-Like Regional Centromeres in the Ascomycetous Budding Yeast Candida tropicalis	journal.pgen.1005839	null	[ [ "The high fidelity segregation of replicated chromosomes to daughter cells during cell division is essential in maintaining genome integrity .", "It is achieved by a dynamic and well-coordinated kinetochore-microtubule interaction on a specialized chromosomal element , known as the centromere .", "Str...	[ "The centromere , on which kinetochore proteins assemble , ensures precise chromosome segregation .", "Centromeres are largely specified by the histone H3 variant CENP-A ( also known as Cse4 in yeasts ) .", "Structurally , centromere DNA sequences are highly diverse in nature .", "However , the evolutionary c...	[ "Centromeres aid in high fidelity chromosome segregation .", "Paradoxically , centromere DNA sequences are rapidly evolving in fungi , plants , and animals .", "Centromere DNA sequences in fungi can be unique in each chromosome or share conserved features such as motifs for sequence specific protein binding , p...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Identification and Functional Characterization of G6PC2 Coding Variants Influencing Glycemic Traits Define an Effector Transcript at the G6PC2-ABCB11 Locus	journal.pgen.1004876	null	[ [ "Large-scale GWAS of non-diabetic individuals have successfully identified > 60 loci associated with FG and FI levels , many of which are also implicated in susceptibility to T2D [1 , 2 , 3 , 4] .", "Despite these successes , lead SNPs at GWAS loci have modest effects and cumulatively explain only a small...	[ "Genome wide association studies ( GWAS ) for fasting glucose ( FG ) and insulin ( FI ) have identified common variant signals which explain 4 . 8% and 1 . 2% of trait variance , respectively .", "It is hypothesized that low-frequency and rare variants could contribute substantially to unexplained genetic varianc...	[ "Understanding how FI and FG levels are regulated is important because their derangement is a feature of T2D .", "Despite recent success from GWAS in identifying regions of the genome influencing glycemic traits , collectively these loci explain only a small proportion of trait variance .", "Unlocking the biolo...	2015
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "amphibian genomics", "taxonomy", "invertebrate genomics", "phylogenetics", "data management", "phylogenetic analysis", "genome analysis", "research and analysis methods", "sequence analysis", "genomic libraries", "computer and information sciences", "sequence alignment", "bioinformatics", ...	Hybridization and polyploidy enable genomic plasticity without sex in the most devastating plant-parasitic nematodes	journal.pgen.1006777	null	[ [ "Fully asexual reproduction occurs in only ~0 . 1% of animal lineages , which generally occupy shallow branches in the tree of life [1 , 2] .", "Although there are some exceptions [3–5] , the majority of asexual lineages of animals seem to be recently derived from sexual lineages , suggesting they are gen...	[ "Root-knot nematodes ( genus Meloidogyne ) exhibit a diversity of reproductive modes ranging from obligatory sexual to fully asexual reproduction .", "Intriguingly , the most widespread and devastating species to global agriculture are those that reproduce asexually , without meiosis .", "To disentangle this su...	[ "Sexual reproduction is evolutionary successful in animals as more than 99% of species reproduce sexually .", "The few animals that have abandoned sex are usually believed to be short-lived and outcompeted by their sexual relatives .", "Yet , in the root-knot nematodes , plant pests of global economic importanc...	2017
[ "Introduction", "Design and Implementation", "Results" ]	[ "biodiversity", "ecology", "biology and life sciences", "computational biology" ]	A RESTful API for Accessing Microbial Community Data for MG-RAST	journal.pcbi.1004008	null	[ [ "Over 110 , 000 metagenomic data sets have been uploaded and analyzed in MG-RAST [1] since 2007 , totaling over 43 Terabases ( TBp ) .", "Data uploaded falls in three classes: shotgun metagenomic data , amplicon data , and , more recently , metatranscriptomic data .", "The MG-RAST pipeline normalizes ...	[ "Metagenomic sequencing has produced significant amounts of data in recent years .", "For example , as of summer 2013 , MG-RAST has been used to annotate over 110 , 000 data sets totaling over 43 Terabases .", "With metagenomic sequencing finding even wider adoption in the scientific community , the existing we...	[ "Metagenomic sequencing has produced significant amounts of data in recent years .", "For example , as of summer 2013 , the MG-RAST metagenomics analysis system has been used to annotate over 110 , 000 data sets totaling over 43 Terabases .", "With metagenomic sequencing finding even wider adoption in the scien...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "dictyostelium discoideum", "model organisms", "protozoan models", "biology", "evolutionary biology", "microbiology", "evolutionary genetics" ]	A Simple Mechanism for Complex Social Behavior	journal.pbio.1001039	null	[ [ "Despite the appearance of cooperation in many social systems , natural selection will generally favor exploitative individuals that can maximize fitness by performing less of a costly cooperative act while maintaining the benefits accrued from the cooperative behavior of others .", "The evolution and mai...	[ "The evolution of cooperation is a paradox because natural selection should favor exploitative individuals that avoid paying their fair share of any costs .", "Such conflict between the self-interests of cooperating individuals often results in the evolution of complex , opponent-specific , social strategies and ...	[ "Despite the appearance of cooperation in nature , selection should often favor exploitative individuals who perform less of any cooperative behaviors while maintaining the benefits accrued from the cooperative behavior of others .", "This conflict of interest among cooperating individuals can lead to the evoluti...	2011
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "invertebrates", "medicine and health sciences", "reactive oxygen species", "gene regulation", "animals", "animal models", "c-jun n-terminal kinase signaling cascade", "developmental biology", "drosophila melanogaster", "model organisms", "organism development", "experimental organism systems"...	The Drosophila Duox maturation factor is a key component of a positive feedback loop that sustains regeneration signaling	journal.pgen.1006937	null	[ [ "The capacity to regenerate damaged or lost organs or limbs is significantly greater in some animals than others .", "The use of model organisms with varying degrees of regenerative capacity , from whole-body regeneration in planaria and hydra , to limb regeneration in amphibians , organ and fin regenerat...	[ "Regenerating tissue must initiate the signaling that drives regenerative growth , and sustain that signaling long enough for regeneration to complete .", "How these key signals are sustained is unclear .", "To gain a comprehensive view of the changes in gene expression that occur during regeneration , we perfo...	[ "Regenerating tissue must initiate the signaling that drives regenerative growth , and then sustain that signaling long enough for regeneration to complete .", "Drosophila imaginal discs , the epithelial structures in the larva that will form the adult animal during metamorphosis , have been an important model sy...	2017
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "blood cells", "medicine and health sciences", "immune cells", "pathology and laboratory medicine", "intracellular pathogens", "pathogens", "immunology", "cell processes", "microbiology", "light microscopy", "pseudomonas aeruginosa", "physiological processes", "microscopy", "bacteria", "...	Killing from the inside: Intracellular role of T3SS in the fate of Pseudomonas aeruginosa within macrophages revealed by mgtC and oprF mutants	journal.ppat.1007812	null	[ [ "Pathogenic bacteria are commonly classified as intracellular or extracellular pathogens [1] .", "Intracellular bacterial pathogens , such as Mycobacterium tuberculosis or Salmonella enterica , can replicate within host cells , including macrophages .", "In contrast , extracellular pathogens , such as...	[ "While considered solely an extracellular pathogen , increasing evidence indicates that Pseudomonas aeruginosa encounters intracellular environment in diverse mammalian cell types , including macrophages .", "In the present study , we have deciphered the intramacrophage fate of wild-type P . aeruginosa PAO1 strai...	[ "The ability of professional phagocytes to ingest and kill microorganisms is central to host defense and Pseudomonas aeruginosa has developed mechanisms to avoid being killed by phagocytes .", "While considered an extracellular pathogen , P . aeruginosa has been reported to be engulfed by macrophages in animal mo...	2019
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "medicine and health sciences", "gene regulation", "regulatory proteins", "neuronal differentiation", "dna-binding proteins", "social sciences", "cloning", "neuroscience", "pigments", "cell differentiation", "dna transcription", "developmental biology", "materials science", "transcription ...	Glass promotes the differentiation of neuronal and non-neuronal cell types in the Drosophila eye	journal.pgen.1007173	null	[ [ "Cell fate specification is achieved by integrating extrinsic signals with intrinsic transcriptional and epigenetic networks [1–3] .", "Certain transcription factors have been described as “master regulators” for their ability to specify entire organs [4–6] , while downstream “terminal selectors” activate...	[ "Transcriptional regulators can specify different cell types from a pool of equivalent progenitors by activating distinct developmental programs .", "The Glass transcription factor is expressed in all progenitors in the developing Drosophila eye , and is maintained in both neuronal and non-neuronal cell types .",...	[ "Distinct cell types within an organ are specified by the activity of cell type-specific transcription factors , which activate distinct gene networks that confer the appropriate cellular identities .", "The Drosophila eye is derived from a field of equivalent progenitors that develop into photoreceptor neurons a...	2018
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[]	Animal Reservoirs of Zoonotic Tungiasis in Endemic Rural Villages of Uganda	journal.pntd.0004126	null	[ [ "Tungiasis is an ectoparasitosis that accrues from the penetration of female sand fleas into the skin .", "Tunga penetrans [1] and Tunga trimamillata [2] are the only species known to cause tungiasis in both humans and animals .", "Currently , zoonotic tungiasis is endemic in southern America , the Ca...	[ "Animal tungiasis is believed to increase the prevalence and parasite burden in humans .", "Animal reservoirs of Tunga penetrans differ among endemic areas and their role in the epidemiology of tungiasis had never been investigated in Uganda .", "To identify the major animal reservoirs of Tunga penetrans and th...	[ "Tungiasis is a neglected skin disease , frequent in resource-poor communities in the tropics .", "It is caused by sand fleas ( also called jigger fleas ) which burrow in the skin of humans and animals .", "Tungiasis can cause physical disabilities and the associated wounds facilitate entry of pathogens includi...	2015
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "blood cells", "cell death", "urinary system procedures", "medicine and health sciences", "organ transplantation", "immune cells", "immune physiology", "enzyme-linked immunoassays", "viral transmission and infection", "immunology", "cell processes", "microbiology", "surgical and invasive med...	Differential T cell response against BK virus regulatory and structural antigens: A viral dynamics modelling approach	journal.pcbi.1005998	null	[ [ "In the last years , BK virus-associated nephropathy ( BKVN ) has become the most challenging infectious cause of renal graft dysfunction in kidney transplant , leading to graft failure in over 50% of cases [1 , 2] .", "The rise in BKVN incidence has been attributed , at least to some degree , to the incr...	[ "BK virus ( BKV ) associated nephropathy affects 1–10% of kidney transplant recipients , leading to graft failure in about 50% of cases .", "Immune responses against different BKV antigens have been shown to have a prognostic value for disease development .", "Data currently suggest that the structural antigens...	[ "BK virus ( BKV ) is the cause of a kidney disease affecting 1–10% of kidney transplant recipients , which leads to transplantation failure in about 50% of the cases .", "This disease is not well understood , but there are indications that markers of the immune response against BKV can be used to predict the outc...	2018
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "medicine and health sciences", "pathology and laboratory medicine", "ears", "immunology", "animal models", "middle ear", "developmental biology", "otology", "model organisms", "organism development", "signs and symptoms", "experimental organism systems", "skeleton", "lung development", ...	A mutation in Nischarin causes otitis media via LIMK1 and NF-κB pathways	journal.pgen.1006969	null	[ [ "Otitis media ( OM ) is characterised by inflammation of the middle ear ( ME ) , often associated with a conductive hearing impairment , and is the commonest cause of hearing loss in children .", "It is perceived by many to be a transient affliction that in reality places a substantial social , medical an...	[ "Otitis media ( OM ) , inflammation of the middle ear ( ME ) , is a common cause of conductive hearing impairment .", "Despite the importance of the disease , the aetiology of chronic and recurrent forms of middle ear inflammatory disease remains poorly understood .", "Studies of the human population suggest th...	[ "Otitis media ( OM ) is the most common cause of deafness in children and is primarily characterised by inflammation of the middle ear .", "It is the most common cause of surgery in children in the developed world , with many children developing recurrent and chronic forms of OM undergoing tympanostomy tube inser...	2017
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "genetics", "biology and life sciences", "human genetics" ]	Genetic Predisposition to In Situ and Invasive Lobular Carcinoma of the Breast	journal.pgen.1004285	null	[ [ "Invasive lobular breast cancer ( ILC ) accounts for 10–15% of all invasive breast carcinomas and it has distinct etiological , clinical and biological characteristics compared with the more common invasive ductal/no special type carcinoma ( IDC ) [1] .", "Lobular cancers show stronger associations with t...	[ "Invasive lobular breast cancer ( ILC ) accounts for 10–15% of all invasive breast carcinomas .", "It is generally ER positive ( ER+ ) and often associated with lobular carcinoma in situ ( LCIS ) .", "Genome-wide association studies have identified more than 70 common polymorphisms that predispose to breast can...	[ "Invasive lobular breast cancer ( ILC ) accounts for 10–15% of invasive breast cancer and is generally ER positive ( ER+ ) .", "To date , none of the genome-wide association studies that have identified loci that predispose to breast cancer in general or to ER+ or ER-negative breast cancer have focused on lobular...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "chitin", "cell physiology", "g1 phase", "cell cycle and cell division", "cell processes", "mitosis", "fungi", "model organisms", "materials science", "cytokinesis", "macromolecules", "cellular structures and organelles", "materials by structure", "saccharomyces", "research and analysis ...	Ingression Progression Complexes Control Extracellular Matrix Remodelling during Cytokinesis in Budding Yeast	journal.pgen.1005864	null	[ [ "Eukaryotic cells divide their cytoplasm at the end of mitosis in a highly regulated process called cytokinesis , which safeguards inheritance of the genome and organelles by the two daughter cells .", "The failure of cell division results in the formation of genetically unstable tetraploid cells , which ...	[ "Eukaryotic cells must coordinate contraction of the actomyosin ring at the division site together with ingression of the plasma membrane and remodelling of the extracellular matrix ( ECM ) to support cytokinesis , but the underlying mechanisms are still poorly understood .", "In eukaryotes , glycosyltransferases...	[ "Cytokinesis is the process by which a cell divides in two and occurs once cells have replicated and segregated their chromosomes .", "Eukaryotic cells assemble a molecular machine called the actomyosin ring that drives cytokinesis .", "Contraction of the actomyosin ring is coupled to ingression of the plasma m...	2016
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "medicine and health sciences", "decision making", "reaction time", "brain", "vertebrates", "social sciences", "neuroscience", "animals", "mammals", "primates", "cognitive neuroscience", "cognitive psychology", "cognition", "monkeys", "animal cells", "basal ganglia", "neostriatum", ...	A probabilistic, distributed, recursive mechanism for decision-making in the brain	journal.pcbi.1006033	null	[ [ "Decisions rely on evidence that is collected for , accumulated about , and contrasted between available options .", "Neural activity consistent with evidence accumulation over time has been reported in parietal and frontal sensorimotor cortex [1–5] , and in the subcortical striatum [6 , 7] .", "What ...	[ "Decision formation recruits many brain regions , but the procedure they jointly execute is unknown .", "Here we characterize its essential composition , using as a framework a novel recursive Bayesian algorithm that makes decisions based on spike-trains with the statistics of those in sensory cortex ( MT ) .", ...	[ "Decision-making is central to cognition .", "Abnormally-formed decisions characterize disorders like over-eating , Parkinson’s and Huntington’s diseases , OCD , addiction , and compulsive gambling .", "Yet , a unified account of decision-making has , hitherto , remained elusive .", "Here we show the essentia...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods", "Supporting Information" ]	[ "dermatology", "mammals", "horse", "eukaryotes", "vertebrates", "animals", "genetics and genomics" ]	Allelic Heterogeneity at the Equine KIT Locus in Dominant White (W) Horses	journal.pgen.0030195	null	[ [ "Dominant white ( W ) is an autosomal dominant trait that is characterized by coat depigmentation of variable extent .", "Caused by the absence of melanocytes from the depigmented skin areas , expressivity can range from ∼50% depigmented areas up to a nearly completely white coat .", "In contrast to h...	[ "White coat color has been a highly valued trait in horses for at least 2 , 000 years .", "Dominant white ( W ) is one of several known depigmentation phenotypes in horses .", "It shows considerable phenotypic variation , ranging from ∼50% depigmented areas up to a completely white coat .", "In the horse , th...	[ "White horses have always been highly valued by their human owners .", "Their important role in history is reflected by their widespread use as heraldic animals ( e . g . , on the flags of the German states of Lower Saxony and North Rhine-Westphalia ) .", "In the Swiss Franches-Montagnes Horse population , a co...	2007
[ "Introduction", "Results", "Discussion", "Materials and Methods", "Supporting Information" ]	[ "ecology", "arthropods", "eukaryotes", "evolutionary biology", "drosophila", "neuroscience", "animals", "genetics and genomics", "insects" ]	Odorant-Binding Proteins OBP57d and OBP57e Affect Taste Perception and Host-Plant Preference in Drosophila sechellia	journal.pbio.0050118	Hybrids ofDrosophila melanogaster mutants andD. sechellia reveal genes involved in the behavioral difference that makessechellia specialized to its host plant, with implications for understanding plant-herbivore interactions and speciation.	[ [ "Every animal must locate and identify sufficient food to meet its biological requirements .", "For herbivorous insects , this results in an endless battle with their host plants [1] .", "For example , some plants develop a chemical defense system that causes toxicity to generalist herbivores [2] .", ...	[ "Despite its morphological similarity to the other species in the Drosophila melanogaster species complex , D . sechellia has evolved distinct physiological and behavioral adaptations to its host plant Morinda citrifolia , commonly known as Tahitian Noni .", "The odor of the ripe fruit of M . citrifolia originate...	[ "Most herbivorous insects specialize on one or a few host plants; understanding the processes and genetics underlying this specialization has broad implications across biology .", "Drosophila sechellia , a fruit fly endemic to the Seychelles , feeds exclusively on the ripe fruit of Morinda citrifolia , a tropical...	2007
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Inhibition of the Smc5/6 Complex during Meiosis Perturbs Joint Molecule Formation and Resolution without Significantly Changing Crossover or Non-crossover Levels	journal.pgen.1003898	null	[ [ "Meiosis is the cell division by which haploid gametes are created in sexually reproducing organisms .", "It is specialized to preserve the chromosome number among generations and to create genetic diversity in a population .", "Meiosis begins with the replication of each homologous parental chromosom...	[ "Meiosis is a specialized cell division used by diploid organisms to form haploid gametes for sexual reproduction .", "Central to this reductive division is repair of endogenous DNA double-strand breaks ( DSBs ) induced by the meiosis-specific enzyme Spo11 .", "These DSBs are repaired in a process called homolo...	[ "Most eukaryotic cells are diploid , which means that they contain two copies of each chromosome – one from each parent .", "In order to preserve the chromosome number from generation to generation , diploid organisms employ a process called meiosis to form gametes containing only one copy of each chromosome .", ...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine", "infectious diseases", "veterinary diseases", "vector biology", "neglected tropical diseases", "protozoology", "biology", "microbiology", "parasitic diseases", "veterinary science" ]	The Influence of Sex and Fly Species on the Development of Trypanosomes in Tsetse Flies	journal.pntd.0001515	null	[ [ "During transmission of a pathogen , selection in the invertebrate vector may be of profound importance in dictating which pathogen genotypes are most prevalent in mammalian hosts .", "This evolutionary pressure can select for particular combinations of pathogen and vector species , and weed out less fit ...	[ "Unlike other dipteran disease vectors , tsetse flies of both sexes feed on blood and transmit pathogenic African trypanosomes .", "During transmission , Trypanosoma brucei undergoes a complex cycle of proliferation and development inside the tsetse vector , culminating in production of infective forms in the sal...	[ "In tropical Africa human and livestock diseases caused by parasitic trypanosomes are transmitted by bloodsucking tsetse flies .", "In the fly , trypanosomes undergo a complex cycle of proliferation and development during their remarkable journey from the midgut to the salivary glands .", "At every step of the ...	2012
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "livestock", "medicine and health sciences", "ecology and environmental sciences", "ecological niches", "pathology and laboratory medicine", "pathogens", "population dynamics", "bacillus", "microbiology", "geographical locations", "australia", "bacterial diseases", "farms", "population bio...	Redefining the Australian Anthrax Belt: Modeling the Ecological Niche and Predicting the Geographic Distribution of Bacillus anthracis	journal.pntd.0004689	null	[ [ "Anthrax is a zoonotic disease caused by Bacillus anthracis , an aerobic , gram-positive spore-forming bacterium .", "Bacillus anthracis primarily affects herbivores; though most warmed-blooded mammals may be susceptible [1] , including humans .", "Anthrax is an ancient disease that has caused losses ...	[ "The ecology and distribution of B . anthracis in Australia is not well understood , despite the continued occurrence of anthrax outbreaks in the eastern states of the country .", "Efforts to estimate the spatial extent of the risk of disease have been limited to a qualitative definition of an anthrax belt extend...	[ "This study explores the spatial ecology of Bacillus anthracis , the causative agent of anthrax disease , in Australia .", "Globally , anthrax is a neglected zoonotic disease that primarily affect herbivores and incidentally humans and all warm-blooded animals .", "Here , we used historic anthrax outbreaks for ...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "protozoan classification", "immune cells", "immunology", "microbiology", "host-pathogen interaction", "parasitology", "immune defense", "immunoregulation", "inflammation", "biology", "pathogenesis", "immune response", "immunopathology", "immunity", "protozoology" ]	IL-27 Receptor Signalling Restricts the Formation of Pathogenic, Terminally Differentiated Th1 Cells during Malaria Infection by Repressing IL-12 Dependent Signals	journal.ppat.1003293	null	[ [ "IL-27 , a member of the IL-12 super-family , was initially described as a Th1 polarising cytokine due to its ability to increase the sensitivity of CD4+ T cells to IL-12 and to promote T-bet expression [Reviewed 1 , 2] .", "More recently , however , IL-27 has been shown to exert diverse suppressive effec...	[ "The IL-27R , WSX-1 , is required to limit IFN-γ production by effector CD4+ T cells in a number of different inflammatory conditions but the molecular basis of WSX-1-mediated regulation of Th1 responses in vivo during infection has not been investigated in detail .", "In this study we demonstrate that WSX-1 sign...	[ "The cytokine interleukin 27 ( IL-27 ) , a member of the IL-12 family , is produced by cells of the innate immune system and has been shown to exert mainly suppressive effects during a wide range of inflammatory conditions , including malaria infection , where it suppresses the development of CD4+ T cell-dependent ...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "infectious diseases/infectious diseases of the nervous system", "virology/viral replication and gene regulation", "cell biology/cell signaling", "virology/immunodeficiency viruses", "virology/viruses and cancer", "virology/immune evasion", "virology/effects of virus infection on host gene expression", ...	HTLV-1 Evades Type I Interferon Antiviral Signaling by Inducing the Suppressor of Cytokine Signaling 1 (SOCS1)	journal.ppat.1001177	null	[ [ "Infection with the Human T cell Leukemia Virus type I ( HTLV-I ) can result in a number of disorders , including the aggressive T cell malignancy Adult T cell Leukemia ( ATL ) and the chronic , progressive neurologic disorder termed HTLV-1-associated myelopathy/tropical spastic paraparesis ( HAM/TSP ) [1] , ...	[ "Human T cell leukemia virus type 1 ( HTLV-1 ) is the etiologic agent of Adult T cell Leukemia ( ATL ) and the neurological disorder HTLV-1-associated myelopathy/tropical spastic paraparesis ( HAM/TSP ) .", "Although the majority of HTLV-1–infected individuals remain asymptomatic carriers ( AC ) during their life...	[ "Infection with HTLV-1 leads to the development of Adult T cell Leukemia ( ATL ) or the neurological disorder HTLV-1-associated myelopathy/tropical spastic paraparesis ( HAM/TSP ) .", "Although the majority of HTLV-1–infected individuals remain asymptomatic carriers ( AC ) during their lifetime , 2–5% will develo...	2010

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