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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", "Methods", "Results", "Discussion" ]	[ "public health and epidemiology/global health", "public health and epidemiology/infectious diseases" ]	A Community-Based Study of Factors Associated with Continuing Transmission of Lymphatic Filariasis in Leogane, Haiti	journal.pntd.0000640	null	[ [ "Lymphatic filariasis ( LF ) is a mosquito-transmitted parasitic disease that is ranked by the World Health Organization ( WHO ) as a leading cause of permanent disability worldwide .", "LF affects an estimated 120 million people in 81 countries , with over 1 billion , or one-fifth of the world's populati...	[ "Seven rounds of mass drug administration ( MDA ) have been administered in Leogane , Haiti , an area hyperendemic for lymphatic filariasis ( LF ) .", "Sentinel site surveys showed that the prevalence of microfilaremia was reduced to <1% from levels as high as 15 . 5% , suggesting that transmission had been reduc...	[ "Lymphatic filariasis ( LF ) is a mosquito-borne parasitic disease that affects an estimated 120 million people worldwide with over 1 billion at risk for infection .", "LF is considered to be a leading cause of permanent disability worldwide due to the clinical manifestations of the disease .", "A global effort...	2010
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "infectious diseases/helminth infections", "infectious diseases/epidemiology and control of infectious diseases", "mathematics/statistics" ]	Individual Predisposition, Household Clustering and Risk Factors for Human Infection with Ascaris lumbricoides: New Epidemiological Insights	journal.pntd.0001047	null	[ [ "Much of our understanding of the epidemiology of Ascaris lumbricoides infections of humans has been acquired from the analysis of worm counts collected from infected individuals .", "The only practical way of obtaining such data is by chemo-expulsion .", "This procedure is best performed using anthel...	[ "Much of our current understanding of the epidemiology of Ascaris lumbricoides infections in humans has been acquired by analyzing worm count data .", "These data are collected by treating infected individuals with anthelmintics so that worms are expelled intact from the gastrointestinal tract .", "Analysis of ...	[ "Numerous analyses have found that people infected with roundworm ( Ascaris lumbricoides ) are predisposed to harbor either many or few worms .", "Members of the same household also tend to harbor similar numbers of worms .", "These phenomena are called individual predisposition and household clustering respect...	2011
[ "Introduction", "Materials and methods", "Results", "Discussion", "Conclusion" ]	[ "medicine and health sciences", "ecology and environmental sciences", "water resources", "pathology and laboratory medicine", "pathogens", "vibrio", "immunology", "tropical diseases", "geographical locations", "microbiology", "health care", "vaccines", "north america", "bacterial diseases"...	Controlling cholera in the Ouest Department of Haiti using oral vaccines	journal.pntd.0005482	null	[ [ "Since the introduction of toxigenic Vibrio cholerae O1 to Haiti in October 2010 , an altered El Tor biotype has spread throughout the country causing over 750 , 000 cases and resulted in the largest national cholera epidemic in recent history [1] [2] [3] .", "Six years later , cholera transmission contin...	[ "Following the 2010 cholera outbreak in Haiti , a plan was initiated to provide massive improvements to the sanitation and drinking water infrastructure in order to eliminate cholera from the island of Hispaniola by 2023 .", "Six years and a half billion dollars later , there is little evidence that any substanti...	[ "After the introduction of toxigenic Vibrio cholerae O1 to the Caribbean nation of Haiti in 2010 , the country experienced the largest national cholera outbreak in recent history .", "With the help of the international community , over $500 , 000 , 000 USD was pledged to finance massive improvements in drinking w...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "computational neuroscience", "biology", "neuroscience" ]	A Model of Reward- and Effort-Based Optimal Decision Making and Motor Control	journal.pcbi.1002716	null	[ [ "Consider a simple living creature that needs to move in its environment to collect food for survival ( foraging problem; [1] ) .", "For instance , it can have to choose between a small amount of food at a short distance and a larger amount at a longer distance [2] , [3] .", "These two choices should ...	[ "Costs ( e . g . energetic expenditure ) and benefits ( e . g . food ) are central determinants of behavior .", "In ecology and economics , they are combined to form a utility function which is maximized to guide choices .", "This principle is widely used in neuroscience as a normative model of decision and act...	[ "Behavior is made of decisions and actions .", "The decisions are based on the costs and benefits of potential actions , and the chosen actions are executed through the proper control of body segments .", "The corresponding processes are generally considered in separate theories of decision making and motor con...	2012
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "biotechnology", "antimicrobials", "luciferase", "medicine and health sciences", "engineering and technology", "enzymes", "drugs", "microbiology", "enzymology", "antifungals", "parasitic diseases", "protozoan life cycles", "electromagnetic radiation", "parasitic protozoans", "development...	Development of NanoLuc-PEST expressing Leishmania mexicana as a new drug discovery tool for axenic- and intramacrophage-based assays	journal.pntd.0006639	null	[ [ "The leishmaniases are a spectrum of diseases caused by infection with protozoan pathogens of the Leishmania genus , with an estimated 1 million new cases per annum .", "[1] Leishmania parasites are transmitted to a mammalian host via the bite of an infected sand fly .", "Highly motile metacyclic prom...	[ "The protozoan parasite Leishmania causes leishmaniasis; a spectrum of diseases of which there are an estimated 1 million new cases each year .", "Current treatments are toxic , expensive , difficult to administer , and resistance to them is emerging .", "New therapeutics are urgently needed , however , screeni...	[ "The protozoan parasite Leishmania causes a spectrum of diseases collectively known as leishmaniasis .", "The parasite is transmitted to humans by the bite of its vector , the sand fly , following which the parasite invades host white blood cells , particularly macrophages .", "Leishmaniasis is classified as a ...	2018
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "medicine", "immunology", "biology", "toxicology", "immunoglobulins" ]	Cross Neutralization of Afro-Asian Cobra and Asian Krait Venoms by a Thai Polyvalent Snake Antivenom (Neuro Polyvalent Snake Antivenom)	journal.pntd.0001672	null	[ [ "The global figure of snake envenoming cases has been estimated to be greater than 1 . 8 million annually , with an annual death toll of more than 90 , 000 .", "Most of the snake envenoming cases occurs in South Asia and Southeast Asia ( estimated 720 , 000 cases , 53 , 000 fatality ) , followed by Africa...	[ "Snake envenomation is a serious public health threat in the rural areas of Asian and African countries .", "To date , the only proven treatment for snake envenomation is antivenom therapy .", "Cross-neutralization of heterologous venoms by antivenom raised against venoms of closely related species has been rep...	[ "Snake envenomation is a serious public health threat in the rural areas of Asia and Africa .", "To date , the only proven treatment for snake envenomation is antivenom therapy .", "Owing to the difficulties in the diagnosis of the biting species , there is a need to develop polyvalent antivenoms that could cro...	2012
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "antibody-producing cells", "immune cells", "cytokines", "b cells", "immunity", "immunity to infections", "immunology", "biology", "immune response", "immune system" ]	Alterations in Peripheral Blood B Cell Subsets and Dynamics of B Cell Responses during Human Schistosomiasis	journal.pntd.0002094	null	[ [ "Schistosomiasis is a major parasitic disease of humans in the developing world , with over 200 million people infected worldwide [1] .", "As with other chronic helminth infections , schistosomes cause widespread immune activation and deregulation leading to general T cell hyporesponsiveness supporting th...	[ "Antibody responses are thought to play an important role in control of Schistosoma infections , yet little is known about the phenotype and function of B cells in human schistosomiasis .", "We set out to characterize B cell subsets and B cell responses to B cell receptor and Toll-like receptor 9 stimulation in G...	[ "Schistosomiasis affects over 200 million people and especially children in developing countries .", "It causes general hyporesponsiveness of the immune system , which until now has predominantly been described for various T cell subsets as well as dendritic cells .", "B cells in this context have not yet been ...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "visual system", "computational neuroscience", "sensory systems", "biology", "neuroscience", "coding mechanisms" ]	Shape Similarity, Better than Semantic Membership, Accounts for the Structure of Visual Object Representations in a Population of Monkey Inferotemporal Neurons	journal.pcbi.1003167	null	[ [ "In primates , visual object information is processed through a hierarchy of cortico-cortical stages ( the ventral visual pathway ) that culminates with the inferotemporal cortex ( IT ) [1]–[6] .", "Uncovering the nature of visual object representations in IT is central to our understanding of how visuall...	[ "The anterior inferotemporal cortex ( IT ) is the highest stage along the hierarchy of visual areas that , in primates , processes visual objects .", "Although several lines of evidence suggest that IT primarily represents visual shape information , some recent studies have argued that neuronal ensembles in IT co...	[ "To build meaningful representations of the external word , the stream of sensory information that reaches our senses is continuously processed and interpreted by the brain .", "Ultimately , such a processing allows the brain to arrange sensory ( e . g . , visual ) inputs into a hierarchy of categories ( such as ...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods", "Supporting Information" ]	[ "plant biology", "evolutionary biology", "plants", "genetics and genomics" ]	Autoimmune Response as a Mechanism for a Dobzhansky-Muller-Type Incompatibility Syndrome in Plants	journal.pbio.0050236	Sometimes, genes that are innocuous in the parents are deleterious when combined in the offspring. Here, some genes involved in hybrid necrosis in plants have been identified.	[ [ "Epistasis—the nonadditive interaction between genes—is a critical determinant for the performance of hybrid genotypes .", "It encompasses a spectrum of important genetic phenomena , from positive heterosis ( hybrid vigor ) to negative heterosis ( hybrid sterility or lethality ) .", "In plants , two p...	[ "Epistatic interactions between genes are a major factor in evolution .", "Hybrid necrosis is an example of a deleterious phenotype caused by epistatic interactions that is observed in many intra- and interspecific plant hybrids .", "A large number of hybrid necrosis cases share phenotypic similarities , sugges...	[ "Hybridization brings together genetic material from different genomes .", "Sometimes , the novel combinations of genes are deleterious in the offspring , even though the genes were innocuous , or even beneficial , in their parents .", "Such “genetic incompatibilities” have been observed in crosses within and b...	2007
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "developmental biology", "developmental neuroscience", "axon guidance", "molecular development", "biology", "neuroscience" ]	Npn-1 Contributes to Axon-Axon Interactions That Differentially Control Sensory and Motor Innervation of the Limb	journal.pbio.1001020	null	[ [ "The establishment of concerted locomotor behaviors in vertebrates relies on the formation of integrated motor and sensory circuits that form between defined populations of neurons and their appropriate targets in the periphery .", "During the development of the spinal neuromuscular circuitry , motoneuron...	[ "The initiation , execution , and completion of complex locomotor behaviors are depending on precisely integrated neural circuitries consisting of motor pathways that activate muscles in the extremities and sensory afferents that deliver feedback to motoneurons .", "These projections form in tight temporal and sp...	[ "During embryonic development , growing axons establish intricate neural networks with their peripheral targets , a process that builds the basis for complex behaviors .", "While wiring up the proper circuits in peripheral limbs , for example , motor axons from the spinal cord and sensory axons from the dorsal ro...	2011
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "chromosome structure and function", "vertebrates", "animals", "dna transcription", "osteichthyes", "animal models", "developmental biology", "model organisms", "organism development", "molecular development", "morphogenesis", "limb development", "research and analysis methods", "fishes", ...	Nipbl and Mediator Cooperatively Regulate Gene Expression to Control Limb Development	journal.pgen.1004671	null	[ [ "Cohesin , a ring-shaped , DNA-associated protein complex , is best known for its role in tethering sister chromatids together until mitosis [1] , [2] .", "However , growing evidence indicates that cohesin , and proteins such as Nipped-B-like ( Nipbl ) that regulate cohesin loading onto DNA , also play cr...	[ "Haploinsufficiency for Nipbl , a cohesin loading protein , causes Cornelia de Lange Syndrome ( CdLS ) , the most common “cohesinopathy” .", "It has been proposed that the effects of Nipbl-haploinsufficiency result from disruption of long-range communication between DNA elements .", "Here we use zebrafish and m...	[ "Limb malformations are a striking feature of Cornelia de Lange Syndrome ( CdLS ) , a multi-system birth defects disorder most commonly caused by haploinsufficiency for NIPBL .", "In addition to its role as a cohesin-loading factor , Nipbl also regulates gene expression , but how partial Nipbl deficiency causes l...	2014
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "medicine and health sciences", "animal diseases", "prions", "neuroscience", "animal prion diseases", "zoology", "neuronal dendrites", "mapk signaling cascades", "contractile proteins", "infectious diseases", "actins", "intracellular receptors", "zoonoses", "animal cells", "proteins", ...	Prions activate a p38 MAPK synaptotoxic signaling pathway	journal.ppat.1007283	null	[ [ "Prion diseases are a group of fatal , infectious neurodegenerative diseases affecting humans and animals .", "The infectious agent , or prion , is composed of PrPSc , a conformationally altered form of a normal , cell-surface glycoprotein designated PrPC .", "Prions propagate themselves by a highly s...	[ "Synaptic degeneration is one of the earliest pathological correlates of prion disease , and it is a major determinant of the progression of clinical symptoms .", "However , the cellular and molecular mechanisms underlying prion synaptotoxicity are poorly understood .", "Previously , we described an experimenta...	[ "Prion diseases are a group of fatal neurodegenerative disorders that includes Creutzfeldt-Jakob disease and kuru in humans , and bovine spongiform encephalopathy in cattle .", "The infectious agent , or prion , that transmits these diseases is a naked protein molecule , the prion protein ( PrP ) , which is an al...	2018
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "infectious diseases", "immunology/immunity to infections", "immunology/immune response" ]	Phenotypic and Functional Characterization of Human Memory T Cell Responses to Burkholderia pseudomallei	journal.pntd.0000407	null	[ [ "Melioidosis is a serious infectious disease in Southeast Asia and Northern Australia caused by the soil-dwelling Gram-negative bacterium , Burkholderia pseudomallei [1] .", "In Northeast Thailand , the mortality rate for acute melioidosis remains high , approximately 50% , despite recent advances in anti...	[ "Infection with the Gram-negative bacterium Burkholderia pseudomallei is an important cause of community-acquired lethal sepsis in endemic regions in southeast Asia and northern Australia and is increasingly reported in other tropical areas .", "In animal models , production of interferon-gamma ( IFN-γ ) is criti...	[ "The Gram-negative bacterium , Burkholderia pseudomallei , is a public health problem in southeast Asia and northern Australia and a Centers for Disease Control and Prevention listed Category B potential bioterrorism agent .", "It is the causative agent of melioidosis , and clinical manifestations vary from acute...	2009
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine and health sciences", "classical mechanics", "pathology and laboratory medicine", "electrophoretic mobility shift assay", "gene regulation", "pathogens", "vibrio", "rna extraction", "mechanical stress", "dna", "molecular biology techniques", "bacteria", "extraction techniques", "...	A σE-Mediated Temperature Gauge Controls a Switch from LuxR-Mediated Virulence Gene Expression to Thermal Stress Adaptation in Vibrio alginolyticus	journal.ppat.1005645	null	[ [ "It has been established that warming sea surface temperatures ( SST ) threatens marine ecosystems , including coral species that reside in coral reefs [1 , 2] .", "In addition , elevated sea temperatures are associated with mass mortalities in farmed sea animals [3] , and these are often associated with ...	[ "In vibrios , the expression of virulence factors is often controlled by LuxR , the master quorum-sensing regulator .", "Here , we investigate the interplay between LuxR and σE , an alternative sigma factor , during the control of virulence-related gene expression and adaptations to temperature elevations in the ...	[ "Zoonotic Vibrio outbreaks are believed to be closely associated with increases in environmental temperature .", "The mechanisms underlying this phenomenon have not been defined .", "Here , we show that the expression of the V . alginolyticus exotoxin Asp and other quorum-sensing ( QS ) -regulated virulence fac...	2016
[ "Introduction", "Results and discussion", "Methods" ]	[ "cell physiology", "g-protein signaling", "receptor physiology", "protein structure", "protein structure databases", "molecular biology techniques", "g protein coupled receptors", "research and analysis methods", "amino acid analysis", "proteins", "biological databases", "transmembrane recepto...	Unifying view of mechanical and functional hotspots across class A GPCRs	journal.pcbi.1005381	null	[ [ "Mammalian G protein-coupled receptors ( GPCRs ) are the largest family of signaling proteins , with approximately ∼850 unique members up to now identified in the human genome [1 , 2] .", "Given the size of this family , their ubiquitous expression , and their involvement in virtually every ( patho ) phys...	[ "G protein-coupled receptors ( GPCRs ) are the largest superfamily of signaling proteins .", "Their activation process is accompanied by conformational changes that have not yet been fully uncovered .", "Here , we carry out a novel comparative analysis of internal structural fluctuations across a variety of rec...	[ "The biological functionality of several receptors and enzymes depends on their capability to sustain large-scale structural fluctuations and adopt different conformational states in response to ligand binding .", "This is the case for G protein-coupled receptors ( GPCRs ) , the largest superfamily of signaling p...	2017
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[]	Proteomics Profiling of Chikungunya-Infected Aedes albopictus C6/36 Cells Reveal Important Mosquito Cell Factors in Virus Replication	journal.pntd.0003544	null	[ [ "Chikungunya virus ( CHIKV ) is an emerging mosquito-borne virus of the genus Alphaviruses , family Togaviridae .", "The long-neglected viral disease was first discovered in Tanzania in 1952 .", "CHIKV is an enveloped , single-stranded , positive-sense RNA virus with a genome size of approximately 12 ...	[ "Chikungunya virus ( CHIKV ) is the only causative agent of CHIKV fever with persistent arthralgia , and in some cases may lead to neurological complications which can be highly fatal , therefore it poses severe health issues in many parts of the world .", "CHIKV transmission can be mediated via the Aedes albopic...	[ "Chikungunya virus ( CHIKV ) , a re-emerging mosquito-borne virus , is the main cause of CHIKV fever , persistent arthralgia and serious neurological complications which can be highly fatal; therefore , it poses serious health threats worldwide .", "Unraveling the underappreciated aspects of mosquito cellular fac...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "dna damage", "biochemistry", "genetics", "biology and life sciences", "dna repair", "dna", "non-homologous end joining" ]	Canonical Non-Homologous End Joining in Mitosis Induces Genome Instability and Is Suppressed by M-phase-Specific Phosphorylation of XRCC4	journal.pgen.1004563	null	[ [ "Double-strand breaks ( DSBs ) are one of the most consequential types of DNA damage .", "DSBs are usually repaired by one of two main repair pathways—canonical non-homologous end joining ( C-NHEJ ) or homologous recombination ( HR ) [1] , [2] .", "Recently , however , a third less-characterized repai...	[ "DNA double-strand breaks ( DSBs ) can be repaired by one of two major pathways—non-homologous end-joining ( NHEJ ) and homologous recombination ( HR ) —depending on whether cells are in G1 or S/G2 phase , respectively .", "However , the mechanisms of DSB repair during M phase remain largely unclear .", "In thi...	[ "DNA double-strand breaks ( DSBs ) are highly toxic to cells and often lead to genome instability and cell death .", "Organisms have several DSB repair mechanisms to prevent such instability .", "Proper choice of DSB repair pathways is highly regulated during the cell cycle .", "Inappropriate choice of the DS...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "borrelia infection", "fluorescence imaging", "medicine and health sciences", "animal models of disease", "vector-borne diseases", "microbiology", "animal models", "bacterial diseases", "fungi", "lyme disease", "model organisms", "research and analysis methods", "saccharomyces", "animal mo...	A Tick Gut Protein with Fibronectin III Domains Aids Borrelia burgdorferi Congregation to the Gut during Transmission	journal.ppat.1004278	null	[ [ "Ixodes scapularis is the predominant vector of several human pathogens including Borrelia burgdorferi , the agent of Lyme borreliosis in North America [1] , [2] .", "There is currently no commercial vaccine to prevent Lyme borreliosis in humans [3] , although recent efforts have been made in that directi...	[ "Borrelia burgdorferi transmission to the vertebrate host commences with growth of the spirochete in the tick gut and migration from the gut to the salivary glands .", "This complex process , involving intimate interactions of the spirochete with the gut epithelium , is pivotal to transmission .", "We utilized ...	[ "Lyme borreliosis , the most common vector-borne illness in Northeastern parts of USA , is caused by Borrelia burgdorferi sensu lato spirochetes , and transmitted by the Ixodes scapularis ticks .", "Currently there is no vaccine available to prevent Lyme borreliosis .", "A better understanding of tick proteins ...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "systems biology", "biology and life sciences" ]	Robustness and Evolvability of the Human Signaling Network	journal.pcbi.1003763	null	[ [ "Organisms have evolved so that their networks are robust against the effects of mutations , but evolvable in response to environmental changes [1]–[4] .", "Genetic mutations can profoundly change network structures , so mutational robustness of a network indicates how well the network can preserve its ow...	[ "Biological systems are known to be both robust and evolvable to internal and external perturbations , but what causes these apparently contradictory properties ?", "We used Boolean network modeling and attractor landscape analysis to investigate the evolvability and robustness of the human signaling network .", ...	[ "Biological systems are known to be robust and evolvable to internal mutations and external environmental changes .", "What causes these apparently contradictory properties ?", "This study shows that the human signaling network can be decomposed into two structurally distinct subgroups of links that provide bot...	2014
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "insulin-dependent signal transduction", "invertebrates", "caenorhabditis", "microbiology", "animals", "parasitology", "dna transcription", "parasite physiology", "animal models", "caenorhabditis elegans", "model organisms", "research and analysis methods", "gene expression", "nuclear rece...	cGMP and NHR Signaling Co-regulate Expression of Insulin-Like Peptides and Developmental Activation of Infective Larvae in Strongyloides stercoralis	journal.ppat.1004235	null	[ [ "Parasitic nematodes infect approximately one in four persons globally , with the vast burden of disease concentrated in tropical and developing regions [1] .", "The parasitic nematode Strongyloides stercoralis infects an estimated 30–100 million people worldwide [2]; in corticosteroid-treated or human T-...	[ "The infectious form of the parasitic nematode Strongyloides stercoralis is a developmentally arrested third-stage larva ( L3i ) , which is morphologically similar to the developmentally arrested dauer larva in the free-living nematode Caenorhabditis elegans .", "We hypothesize that the molecular pathways regulat...	[ "Human parasitic nematodes , including Strongyloides stercoralis , cause extensive morbidity in the developing world .", "The infectious form of S . stercoralis is a developmentally arrested third-stage larva ( L3i ) , which resumes development into a parasitic adult upon entering a host .", "The molecular mech...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "cell physiology", "cellular stress responses", "oxidative stress", "cell processes", "metabolic networks", "cell metabolism", "network analysis", "mitochondria", "bioenergetics", "cellular structures and organelles", "cell aging", "computer and information sciences", "stress signaling casca...	Dynamic Modelling of Pathways to Cellular Senescence Reveals Strategies for Targeted Interventions	journal.pcbi.1003728	null	[ [ "Cellular senescence , characterised by permanent cell cycle arrest , plays an important but complex role both in ageing and cancer .", "Like apoptosis , cell senescence is a cell-autonomous tumour protection mechanism [1] , [2] .", "Senescent cells can persist in tissues for long periods of time and ...	[ "Cellular senescence , a state of irreversible cell cycle arrest , is thought to help protect an organism from cancer , yet also contributes to ageing .", "The changes which occur in senescence are controlled by networks of multiple signalling and feedback pathways at the cellular level , and the interplay betwee...	[ "Ageing is characterised by a gradual loss of homeostasis within organs , which is known to be driven by the accumulation of senescent cells .", "Cellular senescence helps prevent cells from becoming cancerous , but their detrimental effect on organ function becomes debilitating once they accumulate .", "These ...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biotechnology", "cell death", "plant anatomy", "medicine and health sciences", "enzymes", "cell processes", "immunology", "enzymology", "cell-mediated immunity", "plant physiology", "phosphatases", "cereal crops", "plant science", "rice", "model organisms", "genetically modified plant...	The Multivesicular Bodies (MVBs)-Localized AAA ATPase LRD6-6 Inhibits Immunity and Cell Death Likely through Regulating MVBs-Mediated Vesicular Trafficking in Rice	journal.pgen.1006311	null	[ [ "Plants are exposed to a vast diversity of micro-organisms such as bacteria , fungi and oomycetes .", "To protect themselves from pathogenic plant–microbe interactions , plants have developed a sophisticated innate immunity system [1] .", "Pattern triggered immunity ( PTI ) and effector triggered immu...	[ "Previous studies have shown that multivesicular bodies ( MVBs ) /endosomes-mediated vesicular trafficking may play key roles in plant immunity and cell death .", "However , the molecular regulation is poorly understood in rice .", "Here we report the identification and characterization of a MVBs-localized AAA ...	[ "Plants have evolved sophistical immunity system in fighting against pathogenic micro-organisms including bacteria , fungi and oomycetes .", "Upon perception of pathogens , the immune system activates rapid cell death , characterized as a form of hypersensitive response typically in and around the infection sites...	2016
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "cell biology/cellular death and stress responses", "genetics and genomics/functional genomics", "cell biology", "genetics and genomics/disease models", "genetics and genomics", "cell biology/cytoskeleton" ]	Prion Formation and Polyglutamine Aggregation Are Controlled by Two Classes of Genes	journal.pgen.1001386	null	[ [ "Prions are associated with transmissible spongiform encephalopathies , a family of neurological diseases that include Creutzfeldt-Jakob disease in humans , Scrapie in sheep , and the well-publicized “Mad Cow” disease .", "Transmission of prions occurs when a normally folded protein is converted to an alt...	[ "Prions are self-perpetuating aggregated proteins that are not limited to mammalian systems but also exist in lower eukaryotes including yeast .", "While much work has focused around chaperones involved in prion maintenance , including Hsp104 , little is known about factors involved in the appearance of prions ."...	[ "Certain proteins that exist in functional unaggregated conformers can also form self-perpetuating infectious aggregates called prions .", "Here we investigate factors involved in the initial switch to the prion form .", "De novo appearance of the [PSI+] prion , which is the aggregated form of the Sup35 protein...	2011
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Mechanistic Model of Natural Killer Cell Proliferative Response to IL-15 Receptor Stimulation	journal.pcbi.1003222	null	[ [ "Effective immunity against pathogens requires the rapid expansion of lymphocytes capable of an appropriate response .", "This is illustrated by the substantial numeric increase of murine NK cells early during viral infections [1]–[6] .", "Vigorous expansion of human NK cells has also been observed du...	[ "Natural killer ( NK ) cells are innate lymphocytes that provide early host defense against intracellular pathogens , such as viruses .", "Although NK cell development , homeostasis , and proliferation are regulated by IL-15 , the influence of IL-15 receptor ( IL-15R ) -mediated signaling at the cellular level ha...	[ "Natural killer ( NK ) cells are innate immune cells that are important in our bodies' initial defenses against pathogens , like viruses .", "NK cells rapidly proliferate early during viral infections to provide an expanded pool of effector cells to suppress the infection .", "This proliferative response is dri...	2013
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "schistosoma", "invertebrates", "children", "cognitive neurology", "medicine and health sciences", "learning", "education", "helminths", "sociology", "social sciences", "neuroscience", "animals", "learning and memory", "pediatrics", "age groups", "cognitive neuroscience", "cognitive ...	Cognitive deficits and educational loss in children with schistosome infection—A systematic review and meta-analysis	journal.pntd.0005524	null	[ [ "An estimated 800 million persons in tropical and sub-tropical countries are at risk of infection by one of three main human Schistosoma parasites–S .", "mansoni , S . haematobium , and S . japonicum [1] .", "As many as 240 million adults and children are actively infected [2–4] resulting in as much a...	[ "By means of meta-analysis of information from all relevant epidemiologic studies , we examined the hypothesis that Schistosoma infection in school-aged children ( SAC ) is associated with educational loss and cognitive deficits .", "This review was prospectively registered in the PROSPERO database ( CRD420160400...	[ "Empirical evidence for cognitive or educational benefits of anti-Schistosoma treatment is currently uncertain , despite the recommended practice of wide-scale deworming with praziquantel .", "We addressed this knowledge gap by synthesizing information from 30 relevant epidemiologic studies reporting on 38 , 992 ...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "developmental biology", "signal transduction", "rna interference", "stem cells", "gene expression", "signaling pathways", "biology", "molecular cell biology", "cell fate determination", "adult stem cells" ]	miR-133a Regulates Adipocyte Browning In Vivo	journal.pgen.1003626	null	[ [ "Adipose tissues are classified as brown ( BAT ) and white ( WAT ) , and an intermediate category of “brite” or “beige” adipocytes exist within subcutaneous WAT [1] , [2] .", "WAT are located in multiple subcutaneous or visceral locations of body , in the form of distinct fat depots , and contribute to ov...	[ "Prdm16 determines the bidirectional fate switch of skeletal muscle/brown adipose tissue ( BAT ) and regulates the thermogenic gene program of subcutaneous white adipose tissue ( SAT ) in mice .", "Here we show that miR-133a , a microRNA that is expressed in both BAT and SATs , directly targets the 3′ UTR of Prdm...	[ "Global obesity and associated health issues have raised the significance of adipocyte biology .", "Adipose tissues are classified as brown and white adipose .", "White adipose tissues store lipids , leading to overweight , obesity , insulin resistance and Type2 diabetes .", "In contrast , brown adipose tissu...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biochemistry", "proteins", "biology", "microbiology" ]	Specialized Peptidoglycan Hydrolases Sculpt the Intra-bacterial Niche of Predatory Bdellovibrio and Increase Population Fitness	journal.ppat.1002524	null	[ [ "Bdellovibrio bacteriovorus are small predatory bacteria which invade the periplasm of other Gram-negative bacteria , round up these ( typically formerly rod-shaped ) prey bacteria into spherical , osmotically stable structures called bdelloplasts , kill the prey and replicate within them .", "Constructin...	[ "Bdellovibrio are predatory bacteria that have evolved to invade virtually all Gram-negative bacteria , including many prominent pathogens .", "Upon invasion , prey bacteria become rounded up into an osmotically stable niche for the Bdellovibrio , preventing further superinfection and allowing Bdellovibrio to rep...	[ "Bdellovibrio bacteriovorus is a small predatory bacterium that invades other bacteria including pathogens of humans and animals .", "Bdellovibrio digest the pathogens from within , growing at their expense .", "Bdellovibrio do not attack human , plant or animal cells and so could be applied as “living antibiot...	2012
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "genome-wide association studies", "plant anatomy", "medicine and health sciences", "pathology and laboratory medicine", "brassica", "alleles", "genetic mapping", "plant science", "model organisms", "signs and symptoms", "experimental organism systems", "genome analysis", "plant pathology", ...	RPW8/HR repeats control NLR activation in Arabidopsis thaliana	journal.pgen.1008313	null	[ [ "The combination of divergent parental genomes in hybrids can produce new phenotypes not seen in either parent .", "At one end of the spectrum is hybrid vigor , with progeny being superior to the parents , while at the other end there is hybrid weakness , with progeny being inferior to the parents , and i...	[ "In many plant species , conflicts between divergent elements of the immune system , especially nucleotide-binding oligomerization domain-like receptors ( NLR ) , can lead to hybrid necrosis .", "Here , we report deleterious allele-specific interactions between an NLR and a non-NLR gene cluster , resulting in not...	[ "In many plant species , conflicts between divergent elements of the immune system can cause hybrids to express autoimmunity , a generally deleterious syndrome known as hybrid necrosis .", "We are investigating multiple hybrid necrosis cases in Arabidopsis thaliana that are caused by allele-specific interactions ...	2019
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[]	Type 2 Diabetes Mellitus Is Associated with Strongyloides stercoralis Treatment Failure in Australian Aboriginals	journal.pntd.0003976	null	[ [ "S . stercoralis is a soil transmitted helminth infection and as such is a neglected tropical disease .", "It is thought to have a worldwide prevalence of at least 100 million people , and is endemic in regions where people are in contact with fecal material or contaminated soil .", "The majority of i...	[ "To explore the efficacy of ivermectin in the treatment of serologically diagnosed cases of Strongyloides stercoralis ( S . stercoralis ) infection in an Aboriginal community and to describe factors that may influence the outcome of treatment .", "Longitudinal study of a group of 92 individuals with serologically...	[ "In this study we examine the treatment of the intestinal worm infection Strongyloides stercoralis , a soil transmitted helminth that is common in the developing world and in the Aboriginal communities of northern Australia .", "Oral ivermectin is generally accepted as the treatment of choice for this condition ....	2015
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "infectious diseases/epidemiology and control of infectious diseases", "infectious diseases/neglected tropical diseases", "infectious diseases/antimicrobials and drug resistance", "infectious diseases/protozoal infections" ]	Genotypic Status of the TbAT1/P2 Adenosine Transporter of Trypanosoma brucei gambiense Isolates from Northwestern Uganda following Melarsoprol Withdrawal	journal.pntd.0000523	null	[ [ "Human African trypanosomiasis ( HAT ) or sleeping sickness is caused by T . brucei gambiense and T . b .", "rhodesiense .", "The disease affects 36 countries in sub-Saharan Africa with Angola , DR Congo , South Sudan , Uganda and Central African Republic as the most affected [1] .", "Current figu...	[ "The development of arsenical and diamidine resistance in Trypanosoma brucei is associated with loss of drug uptake by the P2 purine transporter as a result of alterations in the corresponding T . brucei adenosine transporter 1 gene ( TbAT1 ) .", "Previously , specific TbAT1 mutant type alleles linked to melarsop...	[ "Human African trypanosomiasis ( HAT ) manifests as a chronic infection caused by Trypanosoma brucei gambiense , or as a more acute form due to T . b .", "rhodesiense .", "Both manifestations occur in Uganda and melarsoprol use against the former was jeopardised in the 1990s as reports of reduced efficacy incre...	2009
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "infectious diseases", "medicine and health sciences", "emerging infectious diseases", "virology", "biology and life sciences", "microbiology" ]	Sero-Prevalence and Cross-Reactivity of Chikungunya Virus Specific Anti-E2EP3 Antibodies in Arbovirus-Infected Patients	journal.pntd.0003445	null	[ [ "Chikungunya virus ( CHIKV ) has re-emerged as an important arbovirus that has caused unprecedented Chikungunya Fever ( CHIKF ) epidemics in Asia , Africa and more recently in the Americas [1]–[5] .", "Typical symptoms caused by CHIKV infection include fever , headache , myalgia , rash and debilitating ar...	[ "Chikungunya virus ( CHIKV ) and clinically-related arboviruses cause large epidemics with serious economic and social impact .", "As clinical symptoms of CHIKV infections are similar to several flavivirus infections , good detection methods to identify CHIKV infection are desired for improved treatment and clini...	[ "Chikungunya virus ( CHIKV ) causes Chikungunya fever in humans .", "The symptoms , particularly joint pain , can be severe and long lasting , and outbreaks can have serious socioeconomic impact .", "CHIKV is a mosquito-borne alphavirus that co-exists geographically with other mosquito-borne flaviviruses such a...	2015
[ "Introduction", "Materials and Methods", "Results and Discussion" ]	[]	Comparative Analysis of Transcriptional Profiles of Adult Schistosoma japonicum from Different Laboratory Animals and the Natural Host, Water Buffalo	journal.pntd.0003993	null	[ [ "Schistosomiasis is one of the most serious parasitic diseases and affects more than 200 million people globally , based on conservative estimates [1 , 2] .", "Schistosomiasis is caused mainly by three Schistosoma species: Schistosoma japonicum , Schistosoma mansoni , and Schistosoma haematobium .", "...	[ "Schistosomiasis is one of the most widely distributed parasitic diseases in the world .", "Schistosoma japonicum , a zoonotic parasite with a wide range of mammalian hosts , is one of the major pathogens of this disease .", "Although numerous studies on schistosomiasis japonica have been performed using labora...	[ "The zoonotic parasite Schistosoma japonicum is one of the major pathogens of schistosomiasis and can parasitize a wide range of mammals .", "Although numerous schistosome transcriptional profiling studies have been performed using laboratory animal models , the differences in the global gene expression profiles ...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "model organisms", "genetics", "biology", "molecular cell biology", "genetics and genomics" ]	CED-10/Rac1 Regulates Endocytic Recycling through the RAB-5 GAP TBC-2	journal.pgen.1002785	null	[ [ "The C . elegans intestine has proven to be a powerful model system for the study of epithelial cell membrane trafficking mechanisms .", "The worm intestine is a simple epithelial tube consisting of 20 enterocyte cells that form nine “donut-like” intestinal rings [1] .", "Each of these 20 cells is ter...	[ "Rac1 is a founding member of the Rho-GTPase family and a key regulator of membrane remodeling .", "In the context of apoptotic cell corpse engulfment , CED-10/Rac1 acts with its bipartite guanine nucleotide exchange factor , CED-5/Dock180-CED-12/ELMO , in an evolutionarily conserved pathway to promote phagocytos...	[ "When cargo is internalized from the cell surface by endocytosis , it enters a series of intracellular organelles called endosomes .", "Endosomes sort cargo , such that some cargos are sent to the lysosome for degradation , while others are recycled to the plasma membrane .", "Small GTPase proteins ( Rabs ) are...	2012
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "virology/diagnosis", "public health and epidemiology/infectious diseases", "virology/emerging viral diseases" ]	Evaluation of Two New Commercial Tests for the Diagnosis of Acute Dengue Virus Infection Using NS1 Antigen Detection in Human Serum	journal.pntd.0000280	null	[ [ "Dengue virus ( DENV ) is a mosquito-borne virus ( family Flaviviridae , genus Flavivirus ) .", "Four viral serotypes of DENV ( DENV-1 to DENV-4 ) cause disease in humans .", "Symptoms range from mild fever , the most common form , to potentially fatal dengue hemorrhagic fever ( DHF ) and dengue shock...	[ "We compared the performance of two new commercial tests for the detection of dengue NS1 protein during the clinical phase of dengue virus ( DENV ) infection—an immunochromatographic test allowing rapid detection of the NS1 antigen , Dengue NS1 Ag STRIP ( Bio-Rad Laboratories - Marnes La Coquette , France ) , and a...	[ "Dengue is a viral disease transmitted by mosquitoes that is endemic in more than 100 countries in tropical areas , threatening over 2 . 5 billion people .", "It causes a wide range of symptoms and has severe forms .", "In reference laboratories , dengue disease is confirmed by virus isolation or genome detecti...	2008
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "cell biology/leukocyte signaling and gene expression", "cell biology/cell signaling", "infectious diseases/neglected tropical diseases", "immunology/innate immunity", "infectious diseases/protozoal infections", "microbiology/parasitology", "evolutionary biology" ]	Leishmania-Induced IRAK-1 Inactivation Is Mediated by SHP-1 Interacting with an Evolutionarily Conserved KTIM Motif	journal.pntd.0000305	null	[ [ "Innate inflammatory responses play a critical role in controlling pathogens [1] .", "However , protozoan parasites such as Leishmania evolved strategies to avoid phagocyte activation by seizing control of key signalling pathways , therefore favouring their invasion and survival within the host cell [2] ....	[ "Parasites of the Leishmania genus can rapidly alter several macrophage ( MØ ) signalling pathways in order to tame down the innate immune response and inflammation , therefore favouring their survival and propagation within their mammalian host .", "Having recently reported that Leishmania and bacterial LPS gene...	[ "Leishmania developed several methods to seize control of macrophage signalling pathways in an effort to inactivate their killing abilities .", "One effective method utilized by the parasite is the activation of host protein tyrosine phosphatases , specifically SHP-1 .", "This increased phosphatase activity con...	2008
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "flow cytometry", "taxonomy", "viral transmission and infection", "microbiology", "phylogenetics", "data management", "protozoans", "phylogenetic analysis", "genome analysis", "research and analysis methods", "computer and information sciences", "spectrum analysis techniques", "genomics", ...	Chromulinavorax destructans, a pathogen of microzooplankton that provides a window into the enigmatic candidate phylum Dependentiae	journal.ppat.1007801	null	[ [ "The candidate phylum Dependentiae ( also known as TM6 ) is a phylogenetic group of bacteria that is only known from metagenomic data and from two isolates that infect free-living amoebae .", "Although relatively little is known about members of the Dependentiae , analysis of environmental 16S-ribosomal R...	[ "Members of the major candidate phylum Dependentiae ( a . k . a . TM6 ) are widespread across diverse environments from showerheads to peat bogs; yet , with the exception of two isolates infecting amoebae , they are only known from metagenomic data .", "The limited knowledge of their biology indicates that they h...	[ "Little is known about the biology of bacteria in the candidate phylum Dependentiae , despite being widespread in nature .", "Here , we describe a novel isolate of this phylum , Chromulinavorax destructans , which infects an abundant aquatic predatory protist , Spumella elongata .", "Chromulinavorax destructans...	2019
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "cell biology/chemical biology of the cell", "immunology/antigen processing and recognition", "chemistry/biochemistry", "microbiology/immunity to infections", "cell biology/morphogenesis and cell biology", "cell biology/cell growth and division", "gastroenterology and hepatology/gastrointestinal infecti...	Rab11 and Actin Cytoskeleton Participate in Giardia lamblia Encystation, Guiding the Specific Vesicles to the Cyst Wall	journal.pntd.0000697	null	[ [ "Giardia lamblia is the causative agent of Giardiasis , a diarrheal disease [1] , [2] .", "Giardia exists in two forms during its life cycle , the trophozoite and the cyst .", "The trophozoite , which is responsible for the symptomatology of Giardiasis , resides in the small intestine , causing the lo...	[ "Giardia passes through two stages during its life cycle , the trophozoite and the cyst .", "Cyst formation involves the synthesis of cyst wall proteins ( CWPs ) and the transport of CWPs into encystation-specific vesicles ( ESVs ) .", "Active vesicular trafficking is essential for encystation , but the molecul...	[ "The encystation process is crucial for survival and transmission of Giardia lamblia to new hosts .", "During this process , vesicular trafficking and the cytoskeleton play important roles .", "In eukaryotic cells , intracellular transport is regulated by proteins , including Rab-GTPases and SNAREs , which regu...	2010
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "neuroscience", "neuroscience/sensory systems" ]	Cholinergic Activation of M2 Receptors Leads to Context-Dependent Modulation of Feedforward Inhibition in the Visual Thalamus	journal.pbio.1000348	The temporal dynamics of inhibition within a neural network is a crucial determinant of information processing. Here, the authors describe in the visual thalamus how neuromodulation governs the magnitude and time course of inhibition in an input-dependent way.	[ [ "Local inhibitory interneurons are important circuit elements that can generate synchrony within populations of neurons , control synaptic integration , and regulate the spiking activity of principal cells .", "In many brain regions , inhibition is mediated by numerous types of interneurons that contact d...	[ "In many brain regions , inhibition is mediated by numerous classes of specialized interneurons , but within the rodent dorsal lateral geniculate nucleus ( dLGN ) , a single class of interneuron is present .", "dLGN interneurons inhibit thalamocortical ( TC ) neurons and regulate the activity of TC neurons evoked...	[ "Within the visual thalamus , a single type of inhibitory interneuron regulates activity evoked by retinal ganglion cells and controls the visual signals that reach the cortex .", "Here , we find that neuromodulation , of the sort thought to occur when an animal is attending to a task , regulates the firing mode ...	2010
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[]	Fascioliasis and Intestinal Parasitoses Affecting Schoolchildren in Atlixco, Puebla State, Mexico: Epidemiology and Treatment with Nitazoxanide	journal.pntd.0002553	null	[ [ "Fascioliasis is a parasitic disease caused by two liver fluke species: Fasciola hepatica of almost global distribution due to the very large presence of their specific lymnaeid snail vectors , and F . gigantica only in Africa and Asia due to the distribution of their specific snail vectors restricted to thes...	[ "The Atlixco municipality , Puebla State , at a mean altitude of 1840 m , was selected for a study of Fasciola hepatica infection in schoolchildren in Mexico .", "This area presents permanent water collections continuously receiving thaw water from Popocatepetl volcano ( 5426 m altitude ) through the community su...	[ "A human fascioliasis endemic area is described for the first time in North America .", "In Atlixco , Puebla State , Mexico , prevalences of 2 . 94–13 . 33% by F . hepatica were found in 865 6–14-year-old schoolchildren by FasciDIG coproantigen test and Lumbreras rapid sedimentation technique , and quantitatively...	2013
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "medicine", "infectious diseases", "gram negative", "diagnostic medicine", "emerging infectious diseases", "medical microbiology", "global health", "biology", "microbiology", "public health", "bacterial pathogens" ]	Development of a Prototype Lateral Flow Immunoassay (LFI) for the Rapid Diagnosis of Melioidosis	journal.pntd.0002727	null	[ [ "Burkholderia pseudomallei is an environmental Gram-negative bacillus and the cause of melioidosis .", "The clinical manifestations of melioidosis are broad and include disseminated disease with organ abscesses , severe sepsis , and mild infection of the skin and soft tissue [1] .", "Most patients hav...	[ "Burkholderia pseudomallei is a soil-dwelling bacterium and the causative agent of melioidosis .", "Isolation of B . pseudomallei from clinical samples is the “gold standard” for the diagnosis of melioidosis; results can take 3–7 days to produce .", "Alternatively , antibody-based tests have low specificity due...	[ "Burkholderia pseudomallei is an environmental bacterium and the cause of melioidosis .", "Culture of patient samples is the “gold standard” diagnostic test , but may take up to 7 days to complete .", "Melioidosis has a 10–40% case fatality rate depending on the geographic location .", "Delays in diagnosis co...	2014
[ "Introduction", "Materials and Methods", "Results", "Discussion", "Conclusions" ]	[ "invertebrates", "livestock", "medicine and health sciences", "pathology and laboratory medicine", "vertebrates", "animals", "mammals", "dogs", "health care", "signs and symptoms", "pharmaceutics", "materials science", "fleas", "materials by structure", "morbidity", "research and analy...	Successful Treatment of Severe Tungiasis in Pigs Using a Topical Aerosol Containing Chlorfenvinphos, Dichlorphos and Gentian Violet	journal.pntd.0005056	null	[ [ "Tungiasis is a parasitosis of humans and animals caused by embedded female sand fleas belonging to the genus Tunga .", "So far 14 different Tunga species have been described [1–4] of which three have been reported in domestic animals: Tunga hexalobulata , Tunga trimamillata and Tunga penetrans [3 , 5] ."...	[ "In endemic communities , zoonotic tungiasis , a severe skin disease caused by penetrating female sand fleas , is a public health hazard causing significant human and animal morbidity .", "No validated drugs are currently available for treatment of animal tungiasis .", "Due to the reservoir in domestic animals ...	[ "Infection with the sand flea Tunga penetrans causes severe disease in humans and animals .", "There are no validated drugs for treatment of animal tungiasis preventing implementation of integrated tungiasis control interventions targeting human and animal infections .", "A field trial was conducted to evaluate...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "developmental biology/germ cells", "cell biology/cellular death and stress responses", "cell biology/cell signaling", "developmental biology/aging", "biochemistry/replication and repair" ]	The Caenorhabditis elegans Werner Syndrome Protein Functions Upstream of ATR and ATM in Response to DNA Replication Inhibition and Double-Strand DNA Breaks	journal.pgen.1000801	null	[ [ "Werner syndrome ( WS ) is associated with rapid acceleration of aging , and is caused by mutations in the RecQ family DNA helicase gene , WRN [1] .", "Clinical symptoms of WS include short stature , hair-graying , cataract formation , type II diabetes , osteoporosis , atherosclerosis , and neoplasm of me...	[ "WRN-1 is the Caenorhabditis elegans homolog of the human Werner syndrome protein , a RecQ helicase , mutations of which are associated with premature aging and increased genome instability .", "Relatively little is known as to how WRN-1 functions in DNA repair and DNA damage signaling .", "Here , we take advan...	[ "Werner syndrome is a premature aging syndrome associated with genomic instability .", "The protein linked to Werner syndrome , WRN , has both helicase and exonuclease activities and is thought to be involved in DNA repair , including the resolution of replication fork arrest as well as in telomere maintenance ."...	2010
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "medicine", "bacterial diseases", "infectious diseases", "clinical epidemiology", "epidemiology", "nephrology", "acute renal failure", "rickettsia" ]	Scrub Typhus Is an Under-recognized Cause of Acute Febrile Illness with Acute Kidney Injury in India	journal.pntd.0002605	null	[ [ "Infections are responsible for a substantial portion of community acquired acute kidney injury ( AKI ) in India .", "The commonly implicated conditions include malaria , leptospirosis , dengue , enteric fever , viral and bacterial infections .", "Despite being endemic in Asia with an estimated one mi...	[ "Infection-related acute kidney injury ( AKI ) is an important preventable cause of morbidity and mortality in the tropical region .", "The prevalence and outcome of kidney involvement , especially AKI , in scrub typhus is not known .", "We investigated all patients with undiagnosed fever and multisystem involv...	[ "A large number of patients present to Indian hospitals with acute febrile illness and multisystem involvement .", "Acute kidney injury is an important component .", "Clinical manifestations do not allow distinction between infectious etiologies with overlapping presentations .", "Many of the cases remain und...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "infectious diseases", "cell biology", "microbiology", "molecular biology", "genetics and genomics" ]	A Histone Methyltransferase Modulates Antigenic Variation in African Trypanosomes	journal.pbio.0060161	Antigenic variation in Trypanosoma brucei relies on monoallelic expression of a multigene family. New evidence shows that a chromatin-modifying enzyme prevents simultaneous expression of different proteins at the parasite's surface.	[ [ "Post-transcriptional histone modifications play important roles in the regulation of chromatin structure and gene expression .", "Unlike acetylation , which is in general associated with transcription activation , histone methylation can activate or repress transcription depending upon the genomic locati...	[ "To evade the host immune system , several pathogens periodically change their cell-surface epitopes .", "In the African trypanosomes , antigenic variation is achieved by tightly regulating the expression of a multigene family encoding a large repertoire of variant surface glycoproteins ( VSGs ) .", "Immune eva...	[ "The surface of Trypanosoma brucei , a unicellular parasite that lives in the bloodstream of its mammalian host , is coated with glycoprotein ( VSG ) molecules .", "To evade elimination by the immune system , this parasite replaces its coat with one tailored from another glycoprotein variant .", "Even though th...	2008
[ "Introduction", "Materials and methods", "Results", "Discussion" ]	[ "velocity", "medicine and health sciences", "body fluids", "classical mechanics", "fluid mechanics", "mechanical stress", "viscosity", "materials science", "materials physics", "cellular structures and organelles", "chemical properties", "physical chemistry", "mucus", "chemistry", "fluid...	A new index for characterizing micro-bead motion in a flow induced by ciliary beating: Part I, experimental analysis	journal.pcbi.1005605	null	[ [ "Mucociliary clearance is one of the major defense mechanisms of the respiratory airway system .", "The mucus layer coating the epithelial surface of the airways filters the inhaled air by trapping potentially harmful material ( fungi , bacteria and other particles ) [1–4] .", "This mucus layer is con...	[ "Mucociliary clearance is one of the major lines of defense of the respiratory system .", "The mucus layer coating the pulmonary airways is moved along and out of the lung by the activity of motile cilia , thus expelling the particles trapped in it .", "Here we compare ex vivo measurements of a Newtonian flow i...	[ "Mucociliary clearance is the first line of defense of the human pulmonary airways .", "Mucus transporting debris , particles , microorganisms and pollutants is carried away by the coordinated motion of cilia beating at the surface of the airway epithelium .", "We present here an experimental , mathematical and...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "molecular cell biology", "genetics", "developmental biology", "biology" ]	Six Homeoproteins Directly Activate Myod Expression in the Gene Regulatory Networks That Control Early Myogenesis	journal.pgen.1003425	null	[ [ "The Pax-Six-Eya-Dach genetic network was first identified in Drosophila as a key transcriptional regulator of compound eye development .", "Within this network , the Pax gene , Eyeless , is an upstream regulator of genes for the Six transcription factor sine oculis and of its co-factor Eyes absent ( Eya ...	[ "In mammals , several genetic pathways have been characterized that govern engagement of multipotent embryonic progenitors into the myogenic program through the control of the key myogenic regulatory gene Myod .", "Here we demonstrate the involvement of Six homeoproteins .", "We first targeted into a Pax3 allel...	[ "The onset of skeletal muscle formation is controlled by complex gene regulatory networks .", "By manipulation of these genetic pathways in the mouse embryo , we have examined the interplay between genes encoding the transcriptional regulator Pax3; the major myogenic determination proteins Myf5 , Mrf4 , and Myod;...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "immunology/cellular microbiology and pathogenesis", "microbiology/innate immunity", "immunology/innate immunity", "infectious diseases/bacterial infections", "microbiology/cellular microbiology and pathogenesis" ]	Inflammasome Sensor Nlrp1b-Dependent Resistance to Anthrax Is Mediated by Caspase-1, IL-1 Signaling and Neutrophil Recruitment	journal.ppat.1001222	null	[ [ "Anthrax disease occurs following germination of Bacillus anthracis spores that enter an animal host through inhalational , oral , or cutaneous routes .", "Anthrax lethal toxin ( LT ) , responsible for the lethality associated with terminal anthrax disease , is composed of two polypeptides .", "LF ( l...	[ "Bacillus anthracis infects hosts as a spore , germinates , and disseminates in its vegetative form .", "Production of anthrax lethal and edema toxins following bacterial outgrowth results in host death .", "Macrophages of inbred mouse strains are either sensitive or resistant to lethal toxin depending on wheth...	[ "In this study , we show that anthrax lethal toxin activation of Nlrp1b in toxin-sensitive mouse macrophages imparts resistance to infection .", "Inbred and congenic mice harboring macrophage-sensitizing Nlrp1b alleles control bacterial growth and dissemination independent of infection route or effects on germina...	2010
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "cryptococcosis", "cellular stress responses", "medicine and health sciences", "cell processes", "microbiology", "fungal physiology", "gene function", "developmental biology", "fungi", "cell growth", "fungal diseases", "microbial growth and development", "infectious diseases", "mycology", ...	Molecular Mechanisms of Hypoxic Responses via Unique Roles of Ras1, Cdc24 and Ptp3 in a Human Fungal Pathogen Cryptococcus neoformans	journal.pgen.1004292	null	[ [ "Oxygen availability is critical for many biochemical reactions in eukaryotic cells and their ability to adapt to oxygen limitation is essential for survival .", "Most organisms are able to sense the change in environmental oxygen concentration and respond swiftly .", "For instance , the human fungal ...	[ "Cryptococcus neoformans encounters a low oxygen environment when it enters the human host .", "Here , we show that the conserved Ras1 ( a small GTPase ) and Cdc24 ( the guanine nucleotide exchange factor for Cdc42 ) play an essential role in cryptococcal growth in hypoxia .", "Suppressor studies indicate that ...	[ "When Cryptococcus neoformans , an environmental fungal pathogen , enters the human host , it encounters a low oxygen condition .", "The well conserved Ras1 and Cdc24 proteins are known for their key roles in maintenance of the actin cytoskeletal integrity in eukaryotic cells .", "In this work , we show a uniqu...	2014
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "medicine", "infectious diseases", "diagnostic medicine", "leishmaniasis", "biology", "microbiology", "parasitic diseases", "parasitology" ]	Comparison of Visceral Leishmaniasis Diagnostic Antigens in African and Asian Leishmania donovani Reveals Extensive Diversity and Region-specific Polymorphisms	journal.pntd.0002057	null	[ [ "Visceral leishmaniasis ( VL ) remains a major public health concern in many parts of the tropical world , with the great majority of the estimated 200 , 000 to 400 , 000 annual new cases found in South Asia , East Africa , and Brazil [1] , [2] .", "VL is caused by kinetoplastid protozoa of the Leishmania...	[ "Visceral leishmaniasis ( VL ) , caused by infection with Leishmania donovani complex , remains a major public health problem in endemic regions of South Asia , East Africa , and Brazil .", "If untreated , symptomatic VL is usually fatal .", "Rapid field diagnosis relies principally on demonstration of anti-Lei...	[ "Visceral leishmaniasis ( VL ) is caused by infection with parasites of the Leishmania donovani complex , spread by the bite of blood-sucking sandflies , especially in South Asia , East Africa , and Brazil .", "If untreated , symptomatic VL leads to systemic pathologies and is usually fatal .", "Up to approxima...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "viral classification", "emerging viral diseases", "viral enzymes", "microbiology", "viral genera unassigned to a family", "rna viruses", "comparative genomics", "biology", "viral replication complex", "viral replication", "viral evolution", "virology", "evolutionary biology", "genomic evo...	Discovery of the First Insect Nidovirus, a Missing Evolutionary Link in the Emergence of the Largest RNA Virus Genomes	journal.ppat.1002215	null	[ [ "Viruses employing positive-sense , single-stranded RNA genomes ( ssRNA+ ) form the most abundant class and its members are known to infect all types of hosts except Archaea .", "They have evolved genome sizes in the range of ∼3 . 0 to 31 . 6 kb ( Fig . 1 ) .", "This size range is the largest among th...	[ "Nidoviruses with large genomes ( 26 . 3–31 . 7 kb; ‘large nidoviruses’ ) , including Coronaviridae and Roniviridae , are the most complex positive-sense single-stranded RNA ( ssRNA+ ) viruses .", "Based on genome size , they are far separated from all other ssRNA+ viruses ( below 19 . 6 kb ) , including the dist...	[ "Research in virology is driven towards the characterization of a limited number of socioeconomically important pathogens , mostly those infecting humans .", "Yet , characterization of other viruses may advance our understanding of these topical pathogens and the fundamentals of virology .", "Here we describe t...	2011
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "chromosome structure and function", "microbiology", "escherichia coli", "prokaryotic models", "model organisms", "cell division", "cytokinesis", "molecular genetics", "microbial growth and development", "chromosome biology", "biology", "biochemistry", "cell biology", "genetic screens", ...	Identification of the SlmA Active Site Responsible for Blocking Bacterial Cytokinetic Ring Assembly over the Chromosome	journal.pgen.1003304	null	[ [ "Cell division in bacteria typically begins with the assembly of a membrane-associated cytoskeletal structure composed of polymers of the tubulin-like FtsZ protein and its associated binding partners [1]–[5] .", "This ring-shaped collection of polymers is called the Z-ring and it is ultimately responsible...	[ "Bacterial cells use chromosome-associated division inhibitors to help coordinate the processes of DNA replication and segregation with cytokinesis .", "SlmA from Escherichia coli , a member of the tetracycline repressor ( TetR ) –like protein family , is one example of this class of regulator .", "It blocks th...	[ "The tetracycline repressor ( TetR ) –like protein family is broadly distributed among bacteria .", "These factors typically regulate the expression of genes coding for drug resistance pumps .", "When they bind drug molecules , the repressors undergo a conformational change that releases them from their specifi...	2013
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "medicine", "infectious diseases", "cytokines", "clinical immunology", "immunity", "immunity to infections", "immunology", "biology", "parasitic diseases", "onchocerciasis", "immunomodulation", "immune response", "immune system" ]	Immunoepidemiological Profiling of Onchocerciasis Patients Reveals Associations with Microfilaria Loads and Ivermectin Intake on Both Individual and Community Levels	journal.pntd.0002679	null	[ [ "Infections with Onchocerca volvulus commence with the transmission of larvae by biting vector hosts ( black flies ) [1] , [2] .", "Female filariae create and dwell within subcutaneous nodules called onchocercomas [3] , [4] whereas male worms do not take up permanent residency but migrate in the subcutane...	[ "Mass drug administration ( MDA ) programmes against Onchocerca volvulus use ivermectin ( IVM ) which targets microfilariae ( MF ) , the worm's offspring .", "Most infected individuals are hyporesponsive and present regulated immune responses despite high parasite burden .", "Recently , with MDA programmes , th...	[ "Onchocerciasis affects over 37 million people in poor communities .", "Infected individuals usually present a generalized form which is characterized by low inflammation , tightly-controlled immune responses and high parasite burden .", "In contrast , patients with chronic dermatitis ( sowda ) have reduced par...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "signal transduction", "cell biology", "biology and life sciences", "cell processes", "molecular cell biology", "molecular biology" ]	Maf1 Is a Novel Target of PTEN and PI3K Signaling That Negatively Regulates Oncogenesis and Lipid Metabolism	journal.pgen.1004789	null	[ [ "Obesity , characterized by an elevation in circulating lipids , has been associated with increased incidence of cancer [1] .", "A hallmark of cancer cells is an increase in de novo fatty acid synthesis .", "This occurs as a result of induction in the expression and function of lipogenic enzymes inclu...	[ "Maf1 was initially identified as a transcriptional repressor of RNA pol III-transcribed genes , yet little is known about its other potential target genes or its biological function .", "Here , we show that Maf1 is a key downstream target of PTEN that drives both its tumor suppressor and metabolic functions .", ...	[ "Obesity is a strong risk factor for human cancers , yet the biological basis for this is unclear .", "In addition to aberrant growth , abnormal lipid synthesis is a hallmark of cancer cells .", "Our results have identified a novel role for Maf1 in suppressing both lipid biogenesis and tumor formation .", "Ma...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "computational biology/evolutionary modeling", "genetics and genomics/microbial evolution and genomics", "virology/virus evolution and symbiosis" ]	Viral Genome Segmentation Can Result from a Trade-Off between Genetic Content and Particle Stability	journal.pgen.1001344	null	[ [ "A biological clone of foot-and-mouth disease virus ( FMDV ) , termed C-S8c1 , evolved in BHK-21 cell culture infections at high multiplicity of infection ( MOI ) , towards a population dominated by defective genomic forms that were infectious by complementation in the absence of standard size ( ST ) genomes ...	[ "The evolutionary benefit of viral genome segmentation is a classical , yet unsolved question in evolutionary biology and RNA genetics .", "Theoretical studies anticipated that replication of shorter RNA segments could provide a replicative advantage over standard size genomes .", "However , this question has r...	[ "Genome segmentation , the splitting of a linear genome into two or more segments , is a major evolutionary transition from independent towards complementing transmission of genetic information .", "Many viruses with RNA as genetic material have segmented genomes , but the molecular forces behind genome segmentat...	2011
[ "Introduction", "Results/Discussion", "Methods" ]	[ "genome analysis tools", "genomics", "gene prediction", "biology", "computational biology", "comparative genomics" ]	Genome Majority Vote Improves Gene Predictions	journal.pcbi.1002284	null	[ [ "All of genomics depends on accurate identification of coding regions .", "Most gene boundaries are predicted using computational methods , and only a tiny fraction have been verified experimentally .", "Unfortunately , the accuracy of current gene-finding algorithms is not perfect .", "Error rate...	[ "Recent studies have noted extensive inconsistencies in gene start sites among orthologous genes in related microbial genomes .", "Here we provide the first documented evidence that imposing gene start consistency improves the accuracy of gene start-site prediction .", "We applied an algorithm using a genome ma...	[ "The genetic code tells us precisely how a DNA sequence will be translated into a protein .", "However , it is more difficult to identify where translation will start and stop in the entire length of an organism's genome sequence .", "Computer software can predict where the start sites are , and this is success...	2011
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine", "infectious diseases", "biology", "microbiology" ]	Human-like PB2 627K Influenza Virus Polymerase Activity Is Regulated by Importin-α1 and -α7	journal.ppat.1002488	null	[ [ "Influenza A viruses are able to cross species barriers and transmit to humans leading to disease of various severity .", "Interspecies transmission of influenza viruses is multigenic involving several viral and cellular factors .", "Host restriction occurs mainly by two cellular barriers which need t...	[ "Influenza A viruses may cross species barriers and transmit to humans with the potential to cause pandemics .", "Interplay of human- ( PB2 627K ) and avian-like ( PB2 627E ) influenza polymerase complexes with unknown host factors have been postulated to play a key role in interspecies transmission .", "Here ,...	[ "Adaptive mutations in the polymerase complex , such as PB2 E627K and PB2 D701N play a crucial role in influenza virus interspecies transmission .", "We have shown earlier that PB2 D701N promotes nuclear entry of PB2 by enhanced importin-α binding in mammalian cells ( Gabriel et al . , PLoS Pathogens 2008; Gabrie...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Recurrent Tissue-Specific mtDNA Mutations Are Common in Humans	journal.pgen.1003929	null	[ [ "Mitochondrial DNA ( mtDNA ) heteroplasmy is commonly thought to be the product of either maternal inheritance [1] or rare , random somatic mutations that undergo subsequent expansion within an individual via genetic drift [2] , [3] .", "Inherited heteroplasmy should be present in many , but perhaps not a...	[ "Mitochondrial DNA ( mtDNA ) variation can affect phenotypic variation; therefore , knowing its distribution within and among individuals is of importance to understanding many human diseases .", "Intra-individual mtDNA variation ( heteroplasmy ) has been generally assumed to be random .", "We used massively pa...	[ "DNA mutations are expected to be formed randomly , thus any reproducible pattern of DNA somatic mutations across multiple individuals or even across organs within each individual is highly unexpected .", "Using next generation sequencing of multiple tissues from the same individuals we found several somatic muta...	2013
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[]	Classification of Bartonella Strains Associated with Straw-Colored Fruit Bats (Eidolon helvum) across Africa Using a Multi-locus Sequence Typing Platform	journal.pntd.0003478	null	[ [ "Bartonellae are both Gram-negative alpha-proteobacteria and hemotropic bacteria highly adapted to facultative intracellular lifestyle in a wide variety of mammals , such as rodents , bats , insectivores , carnivores , ungulates , and other vertebrates .", "During the last two decades , progressively more...	[ "Bartonellae are facultative intracellular bacteria and are highly adapted to their mammalian host cell niches .", "Straw-colored fruit bats ( Eidolon helvum ) are commonly infected with several bartonella strains .", "To elucidate the genetic diversity of these bartonella strains , we analyzed 79 bartonella is...	[ "Bats , with over 1000 recognized species , represent about 20% of all classified mammalian species worldwide .", "These mammals have a wide range of ecologies and life-history traits , and are now widely recognized as important reservoirs of many pathogens .", "Bartonella species have been found distributed in...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genetics", "immunology", "biology" ]	Distinct Translational Control in CD4+ T Cell Subsets	journal.pgen.1003494	null	[ [ "Regulation of gene expression is a multi-step process involving transcriptional , post-transcriptional and post-translational mechanisms .", "Recent studies have revealed that only 30–40% of steady state protein levels correspond to steady-state mRNA levels and identified mRNA translation as the principa...	[ "Regulatory T cells expressing the transcription factor Foxp3 play indispensable roles for the induction and maintenance of immunological self-tolerance and immune homeostasis .", "Genome-wide mRNA expression studies have defined canonical signatures of T cell subsets .", "Changes in steady-state mRNA levels , ...	[ "Regulatory T cells expressing the nuclear protein Foxp3 are essential for the control of immune responses towards self and foreign antigens .", "Genome-wide gene expression studies have defined canonical signatures of T cell subsets .", "However , changes in mRNA levels often do not reflect those of correspond...	2013
[ "Introduction", "Materials and methods", "Results", "Discussion" ]	[ "medicine and health sciences", "population genetics", "vertebrates", "parasitic diseases", "animals", "mammals", "microsatellite loci", "tongue", "gene types", "molecular biology techniques", "population biology", "genotyping", "genetic epidemiology", "research and analysis methods", "d...	Genetic variability of Taenia solium cysticerci recovered from experimentally infected pigs and from naturally infected pigs using microsatellite markers	journal.pntd.0006087	null	[ [ "Taenia solium is a zoonotic parasite that affects both humans and pigs .", "Larval infection in the human brain results in neurocysticercosis , the sole main cause of acquired adult epilepsy in developing countries [2] .", "Neurocysticercosis is considered a potentially eradicable disease [3] , and m...	[ "The adult Taenia solium , the pork tapeworm , usually lives as a single worm in the small intestine of humans , its only known definitive host .", "Mechanisms of genetic variation in T . solium are poorly understood .", "Using three microsatellite markers previously reported [1] , this study explored the genet...	[ "Taenia solium , the pork tapeworm , is a major cause of epilepsy in developing countries .", "Although it has been deemed a potentially eradicable pathogen , it remains prevalent in rural communities .", "This two-part study aims to evaluate the utility of three microsatellite markers previously reported , to ...	2017
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "medicine and health sciences", "action potentials", "membrane potential", "electrophysiology", "neuroscience", "pharmacology", "waves", "cardiology", "tissue distribution", "arrhythmia", "atrial fibrillation", "behavior", "chemistry", "pharmacokinetics", "physics", "biochemistry", "...	In silico assessment of genetic variation in KCNA5 reveals multiple mechanisms of human atrial arrhythmogenesis	journal.pcbi.1005587	null	[ [ "Mutations in genes encoding the proteins involved in cardiac electrophysiology can result in alterations of the electrical action potential ( AP ) and tissue excitability , which may affect cardiac output and predispose to arrhythmias , such as atrial fibrillation ( AF ) [1 , 2] .", "AF , the world’s mos...	[ "A recent experimental study investigating patients with lone atrial fibrillation identified six novel mutations in the KCNA5 gene .", "The mutants exhibited both gain- and loss-of-function of the atrial specific ultra-rapid delayed rectifier K+ current , IKur .", "The aim of this study is to elucidate and quan...	[ "In a recent study , six mutations resulting in either gain-of-function or loss-of-function in the ultra-rapid delayed rectifier potassium current IKur , were identified to be associated with atrial fibrillation ( AF ) .", "However , the causative link between the mutant IKur ( either gain- or loss-of-function ) ...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Loregic: A Method to Characterize the Cooperative Logic of Regulatory Factors	journal.pcbi.1004132	null	[ [ "The rapidly increasing amount of high throughput sequencing data offers novel and diverse resources to probe molecular functions on a genome-wide scale .", "Integrating and mining these various large-scale datasets is both a central priority and a great challenge for the field of functional genomics and ...	[ "The topology of the gene-regulatory network has been extensively analyzed .", "Now , given the large amount of available functional genomic data , it is possible to go beyond this and systematically study regulatory circuits in terms of logic elements .", "To this end , we present Loregic , a computational met...	[ "Gene expression is controlled by various gene regulatory factors .", "Those factors work cooperatively forming a complex regulatory circuit genome wide .", "Corruptions of regulatory cooperativity may lead to abnormal gene expression activity such as cancer .", "Traditional experimental methods , however , c...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biotechnology", "blood cells", "cell physiology", "bacteriology", "innate immune system", "medicine and health sciences", "immune cells", "pathology and laboratory medicine", "small molecules", "endothelial cells", "immunology", "immune suppression", "microbiology", "epithelial cells", ...	The Pathogenic Mechanism of the Mycobacterium ulcerans Virulence Factor, Mycolactone, Depends on Blockade of Protein Translocation into the ER	journal.ppat.1004061	null	[ [ "Mycolactone is a lipid-like polyketide macrolide virulence factor produced by Mycobacterium ulcerans , the infectious agent of Buruli ulcer ( BU ) [1] , [2] .", "This progressive , necrotizing , cutaneous lesion is common in West Africa but also found in other regions , including Australia , Asia and Sou...	[ "Infection with Mycobacterium ulcerans is characterised by tissue necrosis and immunosuppression due to mycolactone , the necessary and sufficient virulence factor for Buruli ulcer disease pathology .", "Many of its effects are known to involve down-regulation of specific proteins implicated in important cellular...	[ "Buruli ulcer is a progressive necrotic skin lesion caused by infection with the human pathogen Mycobacterium ulcerans .", "Mycolactone , a small compound produced by the mycobacterium , is the root cause of the disease pathology , but until now there has been no unifying mechanism explaining why .", "We have b...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genetics and genomics/epigenetics", "molecular biology/chromatin structure" ]	The Impact of Local Genome Sequence on Defining Heterochromatin Domains	journal.pgen.1000453	null	[ [ "Correct patterns of gene expression are established by orchestrated interactions among cis-regulatory elements , trans-acting factors and the surrounding chromatin environment .", "How these interactions are coordinated and to what extent genomic sequence serves as a blueprint , directing these interacti...	[ "Characterizing how genomic sequence interacts with trans-acting regulatory factors to implement a program of gene expression in eukaryotic organisms is critical to understanding genome function .", "One means by which patterns of gene expression are achieved is through the differential packaging of DNA into dist...	[ "Epigenetic packaging of DNA sequence into chromatin is a major force in shaping the function of complex genomes .", "Different types of chromatin have distinct effects on gene expression , and thus chromatin state imparts distinct features on the associated genomic DNA .", "Our study focuses on the transition ...	2009
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	A Genomic Duplication is Associated with Ectopic Eomesodermin Expression in the Embryonic Chicken Comb and Two Duplex-comb Phenotypes	journal.pgen.1004947	null	[ [ "In the domestic chicken ( Gallus domesticus ) the comb serves as a sexual ornament and the size of the comb is associated with mate choice in both sexes as well as fecundity in females [1 , 2] .", "The vast majority of chicken populations used for commercial meat and egg production around the world are f...	[ "Duplex-comb ( D ) is one of three major loci affecting comb morphology in the domestic chicken .", "Here we show that the two Duplex-comb alleles , V-shaped ( DV ) and Buttercup ( DC ) , are both associated with a 20 Kb tandem duplication containing several conserved putative regulatory elements located 200 Kb...	[ "There are three major variant comb types found in the domestic chicken; Rose-comb , Pea-comb and Duplex-comb .", "Within the Duplex-comb there are two distinct types , V-shaped and Buttercup .", "Previous experiments have shown that these two Duplex-comb types represent different alleles at a single locus .", ...	2015
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "chemical compounds", "plant growth and development", "brassica", "organic compounds", "developmental biology", "plant science", "model organisms", "tyrosine", "experimental organism systems", "amino acids", "dna", "embryos", "plants", "arabidopsis thaliana", "research and analysis metho...	The topoisomerase 3α zinc-finger domain T1 of Arabidopsis thaliana is required for targeting the enzyme activity to Holliday junction-like DNA repair intermediates	journal.pgen.1007674	null	[ [ "The processing of DNA recombination intermediates like Holliday junctions ( HJs ) is of utmost importance for all cells to prevent chromosome breakage and ultimately cell death .", "While the concerted activity of nucleases in the resolution pathway resolves double Holliday junctions ( dHJs ) to crossove...	[ "Topoisomerase 3α , a class I topoisomerase , consists of a TOPRIM domain , an active centre and a variable number of zinc-finger domains ( ZFDs ) at the C-terminus , in multicellular organisms .", "Whereas the functions of the TOPRIM domain and the active centre are known , the specific role of the ZFDs is still...	[ "DNA Topoisomerases are essential for transcription , DNA repair and DNA replication due to their function to break and change the topological state of DNA molecules .", "Topoisomerase 3α is especially important for DNA repair as it is able to process different DNA recombination and repair intermediates .", "Th...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine and health sciences" ]	Recent Mitochondrial DNA Mutations Increase the Risk of Developing Common Late-Onset Human Diseases	journal.pgen.1004369	null	[ [ "Mitochondria are the principal source of cellular adenosine triphosphate ( ATP ) generated through oxidative phosphorylation ( OXPHOS ) , which is linked to the respiratory chain .", "In humans , thirteen OXPHOS proteins are synthesised from the 16 . 5 Kb mitochondrial genome ( mtDNA ) .", "MtDNA has...	[ "Mitochondrial DNA ( mtDNA ) is highly polymorphic at the population level , and specific mtDNA variants affect mitochondrial function .", "With emerging evidence that mitochondrial mechanisms are central to common human diseases , it is plausible that mtDNA variants contribute to the “missing heritability” of se...	[ "There is a growing body of evidence indicating that mitochondrial dysfunction , a result of genetic variation in the mitochondrial genome , is a critical component in the aetiology of a number of complex traits .", "Here , we take advantage of recent technical and methodological advances to examine the role of c...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "virology/virulence factors and mechanisms", "virology/virus evolution and symbiosis", "molecular biology/recombination", "neurological disorders/infectious diseases of the nervous system", "molecular biology/molecular evolution", "virology/emerging viral diseases", "infectious diseases/viral infections...	Recombination between Polioviruses and Co-Circulating Coxsackie A Viruses: Role in the Emergence of Pathogenic Vaccine-Derived Polioviruses	journal.ppat.1000412	null	[ [ "The Sabin's trivalent live-attenuated oral poliovirus vaccine ( OPV ) includes viral strains of three serotypes ( Sabin 1 , 2 and 3 ) .", "These strains replicate in the digest tract following vaccination , inducing a strong local intestinal immune response that limits subsequent poliovirus ( PV ) replic...	[ "Ten outbreaks of poliomyelitis caused by pathogenic circulating vaccine-derived polioviruses ( cVDPVs ) have recently been reported in different regions of the world .", "Two of these outbreaks occurred in Madagascar .", "Most cVDPVs were recombinants of mutated poliovaccine strains and other unidentified ente...	[ "Following intense vaccination campaigns with Sabin's trivalent live-attenuated oral poliovirus vaccine , poliomyelitis caused by wild polioviruses has disappeared from large parts of the world .", "However , poliomyelitis outbreaks due to pathogenic circulating vaccine-derived polioviruses ( cVDPVs ) have recent...	2009
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biology" ]	Phospholipids Trigger Cryptococcus neoformans Capsular Enlargement during Interactions with Amoebae and Macrophages	journal.ppat.1002047	null	[ [ "Certain environmental microbes exist that have no obvious need for animal virulence", "with regards to their survival or propagation yet these organisms have the ability", "to cause infection and disease in a human host .", "One such organism is the soil fungus", "Cryptococcus neoformans , a ...	[ "A remarkable aspect of the interaction of Cryptococcus", "neoformans with mammalian hosts is a consistent increase in capsule", "volume .", "Given that many aspects of the interaction of C .", "neoformans with macrophages are also observed with amoebae , we", "hypothesized that the capsule enlargement ph...	[ "A key event in C . neoformans pathogenesis is capsule enlargement", "in mammalian hosts .", "Historically , this phenomenon was attributed to high", "CO2 and iron deprivation but the magnitude of capsular", "enlargement observed in vivo cannot be consistently replicated", "in vitro .", "This paper repo...	2011
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "medicine", "infectious diseases", "neglected tropical diseases", "parasitic diseases" ]	A Multicenter Evaluation of Diagnostic Tools to Define Endpoints for Programs to Eliminate Bancroftian Filariasis	journal.pntd.0001479	null	[ [ "In 2000 the Global Programme to Eliminate Lymphatic Filariasis ( GPELF ) was launched , providing antifilarial drugs to millions of people through mass drug administration ( MDA ) programs .", "During the GPELF's first nine years over 2 . 6 billion treatments of antifilarial drugs were given to people in...	[ "Successful mass drug administration ( MDA ) campaigns have brought several countries near the point of Lymphatic Filariasis ( LF ) elimination .", "A diagnostic tool is needed to determine when the prevalence levels have decreased to a point that MDA campaigns can be discontinued without the threat of recrudesce...	[ "Lymphatic filariasis ( LF ) , a mosquito-borne parasitic disease , is a candidate for elimination largely because of the success of mass drug administration ( MDA ) campaigns , in which entire at-risk populations are given a once-yearly regimen of single-dose treatment with two medications .", "As a result , a d...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "computer science", "mathematics", "statistics", "computerized simulations", "statistical methods" ]	GUESS-ing Polygenic Associations with Multiple Phenotypes Using a GPU-Based Evolutionary Stochastic Search Algorithm	journal.pgen.1003657	null	[ [ "The recently proposed piMASS algorithm implements a BVS strategy for genome-wide association analysis of single continuous phenotypes with a novel prior specification for the variance of the regression coefficients .", "The implementation of piMASS is based on a single chain Monte Carlo Markov Chain ( MC...	[ "Genome-wide association studies ( GWAS ) yielded significant advances in defining the genetic architecture of complex traits and disease .", "Still , a major hurdle of GWAS is narrowing down multiple genetic associations to a few causal variants for functional studies .", "This becomes critical in multi-phenot...	[ "Nowadays , the availability of cheaper and accurate assays to quantify multiple ( endo ) phenotypes in large population cohorts allows multi-trait studies .", "However , these studies are limited by the lack of flexible models integrated with efficient computational tools for genome-wide multi SNPs-traits analys...	2013
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "genome analysis tools", "genomics", "genetic association studies", "genetics", "biology", "computational biology", "genetics and genomics", "human genetics" ]	A Hybrid Likelihood Model for Sequence-Based Disease Association Studies	journal.pgen.1003224	null	[ [ "Research efforts over the past few years have yielded an explosion of exome sequencing studies and exomic variation data ( reviewed in [1] , [2] ) .", "One surprising result has been the discovery of hundreds of thousands of novel and rare nonsilent variants in protein coding genes , some of which may ha...	[ "In the past few years , case-control studies of common diseases have shifted their focus from single genes to whole exomes .", "New sequencing technologies now routinely detect hundreds of thousands of sequence variants in a single study , many of which are rare or even novel .", "The limitation of classical s...	[ "Inexpensive , high-throughput sequencing has transformed the field of case-control association studies .", "For the first time , it may be possible to identify the genetic underpinnings of complex diseases , by sequencing the DNA of hundreds ( even thousands ) of cases and controls and comparing patterns of DNA ...	2013
[ "Introduction", "Materials and methods", "Results", "Discussion" ]	[ "blood serum", "invertebrates", "medicine and health sciences", "immune physiology", "body fluids", "helminths", "immunology", "bile", "vertebrates", "animals", "mammals", "trematodes", "preventive medicine", "vaccines", "immunologic adjuvants", "infectious disease control", "antibod...	Vaccination of hamsters with Opisthorchis viverrini extracellular vesicles and vesicle-derived recombinant tetraspanins induces antibodies that block vesicle uptake by cholangiocytes and reduce parasite burden after challenge infection	journal.pntd.0007450	null	[ [ "The human liver fluke Opisthorchis viverrini is endemic in different countries of Southeast Asia including Thailand , Lao PDR , Cambodia , southern part of Vietnam and Myanmar [1 , 2] .", "Furthermore , liver fluke infection is associated with a high incidence of liver pathology including cholangiocarcin...	[ "The liver fluke Opisthorchis viverrini infects several million people in Southeast Asia .", "Adult flukes live in the bile ducts of humans , where they cause hepatobiliary pathology , including cholangiocarcinoma .", "Here , we investigated the potential of extracellular vesicles ( EVs ) secreted by the fluke ...	[ "Cholangiocarcinoma ( CCA ) is a significant public health problem in countries throughout Southeast Asia .", "In these areas CCA has a strong association with chronic infection with the food-borne liver fluke Opisthorchis viverrini .", "Current control of the infection relies on chemotherapy and health educati...	2019
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "viral classification", "immunity to infections", "immunology", "microbiology", "host-pathogen interaction", "rna viruses", "immune defense", "animal models of infection", "virulence factors and mechanisms", "viral immune evasion", "biology", "immune response", "immunity", "virology", "i...	2′-O Methylation of the Viral mRNA Cap by West Nile Virus Evades Ifit1-Dependent and -Independent Mechanisms of Host Restriction In Vivo	journal.ppat.1002698	null	[ [ "Type I interferon ( IFN ) restricts infection of many viruses through cell-intrinsic and cell-extrinsic effects on replication , and by priming adaptive B and T cell responses ( reviewed in [1] ) .", "Expression of type I IFN after RNA virus infection generally occurs after recognition of viral RNA by pa...	[ "Prior studies have shown that 2′-O methyltransferase activity of flaviviruses , coronaviruses , and poxviruses promotes viral evasion of Ifit1 , an interferon-stimulated innate immune effector protein .", "Viruses lacking 2′-O methyltransferase activity exhibited attenuation in primary macrophages that was rescu...	[ "We recently showed that a West Nile virus ( WNV ) mutant in NS5 ( WNV-E218A ) lacking 2′-O methyltransferase activity was attenuated in primary macrophages but replicated well in cells lacking type I interferon ( IFN ) signaling or expression of Ifit1 , an IFN-stimulated gene .", "Here , we follow-up these studi...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biochemistry", "developmental biology", "genetics", "biology", "molecular cell biology", "neuroscience", "genetics and genomics" ]	Three-Dimensional Regulation of Radial Glial Functions by Lis1-Nde1 and Dystrophin Glycoprotein Complexes	journal.pbio.1001172	Lis1-Nde1 integrates cerebral cortical neurogenesis with neuronal migration by stabilizing the basal-lateral surface of radial glial cells.	[ [ "Radial glial cells ( RGCs ) in the developing cerebral cortex are the most distinctive stem cells , having unique morphology and cytoarchitectural environments .", "Derived from neuroepithelial cells ( NECs ) at the onset of neurogenesis , RGCs maintain the apical-basal polarity of NECs but elongate whil...	[ "Radial glial cells ( RGCs ) are distinctive neural stem cells with an extraordinary slender bipolar morphology and dual functions as precursors and migration scaffolds for cortical neurons .", "Here we show a novel mechanism by which the Lis1-Nde1 complex maintains RGC functions through stabilizing the dystrophi...	[ "The processes of neurogenesis and neuronal migration within the developing cerebral cortex must be tightly orchestrated to enable ordered generation and transportation of neurons to designated cortical layers .", "The mechanism by which these two processes are integrated remains elusive .", "Radial glial cells...	2011
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "blood cells", "antimicrobials", "periplasm", "medicine and health sciences", "immune cells", "pathology and laboratory medicine", "chemical compounds", "pathogens", "drugs", "immunology", "microbiology", "carbohydrates", "salmonellosis", "organic compounds", "glucose", "bacterial dise...	A cell-based infection assay identifies efflux pump modulators that reduce bacterial intracellular load	journal.ppat.1007115	null	[ [ "Human pathogens have become increasingly resistant to clinical antibiotics .", "Gram-negative bacterial pathogens are particularly problematic because their outer membranes are impermeable to many chemicals , and because many compounds that do enter the periplasm or cross the cellular membrane are immedi...	[ "Bacterial efflux pumps transport small molecules from the cytoplasm or periplasm outside the cell .", "Efflux pump activity is typically increased in multi-drug resistant ( MDR ) pathogens; chemicals that inhibit efflux pumps may have potential for antibiotic development .", "Using an in-cell screen , we ident...	[ "Bacteria evolved molecular machines called efflux pumps to export toxic chemicals , including antibiotics encountered in the environment .", "Multi-drug resistant ( MDR ) bacteria use efflux pumps to rapidly transport clinical antibiotics out of the cell and thereby increase the dosage at which they tolerate ant...	2018
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "medicine", "biochemical simulations", "infectious diseases", "public health and epidemiology", "parasitic diseases", "epidemiology", "environmental epidemiology", "neglected tropical diseases", "biology", "computational biology", "spatial epidemiology", "infectious disease modeling" ]	Transmission Risks of Schistosomiasis Japonica: Extraction from Back-propagation Artificial Neural Network and Logistic Regression Model	journal.pntd.0002123	null	[ [ "In spite of schistosomiasis has been considered as one of neglected tropical diseases distributed in tropical and subtropical areas of the world , schistosomiasis ranks higher priority among four infectious diseases in alliance with HIV/AIDS , tuberculosis and hepatitis B in the People's Republic of China ( ...	[ "The transmission of schistosomiasis japonica in a local setting is still poorly understood in the lake regions of the People's Republic of China ( P . R . China ) , and its transmission patterns are closely related to human , social and economic factors .", "We aimed to apply the integrated approach of artificia...	[ "Schistosomiasis japonica is one of the serious infectious diseases causing problems in public health in People's Republic of China ( P . R . China ) .", "The prevalence of schistosomiasis japonica is easily rebounding in the lake regions due to unique environmental settings .", "By considering the importance i...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine and health sciences", "pathology and laboratory medicine", "affinity chromatography", "pathogens", "microbiology", "viruses", "hpv-18", "oncology", "dna viruses", "human papillomavirus", "glutathione chromatography", "research and analysis methods", "spectrum analysis techniques", ...	Analysis of Multiple HPV E6 PDZ Interactions Defines Type-Specific PDZ Fingerprints That Predict Oncogenic Potential	journal.ppat.1005766	null	[ [ "High-risk human alpha-papillomaviruses are the causative agents of cervical cancer , other anogenital cancers , and an increasing proportion of head-and-neck cancers [1 , 2] .", "They express two major oncoproteins , E6 and E7 , which are essential for maintenance of the transformed phenotype , and block...	[ "The high-risk Human Papillomavirus ( HPV ) E6 oncoproteins are characterised by the presence of a class I PDZ-binding motif ( PBM ) on their extreme carboxy termini .", "The PBM is present on the E6 proteins derived from all cancer-causing HPV types , but can also be found on some related non-cancer-causing E6 p...	[ "The cancer-causing Human Papillomavirus ( HPV ) E6 oncoproteins have a unique carboxy terminal PDZ binding motif ( PBM ) , which interacts with a number of different cellular PDZ domain-containing substrates .", "The PBM has important functions in both the viral life cycle and in HPV-induced malignancy .", "In...	2016
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "medicine", "biology" ]	Immunoprotection of Mice against Schistosomiasis Mansoni Using Solubilized Membrane Antigens	journal.pntd.0002254	null	[ [ "Schistosomiasis is still one of the most prevalent and serious parasitic diseases worldwide; over 200 million persons are currently infected in endemic areas , over 85% of which live in sub-Sahara Africa [1] , [2] .", "Praziquantel ( PZQ ) remains the main anti-schistosome drug for treatment [3]; however...	[ "Schistosomiasis continues to be one of the most prevalent parasitic diseases in the world .", "Despite the existence of a highly effective antischistosome drug , the disease is spreading into new areas , and national control programs do not arrive to complete their tasks particularly in low endemic areas .", "...	[ "Schistosomiasis is a neglected disease affecting more than 200 million people globally , especially in sub-Saharan Africa .", "The mainstay of control of schistosomiasis is Praziquantel , but the mass administration of this drug is unsustainable due to the high rates of re-infection after treatment .", "These ...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "virology/viral replication and gene regulation" ]	Mouse Hepatitis Coronavirus RNA Replication Depends on GBF1-Mediated ARF1 Activation	journal.ppat.1000088	null	[ [ "Viruses rely on cellular host factors for virtually all steps of their infection cycle .", "However , the cellular proteins required and the cellular pathways hijacked by viruses have hardly been elucidated .", "All positive-strand RNA viruses assemble in infected cells their replication complexes ( ...	[ "Coronaviruses induce in infected cells the formation of double membrane vesicles , which are the sites of RNA replication .", "Not much is known about the formation of these vesicles , although recent observations indicate an important role for the endoplasmic reticulum in the formation of the mouse hepatitis co...	[ "Coronaviruses are the causative agents of many respiratory and enteric infections in humans and animals .", "As with all viruses , virtually all of the steps of their infection cycle depend on host cellular factors .", "As the first and most crucial step after their entry into cells , coronaviruses assemble th...	2008
[ "Introduction", "Results", "Discussion", "Materials and Methods", "Supporting Information" ]	[ "neuroscience", "drosophila", "genetics and genomics" ]	Dominant-Negative CK2α Induces Potent Effects on Circadian Rhythmicity	journal.pgen.0040012	null	[ [ "Circadian rhythms that orchestrate daily fluctuations in biochemistry , physiology and behavior are observed across distinct phylogenetic kingdoms .", "Underscoring the evolutionary importance of these clocks , the molecular processes that drive circadian rhythms are also highly conserved .", "At the...	[ "Circadian clocks organize the precise timing of cellular and behavioral events .", "In Drosophila , circadian clocks consist of negative feedback loops in which the clock component PERIOD ( PER ) represses its own transcription .", "PER phosphorylation is a critical step in timing the onset and termination of ...	[ "The molecular mechanism that governs organization of physiology and behavior into 24-h rhythms is a conserved transcriptional feedback process that is strikingly similar across distinct phyla .", "Notably , cyclic phosphorylation of negative feedback regulators is critical to time molecular rhythms .", "Indeed...	2008
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genetics", "biology and life sciences", "human genetics" ]	Meta-analysis of SHANK Mutations in Autism Spectrum Disorders: A Gradient of Severity in Cognitive Impairments	journal.pgen.1004580	null	[ [ "Autism spectrum disorders ( ASD ) are characterized by impairments in reciprocal social communication and stereotyped behaviors .", "There is strong evidence of the involvement of different forms of genetic variations in ASD [1] , [2] .", "In particular , chromosomal rearrangements , rare de novo cop...	[ "SHANK genes code for scaffold proteins located at the post-synaptic density of glutamatergic synapses .", "In neurons , SHANK2 and SHANK3 have a positive effect on the induction and maturation of dendritic spines , whereas SHANK1 induces the enlargement of spine heads .", "Mutations in SHANK genes have been as...	[ "Autism spectrum disorders ( ASD ) are a heterogeneous group of neurodevelopmental disorders .", "Mutations altering genes involved in the junction between brain cells have been repeatedly associated in ASD .", "For example , SHANK1 , SHANK2 and SHANK3 emerged as one family of genes that are associated with ASD...	2014
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "computational biology/macromolecular structure analysis", "cell biology/cell signaling", "biochemistry/bioinformatics", "biochemistry/macromolecular assemblies and machines", "computational biology", "genetics and genomics/bioinformatics" ]	SpaK/SpaR Two-component System Characterized by a Structure-driven Domain-fusion Method and in Vitro Phosphorylation Studies	journal.pcbi.1000401	null	[ [ "Because proteins so frequently function in coordination with other proteins ,", "identification and characterization of protein-protein complexes are essential", "aspects of protein sequence annotation and function determination [1] .", "A", "variety of empirical [2]–[4] and computational [5]...	[ "Here we introduce a quantitative structure-driven computational domain-fusion", "method , which we used to predict the structures of proteins believed to be", "involved in regulation of the subtilin pathway in Bacillus", "subtilis , and used to predict a protein-protein complex formed by", "interaction bet...	[ "Because proteins so frequently function in coordination with other proteins ,", "identification and characterization of the interactions among proteins are", "essential for understanding how proteins work .", "Computational methods for", "identification of protein-protein interactions have been limited by ...	2009
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[]	Population Structure and Evidence for Both Clonality and Recombination among Brazilian Strains of the Subgenus Leishmania (Viannia)	journal.pntd.0002490	null	[ [ "The species of the subgenus Leishmania ( Viannia ) Lainson and Shaw , 1987 , are exclusively endemic in the New World ( NW ) and infections of humans with these protozoan parasites constitute a significant public health problem in at least 18 countries of Latin America [1] .", "Subgenus L . ( Viannia ) p...	[ "Background/Objectives: Parasites of the subgenus Leishmania ( Viannia ) cause varying clinical symptoms ranging from cutaneous leishmaniases ( CL ) with single or few lesions , disseminated CL ( DL ) with multiple lesions to disfiguring forms of mucocutaneous leishmaniasis ( MCL ) .", "In this population genetic...	[ "Cutaneous leishmaniasis ( CL ) constitutes a significant public health problem in all federal states of Brazil .", "Most cases are caused by parasites of the subgenus Leishmania ( Viannia ) which can cause a variety of clinical symptoms ranging from single or few lesions , disseminated CL with multiple lesions ,...	2013
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "evolutionary ecology", "medicine and health sciences", "ecology", "viral transmission and infection", "infectious disease epidemiology", "virology", "epidemiology", "vector biology", "genetics", "biology and life sciences", "population genetics", "microbiology", "population biology", "evo...	Origin of the Dengue Fever Mosquito, Aedes aegypti, in California	journal.pntd.0003029	null	[ [ "Dengue fever is re-emerging in the United States of America ( USA ) after many years of absence [1] , a trend also observed around the world [2] .", "Risk for dengue infection coincides with the distribution of mosquitoes capable of transmitting dengue virus ( DENV ) .", "In most areas of the world ,...	[ "Dengue fever is among the most widespread vector-borne infectious diseases .", "The primary vector of dengue is the Aedes aegypti mosquito .", "Ae .", "aegypti is prevalent in the tropics and sub-tropics and is closely associated with human habitats outside its native range of Africa .", "While long establ...	[ "Dengue fever is a vector-borne disease that has dramatically increased in frequency and severity in recent decades , affecting over half of the world's population .", "The primary vector of dengue is Aedes aegypti .", "Breeding populations of this mosquito were reported for the first time in California in summ...	2014
[ "Introduction", "Materials and methods", "Results", "Discussion" ]	[ "medicine and health sciences", "liver", "body fluids", "mathematical models", "saliva", "photolysis", "simulation and modeling", "physiological processes", "cellular structures and organelles", "research and analysis methods", "animal cells", "mathematical and statistical techniques", "hepa...	A mathematical model of calcium dynamics in HSY cells	journal.pcbi.1005275	null	[ [ "Saliva secretion and regulation are vital for a range of activities , but can be compromised in a number of ways .", "Radiation therapy for head and/or neck cancer often causes salivary gland hypo-function , which can lead to xerostomia , commonly known as dry mouth [1 , 2] .", "Patients with Sjögren...	[ "Saliva is an essential part of activities such as speaking , masticating and swallowing .", "Enzymes in salivary fluid protect teeth and gums from infectious diseases , and also initiate the digestion process .", "Intracellular calcium ( Ca2+ ) plays a critical role in saliva secretion and regulation .", "Ex...	[ "We construct a mathematical model of Ca2+ and IP3 oscillations in HSY cells , a salivary ductal cell line from human parotid .", "The model reproduces the experimental data that exhibit coupled oscillations of [Ca2+] and [IP3] with the peak of each Ca2+ spike being followed by the peak of an IP3 spike .", "Rec...	2017
[ "Introduction", "Results and Discussion", "Materials and Methods" ]	[ "evolutionary ecology", "ecology and environmental sciences", "coevolution", "ecology", "evolutionary modeling", "biology and life sciences", "computational biology", "evolutionary biology", "evolutionary emergence", "evolutionary processes", "evolutionary theory" ]	Coevolution Drives the Emergence of Complex Traits and Promotes Evolvability	journal.pbio.1002023	Experiments using a digital host-parasite model system show that coevolution can drive the emergence of complex traits and more evolvable genomes. Homepage Title: Parasitism Drives the Evolution of Complexity	[ [ "Life emerged on Earth some 4 billion years ago and has evolved increasingly complex traits , including intricate biochemical pathways , elaborate developmental networks , and powerful neural architectures [1] , [2] .", "However , the processes responsible for promoting this complexity remain poorly under...	[ "The evolution of complex organismal traits is obvious as a historical fact , but the underlying causes—including the role of natural selection—are contested .", "Gould argued that a random walk from a necessarily simple beginning would produce the appearance of increasing complexity over time .", "Others conte...	[ "Over billions of years , life has evolved into the extraordinarily diverse and complex organisms that populate the Earth today .", "Although evolution often proceeds toward increasing complexity , more complex traits do not necessarily make organisms more fit .", "So when and why is greater complexity favored ...	2014
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "learning", "medicine and health sciences", "engineering and technology", "statistics", "nervous system", "applied mathematics", "signal processing", "social sciences", "neuroscience", "learning and memory", "noise reduction", "simulation and modeling", "algorithms", "regression analysis",...	Conventional analysis of trial-by-trial adaptation is biased: Empirical and theoretical support using a Bayesian estimator	journal.pcbi.1006501	null	[ [ "The way that people adapt their movements provides important insight into the motor learning processes of the brain [1–4] .", "Motor learning , and more specifically motor adaptation , is a key aspect in the study of human movement , particularly in understanding its deficit and developing corresponding ...	[ "Research on human motor adaptation has often focused on how people adapt to self-generated or externally-influenced errors .", "Trial-by-trial adaptation is a person’s response to self-generated errors .", "Externally-influenced errors applied as catch-trial perturbations are used to calculate a person’s pertu...	[ "By observing the learning rate of a person making a movement under new conditions , researchers can better understand how the nervous system handles uncertainty .", "Patients suffering from motor deficits or using prostheses will often display different motor abilities that can be observed as changes in error co...	2018
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "death rates", "invertebrates", "medicine and health sciences", "population dynamics", "geographical locations", "vector-borne diseases", "animals", "seasons", "population biology", "insect vectors", "africa", "infectious diseases", "aedes aegypti", "disease vectors", "insects", "arthr...	The seasonal influence of climate and environment on yellow fever transmission across Africa	journal.pntd.0006284	null	[ [ "Yellow fever ( YF ) is a viral disease caused by the mosquito transmitted yellow fever virus ( YFV ) of the genus Flavivirus [1] .", "Though endemic to both Africa and South America it is thought that 90% of cases occur in Africa [2] , where the virus causes between 51 , 000 and 380 , 000 severe cases pe...	[ "Yellow fever virus ( YFV ) is a vector-borne flavivirus endemic to Africa and Latin America .", "Ninety per cent of the global burden occurs in Africa where it is primarily transmitted by Aedes spp , with Aedes aegypti the main vector for urban yellow fever ( YF ) .", "Mosquito life cycle and viral replication...	[ "In this article , we describe the development of a model to quantify the seasonal dynamics of yellow fever virus ( YFV ) transmission across Africa .", "YFV is a flavivirus transmitted , within Africa , primarily by Aedes spp where it causes an estimated 78 , 000 deaths a year despite the presence of a safe and ...	2018
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "genetics and genomics/bioinformatics", "computational biology/genomics", "computational biology" ]	Fast Mapping of Short Sequences with Mismatches, Insertions and Deletions Using Index Structures	journal.pcbi.1000502	null	[ [ "Since the 454 pyrosequencing technology [3] has been introduced to the market , the need for algorithms that efficiently map huge amounts of reads to reference genomes has rapidly increased .", "Later , high throughput sequencing ( HTS ) methods such as Illumina [4] and SOLiD ( Applied Biosystems ) have ...	[ "With few exceptions , current methods for short read mapping make use of simple seed heuristics to speed up the search .", "Most of the underlying matching models neglect the necessity to allow not only mismatches , but also insertions and deletions .", "Current evaluations indicate , however , that very diffe...	[ "The successful mapping of high-throughput sequencing ( HTS ) reads to reference genomes largely depends on the accuracy of both the sequencing technologies and reference genomes .", "Current mapping algorithms focus on mapping with mismatches but largely neglect insertions and deletions—regardless of whether the...	2009
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "blood cells", "medicine and health sciences", "immune cells", "immune physiology", "nuclear staining", "respiratory infections", "spleen", "immunology", "microbiology", "viral structure", "pulmonology", "research and analysis methods", "specimen preparation and treatment", "staining", "...	Type I Interferons Direct Gammaherpesvirus Host Colonization	journal.ppat.1005654	null	[ [ "The γ-herpesviruses persist in lymphocytes and cause lymphoid and epithelial cancers .", "MuHV-4 , like Epstein-Barr virus ( EBV ) and the Kaposi's Sarcoma-associated Herpesvirus ( KSHV ) , persists in B cells [1] .", "After epithelial entry , it reaches B cells in organized lymphoid tissue via dendr...	[ "Gamma-herpesviruses colonise lymphocytes .", "Murid Herpesvirus-4 ( MuHV-4 ) infects B cells via epithelial to myeloid to lymphoid transfer .", "This indirect route entails exposure to host defences , and type I interferons ( IFN-I ) limit infection while viral evasion promotes it .", "To understand how IFN-...	[ "Gamma-herpesviruses establish chronic infections and cause cancers .", "They achieve this by immune evasion .", "Immune responses nonetheless suppress infection to a degree .", "By understanding how immune responses and viral evasion come together we can potentially control infection and prevent disease .", ...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "animal models of infection", "veterinary diseases", "virulence factors and mechanisms", "viral transmission and infection", "virology", "zoonotic diseases", "biology", "microbiology", "veterinary science", "animal influenza" ]	Pathogenicity and Transmissibility of North American Triple Reassortant Swine Influenza A Viruses in Ferrets	journal.ppat.1002791	null	[ [ "For nearly 70 years , swine influenza virus in North America was relatively stable , dominated by the classical-swine H1N1 ( cH1N1 ) subtype [1] .", "However , H3 seasonal human influenza A viruses were circulating at low frequency in U . S . swine [2] .", "In 1998 , influenza epidemiology in North A...	[ "North American triple reassortant swine ( TRS ) influenza A viruses have caused sporadic human infections since 2005 , but human-to-human transmission has not been documented .", "These viruses have six gene segments ( PB2 , PB1 , PA , HA , NP , and NS ) closely related to those of the 2009 H1N1 pandemic viruses...	[ "North American triple reassortant swine ( TRS ) influenza A viruses have caused sporadic human infections , but human-to-human transmission has not been established .", "We wished to elucidate potential human health threats posed by the TRS viruses and to identify determinants of virulence in the TRS and closely...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "computer and information sciences", "computer modeling", "systems science", "cell biology", "biology and life sciences", "computerized simulations", "systems analysis" ]	Cell Type Specific Alterations in Interchromosomal Networks across the Cell Cycle	journal.pcbi.1003857	null	[ [ "At the highest structural level , chromosomes form discrete bodies termed chromosome territories ( CT ) [1]–[6] .", "The three-dimensional organization of these CT and the genes within them have been implicated in genomic regulation [5]–[14] .", "Furthermore , interactions between CT and other nuclea...	[ "The interchromosomal organization of a subset of human chromosomes ( #1 , 4 , 11 , 12 , 16 , 17 , and 18 ) was examined in G1 and S phase of human WI38 lung fibroblast and MCF10A breast epithelial cells .", "Radial positioning of the chromosome territories ( CTs ) was independent of gene density , but size depen...	[ "During interphase , chromosomes occupy discrete bodies within the cell nucleus termed chromosome territories ( CT ) .", "The organization of CT and the genes within them have been implicated in genomic regulation .", "Numerous reports suggest that specific interchromosomal interactions enable distally located ...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine", "applied mathematics", "cancer treatment", "oncology", "mathematical computing", "mathematics", "theoretical biology", "chemotherapy and drug treatment", "biology", "systems biology", "biochemical simulations", "computer science", "computer modeling", "computational biology", ...	A Combined Experimental and Mathematical Approach for Molecular-based Optimization of Irinotecan Circadian Delivery	journal.pcbi.1002143	null	[ [ "Circadian timing largely modifies efficacy and toxicity of many anticancer drugs .", "Chronomodulated administration schemes for patients have been designed based on chronotoxicity results obtained in mice and subsequently validated in clinical trials in which all patients have received the same regimen ...	[ "Circadian timing largely modifies efficacy and toxicity of many anticancer drugs .", "Recent findings suggest that optimal circadian delivery patterns depend on the patient genetic background .", "We present here a combined experimental and mathematical approach for the design of chronomodulated administration...	[ "Treatment timing within the 24-h timescale , that is , circadian ( circa , about; dies , day ) timing , can change by several fold the tolerability and antitumor efficacy of anticancer agents both in experimental models and in cancer patients .", "Chronotherapeutics aims at improving the tolerability and/or the ...	2011
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "infectious diseases/protozoal infections", "infectious diseases/tropical and travel-associated diseases", "immunology/immunity to infections" ]	Functional Memory B Cells and Long-Lived Plasma Cells Are Generated after a Single Plasmodium chabaudi Infection in Mice	journal.ppat.1000690	null	[ [ "There is longstanding evidence that naturally acquired immunity to the erythrocytic stages of malaria is strongly dependent on antibodies ( Abs ) [1]–[6] .", "However , acquisition of immunity to P . falciparum malaria in humans is a relatively inefficient process; slow to develop , never sterile and wan...	[ "Antibodies have long been shown to play a critical role in naturally acquired immunity to malaria , but it has been suggested that Plasmodium-specific antibodies in humans may not be long lived .", "The cellular mechanisms underlying B cell and antibody responses are difficult to study in human infections; there...	[ "Malaria causes considerable human suffering resulting from associated high mortality , morbidity and reduced economic productivity in endemic areas .", "Current control methods are thwarted by a multiplicity of problems including rapidly developing resistance for anti-malarial drugs and insecticide-treated nets ...	2009
[ "Introduction", "Results", "Discussion", "Methods" ]	[]	Catalysis of Protein Folding by Chaperones Accelerates Evolutionary Dynamics in Adapting Cell Populations	journal.pcbi.1003269	null	[ [ "Evolutionary selection of protein sequences is a complex task whereby several traits such as translation efficiency , structural integrity ( i . e . folding stability and kinetics ) , molecular function , as well as interactions with other proteins in the cellular milieu should be simultaneously optimized ."...	[ "Although molecular chaperones are essential components of protein homeostatic machinery , their mechanism of action and impact on adaptation and evolutionary dynamics remain controversial .", "Here we developed a physics-based ab initio multi-scale model of a living cell for population dynamics simulations to el...	[ "Molecular chaperones or heat-shock proteins are essential components of protein homeostatic machinery in all three domains of life , whose role is not only to prevent protein aggregation but also catalyze the protein folding process by decreasing the energetic barrier for folding .", "Importantly , chaperones ha...	2013
[ "Introduction", "Methods", "Results", "Discussion" ]	[]	Distribution of Lutzomyia longipalpis Chemotype Populations in São Paulo State, Brazil	journal.pntd.0003620	null	[ [ "Recording the geographic distribution and identifying the possible routes of expansion of both arthropod-borne diseases and their associated vectors is essential information for surveillance as well as the execution and elaboration of control strategies [1] .", "In Brazil , the expansion of the geographi...	[ "American visceral leishmaniasis ( AVL ) is an emerging disease in the state of São Paulo , Brazil .", "Its geographical expansion and the increase in the number of human cases has been linked to dispersion of Lutzomyia longipalpis into urban areas .", "To produce more accurate risk maps we investigated the geo...	[ "Information on the geographical distribution , dispersal mechanisms and dispersion route of insect-borne diseases can help to identify ongoing transmission areas , new risk areas and guide surveillance and control activities .", "Lutzomyia longipalpis , the principal vector of American visceral leishmaniasis dis...	2015
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "medicine", "infectious diseases", "giardiasis", "parasitic diseases" ]	Multilocus Genotyping of Human Giardia Isolates Suggests Limited Zoonotic Transmission and Association between Assemblage B and Flatulence in Children	journal.pntd.0001262	null	[ [ "Giardia intestinalis ( synonyms: G . lamblia , G . duodenalis ) is a protozoan parasite that infects a wide array of vertebrates , including humans , pets , livestock , wildlife , and marine animals [1] , [2] .", "Giardia has a global distribution and is one of the most common diarrhea-related parasites ...	[ "Giardia intestinalis is one of the most common diarrhea-related parasites in humans , where infection ranges from asymptomatic to acute or chronic disease .", "G . intestinalis consists of eight genetically distinct genotypes or assemblages , designated A–H , and assemblages A and B can infect humans .", "Giar...	[ "Giardia intestinalis is a protozoan parasite found world-wide and it is a major cause of diarrhea in humans and other mammals .", "The genetic variability within G . intestinalis is high with eight distinct genotypes or assemblages ( A-H ) .", "Here we performed sequence-based multilocus genotyping of around 2...	2011
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "chemistry", "biology", "veterinary science" ]	Down-Regulation of Shadoo in Prion Infections Traces a Pre-Clinical Event Inversely Related to PrPSc Accumulation	journal.ppat.1002391	null	[ [ "Prion diseases , including the prototypical scrapie of sheep and Creutzfeldt-Jakob Disease ( CJD ) of humans , are fatal and incurable neurodegenerative disorders .", "They are unusual in that they are often transmissible or infectious diseases .", "While they can be studied to great effect in a lab ...	[ "During prion infections of the central nervous system ( CNS ) the cellular prion protein , PrPC , is templated to a conformationally distinct form , PrPSc .", "Recent studies have demonstrated that the Sprn gene encodes a GPI-linked glycoprotein Shadoo ( Sho ) , which localizes to a similar membrane environment ...	[ "In prion infections of the nervous system the cellular prion protein , PrPC , changes to a distinct form , PrPSc .", "Recent studies have demonstrated that another glycoprotein Shadoo ( Sho ) , which occupies a similar membrane environment as PrPC , is reduced in the brains of rodents with terminal prion disease...	2011
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "molecular biology/histone modification", "molecular biology/chromatin structure", "molecular biology/transcription initiation and activation" ]	H3 Lysine 4 Is Acetylated at Active Gene Promoters and Is Regulated by H3 Lysine 4 Methylation	journal.pgen.1001354	null	[ [ "Histones are covalently modified on many lysine residues .", "The outcome of these modifications is either to modify chromatin structure directly or provide docking sites for the binding of non-histone proteins [1] .", "The same chemical modification ( e . g . methylation ) on different residues can ...	[ "Methylation of histone H3 lysine 4 ( H3K4me ) is an evolutionarily conserved modification whose role in the regulation of gene expression has been extensively studied .", "In contrast , the function of H3K4 acetylation ( H3K4ac ) has received little attention because of a lack of tools to separate its function f...	[ "In the nucleus of mammals and yeast , DNA is packaged by forming complexes with histone proteins in a structure called the nucleosome , the basic building block of chromatin .", "The tails of the histones protrude from the nucleosome and can be marked on many amino acid residues by chemical modifications such as...	2011

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