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headings list	keywords list	title stringlengths 20 281	id stringlengths 20 20	toc stringlengths 57 522 ⌀	sections list	abstract list	summary list	year stringclasses 13 values
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genetics", "immunology", "biology", "molecular cell biology", "genetics and genomics" ]	Identification of Orch3, a Locus Controlling Dominant Resistance to Autoimmune Orchitis, as Kinesin Family Member 1C	journal.pgen.1003140	null	[ [ "Experimental autoimmune orchitis ( EAO ) is a model of idiopathic male infertility mediated by autoreactive T cells [1] , [2] .", "It can be induced in mice by active immunization with mouse testicular homogenate ( TH ) emulsified in complete Freund's adjuvant ( CFA ) and Bordetella pertussis toxin ( PTX...	[ "Experimental autoimmune orchitis ( EAO ) , the principal model of non-infectious testicular inflammatory disease , can be induced in susceptible mouse strains by immunization with autologous testicular homogenate and appropriate adjuvants .", "As previously established , the genome of DBA/2J mice encodes genes t...	[ "Although the etiology of autoimmunity is not well known , a variety of studies have demonstrated that genetic predisposition is a major contributor to disease susceptibility and resistance .", "The major histocompatibility complex ( MHC ) is the primary genetic determinant of autoimmune disease susceptibility wi...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "molecular biology/dna replication", "genetics and genomics/gene discovery", "genetics and genomics/functional genomics", "genetics and genomics/gene expression", "cell biology/cell growth and division", "cell biology/developmental molecular mechanisms", "molecular biology", "genetics and genomics/dis...	Paternal Effect of the Nuclear Formin-like Protein MISFIT on Plasmodium Development in the Mosquito Vector	journal.ppat.1000539	null	[ [ "Malaria pathology is caused by asexual replication of apicomplexan parasites Plasmodium in the host bloodstream , but transmission between hosts requires sexual replication of parasites within mosquitoes .", "Subsets of sexually committed haploid merozoites escape each bloodstream replication cycle and d...	[ "Malaria parasites must undergo sexual and sporogonic development in mosquitoes before they can infect their vertebrate hosts .", "We report the discovery and characterization of MISFIT , the first protein with paternal effect on the development of the rodent malaria parasite Plasmodium berghei in Anopheles mosqu...	[ "The unicellular protozoan parasites that cause malaria must undergo sexual development and subsequent proliferation in mosquitoes before they can infect humans and cause malaria .", "We characterized the first protein with paternal effect on the development of malaria parasites in the mosquito .", "This protei...	2009
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine", "infectious diseases", "immunology", "biology", "microbiology" ]	Lymphoid Tissue Damage in HIV-1 Infection Depletes Naïve T Cells and Limits T Cell Reconstitution after Antiretroviral Therapy	journal.ppat.1002437	null	[ [ "The hallmark of HIV-1 infection , depletion of CD4+ T cells , has been largely attributed to direct mechanisms of infection and cell death from viral replication or killing by virus-specific cytotoxic T-lymphocytes ( CTLs ) , and to indirect mechanisms such as increased apoptosis accompanying chronic immune ...	[ "Highly active antiretroviral therapy ( HAART ) can suppress HIV-1 replication and normalize the chronic immune activation associated with infection , but restoration of naïve CD4+ T cell populations is slow and usually incomplete for reasons that have yet to be determined .", "We tested the hypothesis that damag...	[ "The hallmark of HIV-1 infection is depletion of CD4 T cells , whose loss leads to the opportunistic infections and cancers characteristic of AIDS .", "Highly active antiretroviral therapy ( HAART ) can control HIV-1 replication , but reconstitution particularly of naïve T cells is often incomplete and slow .", ...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	The Engineering of a Novel Ligand in gH Confers to HSV an Expanded Tropism Independent of gD Activation by Its Receptors	journal.ppat.1004907	null	[ [ "Entry of herpes simplex virus ( HSV ) into the cell is a multistep process that involves four virion glycoproteins ( gD , gH/gL , gB ) , all of which are required .", "gD is species-specific , and a major determinant of HSV tropism .", "gH/gL and gB constitute the conserved fusion apparatus across th...	[ "Herpes simplex virus ( HSV ) enters cells by means of four essential glycoproteins - gD , gH/gL , gB , activated in a cascade fashion by gD binding to one of its receptors , nectin1 and HVEM .", "We report that the engineering in gH of a heterologous ligand – a single-chain antibody ( scFv ) to the cancer-specif...	[ "To enter cells , all herpesviruses use the core fusion glycoproteins gH/gL and gB , in addition to species-specific glycoproteins responsible for specific tropism , etc .", "In HSV , the additional glycoprotein is the essential gD .", "We engineered in gH a heterologous ligand to the HER2 cancer receptor .", ...	2015
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "medicine", "neurodegenerative diseases", "neuroscience", "pediatrics", "animal models", "histology", "model organisms", "developmental and pediatric neurology", "glycogen storage diseases", "epilepsy", "pediatrics and child health", "biology", "metabolism", "metabolic disorders", "clini...	PTG Depletion Removes Lafora Bodies and Rescues the Fatal Epilepsy of Lafora Disease	journal.pgen.1002037	null	[ [ "Lafora disease ( LD ) is caused by recessively inherited mutations in the EPM2A or EPM2B genes , encoding laforin ( a carbohydrate binding phosphatase ) and malin ( an E3 ubiquitin ligase ) [1] , [2] .", "The disease begins around age 15 with myoclonus ( jerk-like seizures ) and generalized convulsive se...	[ "Lafora disease is the most common teenage-onset neurodegenerative disease , the main teenage-onset form of progressive myoclonus epilepsy ( PME ) , and one of the severest epilepsies .", "Pathologically , a starch-like compound , polyglucosan , accumulates in neuronal cell bodies and overtakes neuronal small pro...	[ "Lafora disease ( LD ) is a fatal epilepsy that afflicts previously normal teenagers .", "It is caused by mutations in the EPM2A or EPM2B genes encoding the laforin carbohydrate-binding phosphatase and the malin E3 ubiquitin ligase .", "LD is the most common neurodegenerative epilepsy of adolescents .", "Affe...	2011
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "signal transduction", "developmental biology", "plant science", "model organisms", "plant and algal models", "cell biology", "arabidopsis thaliana", "plant growth and development", "biology and life sciences", "brassica", "plants", "molecular cell biology", "cell signaling", "mapk signali...	Phosphorylation of a WRKY Transcription Factor by MAPKs Is Required for Pollen Development and Function in Arabidopsis	journal.pgen.1004384	null	[ [ "Pollen , the male gametophyte of angiosperms , displays highly reduced structure of two or three cells at maturity .", "Because of the simple cell linage and dynamic developmental processes , plant male gametogenesis provides an interesting model for studying many fundamental cellular processes , includi...	[ "Plant male gametogenesis involves complex and dynamic changes in gene expression .", "At present , little is known about the transcription factors involved in this process and how their activities are regulated .", "Here , we show that a pollen-specific transcription factor , WRKY34 , and its close homolog , W...	[ "Pollen development , or male gametogenesis , is a process by which a haploid uninucleate microspore undergoes cell division and specification to form a mature pollen grain containing two sperm cells .", "The highly defined cell linage makes pollen development an ideal model to understand the regulation of plant ...	2014
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "machine learning algorithms", "medicine and health sciences", "action potentials", "neural networks", "engineering and technology", "sleep", "applied mathematics", "membrane potential", "electrophysiology", "neuroscience", "decision tree learning", "decision analysis", "algorithms", "phys...	Brain-state invariant thalamo-cortical coordination revealed by non-linear encoders	journal.pcbi.1006041	null	[ [ "Investigating how the brain operates at the neuronal level is usually addressed by the specification of neuronal responses to an experimentally measurable variable or by the quantification of the temporal coordination of neuronal ensembles [1 , 2] .", "Using various methods , the responses of single neur...	[ "Understanding how neurons cooperate to integrate sensory inputs and guide behavior is a fundamental problem in neuroscience .", "A large body of methods have been developed to study neuronal firing at the single cell and population levels , generally seeking interpretability as well as predictivity .", "Howeve...	[ "The thalamus is a brain structure that relays sensory information to the cortex and mediates cortico-cortical interaction .", "Unraveling the dialogue between the thalamus and the cortex is thus a central question in neuroscience , with direct implications on our understanding of how the brain operates at the ma...	2018
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "cell binding", "cell physiology", "dengue virus", "dimers (chemical physics)", "medicine and health sciences", "chemical characterization", "immune physiology", "vesicles", "pathology and laboratory medicine", "hela cells", "pathogens", "biological cultures", "immunology", "microbiology",...	A novel mechanism of antibody-mediated enhancement of flavivirus infection	journal.ppat.1006643	null	[ [ "Flaviviruses are small , enveloped viruses that cause significant human disease worldwide , including the mosquito-borne dengue , Zika , West Nile , Japanese encephalitis , and yellow fever viruses as well as tick-borne encephalitis virus ( TBEV ) [1] .", "Despite intensive research , the hunt for specif...	[ "Antibody-dependent enhancement of viral infection is a well-described phenomenon that is based on the cellular uptake of infectious virus-antibody complexes following their interaction with Fcγ receptors expressed on myeloid cells .", "Here we describe a novel mechanism of antibody-mediated enhancement of infect...	[ "Antibodies are an important component of antiviral host responses and their binding to the surface of virus particles usually leads to neutralization of viral infectivity .", "In some instances , however , antibodies at sub-neutralizing concentrations can enhance infection of certain cells , because they facilit...	2017
[ "Introduction", "Materials and methods", "Results", "Discussion" ]	[ "medicine and health sciences", "body fluids", "pathology and laboratory medicine", "tropical diseases", "brucellosis", "surgical and invasive medical procedures", "bacterial diseases", "signs and symptoms", "pharmaceutics", "neglected tropical diseases", "cardiology", "cardiovascular procedur...	The clinical features of 590 patients with brucellosis in Xinjiang, China with the emphasis on the treatment of complications	journal.pntd.0005577	null	[ [ "Brucellosis ( or undulant fever ) is a zoonotic disease with a worldwide distribution , mainly in the Mediterranean Basin , Middle East , Central and South America , and Asia [1] .", "Xinjiang Uygur Autonomous Region ( Xinjiang ) in western China is an agricultural area with animal production as its majo...	[ "This study aims to analyze the clinical characteristics and treatment outcomes of 590 patients with brucellosis in Xinjiang , China .", "The clinical characteristics , laboratory findings , complications and prognosis of 590 patients infected with brucellosis were retrospectively analyzed .", "These patients h...	[ "Brucellosis is a highly contagious zoonosis caused by bacteria of the genus Brucella and affecting mammals .", "Human Brucellosis is caused by ingestion of unpasteurized or undercooked food product from infected animals , or close contact with them .", "The infection with same bacteria even with same type can ...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "evolutionary ecology", "microbiology", "host-pathogen interaction", "coevolution", "emerging infectious diseases", "molecular genetics", "bacterial pathogens", "emergence", "forms of evolution", "comparative genomics", "biology", "adaptation", "gene identification and analysis", "computat...	The Non-Flagellar Type III Secretion System Evolved from the Bacterial Flagellum and Diversified into Host-Cell Adapted Systems	journal.pgen.1002983	null	[ [ "Microbial protein secretion facilitates environmental exploitation and manipulation [1] , [2] .", "The most frequent bacterial motility machinery , the flagellum , uses a type 3 secretion system ( T3SS ) to secrete its extracellular components .", "The non-flagellar type 3 protein secretion system ( ...	[ "Type 3 secretion systems ( T3SSs ) are essential components of two complex bacterial machineries: the flagellum , which drives cell motility , and the non-flagellar T3SS ( NF-T3SS ) , which delivers effectors into eukaryotic cells .", "Yet the origin , specialization , and diversification of these machineries re...	[ "Most motile bacteria use a flagellum to move .", "The extracellular components of flagella are secreted by their own Type 3 Secretion System ( T3SS ) .", "The non-flagellar T3SS ( NF-T3SS ) , also named injectisome , includes many proteins that are homologous to flagellar components .", "NF-T3SSs are employe...	2012
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "medicine and health sciences", "chemical characterization", "tropical diseases", "geographical locations", "social sciences", "bacterial diseases", "archaeology", "strontium", "osteology", "neglected tropical diseases", "molecular biology techniques", "united kingdom", "digestive system", ...	Investigation of a Medieval Pilgrim Burial Excavated from the Leprosarium of St Mary Magdalen Winchester, UK	journal.pntd.0005186	null	[ [ "We have recently examined cases of lepromatous leprosy ( LL ) recovered during excavations at the site of the St Mary Magdalen leprosarium , located to the east of Winchester , UK .", "Lepromatous or multibacillary leprosy is the more severe form of the disease , which lies at the opposite end of the spe...	[ "We have examined the remains of a Pilgrim burial from St Mary Magdalen , Winchester .", "The individual was a young adult male , aged around 18–25 years at the time of death .", "Radiocarbon dating showed the remains dated to the late 11th–early 12th centuries , a time when pilgrimages were at their height in ...	[ "This multidisciplinary research article , involving biomolecular analysis , osteology , strontium and oxygen isotopic analyses and archaeology , examines the remains of a Pilgrim burial excavated from the medieval leprosy hospital of St Mary Magdalen , Winchester , UK .", "Radiocarbon dating showed the remains d...	2017
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "bacteriology", "medicine and health sciences", "gut bacteria", "pathology and laboratory medicine", "pathogens", "microbiology", "light microscopy", "pili and fimbriae", "organisms", "microscopy", "genome analysis", "bacterial genetics", "molecular biology techniques", "microbial genetics...	Genome-wide detection of conservative site-specific recombination in bacteria	journal.pgen.1007332	null	[ [ "Seemingly clonal microbial populations often exhibit phenotypic and behavioral heterogeneity .", "This feature is widely observed in the microscopic world–from viruses to protozoa–and reflects the common need to adapt to the ever-changing environmental milieu .", "While point mutations and horizontal...	[ "The ability of clonal bacterial populations to generate genomic and phenotypic heterogeneity is thought to be of great importance for many commensal and pathogenic bacteria .", "One common mechanism contributing to diversity formation relies on the inversion of small genomic DNA segments in a process commonly re...	[ "Bacteria in many ecological niches experience a common challenge in the form of unpredictable environmental fluctuations .", "Rapid adaptation to challenging conditions is important for bacterial survival and successful proliferation .", "Altering gene expression through DNA inversion is a common mechanism ado...	2018
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "meiosis", "medicine and health sciences", "reproductive system", "spermatocytes", "nuclear staining", "cell cycle and cell division", "cell processes", "reproductive physiology", "germ cells", "cellular structures and organelles", "sperm", "research and analysis methods", "acrosomes", "sp...	Genetic, structural, and chemical insights into the dual function of GRASP55 in germ cell Golgi remodeling and JAM-C polarized localization during spermatogenesis	journal.pgen.1006803	null	[ [ "Members of the Junctional Adhesion Molecular family exhibit a similar structure with two extracellular immunoglobulin domains , a single transmembrane region and a C-terminal PSD-95/Discs Large/ZO-1 ( PDZ ) -binding motif .", "Three of these proteins are highly similar: JAM-A , JAM-B and JAM-C [1] .", ...	[ "Spermatogenesis is a dynamic process that is regulated by adhesive interactions between germ and Sertoli cells .", "Germ cells express the Junctional Adhesion Molecule-C ( JAM-C , encoded by Jam3 ) , which localizes to germ/Sertoli cell contacts .", "JAM-C is involved in germ cell polarity and acrosome formati...	[ "Spermatogenesis defects are a common cause of male sterility .", "Spermatogenesis occurs in the seminiferous tubules of the testes and involves adhesive interactions between developing germ cells and Sertoli cells .", "Knock-out mouse models identified several adhesion molecules that are critically involved in...	2017
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "cell physiology", "cryptococcus neoformans", "medicine and health sciences", "cryptococcus", "pathology and laboratory medicine", "pathogens", "microbiology", "membrane proteins", "fungi", "membrane fusion", "model organisms", "experimental organism systems", "cellular structures and organe...	PRM1 and KAR5 function in cell-cell fusion and karyogamy to drive distinct bisexual and unisexual cycles in the Cryptococcus pathogenic species complex	journal.pgen.1007113	null	[ [ "Sexual reproduction is ubiquitous in eukaryotic systems and promotes genetic diversity important for successful evolutionary adaptation to ever-changing environments [1] .", "In addition to bisexual reproduction between mating partners of opposite sexes , many eukaryotic systems , including fish , amphib...	[ "Sexual reproduction is critical for successful evolution of eukaryotic organisms in adaptation to changing environments .", "In the opportunistic human fungal pathogens , the Cryptococcus pathogenic species complex , C . neoformans primarily undergoes bisexual reproduction , while C . deneoformans undergoes both...	[ "Sexuality is ubiquitous in eukaryotic systems , but it is present in diverse forms , ranging from distinct sexual individuals to parthenogenic organisms in both animals and plants .", "Consequently , different organisms have evolved different reproduction strategies in which cell-cell fusion and nuclear fusion (...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "ophthalmology", "genetics and genomics" ]	Common Genetic Variants near the Brittle Cornea Syndrome Locus ZNF469 Influence the Blinding Disease Risk Factor Central Corneal Thickness	journal.pgen.1000947	null	[ [ "Glaucoma is one of the leading causes of irreversible blindness worldwide .", "It is estimated that by 2010 , approximately 60 . 5 million people globally will be affected by this condition [1] .", "It is characterized by a progressive loss of retinal ganglion cells which will lead to visual field da...	[ "Central corneal thickness ( CCT ) , one of the most highly heritable human traits ( h2 typically>0 . 9 ) , is important for the diagnosis of glaucoma and a potential risk factor for glaucoma susceptibility .", "We conducted genome-wide association studies in five cohorts from Australia and the United Kingdom ( t...	[ "Central corneal thickness ( CCT ) is an important eye measurement .", "It has been considered as a prognosticator for the development of glaucoma , with a thin cornea potentially increasing the risk of developing a subtype known as open-angle glaucoma .", "CCT is highly heritable , yet its genetic determinants...	2010
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "infectious diseases/helminth infections", "infectious diseases/epidemiology and control of infectious diseases", "infectious diseases/neglected tropical diseases" ]	The Impact of Repeated Rounds of Mass Drug Administration with Diethylcarbamazine Plus Albendazole on Bancroftian Filariasis in Papua New Guinea	journal.pntd.0000344	null	[ [ "Lymphatic filariasis ( LF ) is a deforming and disabling infectious disease that causes elephantiasis and hydroceles .", "The infection affects some 120 million people in an estimated 83 countries in tropical and subtropical regions , with an estimated 1 . 2 billion individuals at risk [1] .", "Most ...	[ "This study employed various monitoring methods to assess the impact of repeated rounds of mass drug administration ( MDA ) on bancroftian filariasis in Papua New Guinea , which has the largest filariasis problem in the Pacific region .", "Residents of rural villages near Madang were studied prior to and one year...	[ "Lymphatic filariasis ( LF ) is a deforming and disabling disease that is caused by parasitic worms that are transmitted by mosquitoes .", "While a number of countries have initiated LF elimination programs based on mass drug administration ( MDA ) , relatively little good information is available on the impact o...	2008
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "computer science", "computer modeling", "theoretical biology", "ecology", "biology", "computational biology", "evolutionary biology", "numerical analysis" ]	Strategy Diversity Stabilizes Mutualism through Investment Cycles, Phase Polymorphism, and Spatial Bubbles	journal.pcbi.1002660	null	[ [ "Investigating factors that promote cooperation is one of the main topics in evolutionary biology [1] , [2] .", "Cooperation , a costly act that provides benefit for a partner [3] , [4] , is widespread in nature [5]–[7] and has been essential in shaping our biosphere [8] , [9] .", "The basic dilemma o...	[ "There is continuing interest in understanding factors that facilitate the evolution and stability of cooperation within and between species .", "Such interactions will often involve plasticity in investment behavior , in response to the interacting partner's investments .", "Our aim here is to investigate the ...	[ "Mutualistic interactions between species are often best understood as gradually adjustable reciprocal investments made continuously or iteratively between participants .", "Prime examples are the mycorrhizal and rhizobial mutualisms so strongly affecting the productivity of plants .", "When such interactions a...	2012
[ "Introduction", "Results and discussion", "Methods" ]	[ "crystal structure", "molecular dynamics", "markov models", "condensed matter physics", "sodium", "simulation and modeling", "mathematics", "crystallography", "thermodynamics", "g protein coupled receptors", "research and analysis methods", "solid state physics", "proteins", "chemistry", ...	Kinetic and thermodynamic insights into sodium ion translocation through the μ-opioid receptor from molecular dynamics and machine learning analysis	journal.pcbi.1006689	null	[ [ "Evidence of allosteric modulation of receptor signaling by cations was first presented in the literature for opioid receptors ( ORs ) .", "Specifically , sodium ( Na+ ) and lithium , but not other monovalent or divalent cations , were shown to enhance receptor binding of opiate antagonists and to reduce ...	[ "The differential modulation of agonist and antagonist binding to opioid receptors ( ORs ) by sodium ( Na+ ) has been known for decades .", "To shed light on the molecular determinants , thermodynamics , and kinetics of Na+ translocation through the μ-OR ( MOR ) , we used a multi-ensemble Markov model framework c...	[ "Notwithstanding years of research supporting the notion that μ-opioid receptor ( MOR ) function can be modulated by sodium ions ( Na+ ) , a complete understanding of Na+ translocation through the receptor and its effect on ligand binding at MOR requires additional information .", "Here , we use computer simulati...	2019
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "computer and information sciences", "computational techniques", "network analysis", "biology and life sciences", "graph theory", "neuroscience", "research and analysis methods" ]	Analysis of Graph Invariants in Functional Neocortical Circuitry Reveals Generalized Features Common to Three Areas of Sensory Cortex	journal.pcbi.1003710	null	[ [ "Transmission and processing of information in the brain is in large part determined by the connectivity between neurons [1] .", "The neocortical microcircuit hypothesis states that the neocortex is composed of repeated elements of a generalized circuit that are tweaked for specialization in each area [2]...	[ "Correlations in local neocortical spiking activity can provide insight into the underlying organization of cortical microcircuitry .", "However , identifying structure in patterned multi-neuronal spiking remains a daunting task due to the high dimensionality of the activity .", "Using two-photon imaging , we m...	[ "Information in the brain is represented and processed by populations of interconnected neurons .", "However , there is a lack of a clear understanding of the structure and organization of circuit wiring , particularly at the mesoscale which spans multiple columns and layers .", "In this study , we sought to ev...	2014
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[]	Randomized Controlled Field Trial to Assess the Immunogenicity and Safety of Rift Valley Fever Clone 13 Vaccine in Livestock	journal.pntd.0003550	null	[ [ "Rift Valley fever ( RVF ) is an acute disease that is caused by a phlebovirus of the Bunyaviridae family of viruses that affects livestock ( cattle , sheep , goats , camels ) and humans in Africa and the Arabian Peninsula [1–3] .", "In Africa , periodic and severe epidemics have been reported in Kenya , ...	[ "Although livestock vaccination is effective in preventing Rift Valley fever ( RVF ) epidemics , there are concerns about safety and effectiveness of the only commercially available RVF Smithburn vaccine .", "We conducted a randomized controlled field trial to evaluate the immunogenicity and safety of the new RVF...	[ "Although livestock vaccination is effective in preventing Rift Valley fever ( RVF ) outbreaks , there are concerns about safety and effectiveness of the only commercially available vaccine for the disease .", "Here , we conducted a field trial in Kenya to evaluate the safety and ability to induce protection for ...	2015
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "rheumatology", "medicine and health sciences", "pathology and laboratory medicine", "chondrocytes", "immunology", "simulation and modeling", "signs and symptoms", "connective tissue cells", "cartilage", "research and analysis methods", "osteoarthritis", "inflammation", "animal cells", "ar...	Systems biology reveals how altered TGFβ signalling with age reduces protection against pro-inflammatory stimuli	journal.pcbi.1006685	null	[ [ "Osteoarthritis ( OA ) is a spectrum of degenerative disorders that become much more prevalent with age to the extent that 50% of those aged ≥65 years suffer from the disease globally [1] .", "Treatments are limited with no therapies that directly target the disease; instead , the focus is on relieving sy...	[ "Osteoarthritis ( OA ) is a degenerative condition caused by dysregulation of multiple molecular signalling pathways .", "Such dysregulation results in damage to cartilage , a smooth and protective tissue that enables low friction articulation of synovial joints .", "Matrix metalloproteinases ( MMPs ) , especia...	[ "Osteoarthritis ( OA ) is a debilitating disease that is a consequence of cartilage degeneration , often for a variety of reasons .", "Age is typically the driving force behind OA , and one reason is that biological pathways change as we get older and can become damaging .", "Transforming growth factor beta ( T...	2019
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "physics", "biochemistry", "chemistry", "biology", "computational biology", "chemical biology", "biophysics" ]	Molecular Mechanism of Allosteric Communication in Hsp70 Revealed by Molecular Dynamics Simulations	journal.pcbi.1002844	null	[ [ "Heat shock proteins ( HSPs ) are essential macromolecules involved in housekeeping cellular activities , whose expression levels can be modulated in response to environmental conditions .", "The Hsp70 family of proteins plays essential roles in maintaining cellular protein homeostasis .", "Under norm...	[ "Investigating ligand-regulated allosteric coupling between protein domains is fundamental to understand cell-life regulation .", "The Hsp70 family of chaperones represents an example of proteins in which ATP binding and hydrolysis at the Nucleotide Binding Domain ( NBD ) modulate substrate recognition at the Sub...	[ "Allostery , or the capability of proteins to respond to ligand binding events with a variation in structure or dynamics at a distant site , is a common feature for biomolecular function and regulation in a large number of proteins .", "Intra-protein connections and inter-residue coordinations underlie allosteric...	2012
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "molecular probe techniques", "gene regulation", "dna-binding proteins", "polymerases", "dna replication", "hirt extraction", "dna", "molecular biology techniques", "gel electrophoresis", "extraction techniques", "research and analysis methods", "small interfering rnas", "electrophoretic tec...	DNA Polymerase alpha is essential for intracellular amplification of hepatitis B virus covalently closed circular DNA	journal.ppat.1007742	null	[ [ "Hepatitis B virus ( HBV ) chronically infects 257 million people worldwide [1] .", "Chronic HBV carriers have a higher risk of developing cirrhosis and hepatocellular carcinoma ( HCC ) , which accounts for approximately 686 , 000 annual deaths [1] .", "Current therapies with viral polymerase inhibito...	[ "Persistent hepatitis B virus ( HBV ) infection relies on the establishment and maintenance of covalently closed circular ( ccc ) DNA , a 3 . 2 kb episome that serves as a viral transcription template , in the nucleus of an infected hepatocyte .", "Although evidence suggests that cccDNA is the repair product of n...	[ "CCC DNA is the most refractory HBV replication intermediate under long-term antiviral therapies and is responsible for the viral rebound after treatment cessation .", "Therefore , understanding the biosynthesis and maintenance of cccDNA minichromosome is crucial for the development of novel antiviral therapeutic...	2019
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "protein interactions", "immunology", "microbiology", "host-pathogen interaction", "chemical biology", "parasitology", "parastic protozoans", "protein structure", "veterinary science", "veterinary medicine", "veterinary diseases", "veterinary parasitology", "proteins", "chemistry", "biol...	The Role of Sialyl Glycan Recognition in Host Tissue Tropism of the Avian Parasite Eimeria tenella	journal.ppat.1002296	null	[ [ "The phylum Apicomplexa contains some of the most widespread protozoan parasites of humans and animals .", "Key members include Plasmodium spp .", ", Eimeria spp .", ", Neospora caninum and Toxoplasma gondii .", "Eimeria spp .", "are a highly successful group of host-specific , intracellul...	[ "Eimeria spp .", "are a highly successful group of intracellular protozoan parasites that develop within intestinal epithelial cells of poultry , causing coccidiosis .", "As a result of resistance against anticoccidial drugs and the expense of manufacturing live vaccines , it is necessary to understand the rela...	[ "Eimeria spp .", "are highly successful protozoan parasites of the intestine of birds and one of the most important diseases in modern poultry farming .", "The economic impact is significant causing billion dollar losses to the industry and as a result there is pressing need for new therapeutic approaches .", ...	2011
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "phosphorylation", "invertebrates", "rna interference", "chemical compounds", "caenorhabditis", "cell cycle and cell division", "cell processes", "animals", "organic compounds", "biochemical analysis", "animal models", "developmental biology", "caenorhabditis elegans", "in vitro kinase ass...	Multisite Phosphorylation of NuMA-Related LIN-5 Controls Mitotic Spindle Positioning in C. elegans	journal.pgen.1006291	null	[ [ "Animal development and tissue homeostasis depend critically on cell divisions that create cells with specific shapes and functions , in the right numbers and at the proper positions .", "The spindle apparatus plays a central role in the cell division process , as it segregates the chromosomes in mitosis ...	[ "During cell division , the mitotic spindle segregates replicated chromosomes to opposite poles of the cell , while the position of the spindle determines the plane of cleavage .", "Spindle positioning and chromosome segregation depend on pulling forces on microtubules extending from the centrosomes to the cell c...	[ "Protein kinases control biological processes by phosphorylating specific amino acids of substrate proteins .", "It remains a major challenge to identify which phosphorylation events are critical in vivo and how phosphorylation affects protein function .", "Recent developments in CRISPR/Cas9-based genetic engin...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "molecular biology/recombination", "molecular biology/chromosome structure" ]	Telomere Recombination Accelerates Cellular Aging in Saccharomyces cerevisiae	journal.pgen.1000535	null	[ [ "Telomeres are the physical ends of linear eukaryotic chromosomes and are composed of specific repetitive DNA sequences and binding proteins [1] , [2] .", "The functional integrity of telomeres is required for cell proliferation and survival because they protect chromosome ends from nucleolytic degradatio...	[ "Telomeres are nucleoprotein structures located at the linear ends of eukaryotic chromosomes .", "Telomere integrity is required for cell proliferation and survival .", "Although the vast majority of eukaryotic species use telomerase as a primary means for telomere maintenance , a few species can use recombinat...	[ "Telomeres are the specialized structures at the ends of eukaryotic linear chromosomes .", "The simple guanine-rich DNA repeats at telomeres and their associated proteins are important for chromosome stability .", "Most eukaryotic species have evolved an enzyme named telomerase to replicate their telomeric DNA ...	2009
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "animal types", "ecology and environmental sciences", "ecological niches", "microbiology", "vertebrates", "animals", "mammals", "primates", "habitats", "theoretical ecology", "zoology", "fruit bats", "microbial ecology", "wildlife", "ecology", "gorillas", "bats", "biology and life ...	Ecological Contexts of Index Cases and Spillover Events of Different Ebolaviruses	journal.ppat.1005780	null	[ [ "From the first recognized outbreak of Ebola virus disease ( EVD ) in 1976 to the recent outbreak beginning in 2013 , our knowledge about the molecular biology and epidemiology of viruses belonging to the genus Ebolavirus has increased dramatically .", "Yet after nearly 40 years of research , we still hav...	[ "Ebola virus disease afflicts both human and animal populations and is caused by four ebolaviruses .", "These different ebolaviruses may have distinct reservoir hosts and ecological contexts that determine how , where , and when different ebolavirus spillover events occur .", "Understanding these virus-specific...	[ "Multiple Ebola virus disease outbreaks have occurred over the past 40 years , yet we still do not know the geographical distributions , definitive host species , and suitable habitats for animal-to-human transmission of different ebolaviruses .", "Each Ebola virus disease outbreak has started with at least one t...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Mechanism of Membranous Tunnelling Nanotube Formation in Viral Genome Delivery	journal.pbio.1001667	Abrescia and colleagues demonstrate how the bacteriophage PRD1, a model membrane-containing virus, generates a self-polymerizing protein-lipid nanotube to deliver its viral genome to a host cell.	[ [ "A fundamental step in the lifecycle of all known viruses is the genome translocation into the target cell .", "Although this process has been elucidated for several enveloped viruses [1] , [2] , and for double-stranded ( ds ) DNA head-tailed bacteriophages [3]–[7] , equivalent information on internal mem...	[ "In internal membrane-containing viruses , a lipid vesicle enclosed by the icosahedral capsid protects the genome .", "It has been postulated that this internal membrane is the genome delivery device of the virus .", "Viruses built with this architectural principle infect hosts in all three domains of cellular ...	[ "Viral survival and propagation depend on the ability of the viruses to transfer their genetic material to a host cell .", "Viral genome delivery has been described for viruses that directly enclose their genome in a capsid or nucleocapsid , but not for internal membrane-containing viruses in which the genome is ...	2013
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "microbiology/immunity to infections", "infectious diseases/neglected tropical diseases", "infectious diseases/skin infections", "infectious diseases/bacterial infections", "immunology/immunity to infections", "public health and epidemiology/immunization" ]	BCG-Mediated Protection against Mycobacterium ulcerans Infection in the Mouse	journal.pntd.0000985	null	[ [ "BCG vaccination is widely practiced around the world , primarily to protect against tuberculosis .", "BCG is a safe vaccine but its efficacy against tuberculosis varies by geographical region and possibly by BCG strain due to mutations related to culturing practices in multiple laboratories for many deca...	[ "Vaccination with Mycobacterium bovis bacille Calmette-Guérin ( BCG ) is widely used to reduce the risk of childhood tuberculosis and has been reported to have efficacy against two other mycobacterial diseases , leprosy and Buruli ulcer caused by M . ulcerans ( Mu ) .", "Studies in experimental models have also s...	[ "Vaccination with Mycobacterium bovis bacille Calmette-Guérin ( BCG ) is used to reduce the risk of childhood tuberculosis and is reported to have efficacy against two other diseases also caused by mycobacteria , leprosy and Buruli ulcer caused by M . ulcerans .", "We hypothesized that there may be differences in...	2011
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	IL-1α Signaling Is Critical for Leukocyte Recruitment after Pulmonary Aspergillus fumigatus Challenge	journal.ppat.1004625	null	[ [ "The mold Aspergillus fumigatus is one of the leading causes of invasive fungal infections .", "It is the causative agent of severe pulmonary infections such as invasive pulmonary aspergillosis ( IPA ) , a disease of high morbidity and mortality which affects immunocompromised individuals [1] .", "IPA...	[ "Aspergillus fumigatus is a mold that causes severe pulmonary infections .", "Our knowledge of how A . fumigatus growth is controlled in the respiratory tract is developing , but still limited .", "Alveolar macrophages , lung resident macrophages , and airway epithelial cells constitute the first lines of defen...	[ "Aspergillus spp .", "are ubiquitous in the environment , and even though individuals are regularly exposed to fungal spores clinical invasive disease is a rare manifestation .", "In contrast , individuals with weakened immune systems develop severe disease , such as invasive pulmonary aspergillosis ( IPA ) .",...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "bacteriology", "functional genomics", "protein interactions", "macromolecular assemblies", "microbiology", "gene function", "escherichia coli", "prokaryotic models", "model organisms", "medical microbiology", "comparative genomics", "biology", "proteomics", "systems biology", "biochemis...	Quantitative Genome-Wide Genetic Interaction Screens Reveal Global Epistatic Relationships of Protein Complexes in Escherichia coli	journal.pgen.1004120	null	[ [ "A key feature of the molecular organization of microbes is the tendency of functionally-linked proteins to associate as components of macromolecular complexes , operons , or other biological groupings .", "As a consequence , the gene products present in a bacterial cell are organized into functional modu...	[ "Large-scale proteomic analyses in Escherichia coli have documented the composition and physical relationships of multiprotein complexes , but not their functional organization into biological pathways and processes .", "Conversely , genetic interaction ( GI ) screens can provide insights into the biological role...	[ "Genome-wide genetic interaction ( GI ) screens have been performed in yeast , but no analogous large-scale studies have yet been reported for bacteria .", "Here , we have used E . coli synthetic genetic array ( eSGA ) technology developed by our group to quantitatively map GIs to reveal epistatic dependencies an...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "blood cells", "infectious disease immunology", "white blood cells", "immune cells", "cell biology", "animal cells", "clinical immunology", "medical microbiology", "yersinia", "microbial pathogens", "biology and life sciences", "cellular types", "immunology", "macrophages", "microbiology...	The GAP Activity of Type III Effector YopE Triggers Killing of Yersinia in Macrophages	journal.ppat.1004346	null	[ [ "Innate immunity provides an early and critical protection against pathogenic infection .", "In the dominant paradigm of innate immunity , host cells detect pathogens by recognition of “microorganism-associated molecular patterns” ( MAMPs ) via pattern recognition receptors ( PRRs ) [1] .", "However ,...	[ "The mammalian immune system has the ability to discriminate between pathogens and innocuous microbes by detecting conserved molecular patterns .", "In addition to conserved microbial patterns , the mammalian immune system may recognize distinct pathogen-induced processes through a mechanism which is poorly under...	[ "The type III secretion system ( T3SS ) is a macromolecular protein export pathway found in gram-negative bacteria .", "It delivers bacterial toxins into eukaryotic cells to promote pathogenic infection .", "T3SSs and the bacterial toxins delivered are critical arsenals for many bacterial pathogens of clinical ...	2014
[ "Introduction", "Materials and methods", "Results", "Discussion" ]	[ "invertebrates", "medicine and health sciences", "onchocerca volvulus", "chemical compounds", "helminths", "tropical diseases", "black flies", "vector-borne diseases", "geographical locations", "parasitic diseases", "animals", "onchocerca", "diptera", "organic compounds", "oils", "mate...	Blackflies in the ointment: O. volvulus vector biting can be significantly reduced by the skin-application of mineral oil during human landing catches	journal.pntd.0007234	null	[ [ "A key component of the WHO´s nascent onchocerciasis elimination programme is the entomological monitoring of O . volvulus transmission by its blackfly vectors [1 , 2] .", "Historically , the African Programme for Onchocerciasis Control ( APOC ) and Onchocerciasis Elimination Program for the Americas ( OE...	[ "Standard human landing catches ( sHLCs ) have historically been a key component of Onchocerca volvulus transmission monitoring , but expose health-workers to potentially hazardous vector bites .", "Novel human-bait-free trapping methods have been developed , but do not always work where they are needed and may n...	[ "Standard human landing catches ( sHLCs ) have historically been used to obtain key Onchocerca volvulus transmission data that has helped with the design and monitoring of the WHO´s onchocerciasis control programmes .", "To avoid the health risks associated with sHLCs , alternative human-bait-free blackfly trappi...	2019
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	An Atypical Mitochondrial Carrier That Mediates Drug Action in Trypanosoma brucei	journal.ppat.1004875	null	[ [ "African trypanosomes are vector-borne protozoans that cause serious public health problems and severe economic losses in sub-Saharan African countries .", "The current chemotherapy against Trypanosoma brucei , the causative agent of human African trypanosomiasis , or sleeping sickness , and the related c...	[ "Elucidating the mechanism of action of trypanocidal compounds is an important step in the development of more efficient drugs against Trypanosoma brucei .", "In a screening approach using an RNAi library in T . brucei bloodstream forms , we identified a member of the mitochondrial carrier family , TbMCP14 , as a...	[ "Human and animal trypanosomiases caused by Trypanosoma brucei parasites represent major burdens to human welfare and agricultural development in rural sub-Saharan Africa .", "Although the numbers of infected humans have decreased continuously during the last decades , emerging resistance and adverse side effects...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genetics and genomics/comparative genomics", "evolutionary biology/evolutionary and comparative genetics", "molecular biology/molecular evolution", "developmental biology/developmental evolution", "evolutionary biology/pattern formation", "developmental biology/molecular development", "evolutionary bio...	Functional Evolution of cis-Regulatory Modules at a Homeotic Gene in Drosophila	journal.pgen.1000709	null	[ [ "The Drosophila bithorax complex ( BX-C ) is over 300 kb in size [1] , but contains only three homeotic ( Hox ) genes , Ultrabithorax ( Ubx ) , abdominal-A ( abd-A ) , and Abdominal-B ( Abd-B ) [2] .", "These genes control the identity of ten parasegments ( PS5-14 ) in the posterior thorax and abdomen of ...	[ "It is a long-held belief in evolutionary biology that the rate of molecular evolution for a given DNA sequence is inversely related to the level of functional constraint .", "This belief holds true for the protein-coding homeotic ( Hox ) genes originally discovered in Drosophila melanogaster .", "Expression of...	[ "The fertilized animal embryo is a mass of uniform cells that becomes a complex , segmented , and highly organized structure of differentiated cells through the process of development .", "This vital process is controlled by networks of developmental genes interacting with each other on the molecular level .", ...	2009
[ "Introduction", "Results/Discussion", "Methods" ]	[ "microbiology/cellular microbiology and pathogenesis", "genetics and genomics" ]	Molecular Mechanisms of Ethanol-Induced Pathogenesis Revealed by RNA-Sequencing	journal.ppat.1000834	null	[ [ "Acinetobacters are Gram-negative bacteria that belong to the Moraxellaceae family [1] .", "The members of the Acinetobacter group are metabolically versatile since they can metabolize an important number of compounds such as aliphatic alcohols , some amino acids , decarboxylic and fatty acids , unbranche...	[ "Acinetobacter baumannii is a common pathogen whose recent resistance to drugs has emerged as a major health problem .", "Ethanol has been found to increase the virulence of A . baumannii in Dictyostelium discoideum and Caenorhabditis elegans models of infection .", "To better understand the causes of this effe...	[ "Acinetobacter baumannii has recently emerged as a frequent opportunistic pathogen .", "In the presence of ethanol A . baumannii increases its pathogenicity towards Dictyostelium discoideum and Caenorhabditis elegans , and community-acquired infections of A . baumannii are associated with alcoholism .", "Ethano...	2010
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "bacteriology", "systems biology", "bacterial physiology", "microbial metabolism", "microbial physiology", "gene regulatory networks", "biology and life sciences", "microbiology", "computational biology" ]	Memory and Fitness Optimization of Bacteria under Fluctuating Environments	journal.pgen.1004556	null	[ [ "Escherichia coli cells grown in the presence of both glucose and lactose first consume glucose , which is more easily metabolized , before expressing the genes necessary for lactose catabolism [1]–[3] .", "The prioritization of bacterial metabolism toward a specific substrate is achieved by catabolite re...	[ "Bacteria prudently regulate their metabolic phenotypes by sensing the availability of specific nutrients , expressing the required genes for their metabolism , and repressing them after specific metabolites are depleted .", "It is unclear , however , how genetic networks maintain and transmit phenotypic states b...	[ "Bacterial adaptation to new environments typically involves reorganization of gene expression that temporarily decreases growth rates .", "By exposing cells to fluctuating conditions using an innovative microfluidic device , we discover that E . coli cells can remember past environments , which accelerates their...	2014
[ "Introduction", "Materials and Methods", "Results and Discussion" ]	[ "medicine", "infectious diseases", "schistosomiasis", "neglected tropical diseases", "parasitic diseases" ]	Identification and Characterization of Argonaute Protein, Ago2 and Its Associated Small RNAs in Schistosoma japonicum	journal.pntd.0001745	null	[ [ "Schistosomiasis is a chronic debilitating disease caused by the parasitic blood flukes of the genus Schistosoma , which afflicts more than 230 million individuals in 77 endemic countries ( http://www . who . int/mediacentre/factsheets/fs115/en/index . html ) .", "The schistosomes have a complex developme...	[ "The complex life cycle of the genus Schistosoma drives the parasites to employ subtle developmentally dependent gene regulatory machineries .", "Small non-coding RNAs ( sncRNAs ) are essential gene regulatory factors that , through their impact on mRNA and genome stability , control stage-specific gene expressio...	[ "Schistosomiasis , a chronic disease caused by agents of the genus Schistosoma , still afflicts more than 230 million people worldwide .", "The genomes of the three major pathogenic blood flukes , Schistosoma japonicum , Schistosoma mansoni , and Schistosoma haematobium , have been decoded as valuable entities fo...	2012
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "medicine and health sciences", "messenger rna", "rna extraction", "polyribosomes", "plasmid construction", "fungi", "nutrition", "dna construction", "molecular biology techniques", "cellular structures and organelles", "extraction techniques", "research and analysis methods", "gene expressi...	Yeast Cth2 protein represses the translation of ARE-containing mRNAs in response to iron deficiency	journal.pgen.1007476	null	[ [ "Iron is indispensable for all eukaryotic organisms because it serves as a redox cofactor in a wide range of critical biological processes , including the synthesis of the principal cellular components ( DNA , proteins , lipids and other metabolites ) , mitochondrial respiration , photosynthesis , and oxygen ...	[ "In response to iron deficiency , the budding yeast Saccharomyces cerevisiae undergoes a metabolic remodeling in order to optimize iron utilization .", "The tandem zinc finger ( TZF ) -containing protein Cth2 plays a critical role in this adaptation by binding and promoting the degradation of multiple mRNAs that ...	[ "Iron is essential for eukaryotes because it is required for many fundamental processes such as DNA replication , protein translation or respiration , but it is very insoluble and can , therefore , easily go scarce .", "For this reason , eukaryotic cells have developed adaptive responses to iron deficiency .", ...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biotechnology", "genome-wide association studies", "genome expression analysis", "genome complexity", "genomics", "genome analysis", "transcriptome analysis", "genetics", "biology and life sciences", "genomic medicine", "computational biology", "pharmacogenomics" ]	Protein Quantitative Trait Loci Identify Novel Candidates Modulating Cellular Response to Chemotherapy	journal.pgen.1004192	null	[ [ "Pharmacogenomics aims to identify clinically actionable markers associated with response or toxicity; for oncology , evaluating genotype-phenotype relationships is particularly important because non-response and adverse events associated with chemotherapy can be life-threatening .", "Drug response and to...	[ "Annotating and interpreting the results of genome-wide association studies ( GWAS ) remains challenging .", "Assigning function to genetic variants as expression quantitative trait loci is an expanding and useful approach , but focuses exclusively on mRNA rather than protein levels .", "Many variants remain wi...	[ "The central dogma of biology explains that DNA is transcribed to mRNA that is further translated into protein .", "Many genome-wide studies have implicated genetic variation that influences gene expression and that ultimately affect downstream complex traits including response to drugs .", "However , because o...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Aberrant Gene Expression in Humans	journal.pgen.1004942	null	[ [ "The advent of high-throughput genotyping and sequencing technologies enables a comprehensive characterization of the genomic and transcriptomic landscapes of each individual .", "Deciphering the massive data points associated with individuals presents a major challenge [1 , 2] .", "Over the last coup...	[ "Gene expression as an intermediate molecular phenotype has been a focus of research interest .", "In particular , studies of expression quantitative trait loci ( eQTL ) have offered promise for understanding gene regulation through the discovery of genetic variants that explain variation in gene expression level...	[ "The uniqueness of individuals is due to differences in the combination of genetic , epigenetic and environmental determinants .", "Understanding the genetic basis of phenotypic variation is a key objective in genetics .", "Gene expression has been considered as an intermediate phenotype , and the association b...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods", "Supporting Information" ]	[ "homo (human)", "genetics and genomics" ]	A High-Density Admixture Scan in 1,670 African Americans with Hypertension	journal.pgen.0030196	null	[ [ "Essential hypertension ( HTN ) is a widely prevalent condition with devastating clinical consequences including stroke , myocardial infarction , heart failure , and chronic kidney disease .", "Familial aggregation studies have established HTN as a complex trait , with both environmental and genetic deter...	[ "Hypertension ( HTN ) is a devastating disease with a higher incidence in African Americans than European Americans , inspiring searches for genetic variants that contribute to this difference .", "We report the results of a large-scale admixture scan for genes contributing HTN risk , in which we screened 1 , 670...	[ "High blood pressure is more frequent and severe among African Americans than European Americans .", "To explore whether there are genetic underpinnings to this pattern , we screened the genomes of 1 , 670 African Americans , searching for loci at which people with hypertension ( HTN ) have more than the average ...	2007
[ "Introduction", "Results", "Discussion", "Methods" ]	[]	The Depsipeptide Romidepsin Reverses HIV-1 Latency In Vivo	journal.ppat.1005142	null	[ [ "Antiretroviral therapy ( ART ) effectively suppresses viral replication and partially restores immune functions in human immunodeficiency virus type-1 ( HIV-1 ) infected individuals [1] .", "However , HIV-1 integrates into the host DNA , thus establishing the basis for latent infection .", "As ART ca...	[ "clinicaltrials . gov NTC02092116" ]	[ "One proposed way of curing HIV is to activate virus transcription and kill latently infected cells while the presence of antiretroviral therapy prevents spreading the infection .", "Induction of global T cell activation by mitogenic or other potent activators effectively reverses HIV-1 from latency ex vivo , but...	2015
[ "Introduction", "Materials and Methods", "Results/Discussion" ]	[ "medicine", "growth retardation", "mathematics", "diagnostic medicine", "pathology", "statistics", "clinical pathology", "biostatistics", "clinical microbiology", "pediatrics" ]	Novel Developmental Analyses Identify Longitudinal Patterns of Early Gut Microbiota that Affect Infant Growth	journal.pcbi.1003042	null	[ [ "Gut microbiota has a critical role in human health [1]–[6]; early infancy is of special interest because the early life period is a determinant for the subsequent adult-like microbiota .", "Once the first microbes arrive in the sterile gut of the newborn , a dynamic process starts , where activation of g...	[ "It is acknowledged that some obesity trajectories are set early in life , and that rapid weight gain in infancy is a risk factor for later development of obesity .", "Identifying modifiable factors associated with early rapid weight gain is a prerequisite for curtailing the growing worldwide obesity epidemic .",...	[ "Some obesity trajectories are set early in life , with rapid weight gain being a risk factor for later development of obesity .", "Recently , much attention has been given to findings indicating that gut microbiota may play a role in obesity development .", "The existence of time-dependent exposure windows , w...	2013
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "microbiology/plant-biotic interactions", "genetics and genomics/gene expression", "genetics and genomics/functional genomics", "cell biology/morphogenesis and cell biology", "cell biology/microbial growth and development", "microbiology/cellular microbiology and pathogenesis", "cell biology/gene expres...	The Transcription Factor Rbf1 Is the Master Regulator for b-Mating Type Controlled Pathogenic Development in Ustilago maydis	journal.ppat.1001035	null	[ [ "In a wide range of fungi , complex developmental traits such as cell identity , morphogenesis and sexual development are controlled by mating type loci [1] , [2] , [3] .", "In the smut fungi , a group of plant pathogens , these traits also include the ability to infect their host plants .", "In Ustil...	[ "In the phytopathogenic basidiomycete Ustilago maydis , sexual and pathogenic development are tightly connected and controlled by the heterodimeric bE/bW transcription factor complex encoded by the b-mating type locus .", "The formation of the active bE/bW heterodimer leads to the formation of filaments , induces...	[ "The basidiomycetous fungus Ustilago maydis is the causal agent of the smut disease on corn .", "The fungus exhibits two different life-styles , a saprophytic and a pathogenic stage , where it grows yeast-like by budding , or as filamentous , dikaryotic hyphae , respectively .", "The switch between these two st...	2010
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "infectious diseases/neglected tropical diseases", "public health and epidemiology/infectious diseases", "infectious diseases/protozoal infections", "ecology/population ecology", "infectious diseases/epidemiology and control of infectious diseases" ]	Strong Host-Feeding Preferences of the Vector Triatoma infestans Modified by Vector Density: Implications for the Epidemiology of Chagas Disease	journal.pntd.0000447	null	[ [ "Host choice of hematophagous insects mainly depends on relative host abundance and proximity , host defensive behavior , the density of blood-sucking insects , and the spatial and temporal concurrence of hosts and insects [1] , [2] .", "Examples of innate ( genetically determined ) host-feeding preferenc...	[ "Understanding the factors that affect the host-feeding preferences of triatomine bugs is crucial for estimating transmission risks and predicting the effects of control tactics targeting domestic animals .", "We tested whether Triatoma infestans bugs prefer to feed on dogs vs . chickens and on dogs vs . cats and...	[ "Chagas disease is a complex zoonosis with more than 150 mammalian host species , nearly a dozen blood-sucking triatomine species as main vectors , and 9–11 million people infected with Trypanosoma cruzi ( its causal agent ) in the Americas .", "Triatoma infestans , a highly domesticated species and one of the ma...	2009
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "antimicrobials", "medicine and health sciences", "pathology and laboratory medicine", "medical personnel", "drugs", "sociology", "tropical diseases", "microbiology", "geographical locations", "social sciences", "anthropology", "surgical and invasive medical procedures", "health care", "ba...	Implementation of a decentralized community-based treatment program to improve the management of Buruli ulcer in the Ouinhi district of Benin, West Africa	journal.pntd.0006291	null	[ [ "The endemic Ouinhi district is located along the Ouémé River in southern Benin ( Fig 1 ) .", "It is one of the five most endemic districts ( Fig 2A ) ; of these , it has the highest number of Category III cases ( Fig 2B ) .", "The local population depends on multiple household livelihood strategies ,...	[ "Mycobacterium ulcerans infection , commonly known as Buruli ulcer ( BU ) , is a debilitating neglected tropical disease .", "Its management remains complex and has three main components: antibiotic treatment combining rifampicin and streptomycin for 56 days , wound dressings and skin grafts for large ulcerations...	[ "The management of Buruli ulcer ( BU ) is complex , resulting in high costs to families and health systems .", "Early detection and treatment heals lesions without functional limitations .", "Decentralization of the management of this disease into the peripheral health system remains a challenge for national co...	2018
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "medicine", "infectious diseases", "leishmaniasis", "neglected tropical diseases", "parasitic diseases" ]	Five-Year Field Results and Long-Term Effectiveness of 20 mg/kg Liposomal Amphotericin B (Ambisome) for Visceral Leishmaniasis in Bihar, India	journal.pntd.0002603	null	[ [ "Visceral leishmaniasis ( VL ) , also known as Kala-azar , is a protozoan parasitic disease transmitted by phlebotomine sandflies .", "It is estimated that in 2004 a total of 1 , 071 , 743 disability-adjusted life years were lost to VL in South East Asia alone [1]; if left untreated the disease is fatal ....	[ "Visceral Leishmaniasis ( VL; also known as Kala-azar ) is an ultimately fatal disease endemic in Bihar .", "A 2007 observational cohort study in Bihar of 251 patients with VL treated with 20 mg/Kg intravenous liposomal amphotericin B ( Ambisome ) demonstrated a 98% cure rate at 6-months .", "Between July 2007 ...	[ "Visceral leishmaniasis ( VL ) , also known as Kala-azar , is a protozoan parasitic disease transmitted by phlebotomine sandflies .", "After malaria , VL accounts for the second-highest burden of parasitic diseases worldwide .", "India has half of all the VL patients worldwide , of which up to 90% are in Bihar ...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "mathematics", "immunity", "virology", "innate immunity", "statistics", "immunology", "biology", "microbiology" ]	A Novel Bayesian Method for Detection of APOBEC3-Mediated Hypermutation and Its Application to Zoonotic Transmission of Simian Foamy Viruses	journal.pcbi.1003493	null	[ [ "Simian foamy viruses ( SFV ) comprise a subfamily of retroviruses that naturally infect all primates examined with the notable exception of humans .", "In non-human primates ( NHP ) , they show strong evidence of co-evolution with their hosts [1] .", "Persistent infection with SFV is ubiquitous in po...	[ "Simian Foamy Virus ( SFV ) can be transmitted from non-human primates ( NHP ) to humans .", "However , there are no documented cases of human to human transmission , and significant differences exist between infection in NHP and human hosts .", "The mechanism for these between-host differences is not completel...	[ "Simian Foamy Virus ( SFV ) is a very common retrovirus in monkeys .", "When an infected monkey bites a human it can transmit the virus to the human; however , there are no documented cases of human to human transmission .", "There also appear to be significant differences between infection in monkey and human ...	2014
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[]	The Burden of Rabies in Tanzania and Its Impact on Local Communities	journal.pntd.0002510	null	[ [ "Rabies is a fatal zoonotic infection of the central nervous system caused by a lyssavirus [1] .", "This disease , which can affect all mammals , is transmitted in the saliva of infectious animals [2] .", "Rabies is endemic in low income countries , causing an estimated 55 , 000 human deaths each year...	[ "Rabies remains a major public health threat in many parts of the world and is responsible for an estimated 55 , 000 human deaths annually .", "The burden of rabies is estimated to be around US$20 million in Africa , with the highest financial expenditure being the cost of post-exposure prophylaxis ( PEP ) .", ...	[ "Rabies remains a major public health problem , although the means to control and prevent this disease are available through mass dog vaccination and provision of post-exposure prophylaxis ( PEP ) to people exposed to bites by rabid or suspect rabid animals .", "Despite its necessity as a life-saving measure to p...	2013
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "neuroscience", "immunology", "biology" ]	Type I Interferon Programs Innate Myeloid Dynamics and Gene Expression in the Virally Infected Nervous System	journal.ppat.1003395	null	[ [ "The central nervous system ( CNS ) is an immunologically specialized compartment consisting of the brain and spinal cord [1] .", "These structures are lined by what is referred to as the meninges .", "Most blood vessels within the CNS are non-fenestrated , meaning the endothelial cells that comprise ...	[ "Viral infections of central nervous system ( CNS ) often trigger inflammatory responses that give rise to a wide range of pathological outcomes .", "The CNS is equipped with an elaborate network of innate immune sentinels ( e . g . microglia , macrophages , dendritic cells ) that routinely serve as first respond...	[ "The central nervous system is equipped with innate immune cells that serve as first responders to sterile injuries and infections .", "The mechanisms that program the movement and morphological transformations of these cells following infection remain undefined .", "Here , we utilized a combination of genomic ...	2013
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "infectious diseases", "medicine and health sciences" ]	Miltefosine and Antimonial Drug Susceptibility of Leishmania Viannia Species and Populations in Regions of High Transmission in Colombia	journal.pntd.0002871	null	[ [ "Pentavalent antimonial drugs , ( sodium stibogluconate and meglumine antimoniate ) have been the first-line monotherapeutic treatment for dermal leishmaniasis in Central and South America for decades .", "Parenteral administration , volumes of drug requiring divided doses in adults , frequent and potenti...	[ "Pentavalent antimonials have been the first line treatment for dermal leishmaniasis in Colombia for over 30 years .", "Miltefosine is administered as second line treatment since 2005 .", "The susceptibility of circulating populations of Leishmania to these drugs is unknown despite clinical evidence supporting ...	[ "Treatment of dermal leishmaniasis is unsuccessful in an important proportion of cases and evidence of loss of susceptibility to antimonial drugs and miltefosine has been demonstrated in some cases of treatment failure with these medications .", "Despite the variability in the clinical outcome of treatment , litt...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "animal models", "developmental biology", "cellular structures", "model organisms", "molecular cell biology", "ciona intestinalis", "biology", "evolutionary biology", "morphogenesis", "cytoskeleton", "evolutionary developmental biology" ]	An Equatorial Contractile Mechanism Drives Cell Elongation but not Cell Division	journal.pbio.1001781	A cytokinesis-like contractile mechanism is co-opted in a different developmental scenario to achieve cell elongation instead of cell division in Ciona intestinalis.	[ [ "Individual cell shape changes contribute significantly to morphogenesis during embryonic development [1] .", "The actomyosin network is a central player in the formation and transformation of functional cell shapes .", "Actin and myosin filaments are highly and dynamically organized in different deve...	[ "Cell shape changes and proliferation are two fundamental strategies for morphogenesis in animal development .", "During embryogenesis of the simple chordate Ciona intestinalis , elongation of individual notochord cells constitutes a crucial stage of notochord growth , which contributes to the establishment of th...	[ "The actomyosin cytoskeleton is the primary force that drives cell shape changes .", "These fibers are organized in elaborate structures that form sarcomeres in the muscle and the contractile ring during cytokinesis .", "In cytokinesis , the establishment of an equatorial actomyosin ring is preceded and regulat...	2014
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "medicine", "infectious diseases", "diagnostic medicine", "pathology", "general pathology", "biomarkers", "parasitic diseases" ]	Parasite-Derived MicroRNAs in Host Serum As Novel Biomarkers of Helminth Infection	journal.pntd.0002701	null	[ [ "Helminths are parasitic worms that infect a third of the world's population and cause a diverse range of health consequences leading to significant social and economical burdens [1] , [2] .", "Schistosomiasis is a chronic disease caused by blood flukes of the genus Schistosoma that affects more than 200 ...	[ "MicroRNAs ( miRNAs ) are a class of short non-coding RNA that play important roles in disease processes in animals and are present in a highly stable cell-free form in body fluids .", "Here , we examine the capacity of host and parasite miRNAs to serve as tissue or serum biomarkers of Schistosoma mansoni infecti...	[ "Schistosomiasis is a chronic disease caused by blood flukes that affects over 200 million people worldwide , of which 90% live in Sub-Saharan Africa .", "In the field setting schistosomiasis caused by S . mansoni is diagnosed by detection of parasite eggs in stool samples using microscopic techniques .", "Here...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genetics and genomics/chromosome biology" ]	Indistinguishable Landscapes of Meiotic DNA Breaks in rad50+ and rad50S Strains of Fission Yeast Revealed by a Novel rad50+ Recombination Intermediate	journal.pgen.1000267	null	[ [ "Sexual reproduction involves the fusion of two gametes to create diploid offspring with equal genetic contributions from each parent .", "To maintain the proper chromosome number ( ploidy ) , it is therefore necessary for the gametes to be haploid .", "This is achieved via meiosis , where a single ro...	[ "The fission yeast Schizosaccharomyces pombe Rec12 protein , the homolog of Spo11 in other organisms , initiates meiotic recombination by creating DNA double-strand breaks ( DSBs ) and becoming covalently linked to the DNA ends of the break .", "This protein–DNA linkage has previously been detected only in mutant...	[ "During meiosis , which creates haploid gametes from diploid cells , recombination between two homologous chromosomes increases genetic diversity and , in most organisms , is crucial for proper segregation of chromosomes into haploid nuclei .", "To better understand where recombination occurs and why it occurs th...	2008
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "medicine", "immunotoxicology", "immunology", "toxicology" ]	Death Adder Envenoming Causes Neurotoxicity Not Reversed by Antivenom - Australian Snakebite Project (ASP-16)	journal.pntd.0001841	null	[ [ "Death adders ( genus Acanthophis ) are a member of the snake family Elapidae .", "They inhabit most of Australia ( excluding Victoria and Tasmania ) , Papua New Guinea , Irian Jaya and the Indonesian islands of Seram , Halmahera , Obi and Tanimbar .", "Considerable debate about the taxonomy of indivi...	[ "Death adders ( Acanthophis spp ) are found in Australia , Papua New Guinea and parts of eastern Indonesia .", "This study aimed to investigate the clinical syndrome of death adder envenoming and response to antivenom treatment .", "Definite death adder bites were recruited from the Australian Snakebite Project...	[ "Death adders are a genus of venomous snakes found in Australia , Papua New Guinea and Indonesia .", "Death adder envenoming is a rare but important health problem in Australasia .", "Definite death adder bites were recruited as part of the Australian Snakebite Project ( ASP ) .", "Clinical effects , laborato...	2012
[ "Introduction", "Materials and Methods", "Results/Discussion" ]	[ "biotechnology", "parastic protozoans", "leishmania", "small molecules", "protozoology", "host-pathogen interaction", "microbiology", "biology", "drug discovery" ]	High Content Analysis of Primary Macrophages Hosting Proliferating Leishmania Amastigotes: Application to Anti-leishmanial Drug Discovery	journal.pntd.0002154	null	[ [ "Human leishmaniases are diseases that are endemic throughout tropical and subtropical areas causing severe morbidity and mortality with an estimated worldwide incidence of 1 , 500 , 000 newly reported clinical cases per year .", "More than 12 million people are currently infected and 350 million people a...	[ "Human leishmaniases are parasitic diseases causing severe morbidity and mortality .", "No vaccine is available and numerous factors limit the use of current therapies .", "There is thus an urgent need for innovative initiatives to identify new chemotypes displaying selective activity against intracellular Leis...	[ "Leishmaniases are neglected diseases caused by protozoan parasites that belong to the genus Leishmania .", "No vaccine exists against any form of leishmaniasis and most of the existing anti-leishmanial drugs have serious side effects .", "Current strategies for discovering new leishmanicidal molecules are larg...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine and health sciences", "chemical compounds", "diabetic endocrinology", "carbohydrates", "organic compounds", "glucose", "hormones", "endocrine physiology", "animal models", "model organisms", "mitochondria", "epigenetics", "bioenergetics", "dna", "cellular structures and organel...	A Syntenic Cross Species Aneuploidy Genetic Screen Links RCAN1 Expression to β-Cell Mitochondrial Dysfunction in Type 2 Diabetes	journal.pgen.1006033	null	[ [ "Type 2 diabetes ( T2D ) is a complex metabolic disorder characterised by elevated blood glucose levels .", "Pancreatic β-cell dysfunction and reduced insulin output in the presence of insulin resistance is the primary cause of T2D .", "The mechanisms leading to a switch from β-cell compensation durin...	[ "Type 2 diabetes ( T2D ) is a complex metabolic disease associated with obesity , insulin resistance and hypoinsulinemia due to pancreatic β-cell dysfunction .", "Reduced mitochondrial function is thought to be central to β-cell dysfunction .", "Mitochondrial dysfunction and reduced insulin secretion are also o...	[ "Mitochondrial dysfunction and reduced insulin secretion are key features of β-cell dysfunction in Type 2 diabetes ( T2D ) .", "Down syndrome ( DS ) is a genetic disorder caused by trisomy of chromosome 21 that also displays β-cell mitochondrial dysfunction and reduced insulin secretion in humans .", "Given the...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	A Structural Basis for BRD2/4-Mediated Host Chromatin Interaction and Oligomer Assembly of Kaposi Sarcoma-Associated Herpesvirus and Murine Gammaherpesvirus LANA Proteins	journal.ppat.1003640	null	[ [ "Kaposi sarcoma-associated herpesvirus ( KSHV , also HHV8 ) , the cause of Kaposi Sarcoma and two lymphoid neoplasms , can persist in a latent form in infected endothelial and B-cells [1] .", "The key player in the regulation of KSHV latency is the latency-associated nuclear antigen ( LANA ) , which is de...	[ "Kaposi sarcoma-associated herpesvirus ( KSHV ) establishes a lifelong latent infection and causes several malignancies in humans .", "Murine herpesvirus 68 ( MHV-68 ) is a related γ2-herpesvirus frequently used as a model to study the biology of γ-herpesviruses in vivo .", "The KSHV latency-associated nuclear ...	[ "Kaposi sarcoma-associated herpesvirus ( KSHV ) causes Kaposi Sarcoma , Primary Effusion lymphoma and the plasma cell variant of Multicentric Castleman's Disease .", "Its oncogenic effect is linked to its ability to persist in a latent form for the life time of infected individuals .", "During latency viral gen...	2013
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "complement system", "medicine and health sciences", "immune physiology", "body fluids", "pathology and laboratory medicine", "viral transmission and infection", "hela cells", "pathogens", "vibrio", "immunology", "biological cultures", "microbiology", "operons", "pili and fimbriae", "vib...	A stealth adhesion factor contributes to Vibrio vulnificus pathogenicity: Flp pili play roles in host invasion, survival in the blood stream and resistance to complement activation	journal.ppat.1007767	null	[ [ "Vibrio vulnificus is an opportunistic Gram-negative marine pathogen that causes fatal septicemia and necrotizing wound infections in susceptible individuals with underlying hepatic diseases and other immunocompromised conditions .", "V . vulnificus is halophilic and found worldwide in warm coastal and br...	[ "The tad operons encode the machinery required for adhesive Flp ( fimbrial low-molecular-weight protein ) pili biogenesis .", "Vibrio vulnificus , an opportunistic pathogen , harbors three distinct tad loci .", "Among them , only tad1 locus was highly upregulated in in vivo growing bacteria compared to in vitro...	[ "Vibrio vulnificus is so called “flesh eating bacterium” causing fatal sepsis accompanying destruction ( necrosis ) of soft tissue .", "The fatal infection occurs after eating contaminated seafood such as oysters or exposure of pre-existing wounds to seawater .", "Here we show an important bacterial factor that...	2019
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine", "leukemias", "cancer genetics", "gene regulation", "cancers and neoplasms", "basic cancer research", "dna transcription", "gene function", "histone modification", "hematologic cancers and related disorders", "oncology", "tumor physiology", "chronic lymphoblastic leukemia", "epi...	Epigenetic Upregulation of lncRNAs at 13q14.3 in Leukemia Is Linked to the In Cis Downregulation of a Gene Cluster That Targets NF-kB	journal.pgen.1003373	null	[ [ "Non-coding RNAs ( ncRNA ) are emerging as an important factor for the aberrant gene expression associated with cancer [1] .", "NcRNA genes are mostly involved in the regulation of target gene function [2] .", "Their mode of action varies from posttranscriptional regulation ( i . e . miRNA genes ) [3]...	[ "Non-coding RNAs are much more common than previously thought .", "However , for the vast majority of non-coding RNAs , the cellular function remains enigmatic .", "The two long non-coding RNA ( lncRNA ) genes DLEU1 and DLEU2 map to a critical region at chromosomal band 13q14 . 3 that is recurrently deleted in ...	[ "Recent results suggest that genome regions not coding for proteins are read and transcribed into RNA .", "While the function for the majority of the resulting non-coding RNA molecules remains unclear , some of them are termed according to their length ( typically 200–2 , 000 nucleotides ) as long non-coding RNA ...	2013
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "evolutionary biology/evolutionary and comparative genetics", "computational biology/comparative sequence analysis", "evolutionary biology/genomics", "evolutionary biology/bioinformatics", "computational biology/genomics", "evolutionary biology", "computational biology" ]	Identifying a High Fraction of the Human Genome to be under Selective Constraint Using GERP++	journal.pcbi.1001025	null	[ [ "The identification and annotation of all functional elements in the human genome is one of the main goals of contemporary genetics in general , and the ENCODE project in particular [1] , [2] , [3] .", "Comparative sequence analysis , enabled by multiple sequence alignments of the human genome to dozens o...	[ "Computational efforts to identify functional elements within genomes leverage comparative sequence information by looking for regions that exhibit evidence of selective constraint .", "One way of detecting constrained elements is to follow a bottom-up approach by computing constraint scores for individual positi...	[ "There are millions of sequences in the human genome that perform essential functions , such as protein-coding exons , noncoding RNAs , and regulatory sequences that control the transcription of genes .", "However , these functional sequences are embedded in a background of DNA that serves no discernible function...	2010
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "biology" ]	Detection of Mycobacterium ulcerans in the Environment Predicts Prevalence of Buruli Ulcer in Benin	journal.pntd.0001506	null	[ [ "Mycobacterium ulcerans is the causative agent of Buruli ulcer , a necrotizing skin disease prevalent in at least 30 subtropical countries [1] .", "In Africa , close to 30 , 000 cases were reported between 2005 and 2010 [2] .", "Cote d'Ivoire , with the highest incidence , reported 2533 cases in 2010 ...	[ "Mycobacterium ulcerans is the causative agent of Buruli ulcer ( BU ) .", "In West Africa there is an association between BU and residence in low-lying rural villages where aquatic sources are plentiful .", "Infection occurs through unknown environmental exposure; human-to-human infection is rare .", "Molecul...	[ "Buruli ulcer , a severe , cutaneous disease in West and Central Africa is caused by Mycobacterium ulcerans .", "Person-to-person spread of M . ulcerans is rare .", "There is a strong epidemiological association with residence near slow moving water , but lack of accurate case data in Africa has greatly complic...	2012
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "schistosoma", "invertebrates", "schistosoma mansoni", "schoolchildren", "medicine and health sciences", "education", "helminths", "sociology", "geographical locations", "tropical diseases", "social sciences", "parasitic diseases", "animals", "neglected tropical diseases", "educational s...	Mapping Schistosoma mansoni endemicity in Rwanda: a critical assessment of geographical disparities arising from circulating cathodic antigen versus Kato-Katz diagnostics	journal.pntd.0007723	null	[ [ "Schistosomiasis , caused by parasitic trematode species of the genus Schistosoma , is an infectious disease affecting people throughout the world’s tropical and sub-tropical regions [1 , 2] .", "Chronic infections can lead to impaired growth and development in children , making schistosomiasis one of the...	[ "Schistosomiasis is a neglected tropical disease caused by Schistosoma parasites .", "Intervention relies on identifying high-risk regions , yet rapid Schistosoma diagnostics ( Kato-Katz stool assays ( KK ) and circulating cathodic antigen urine assays ( CCA ) ) yield different prevalence estimates .", "We mapp...	[ "Schistosomiasis control efforts rely on rapid diagnostic tests to generate maps of disease prevalence .", "This is so that high-risk areas can be identified and provided with treatments .", "A range of tests are available , yet it is unclear how their differing results can inform disease mitigation .", "This...	2019
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Prion Infections and Anti-PrP Antibodies Trigger Converging Neurotoxic Pathways	journal.ppat.1004662	null	[ [ "Prion diseases are lethal infectious diseases that propagate through the conversion of the cellular prion protein ( PrPC ) into a pathological conformer , the scrapie-associated prion protein ( PrPSc ) [1] .", "Neuronal expression of PrPC is required to mediate the neurotoxicity of PrPSc [2] and possibly...	[ "Prions induce lethal neurodegeneration and consist of PrPSc , an aggregated conformer of the cellular prion protein PrPC .", "Antibody-derived ligands to the globular domain of PrPC ( collectively termed GDL ) are also neurotoxic .", "Here we show that GDL and prion infections activate the same pathways .", ...	[ "Prion diseases are a group of infectious , invariably fatal neurodegenerative diseases .", "Progress in developing therapeutics is slow , partly because animal models of prion diseases require stringent biosafety and are very slow .", "We recently found that treatment of cerebellar slices with antibodies targe...	2015
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "invertebrates", "medicine and health sciences", "enzyme-linked immunoassays", "onchocerca volvulus", "immune physiology", "engineering and technology", "helminths", "immunology", "tropical diseases", "parasitic diseases", "animals", "onchocerca", "nematode infections", "nanoparticles", ...	A novel rapid test for detecting antibody responses to Loa loa infections	journal.pntd.0005741	null	[ [ "Loiasis , also known as African eye-worm disease , is a vector-borne parasitic infection caused by Loa loa , a filarial worm endemic to Central and West Africa [1] .", "Epidemiological data collected from 11 African countries indicates that at least 10 million people are infected [2] .", "In certain ...	[ "Ivermectin-based mass drug administration ( MDA ) programs have achieved remarkable success towards the elimination of onchocerciasis and lymphatic filariasis .", "However , their full implementation has been hindered in Central Africa by the occurrence of ivermectin-related severe adverse events ( SAEs ) in a s...	[ "Loiasis affects over 10 million people in sub-Saharan Africa , and there are no commercial assays to detect Loa loa infection .", "New diagnostics for L . loa are urgently needed for two different purposes .", "First , although L . loa is generally a relatively asymptomatic infection , it has been associated w...	2017
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "blood cells", "cell motility", "medicine and health sciences", "immune cells", "cd coreceptors", "cardiovascular anatomy", "immunology", "parasitic diseases", "parasitic protozoans", "protozoans", "heart", "cytotoxic t cells", "coreceptors", "immune system proteins", "white blood cells"...	CXCR3 chemokine receptor guides Trypanosoma cruzi-specific T-cells triggered by DNA/adenovirus ASP2 vaccine to heart tissue after challenge	journal.pntd.0007597	null	[ [ "The causative agent of Chagas disease Trypanosoma cruzi is an intracellular parasite that infects a variety of cells of the mammalian host [1 , 2] .", "The activation of adaptive immune response occurs by recruiting T lymphocytes to the infection sites after the presentation of trypomastigote/amastigote-...	[ "CD8+ T lymphocytes play an important role in controlling infections by intracellular pathogens .", "Chemokines and their receptors are crucial for the migration of CD8+ T-lymphocytes , which are the main IFNγ producers and cytotoxic effectors cells .", "Although the participation of chemokine ligands and recep...	[ "Chemokine receptors and cell adhesion molecules are essential for T lymphocytes migration into infected tissues .", "Previously , our group demonstrated that CXCR3 receptor was highly expressed on specific CD8+ T-cells surface after immunization and infection by T . cruzi .", "Also , recirculation of specific ...	2019
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "mus (mouse)", "computational biology" ]	Heat Shock Response in CHO Mammalian Cells Is Controlled by a Nonlinear Stochastic Process	journal.pcbi.0030187	null	[ [ "Complex biological systems are built out of a huge number of components .", "These components are diverse: DNA sequence elements , mRNA , transcription factors , etc .", "The concentration of each component changes over time .", "One way to understand the functions of a complex biological system ...	[ "In many biological systems , the interactions that describe the coupling between different units in a genetic network are nonlinear and stochastic .", "We study the interplay between stochasticity and nonlinearity using the responses of Chinese hamster ovary ( CHO ) mammalian cells to different temperature shock...	[ "The structure of an unknown biological system is uncovered by experimentally perturbing the system with a series of input signals .", "The response to these perturbations is measured as output signals .", "Then , the mathematical relation between the input and the output signals constitutes a model for the sys...	2007
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine and health sciences", "chemical compounds", "blastomas", "cancers and neoplasms", "ocular anatomy", "rna extraction", "nucleotides", "organic compounds", "oncology", "ophthalmologic tumors", "mutation", "forms of dna", "pyrimidines", "epigenetics", "dna", "extraction techniqu...	A Parent-of-Origin Effect Impacts the Phenotype in Low Penetrance Retinoblastoma Families Segregating the c.1981C>T/p.Arg661Trp Mutation of RB1	journal.pgen.1005888	null	[ [ "Retinoblastoma ( Rb ) is the most common pediatric intraocular neoplasm and occurs in 1 of every 15 , 000 births .", "It results from the biallelic inactivation of the RB1 tumor suppressor gene , located on 13q14 [1] .", "RB1 encodes the nuclear phosphoprotein pRB , which plays a prominent role durin...	[ "Retinoblastoma ( Rb ) , the most common pediatric intraocular neoplasm , results from inactivation of both alleles of the RB1 tumor suppressor gene .", "The second allele is most commonly lost , as demonstrated by loss of heterozygosity studies .", "RB1 germline carriers usually develop bilateral tumors , but ...	[ "Complex genotype-phenotype correlations lead to clinically and emotionally difficult situations .", "Improved understanding of these correlations is of utmost importance in medical genetics .", "Low penetrance retinoblastoma families segregating the c . 1981C>T / p . Arg661Trp mutation are a good model as germ...	2016
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "community ecology", "biochemistry", "ecological metrics", "ecology and environmental sciences", "community assembly", "ecology", "ecosystems", "community structure", "biology and life sciences", "bioenergetics", "microbiology", "biodiversity", "species diversity", "microbial ecology" ]	Available energy fluxes drive a transition in the diversity, stability, and functional structure of microbial communities	journal.pcbi.1006793	null	[ [ "Microbial communities inhabit every corner of our planet , from our own nutrient-rich guts to the remote depths of the ocean floor .", "Different environments harbor very different levels of microbial diversity: in some samples of non-saline water at mild temperature and pH , nearly 3 , 000 coexisting ty...	[ "A fundamental goal of microbial ecology is to understand what determines the diversity , stability , and structure of microbial ecosystems .", "The microbial context poses special conceptual challenges because of the strong mutual influences between the microbes and their chemical environment through the consump...	[ "The diversity , stability and functional structure of microbial communities have dramatic effects on the health of humans and of ecosystems .", "The complexity of these communities has so far precluded the development of a general predictive model that would capture the dependence of these features on environmen...	2019
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "medicine", "infectious diseases", "public health and epidemiology", "behavioral and social aspects of health", "epidemiology", "infectious disease epidemiology", "leishmaniasis", "neglected tropical diseases", "infectious disease control", "public health" ]	Factors Associated with Leishmania Asymptomatic Infection: Results from a Cross-Sectional Survey in Highland Northern Ethiopia	journal.pntd.0001813	null	[ [ "Visceral leishmaniasis ( VL ) or kala-azar is a neglected vector-borne parasitic disease that manifests with irregular bouts of fever , substantial weight loss , weakness , hepatosplenomegaly and pancytopenia , and that is fatal if left untreated [1] .", "It has an estimated annual incidence of 500 000 c...	[ "In northern Ethiopia the prevalence of visceral leishmaniasis is steadily rising posing an increasing public health concern .", "In order to develop effective control strategies on the transmission of the disease it is important to generate knowledge on the epidemiological determinants of the infection .", "We...	[ "Visceral leishmaniasis is a vector borne disease that can be fatal if left untreated .", "Its prevalence is steadily rising in northern Ethiopia posing a public health challenge in the region .", "We conducted a study on the factors associated to asymptomatic infection in Libo Kemkem and Fogera , Amhara region...	2012
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "blood cells", "sequencing techniques", "luciferase assay", "medicine and health sciences", "luciferase", "body fluids", "enzymes", "enzymology", "plasmid construction", "biochemical analysis", "enzyme assays", "genome analysis", "platelets", "bioassays and physiological analysis", "dna"...	Functionalization of CD36 cardiovascular disease and expression associated variants by interdisciplinary high throughput analysis	journal.pgen.1008287	null	[ [ "Cardiovascular disease ( CVD ) remains the number one cause of death globally [1] .", "Myocardial infarctions ( MI ) are acute events in CVD which are frequently the proximal causes of death or severe disability which are the result of platelet-rich thrombi [2] .", "Genome wide association studies ( ...	[ "CD36 is a platelet membrane glycoprotein whose engagement with oxidized low-density lipoprotein ( oxLDL ) results in platelet activation .", "The CD36 gene has been associated with platelet count , platelet volume , as well as lipid levels and CVD risk by genome-wide association studies .", "Platelet CD36 expr...	[ "Platelets are anucleate cells that are best known as regulators of vascular hemostasis and thrombosis but also play important roles in cancer , angiogenesis , and inflammation .", "CD36 is a platelet surface marker that can activate platelet in response to oxidized low density lipoprotein ( oxLDL ) .", "CD36 h...	2019
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "genetics and genomics/genetics of the immune system", "genetics and genomics/complex traits", "rheumatology/systemic lupus erythematosos", "rheumatology/autoimmunity, autoimmune, and inflammatory diseases", "genetics and genomics/disease models", "genetics and genomics/genetics of disease" ]	Risk Alleles for Systemic Lupus Erythematosus in a Large Case-Control Collection and Associations with Clinical Subphenotypes	journal.pgen.1001311	null	[ [ "Systemic lupus erythematosus ( SLE ) is a debilitating autoimmune disease affecting multiple organ systems and characterized by the production of multiple autoantibodies .", "It is genetically complex , with an estimated sibling risk ratio s of 8–29 and heritability greater than 66% [1] .", "It is al...	[ "Systemic lupus erythematosus ( SLE ) is a genetically complex disease with heterogeneous clinical manifestations .", "Recent studies have greatly expanded the number of established SLE risk alleles , but the distribution of multiple risk alleles in cases versus controls and their relationship to subphenotypes ha...	[ "Systemic lupus erythematosus is a chronic disabling autoimmune disease , most commonly striking women in their thirties or forties .", "It can cause a wide variety of clinical manifestations , including kidney disease , arthritis , and skin disorders .", "Prognosis varies greatly depending on these clinical fe...	2011
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "gram negative", "plant science", "plant pathogens", "plant pathology", "host-pathogen interaction", "biology", "microbiology", "bacterial pathogens" ]	The Xanthomonas campestris Type III Effector XopJ Targets the Host Cell Proteasome to Suppress Salicylic-Acid Mediated Plant Defence	journal.ppat.1003427	null	[ [ "Plants have to protect themselves from a plethora of microbial enemies .", "In a first layer of defence , conserved microbial molecules called PAMPs/MAMPs ( pathogen/microbe-associated molecular patterns ) are recognized on the cell surface which then leads to the induction of a number of defence respons...	[ "The phytopathogenic bacterium Xanthomonas campestris pv .", "vesicatoria ( Xcv ) requires type III effector proteins ( T3Es ) for virulence .", "After translocation into the host cell , T3Es are thought to interact with components of host immunity to suppress defence responses .", "XopJ is a T3E protein from...	[ "Many bacteria that are pathogens for mammals , insects or plants use a specialized apparatus called the type III secretion system to inject a diverse set of effector proteins into the cytoplasm of their eukaryotic host cells in order to alter cellular processes in favour of the pathogen's lifestyle .", "However ...	2013
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "computational biology/computational neuroscience" ]	Temporal Sensitivity of Protein Kinase A Activation in Late-Phase Long Term Potentiation	journal.pcbi.1000691	null	[ [ "Synaptic plasticity , the activity-dependent change in the strength of neuronal connections , is a cellular mechanism proposed to underlie memory storage .", "One type of synaptic plasticity is long term potentiation ( LTP ) , which typically is induced by brief periods of high-frequency synaptic stimula...	[ "Protein kinases play critical roles in learning and memory and in long term potentiation ( LTP ) , a form of synaptic plasticity .", "The induction of late-phase LTP ( L-LTP ) in the CA1 region of the hippocampus requires several kinases , including CaMKII and PKA , which are activated by calcium-dependent signa...	[ "The hippocampus is a part of the cerebral cortex intimately involved in learning and memory behavior .", "A common cellular model of learning is a long lasting form of long term potentiation ( L-LTP ) in the hippocampus , because it shares several characteristics with learning .", "For example , both learning ...	2010
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "visual system", "specimen preparation and treatment", "mechanical treatment of specimens", "specimen disruption", "biology and life sciences", "sensory systems", "electroporation", "neuroscience", "research and analysis methods" ]	Extracellular ATP Hydrolysis Inhibits Synaptic Transmission by Increasing pH Buffering in the Synaptic Cleft	journal.pbio.1001864	A slow mechanism of retinal synaptic inhibition involves hydrolysis of ATP released from pannexin 1 channels (from the tips of horizontal cell dendrites); the resulting protons and phosphates acidify the synaptic cleft, which inhibits neurotransmitter release.	[ [ "Natural scenes contain a large amount of redundant information both in space and time .", "For optimal coding of the visual scene , most of these redundancies need to be removed .", "The inhibitory interaction between horizontal cells ( HCs ) and cones is the first step in this process .", "HCs e...	[ "Neuronal computations strongly depend on inhibitory interactions .", "One such example occurs at the first retinal synapse , where horizontal cells inhibit photoreceptors .", "This interaction generates the center/surround organization of bipolar cell receptive fields and is crucial for contrast enhancement ."...	[ "At the first retinal synapse , specific cells—horizontal cells ( HCs ) —inhibit photoreceptors and help to organize the receptive fields of another retinal cell type , bipolar cells .", "This synaptic interaction is crucial for visual contrast enhancement .", "Here we show that horizontal cells feed back to ph...	2014
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "eye muscles", "medicine and health sciences", "sleep", "ocular anatomy", "vertebrates", "neuroscience", "animals", "mammals", "lizards", "physiological processes", "reptiles", "bioassays and physiological analysis", "muscle electrophysiology", "research and analysis methods", "cardiolog...	Partial homologies between sleep states in lizards, mammals, and birds suggest a complex evolution of sleep states in amniotes	journal.pbio.2005982	null	[ [ "Based on the 1913 behavioral definition [1] , sleep is characterized by sustained immobility , a species-specific sleep posture and location , and a high arousal threshold .", "In addition , it displays a circadian distribution and is homeostatically regulated .", "Based on these criteria , it has be...	[ "It is crucial to determine whether rapid eye movement ( REM ) sleep and slow-wave sleep ( SWS ) ( or non-REM sleep ) , identified in most mammals and birds , also exist in lizards , as they share a common ancestor with these groups .", "Recently , a study in the bearded dragon ( P . vitticeps ) reported states a...	[ "Until recently , the general understanding about sleep was that only mammals and birds show two sleep states: slow-wave sleep and rapid eye movement ( REM ) sleep .", "Consequently , it was thought that these two states appeared independently in these warm-blooded animals .", "However , a recent paper reported...	2018
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "cardiomyopathies", "medicine and health sciences", "parasitic protozoans", "health care", "ethnicities", "research design", "electrocardiography", "protozoans", "cohort studies", "bioassays and physiological analysis", "families", "research and analysis methods", "cardiology", "public and...	Genomic African and Native American Ancestry and Chagas Disease: The Bambui (Brazil) Epigen Cohort Study of Aging	journal.pntd.0004724	null	[ [ "Chagas disease ( ChD ) , which is caused by the protozoan Trypanosoma cruzi , affects approximately 5 . 7 million people in 21 Latin American countries [1] .", "ChD is known as a neglected tropical disease and is an emerging issue in North America and Europe [2–5] .", "ChD is autochthonous in South a...	[ "The influence of genetic ancestry on Trypanosoma cruzi infection and Chagas disease outcomes is unknown .", "We used 370 , 539 Single Nucleotide Polymorphisms ( SNPs ) to examine the association between individual proportions of African , European and Native American genomic ancestry with T . cruzi infection and...	[ "Chagas disease ( ChD ) , which is caused by the protozoan Trypanosoma cruzi , affects approximately 8 million people worldwide .", "ChD is known as a neglected tropical disease .", "The disease is endemic in South and Central American countries , and is an emerging issue in North America and Europe .", "This...	2016
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "biotechnology", "cell death", "plant anatomy", "autophagic cell death", "rna interference", "gene regulation", "cell processes", "plant science", "genetically modified plants", "epigenetics", "plants", "flowering plants", "genetic engineering", "small interfering rnas", "genetically mod...	A calmodulin-like protein suppresses RNA silencing and promotes geminivirus infection by degrading SGS3 via the autophagy pathway in Nicotiana benthamiana	journal.ppat.1006213	null	[ [ "Post transcriptional gene silencing ( PTGS ) is an important RNA interference ( RNAi ) -based defense mechanism against foreign nucleic acid invasion and is involved in silencing a wide range of endogenous genes in plants .", "PTGS is triggered by double-stranded RNAs ( dsRNAs ) , which are cleaved into ...	[ "A recently characterized calmodulin-like protein is an endogenous RNA silencing suppressor that suppresses sense-RNA induced post-transcriptional gene silencing ( S-PTGS ) and enhances virus infection , but the mechanism underlying calmodulin-like protein-mediated S-PTGS suppression is obscure .", "Here , we sho...	[ "Post-transcriptional gene silencing ( PTGS ) is an elaborately regulated process for defense against virus infection in plants .", "To achieve effective infection , a betasatellite molecule associated with geminivirus induced high levels of an endogenous RNA silencing suppressor , calmodulin-like protein ( CaM )...	2017
[ "Introduction", "Results/Discussion", "Materials and Methods" ]	[ "infectious diseases", "genetics and genomics" ]	In Vitro Whole-Genome Analysis Identifies a Susceptibility Locus for HIV-1	journal.pbio.0060032	Susceptibility to HIV is, to a significant extent, determined by the human genetic background. The authors infected immortalized B lymphocytes from 15 large-pedigree families and mapped a locus in Chromosome 8 associated with HIV susceptibility.	[ [ "Some individuals do not become infected to the HIV-1 virus despite repeated exposures , and among those that do , there is marked variation in the clinical course and progression to AIDS [1] .", "Although a number of host genetic determinants of susceptibility to HIV-1 have been identified through the an...	[ "Advances in large-scale analysis of human genomic variability provide unprecedented opportunities to study the genetic basis of susceptibility to infectious agents .", "We report here the use of an in vitro system for the identification of a locus on HSA8q24 . 3 associated with cellular susceptibility to HIV-1 ....	[ "Individuals differ in their susceptibility to the HIV-1 virus , and the determinants of susceptibility are encoded in the human genome .", "Genetic variants influencing this trait have been identified by investigating candidate genes thought likely to be involved in HIV-1 pathogenesis or by whole-genome associat...	2008
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "evolutionary biology", "ecology/population ecology", "ecology/conservation and restoration ecology", "genetics and genomics/population genetics" ]	Why the Indian Subcontinent Holds the Key to Global Tiger Recovery	journal.pgen.1000585	null	[ [ "As top predators , large carnivores strongly shape ecological interactions in biological communities , thus playing a critical role in maintaining their structure and diversity [1] , [2] .", "However , during historical times , increased anthropogenic impacts have driven range collapses and population de...	[ "With only ∼3 , 000 wild individuals surviving restricted to just 7% of their historical range , tigers are now a globally threatened species .", "Therefore , conservation efforts must prioritize regions that harbor more tigers , as well try to capture most of the remaining genetic variation and habitat diversity...	[ "Tiger range and numbers have collapsed globally despite substantial conservation efforts .", "Genetic data quantifying variation from 73 wild tigers in 28 reserves in the Indian subcontinent suggests historically high numbers for tigers , and simulations reveal a signature of a 200-year-old , possibly human-indu...	2009
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "medicine and health sciences", "engineering and technology", "nervous system", "signal processing", "applied mathematics", "ocular anatomy", "neuroscience", "simulation and modeling", "algorithms", "optimization", "mathematics", "ganglion cells", "algebra", "white noise", "research and ...	Inferring hidden structure in multilayered neural circuits	journal.pcbi.1006291	null	[ [ "Computational models of neural responses to sensory stimuli have played a central role in addressing fundamental questions about the nervous system , including how sensory stimuli are encoded and represented , the mechanisms that generate such a neural code , and the theoretical principles governing both the...	[ "A central challenge in sensory neuroscience involves understanding how neural circuits shape computations across cascaded cell layers .", "Here we attempt to reconstruct the response properties of experimentally unobserved neurons in the interior of a multilayered neural circuit , using cascaded linear-nonlinear...	[ "Computation in neural circuits arises from the cascaded processing of inputs through multiple cell layers .", "Each of these cell layers performs operations such as filtering and thresholding in order to shape a circuit’s output .", "It remains a challenge to describe both the computations and the mechanisms t...	2018
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "infectious diseases", "computational biology/genomics" ]	A Genomic Survey of Positive Selection in Burkholderia pseudomallei Provides Insights into the Evolution of Accidental Virulence	journal.ppat.1000845	null	[ [ "Burkholderia pseudomallei ( Bp ) , the causative agent of the often-fatal disease melioidosis , represents one of the most complex bacterial genomes sequenced to date [1] .", "Comprising two circular chromosomes with a combined length of 7 . 2 Mb , the Bp genome contains an estimated ∼5800 genes involved...	[ "Certain environmental microorganisms can cause severe human infections , even in the absence of an obvious requirement for transition through an animal host for replication ( “accidental virulence” ) .", "To understand this process , we compared eleven isolate genomes of Burkholderia pseudomallei ( Bp ) , a trop...	[ "With recent advances in genomics now permitting the systematic comparison of dozens , if not hundreds , of closely related bacterial strains , the opportunity arises for developing novel approaches to identify the complete repertoire of molecular factors governing interactions between hosts and pathogens .", "We...	2010
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "biology and life sciences" ]	High Content Image-Based Screening of a Protease Inhibitor Library Reveals Compounds Broadly Active against Rift Valley Fever Virus and Other Highly Pathogenic RNA Viruses	journal.pntd.0003095	null	[ [ "Many RNA viruses are highly pathogenic to humans and can cause hemorrhagic fever and/or encephalitis .", "Among these , Rift Valley fever virus ( RVFV ) , a member of the genus Phlebovirus ( family Bunyaviridae ) , causes Rift Valley fever ( RVF ) that severely affects human and livestock throughout Afri...	[ "High content image-based screening was developed as an approach to test a protease inhibitor small molecule library for antiviral activity against Rift Valley fever virus ( RVFV ) and to determine their mechanism of action .", "RVFV is the causative agent of severe disease of humans and animals throughout Africa...	[ "Rift Valley fever ( RVF ) is an arthropod-borne viral zoonosis that occurs in large parts of sub-Saharan and North Africa and in 2000 emerged outside the African continent for the first time , raising concerns that it could further expand its geographical range .", "The disease in humans can result in encephalit...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "immunology/cellular microbiology and pathogenesis", "physiology/immunity to infections", "genetics and genomics/functional genomics", "genetics and genomics/gene function", "infectious diseases/bacterial infections", "immunology/immunity to infections" ]	Central Role of the Holliday Junction Helicase RuvAB in vlsE Recombination and Infectivity of Borrelia burgdorferi	journal.ppat.1000679	null	[ [ "Lyme borreliosis is a multi-stage , systemic disease caused by members of the spirochete genus Borrelia , including Borrelia burgdorferi in North America and Borrelia afzelii , Borrelia garinii , and B . burgdorferi in Eurasia [1] .", "Spirochetes are transmitted to mammalian and avian hosts via the bite...	[ "Antigenic variation plays a vital role in the pathogenesis of many infectious bacteria and protozoa including Borrelia burgdorferi , the causative agent of Lyme disease .", "VlsE , a 35 kDa surface-exposed lipoprotein , undergoes antigenic variation during B . burgdorferi infection of mammalian hosts , and is be...	[ "Lyme disease is the most prevalent tick-borne infection in North America and Eurasia .", "It is caused by the bacterium Borrelia burgdorferi and is transmitted to humans via the bite of infected ticks .", "These spirochetes can cause both acute and chronic infection and inflammation of the skin , joints , hear...	2009
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "microbiology/microbial growth and development", "genetics and genomics/chromosome biology", "microbiology/microbial physiology and metabolism" ]	The Stringent Response and Cell Cycle Arrest in Escherichia coli	journal.pgen.1000300	null	[ [ "Bacterial cells encounter varied environmental stresses and make appropriate adjustments to ensure survival .", "One such stress is amino acid starvation , which triggers physiological reprogramming known as the “stringent response” .", "Signaling of the stringent response is achieved by accumulation...	[ "The bacterial stringent response , triggered by nutritional deprivation , causes an accumulation of the signaling nucleotides pppGpp and ppGpp .", "We characterize the replication arrest that occurs during the stringent response in Escherichia coli .", "Wild type cells undergo a RelA-dependent arrest after tre...	[ "Management of cell growth and division in response to environmental conditions is important for all cells .", "In bacteria , nutritional downturns are signaled by accumulation of the nucleotide ppGpp .", "Amino acid starvation causes a programmed change in transcription , known as the “stringent response”; ppG...	2008
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "engineering and technology", "signal processing", "applied mathematics", "social sciences", "neuroscience", "signal filtering", "autocorrelation", "algorithms", "simulation and modeling", "systems science", "mathematics", "statistics (mathematics)", "bandwidth (signal processing)", "resea...	Dynamic Reweighting of Auditory Modulation Filters	journal.pcbi.1005019	null	[ [ "Natural sounds carry salient amplitude modulations ( AM ) essential for successful interpretation of auditory landscapes and robust source identification [1–5] .", "The human auditory system is exquisitely sensitive to relatively slow AM cues , prompting extensive investigation of this ability over sever...	[ "Sound waveforms convey information largely via amplitude modulations ( AM ) .", "A large body of experimental evidence has provided support for a modulation ( bandpass ) filterbank .", "Details of this model have varied over time partly reflecting different experimental conditions and diverse datasets from dis...	[ "Amplitude modulations are considered the key carriers of intelligible information in auditory signals , and consequently it is of significant interest to discover how they are neurally analyzed and perceptually encoded .", "A dominant model has emerged from extensive experimental and theoretical studies of this ...	2016
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "allosteric regulation", "perturbation (geology)", "enzymology", "random variables", "covariance", "simulation and modeling", "multivariate analysis", "mathematics", "statistics (mathematics)", "geology", "protein structure", "thermodynamics", "enzyme chemistry", "research and analysis met...	Rigid Residue Scan Simulations Systematically Reveal Residue Entropic Roles in Protein Allostery	journal.pcbi.1004893	null	[ [ "Allostery is the process by which signals are transmitted from distal ligand binding sites to functional sites in proteins .", "The concept of allostery originated from early attempts to explain the fact that the binding of oxygen molecules to hemoglobin deviates from the typical Michaelis-Menten kinetic...	[ "Intra-protein information is transmitted over distances via allosteric processes .", "This ubiquitous protein process allows for protein function changes due to ligand binding events .", "Understanding protein allostery is essential to understanding protein functions .", "In this study , allostery in the sec...	[ "Allostery is a fundamental dynamics property of many proteins , and plays a critical role in protein functions .", "Despite extensive experimental and theoretical studies of protein allosteric mechanisms , the current understanding and predicting power of protein allostery are still limited .", "One of the mai...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "danio (zebrafish)", "developmental biology", "computational biology" ]	Repressor Dimerization in the Zebrafish Somitogenesis Clock	journal.pcbi.0030032	null	[ [ "A somitogenesis clock , linked to the vertebrate segmentation process , has been uncovered in mouse , chick , and zebrafish [1] .", "Genes involved show oscillatory expression in the presomitic mesoderm ( PSM ) and are mostly related to the Notch pathway in all three species .", "In zebrafish PSM , o...	[ "The oscillations of the somitogenesis clock are linked to the fundamental process of vertebrate embryo segmentation , yet little is known about their generation .", "In zebrafish , it has been proposed that Her proteins repress the transcription of their own mRNA .", "However , in its simplest form , this mode...	[ "Vertebrate embryos acquire a segmented structure along the anteroposterior axis .", "Segmentation is critical for patterning of other structures ( such as nerves , vertebrae , muscles , and blood vessels ) and occurs by the rhythmic separation of balls of cells , called somites , from the anterior end of their p...	2007
[ "Introduction", "Results", "Discussion", "Methods" ]	[]	Manifold Based Optimization for Single-Cell 3D Genome Reconstruction	journal.pcbi.1004396	null	[ [ "Understanding genomes in three dimensions ( 3D ) is a fundamental problem in biology .", "Recently , the combination of chromosome conformation capture ( 3C ) methods with next-generation sequencing , such as 5C [1] , Hi-C [2] , TCC [3] , and GCC [4] , has enabled the study of contact frequencies across ...	[ "The three-dimensional ( 3D ) structure of the genome is important for orchestration of gene expression and cell differentiation .", "While mapping genomes in 3D has for a long time been elusive , recent adaptations of high-throughput sequencing to chromosome conformation capture ( 3C ) techniques , allows for ge...	[ "Understanding how the genome is folded in three-dimensional ( 3D ) space is crucial for unravelling the complex regulatory mechanisms underlying the differentiation and proliferation of cells .", "With recent high-throughput adaptations of chromosome conformation capture in techniques such as single-cell Hi-C , ...	2015
[ "Introduction", "Results/Discussion", "Materials and Methods" ]	[ "virology/immune evasion", "virology/virus evolution and symbiosis", "immunology/immune response", "cell biology/cellular death and stress responses" ]	Vaccinia Virus Proteins A52 and B14 Share a Bcl-2–Like Fold but Have Evolved to Inhibit NF-κB rather than Apoptosis	journal.ppat.1000128	null	[ [ "Vaccinia virus ( VACV ) , the smallpox vaccine , is the prototypic member of the Poxviridae; a family of large , double-stranded DNA viruses that replicate in the cytoplasm of host cells [1] .", "VACV strain Copenhagen was the first poxvirus to be sequenced and encodes about 200 genes [2] .", "The ce...	[ "Vaccinia virus ( VACV ) , the prototype poxvirus , encodes numerous proteins that modulate the host response to infection .", "Two such proteins , B14 and A52 , act inside infected cells to inhibit activation of NF-κB , thereby blocking the production of pro-inflammatory cytokines .", "We have solved the cryst...	[ "Cells possess formidable defences against virus infection , but viruses have evolved sophisticated counter-measures to evade such defences .", "Vaccinia virus , the vaccine used to eradicate smallpox , has about 200 genes , and many of these encode proteins that help the virus evade the host's immune defences ."...	2008
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "immunity", "vector biology", "immune activation", "innate immunity", "immunity to infections", "immunology", "biology", "microbiology", "tsetse fly", "host-pathogen interaction", "parasitology", "immune response" ]	Trypanosome Infection Establishment in the Tsetse Fly Gut Is Influenced by Microbiome-Regulated Host Immune Barriers	journal.ppat.1003318	null	[ [ "Tsetse flies ( Glossina spp . ) serve as the sole vector of protozoan African trypanosomes ( Trypanosoma brucei spp . ) , which are the causative agents of Human African trypanosomiasis ( HAT ) , or sleeping sickness , throughout most of sub-Saharan Africa .", "Additionally , parasites from this same spe...	[ "Tsetse flies ( Glossina spp . ) vector pathogenic African trypanosomes , which cause sleeping sickness in humans and nagana in domesticated animals .", "Additionally , tsetse harbors 3 maternally transmitted endosymbiotic bacteria that modulate their host's physiology .", "Tsetse is highly resistant to infecti...	[ "Tsetse flies serve as a host to many micro-organisms .", "Specifically , this fly houses beneficial endosymbiotic bacteria , and can also serve as a vector of pathogenic trypanosomes across much of sub-Saharan Africa .", "Although flies feed on parasite-infected reservoir hosts , only a small proportion ( 1–5%...	2013
[ "Introduction", "Materials and methods", "Results", "Discussion" ]	[ "invertebrates", "dengue virus", "medicine and health sciences", "body fluids", "pathology and laboratory medicine", "pathogens", "tropical diseases", "microbiology", "animals", "viruses", "rna viruses", "neglected tropical diseases", "infectious disease control", "insect vectors", "infe...	Antivirus effectiveness of ivermectin on dengue virus type 2 in Aedes albopictus	journal.pntd.0006934	null	[ [ "Dengue fever is the most rapidly spreading mosquito-borne viral disease over the past 50 years , with a 30-fold increase in global incidence [1] .", "To reverse the growing trend , comprehensive technical strategies involving diagnosis and case management , integrated surveillance and outbreak preparedne...	[ "Dengue fever is the most rapidly spreading mosquito-borne viral disease over the past 50 years , with a 30-fold increase in global incidence .", "Dengue vector control is a key component for the dengue control strategy , since no absolutely effective vaccine or drug is available yet .", "However , the rapid ri...	[ "Dengue fever is one of neglected vector-borne tropical diseases with a 30-fold increase in global incidence recently .", "In 2012 , World Health Organization set a goal to reduce dengue mortality by at least 50% by 2020 .", "Being faced with more challenges in the dengue control programs , such as the increase...	2018
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "gastroenterology and hepatology/gastrointestinal infections", "public health and epidemiology/infectious diseases", "microbiology/parasitology", "infectious diseases/protozoal infections", "computer science/information technology", "genetics and genomics/population genetics" ]	Identification of Zoonotic Genotypes of Giardia duodenalis	journal.pntd.0000558	null	[ [ "Giardia is a genus of intestinal flagellates that infect a wide range of vertebrate hosts .", "The genus consists of six species , which are distinguished on the basis of the morphology and ultra-structure of their trophozoites [1] .", "Giardia duodenalis ( syn . G . intestinalis , G . lamblia ) is t...	[ "Giardia duodenalis , originally regarded as a commensal organism , is the etiologic agent of giardiasis , a gastrointestinal disease of humans and animals .", "Giardiasis causes major public and veterinary health concerns worldwide .", "Transmission is either direct , through the faecal-oral route , or indirec...	[ "Giardia duodenalis is a parasite causing a gastrointestinal disease in humans , pets , livestock , and wildlife .", "The role of animals in human disease is unclear , because Giardia from humans and animals is morphologically indistinguishable .", "An international consortium of both veterinary and public heal...	2009
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "pesticides", "medicine", "infectious diseases", "veterinary diseases", "veterinary parasitology", "pest control", "parasitic diseases", "veterinary science", "agriculture" ]	Discovery of Anthelmintic Drug Targets and Drugs Using Chokepoints in Nematode Metabolic Pathways	journal.ppat.1003505	null	[ [ "Parasitic nematode ( roundworm ) infections impose an enormous burden of morbidity on humanity [1] , [2] .", "Only a few drugs are commonly used to treat nematode infections , creating a dangerous environment for the emergence of drug resistance .", "Currently , administering anthelmintic drugs on a ...	[ "Parasitic roundworm infections plague more than 2 billion people ( 1/3 of humanity ) and cause drastic losses in crops and livestock .", "New anthelmintic drugs are urgently needed as new drug resistance and environmental concerns arise .", "A “chokepoint reaction” is defined as a reaction that either consumes...	[ "The World Health Organization estimates that 2 . 9 million people are infected with parasitic roundworms , causing high-morbidity and mortality rates , developmental delays in children , and low productivity of affected individuals .", "The agricultural industry experiences drastic losses in crop and livestock d...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "parasite groups", "genomics", "parasite evolution", "biology", "computational biology", "evolutionary biology", "microbiology", "genetics and genomics", "parasitology" ]	Genome Comparison of Human and Non-Human Malaria Parasites Reveals Species Subset-Specific Genes Potentially Linked to Human Disease	journal.pcbi.1002320	null	[ [ "Malaria remains a serious health threat .", "Every year , more than 250 million people worldwide suffer from malaria and over one million people die as a consequence of the disease , mostly children in Africa under the age of five [1] .", "Malaria is an infectious disease caused by single-celled intr...	[ "Genes underlying important phenotypic differences between Plasmodium species , the causative agents of malaria , are frequently found in only a subset of species and cluster at dynamically evolving subtelomeric regions of chromosomes .", "We hypothesized that chromosome-internal regions of Plasmodium genomes har...	[ "With more than 250 million infections and over a million deaths each year , malaria remains one of the most devastating infectious diseases worldwide .", "With the availability of complete genome sequences of both human and non-human Plasmodium parasites , the causative agents of malaria , it is now possible to ...	2011
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "cell biology/cell signaling", "cell biology", "cell biology/microbial growth and development", "microbiology", "microbiology/microbial growth and development" ]	A Bacterial Ras-Like Small GTP-Binding Protein and Its Cognate GAP Establish a Dynamic Spatial Polarity Axis to Control Directed Motility	journal.pbio.1000430	Directional control of bacterial motility is regulated by dynamic polarity inversions driven by pole-to-pole oscillation of a Ras family small G-protein and its associated GTPase-activating protein.	[ [ "In living cells , environmental changes and cell-cell regulations require transient cellular processes relying on the ability of the cells to regulate their underlying ultrastructures dynamically .", "For example , during chemotaxis , eukaryotic cells sense and migrate towards a chemical gradient , which...	[ "Regulated cell polarity is central to many cellular processes .", "We investigated the mechanisms that govern the rapid switching of cell polarity ( reversals ) during motility of the bacterium Myxococcus xanthus .", "Cellular reversals are mediated by pole-to-pole oscillations of motility proteins and the fre...	[ "Motile cells have evolved complex regulatory networks to respond to environmental cues and change their direction of movement appropriately .", "In this process , an arsenal of receptor-coupled small G-proteins acts as a cellular compass to dynamically polarize the leading edge and regulate the motility response...	2010
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "infectious diseases/protozoal infections", "microbiology/parasitology" ]	A Meta-analysis of the Effectiveness of Albendazole Compared with Metronidazole as Treatments for Infections with Giardia duodenalis	journal.pntd.0000682	null	[ [ "Giardiasis in humans , caused by the protozoan parasite Giardia duodenalis ( syn . G . lamblia , G . intestinalis ) , is a common parasitic disease [1] .", "The prevalence of infection is commonly between 2–5% in the developed world and 20–30% in the developing and underdeveloped countries [2] .", "I...	[ "Metronidazole is the most commonly used drug for the treatment of giardiasis in humans .", "In spite of its therapeutic efficacy for giardiasis , low patient compliance , especially in children , side effects , and the emergence of metronidazole-resistant strains may restrict its use .", "Albendazole has been ...	[ "Giardiasis is one of the most common intestinal protozoal infections worldwide .", "Although metronidazole is the most common drug used to treat giardiasis in humans , its use is associated with a variety of side effects .", "Poor compliance and the emergence of metronidazole-resistant strains may restrict use...	2010
[ "Introduction", "Materials and methods", "Results", "Discussion" ]	[ "blood cells", "inflammatory diseases", "rheumatology", "medicine and health sciences", "immune cells", "pathology and laboratory medicine", "biopsy", "immunology", "tropical diseases", "geographical locations", "surgical and invasive medical procedures", "bacterial diseases", "histology", ...	Clinico-pathological features of erythema nodosum leprosum: A case-control study at ALERT hospital, Ethiopia	journal.pntd.0006011	null	[ [ "Leprosy is a disease caused by Mycobacterium leprae , an intracellular acid-fast bacillus[1] .", "It mainly infects the skin and peripheral nerves[2] .", "The disease manifests with a spectrum of clinical pictures ranging from the localized tuberculoid leprosy ( TT ) to the generalized lepromatous le...	[ "Leprosy reactions are a significant cause of morbidity in leprosy population .", "Erythema nodosum leprosum ( ENL ) is an immunological complication affecting approximately 50% of patients with lepromatous leprosy ( LL ) and 10% of borderline lepromatous ( BL ) leprosy .", "ENL is associated with clinical feat...	[ "Leprosy reactions ( Type 1 and 2 ) are important causes of nerve damage and illness .", "Erythema Nodosum Leprosum ( ENL ) also called type 2 reactions is a severe multisystem immune-mediated complication of borderline and lepromatous leprosy .", "ENL causes high morbidity and mortality and usually requires ur...	2017
[ "Introduction", "Discussion", "Materials and Methods" ]	[ "metabolism", "biochemistry", "biology and life sciences", "metabolomics" ]	Large-scale Metabolomic Profiling Identifies Novel Biomarkers for Incident Coronary Heart Disease	journal.pgen.1004801	null	[ [ "Advances in high-throughput technologies can fuel discovery of novel biomarkers for early detection and prevention of coronary heart disease ( CHD ) .", "Metabolomic profiling , or metabolomics , provides a holistic signature of biochemical activities in humans by detecting and quantifying low-weight mol...	[ "Analyses of circulating metabolites in large prospective epidemiological studies could lead to improved prediction and better biological understanding of coronary heart disease ( CHD ) .", "We performed a mass spectrometry-based non-targeted metabolomics study for association with incident CHD events in 1 , 028 ...	[ "Non-targeted metabolomic profiling of large population-based studies has become feasible only in the past 1–2 years and this hypothesis-free exploration of the metabolome holds a great potential to fuel the discovery of novel biomarkers for coronary heart disease ( CHD ) .", "Such biomarkers are not only importa...	2014

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