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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" ]	[]	Regulation of Active DNA Demethylation by a Methyl-CpG-Binding Domain Protein in Arabidopsis thaliana	journal.pgen.1005210	null	[ [ "DNA methylation is an important epigenetic mark conserved in many eukaryotes .", "Many studies have demonstrated that DNA methylation plays central roles in genome organization , genomic imprinting , transposon silencing , and gene expression [1 , 2 , 3] .", "DNA methylation levels are coordinately d...	[ "Active DNA demethylation plays crucial roles in the regulation of gene expression in both plants and animals .", "In Arabidopsis thaliana , active DNA demethylation is initiated by the ROS1 subfamily of 5-methylcytosine-specific DNA glycosylases via a base excision repair mechanism .", "Recently , IDM1 and IDM...	[ "DNA cytosine methylation ( 5-methylcytosine , 5-meC ) plays important roles in genome organization , genomic imprinting , transposon silencing and gene expression .", "DNA methylation patterns are dynamically controlled by methylation and demethylation reactions during development and reproduction in eukaryotes ...	2015
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "medicine and health sciences", "immune physiology", "enzyme-linked immunoassays", "pathology and laboratory medicine", "pathogens", "immunology", "tropical diseases", "microbiology", "vertebrates", "animals", "mammals", "vaccines", "preventive medicine", "viruses", "rabies", "rna viru...	Persistence of Rabies Virus-Neutralizing Antibodies after Vaccination of Rural Population following Vampire Bat Rabies Outbreak in Brazil	journal.pntd.0004920	null	[ [ "Rabies is a viral zoonosis that affects mammals .", "It is caused by neurotropic viruses belonging to the family Rhabdoviridae , genus Lyssavirus .", "The International Committee on Taxonomy of Viruses ( ICTV ) recognizes today 14 species [1 , 2]; this taxonomy is rapidly evolving and the two more re...	[ "Animal control measures in Latin America have decreased the incidence of urban human rabies transmitted by dogs and cats; currently most cases of human rabies are transmitted by bats .", "In 2004–2005 , rabies outbreaks in populations living in rural Brazil prompted widespread vaccination of exposed and at-risk ...	[ "Animal control measures have decreased the incidence of human rabies in urban regions of Latin America .", "Currently , most cases of human rabies occur in rural areas and are transmitted by bats .", "In 2004–2005 , rabies outbreaks affecting populations living in remote areas of Brazil prompted the widespread...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "haplotypes", "medicine and health sciences", "genetic polymorphism", "genetic association studies", "epidemiology", "genetics", "biology and life sciences", "population genetics", "gene flow", "human genetics", "evolutionary biology", "genetic epidemiology" ]	Cuba: Exploring the History of Admixture and the Genetic Basis of Pigmentation Using Autosomal and Uniparental Markers	journal.pgen.1004488	null	[ [ "The post-Columbian history of the Caribbean has been marked by the encounter of people from different continents .", "This is reflected in the gene pool of the present inhabitants of the Caribbean archipelago , as shown in recent studies using autosomal , mtDNA and Y-chromosome markers [1]–[7] .", "H...	[ "We carried out an admixture analysis of a sample comprising 1 , 019 individuals from all the provinces of Cuba .", "We used a panel of 128 autosomal Ancestry Informative Markers ( AIMs ) to estimate the admixture proportions .", "We also characterized a number of haplogroup diagnostic markers in the mtDNA and ...	[ "Cuba is the largest island of the Greater Antilles and its most populous country .", "The post-Columbian history of the Caribbean has been marked by the encounter of people from different continents .", "Here , we present an admixture analysis of 1 , 019 individuals from all the provinces of Cuba , using autos...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "cell motility", "medicine and health sciences", "body fluids", "pathology and laboratory medicine", "gene regulation", "pathogens", "microbiology", "developmental biology", "nymphs", "bacteria", "bacterial pathogens", "borrelia burgdorferi", "medical microbiology", "gene expression", "m...	Two Different Virulence-Related Regulatory Pathways in Borrelia burgdorferi Are Directly Affected by Osmotic Fluxes in the Blood Meal of Feeding Ixodes Ticks	journal.ppat.1005791	null	[ [ "Borrelia burgdorferi , the Lyme disease agent , survives and grows in mammals and various vertebrate hosts .", "However , the bacteria are not transmitted directly to a new host .", "Instead they are acquired by a hematophagous arthropod ( Ixodes scapularis ) and transmitted to a new host .", "Cy...	[ "Lyme disease , caused by Borrelia burgdorferi , is a vector-borne illness that requires the bacteria to adapt to distinctly different environments in its tick vector and various mammalian hosts .", "Effective colonization ( acquisition phase ) of a tick requires the bacteria to adapt to tick midgut physiology ."...	[ "Borrelia burgdorferi , the Lyme disease agent , exploits a multifaceted enzootic cycle that requires a tick vector for successful transmission between mammalian hosts .", "Two different regulatory systems control genes that are required to complete this infective cycle .", "The Hk1/Rrp1 two-component system af...	2016
[ "Introduction", "Results", "Materials and Methods" ]	[ "physics", "model organisms", "protozoan models", "biology", "microbiology", "biophysics" ]	Cell Shape Dynamics: From Waves to Migration	journal.pcbi.1002392	null	[ [ "During chemotaxis , a chemical gradient directs cell migration .", "Chemotaxis occurs in phenomena as diverse as wound healing [1] and embryonic development [2] , and has also been implicated in a wide array of pathological processes including aberrant angiogenesis [3] and cancer metastasis [4] .", "...	[ "We observe and quantify wave-like characteristics of amoeboid migration .", "Using the amoeba Dictyostelium discoideum , a model system for the study of chemotaxis , we demonstrate that cell shape changes in a wave-like manner .", "Cells have regions of high boundary curvature that propagate from the leading e...	[ "Migration of cells on surfaces and through tissues is an important part of life , from the amazingly coordinated migration of cells during development to the uncontrollable migration of metastatic cancer cells .", "Here we investigate the physics of cell migration with the goal of gaining new insights into how c...	2012
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "medicine", "infectious diseases", "gene expression", "genetics", "immunology", "biology", "genetics and genomics" ]	Myocardial Chemokine Expression and Intensity of Myocarditis in Chagas Cardiomyopathy Are Controlled by Polymorphisms in CXCL9 and CXCL10	journal.pntd.0001867	null	[ [ "Approximately 8 million people are infected with the protozoan parasite Trypanosoma cruzi [1] in Central and South America , with an estimated 300 , 000 cases in the USA alone .", "T . cruzi is a major cause of heart disease and cardiovascular-related deaths in endemic areas located in Latin America , wi...	[ "Chronic Chagas cardiomyopathy ( CCC ) , a life-threatening inflammatory dilated cardiomyopathy , affects 30% of the approximately 8 million patients infected by Trypanosoma cruzi .", "Even though the Th1 T cell-rich myocarditis plays a pivotal role in CCC pathogenesis , little is known about the factors controll...	[ "Chronic Chagas cardiomyopathy ( CCC ) is an inflammatory heart disease that affects millions in Latin America , and in growing numbers in USA and Europe .", "Survival among CCC patients is shorter than among patients with cardiomyopathy of non-inflammatory etiology .", "This suggests that the inflammatory cell...	2012
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "sequencing", "medicine", "dermatology", "inflammatory diseases", "enzymes", "immunology", "toxicology", "toxic agents", "glycobiology", "histology", "proteoglycans", "glycoproteins", "sequence analysis", "proteins", "extracellular matrix", "connective tissue", "biology", "recombin...	A Novel Hyaluronidase from Brown Spider (Loxosceles intermedia) Venom (Dietrich's Hyaluronidase): From Cloning to Functional Characterization	journal.pntd.0002206	null	[ [ "Bites involving brown spiders are characterized by skin injuries at the venom inoculation site , including swelling , erythema , hemorrhage , dermonecrosis , and the hallmark of loxoscelism: gravitational spreading of cutaneous lesions [1] , [2] .", "Systemic involvement has also been reported including ...	[ "Loxoscelism is the designation given to clinical symptoms evoked by Loxosceles spider's bites .", "Clinical manifestations include skin necrosis with gravitational spreading and systemic disturbs .", "The venom contains several enzymatic toxins .", "Herein , we describe the cloning , expression , refolding a...	[ "Accidents involving brown spiders ( Loxosceles genus ) are reported throughout the world .", "South and Southeast of Brazil are endemic areas for this spider .", "Loxosceles bites commonly trigger local signs as swelling , erythema , hemorrhage and the hallmark symptom: a dermonecrotic lesion with gravitationa...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "molecular biology/dna repair", "molecular biology/recombination", "microbiology/microbial evolution and genomics", "microbiology" ]	FtsK-Dependent Dimer Resolution on Multiple Chromosomes in the Pathogen Vibrio cholerae	journal.pgen.1000201	null	[ [ "Vibrio cholerae , the causative agent of cholera , harbors two non-homologous circular chromosomes [1] .", "The majority of genes believed to be necessary for the basic life processes of V . cholerae are carried on the 2 . 96 Mbp chromosome I , whereas the 1 . 07 Mbp chromosome II only harbors a few esse...	[ "Unlike most bacteria , Vibrio cholerae harbors two distinct , nonhomologous circular chromosomes ( chromosome I and II ) .", "Many features of chromosome II are plasmid-like , which raised questions concerning its chromosomal nature .", "Plasmid replication and segregation are generally not coordinated with th...	[ "During proliferation , DNA synthesis , chromosome segregation , and cell division must be coordinated to ensure the stable inheritance of the genetic material .", "In eukaryotes , this is achieved by checkpoint mechanisms that delay certain steps until others are completed .", "No such temporal separation exis...	2008
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "computer science", "biology" ]	A Detailed History of Intron-rich Eukaryotic Ancestors Inferred from a Global Survey of 100 Complete Genomes	journal.pcbi.1002150	null	[ [ "Spliceosomal introns that interrupt most of the protein-coding genes and the concurrent splicing machinery that mediates intron excision and exon splicing are defining features of gene architecture and expression in eukaryotes [1] , [2] .", "To date , eukaryote genomes including the compact genomes of pa...	[ "Protein-coding genes in eukaryotes are interrupted by introns , but intron densities widely differ between eukaryotic lineages .", "Vertebrates , some invertebrates and green plants have intron-rich genes , with 6–7 introns per kilobase of coding sequence , whereas most of the other eukaryotes have intron-poor g...	[ "In eukaryotes , protein-coding genes are interrupted by non-coding introns .", "The intron densities widely differ , from 6–7 introns per kilobase of coding sequence in vertebrates , some invertebrates and plants , to only a few introns across the entire genome in many unicellular forms .", "We applied a robus...	2011
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "fish", "gene regulation", "regulatory proteins", "dna-binding proteins", "vertebrates", "neuroscience", "animals", "dna transcription", "animal models", "osteichthyes", "model organisms", "experimental organism systems", "transcription factors", "genome analysis", "nerve fibers", "res...	Coordination of olfactory receptor choice with guidance receptor expression and function in olfactory sensory neurons	journal.pgen.1007164	null	[ [ "The development of the nervous system requires that cell fate specification be coordinated with axonal pathfinding , dendrite formation , and synapse formation .", "Since specific neuronal populations connect with particular regions in the brain , cellular identity is tightly linked with the expression o...	[ "Olfactory sensory neurons choose to express a single odorant receptor ( OR ) from a large gene repertoire and extend axons to reproducible , OR-specific locations within the olfactory bulb .", "This developmental process produces a topographically organized map of odorant experience in the brain .", "The axon ...	[ "Assembling the brain circuitry responsible for our sense of olfaction is a formidable task .", "The sensory neurons that detect odorants in the nasal epithelium , the olfactory sensory neurons , choose to express a single odorant receptor from a large gene repertoire .", "Sensory neurons that choose a particul...	2018
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "humoral immunity", "medicine", "genetic mutation", "immunity to infections", "immunology", "microbiology", "bacterial diseases", "adaptive immunity", "infectious disease control", "bacterial pathogens", "immunizations", "infectious diseases", "biology", "salmonella", "immune response", ...	Cell-Associated Flagella Enhance the Protection Conferred by Mucosally-Administered Attenuated Salmonella Paratyphi A Vaccines	journal.pntd.0001373	null	[ [ "Four human host-restricted Salmonella enterica serovars cause clinically indistinguishable typhoid ( Salmonella Typhi ) and paratyphoid ( S . Paratyphi A , B and [uncommonly] C ) fever [1] .", "Multiply antibiotic resistant S . Paratyphi A have emerged in Asia , accompanied by increased incidences of par...	[ "Antibiotic-resistant Salmonella enterica serovar Paratyphi A , the agent of paratyphoid A fever , poses an emerging public health dilemma in endemic areas of Asia and among travelers , as there is no licensed vaccine .", "Integral to our efforts to develop a S . Paratyphi A vaccine , we addressed the role of fla...	[ "Salmonella enterica serovar Paratyphi A is a pathogen that causes a systemic disease that is marked by serious complications and , if untreated , high mortality .", "The study of S . Paratyphi A pathogenesis and vaccine development has been extremely challenging since S . Paratyphi A is human host-restricted and...	2011
[ "Introduction", "Results", "Discussion", "Materials and Methods", "Supporting Information" ]	[ "biochemistry", "infectious diseases", "yeast and fungi", "eukaryotes", "microbiology", "mus (mouse)", "genetics and genomics" ]	Distinct Roles for Intra- and Extracellular Siderophores during Aspergillus fumigatus Infection	journal.ppat.0030128	null	[ [ "Animals strategically withhold iron during infection to combat invading microbes [1 , 2] .", "Consequently , the ability to obtain iron from the host , both for essential metabolism and to cope with reactive oxygen species produced by phagocytic cells [3] , is a feature of most pathogens .", "The int...	[ "Siderophore biosynthesis by the highly lethal mould Aspergillus fumigatus is essential for virulence , but non-existent in humans , presenting a rare opportunity to strategize therapeutically against this pathogen .", "We have previously demonstrated that A . fumigatus excretes fusarinine C and triacetylfusarini...	[ "Patients with suppressed immune systems due to cancer treatments , HIV/AIDS , organ transplantation , or genetic disorders are at high risk of infection with the ubiquitously present fungal pathogen Aspergillus fumigatus .", "Treatments for this disease , collectively termed invasive aspergillosis , are often no...	2007
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Admixture in Humans of Two Divergent Plasmodium knowlesi Populations Associated with Different Macaque Host Species	journal.ppat.1004888	null	[ [ "The epidemiological emergence of infections can be traced by genotypic analyses , with a high level of resolution when pathogens have a high mutation rate , as illustrated by recently emerged viruses that now have a massive impact on global public health [1 , 2] .", "Such analysis is more challenging for...	[ "Human malaria parasite species were originally acquired from other primate hosts and subsequently became endemic , then spread throughout large parts of the world .", "A major zoonosis is now occurring with Plasmodium knowlesi from macaques in Southeast Asia , with a recent acceleration in numbers of reported ca...	[ "Extraordinary phases of pathogen evolution may occur during an emerging zoonosis , potentially involving adaptation to human hosts , with changes in patterns of virulence and transmission .", "In a large population genetic survey , we show that the malaria parasite Plasmodium knowlesi in humans is an admixture o...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine", "public health and epidemiology", "veterinary diseases", "veterinary epidemiology", "epidemiology", "genetics", "molecular genetics", "biology", "genetics and genomics", "veterinary science" ]	Reduced Lentivirus Susceptibility in Sheep with TMEM154 Mutations	journal.pgen.1002467	null	[ [ "Visna/Maedi virus ( VMV ) and caprine arthritis encephalitis virus ( CAEV ) are small ruminant lentiviruses ( SRLV ) of the retroviridae family [1] that infect sheep and goats in major sheep producing countries worldwide .", "The exceptions are Iceland where VMV was eradicated after a 30-year effort [2] ...	[ "Visna/Maedi , or ovine progressive pneumonia ( OPP ) as it is known in the United States , is an incurable slow-acting disease of sheep caused by persistent lentivirus infection .", "This disease affects multiple tissues , including those of the respiratory and central nervous systems .", "Our aim was to ident...	[ "Ovine lentivirus targets the host immune system and causes persistent retroviral infections affecting millions of sheep worldwide .", "In primates , lentivirus resistance is attributed to mutant virus coreceptors that are not expressed .", "In sheep , some animals are resistant to lentivirus infection despite ...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "cell death", "medicine and health sciences", "toxins", "immune physiology", "pathology and laboratory medicine", "spleen", "pathogens", "vibrio", "cell processes", "microbiology", "toxicology", "toxic agents", "physiological processes", "vibrio vulnificus", "bacteria", "bacterial path...	The Effector Domain Region of the Vibrio vulnificus MARTX Toxin Confers Biphasic Epithelial Barrier Disruption and Is Essential for Systemic Spread from the Intestine	journal.ppat.1006119	null	[ [ "The United States Department of Agriculture ( USDA ) reports that 1 in 6 Americans fall ill with a foodborne infection every year , resulting in more than 3000 fatalities and an estimated $15 billion in economic burden due to combined medical costs , productivity loss , and death .", "Of the cited foodbo...	[ "Vibrio vulnificus causes highly lethal bacterial infections in which the Multifunctional Autoprocessing Repeats-in-Toxins ( MARTX ) toxin product of the rtxA1 gene is a key virulence factor .", "MARTX toxins are secreted proteins up to 5208 amino acids in size .", "Conserved MARTX N- and C-terminal repeat regi...	[ "The bacterium Vibrio vulnificus causes highly lethal infections in susceptible individuals exposed to contaminated water or seafood .", "V . vulnificus produces a MARTX toxin , which plays a significant role in bacterial virulence .", "The large MARTX toxin has numerous functional regions that have been charac...	2017
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "medicine and health sciences", "action potentials", "membrane potential", "electrophysiology", "neuroscience", "simulation and modeling", "probability distribution", "mathematics", "cardiac pacing", "cellular structures and organelles", "cardiology", "research and analysis methods", "arrhyt...	Arrhythmia mechanisms and spontaneous calcium release: Bi-directional coupling between re-entrant and focal excitation	journal.pcbi.1007260	null	[ [ "Cardiovascular disease is one of the major healthcare problems faced by the developed world , with increasing prevalence associated with aging populations [1–3] .", "Improved understanding of the mechanisms underlying cardiac arrhythmias , a major component of cardiovascular diseases’ impact on morbidity...	[ "Spontaneous sub-cellular calcium release events ( SCRE ) are conjectured to promote rapid arrhythmias associated with conditions such as heart failure and atrial fibrillation: they can underlie the emergence of spontaneous action potentials in single cells which can lead to arrhythmogenic triggers in tissue .", ...	[ "A loss of the regular rhythm of the beating heart , called arrhythmia , can inhibit its pumping function and even lead to sudden death .", "Understanding the processes by which normal rhythm is interrupted presents a major yet critical research problem .", "One challenge is the inherent multi-scale dependence ...	2019
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "neuroscience/behavioral neuroscience", "neuroscience/sensory systems", "neuroscience/motor systems", "computational biology/computational neuroscience", "neuroscience/theoretical neuroscience" ]	Optimal Compensation for Temporal Uncertainty in Movement Planning	journal.pcbi.1000130	null	[ [ "In the execution of any movement , there is always timing uncertainty .", "This uncertainty has two major consequences .", "First , it limits performance on any task for which there are costs associated with temporal imprecision .", "Second , it has implications for how the motor system should pl...	[ "Motor control requires the generation of a precise temporal sequence of control signals sent to the skeletal musculature .", "We describe an experiment that , for good performance , requires human subjects to plan movements taking into account uncertainty in their movement duration and the increase in that uncer...	[ "Many recent models of motor planning are based on the idea that the CNS plans movements to minimize “costs” intrinsic to motor performance .", "A minimum variance model would predict that the motor system plans movements that minimize motor error ( as measured by the variance in movement ) subject to the constra...	2008
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "immunopathology", "medicine", "infectious diseases", "immune cells", "immunity", "hiv", "immune activation", "t cells", "immunity to infections", "immunology", "retrovirology and hiv immunopathogenesis", "biology", "viral diseases" ]	Regulatory T Cells Negatively Affect IL-2 Production of Effector T Cells through CD39/Adenosine Pathway in HIV Infection	journal.ppat.1003319	null	[ [ "Regulatory T cells ( Treg ) play a dominant role in self-tolerance , control of autoimmune diseases and control of chronic infections by suppressing effector T cells activation , proliferation and functions [1] .", "Natural Treg derive from the thymus and are characterized by high levels of IL-2 receptor...	[ "The mechanisms by which Regulatory T cells suppress IL-2 production of effector CD4+ T cells in pathological conditions are unclear .", "A subpopulation of human Treg expresses the ectoenzyme CD39 , which in association with CD73 converts ATP/ADP/AMP to adenosine .", "We show here that Treg/CD39+ suppress IL-2...	[ "Regulatory T cells ( Treg ) represent a subset of T lymphocytes and have a pivotal role in chronic viral infections and cancer by limiting immune activation .", "It has been shown that Treg are expanded in chronic HIV infected patients .", "However , the mechanisms of Treg immune-modulator functions are not cl...	2013
[ "Introduction", "Results", "Discussion", "Material and Methods" ]	[ "livestock", "organismal evolution", "animal diseases", "medicine and health sciences", "ruminants", "enzymes", "italian people", "epitope mapping", "enzymology", "vertebrates", "microbiology", "animals", "mammals", "ethnicities", "animal prion diseases", "microbial evolution", "mole...	Isolation of a Defective Prion Mutant from Natural Scrapie	journal.ppat.1006016	null	[ [ "Transmissible spongiform encephalopathies ( TSEs ) are progressive and fatal neurodegenerative disorders affecting animals and humans , with the most common forms being scrapie of sheep and goats , bovine spongiform encephalopathy ( BSE ) of cattle , chronic wasting disease ( CWD ) of cervids , and Creutzfel...	[ "It is widely known that prion strains can mutate in response to modification of the replication environment and we have recently reported that prion mutations can occur in vitro during amplification of vole-adapted prions by Protein Misfolding Cyclic Amplification on bank vole substrate ( bvPMCA ) .", "Here we e...	[ "Prions are unique infectious agents , consisting of PrPSc , a self-propagating aggregated conformer of the host-encoded prion protein PrPC .", "Despite the absence of any nucleic acid information , prions exist as distinct strains that share the same amino acid sequence but differ in their conformation .", "Mo...	2016
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "medicine and health sciences", "ocular anatomy", "animal models", "model organisms", "immunoprecipitation", "experimental organism systems", "research and analysis methods", "lipids", "animal studies", "proteins", "ubiquitination", "mouse models", "sterols", "precipitation techniques", ...	Schnyder corneal dystrophy-associated UBIAD1 mutations cause corneal cholesterol accumulation by stabilizing HMG-CoA reductase	journal.pgen.1008289	null	[ [ "Schnyder corneal dystrophy ( SCD ) is a rare autosomal dominant genetic eye disease [1] .", "It is characterized by free cholesterol accumulation in the cornea that causes progressive corneal opacification with aging [1] [2] .", "Genetics studies have linked SCD to mutations in UbiA prenyltransferase...	[ "Schnyder corneal dystrophy ( SCD ) is a rare genetic eye disease characterized by corneal opacification resulted from deposition of excess free cholesterol .", "UbiA prenyltransferase domain-containing protein-1 ( UBIAD1 ) is an enzyme catalyzing biosynthesis of coenzyme Q10 and vitamin K2 .", "More than 20 UB...	[ "Schnyder corneal dystrophy ( SCD ) is a rare genetic eye disease caused by deposition of free cholesterol in the cornea .", "It is closely correlated with mutations in the UbiA prenyltransferase domain-containing protein-1 ( UBIAD1 ) gene , which encodes an enzyme catalyzing biosynthesis of coenzyme Q10 and vita...	2019
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "blood cells", "hiv infections", "innate immune system", "medicine and health sciences", "immune cells", "body fluids", "pathology and laboratory medicine", "immune physiology", "viral transmission and infection", "cytokines", "pathogens", "immunology", "microbiology", "vertebrates", "cl...	Long-term persistence and function of hematopoietic stem cell-derived chimeric antigen receptor T cells in a nonhuman primate model of HIV/AIDS	journal.ppat.1006753	null	[ [ "HIV-1 specific cytotoxic T lymphocytes mount a key immune response to HIV and are crucial for the control of viremia and the elimination of HIV infected cells .", "Previous studies have shown that a chimeric antigen receptor containing the CD4 molecule linked to the signaling domain of the T cell recepto...	[ "Chimeric Antigen Receptor ( CAR ) T-cells have emerged as a powerful immunotherapy for various forms of cancer and show promise in treating HIV-1 infection .", "However , significant limitations are persistence and whether peripheral T cell-based products can respond to malignant or infected cells that may reapp...	[ "Hematopoietic Stem/Progenitor Cell ( HSPC ) based gene therapy can be used to treat many infectious and genetic diseases .", "Here , we used an HSPC-based approach to redirect and enhance host immunity against HIV-1 .", "We engineered HSPCs to carry chimeric antigen receptor ( CAR ) genes that detect and destr...	2017
[ "Introduction", "Model", "Results/Discussion" ]	[]	A Dynamical Phyllotaxis Model to Determine Floral Organ Number	journal.pcbi.1004145	null	[ [ "How to determine the numbers of body parts is a fundamental problem for the development of complete body structures in multicellular organisms .", "Digit numbers in vertebrates are evolutionarily optimized for the specific demands of the organism [1]; the body-segment number in insects is constant despit...	[ "How organisms determine particular organ numbers is a fundamental key to the development of precise body structures; however , the developmental mechanisms underlying organ-number determination are unclear .", "In many eudicot plants , the primordia of sepals and petals ( the floral organs ) first arise sequenti...	[ "Why do most eudicot flowers have either four or five petals ?", "This fundamental and attractive problem in botany has been little investigated .", "Here , we identify the properties responsible for organ-number determination in floral development using mathematical modeling .", "Earlier experimental and the...	2015
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "computational biology/literature analysis", "computational biology/macromolecular structure analysis", "biotechnology/protein chemistry and proteomics", "biotechnology/small molecule chemistry", "cardiovascular disorders/hypertension", "pharmacology/adverse reactions", "computational biology/systems bi...	Drug Discovery Using Chemical Systems Biology: Identification of the Protein-Ligand Binding Network To Explain the Side Effects of CETP Inhibitors	journal.pcbi.1000387	null	[ [ "Identification of protein-ligand interaction networks on a proteome-wide scale is crucial to address a wide range of biological problems such as correlating molecular functions to physiological processes and designing safe and efficient therapeutics [1] .", "Recent protein-ligand interaction studies have...	[ "Systematic identification of protein-drug interaction networks is crucial to correlate complex modes of drug action to clinical indications .", "We introduce a novel computational strategy to identify protein-ligand binding profiles on a genome-wide scale and apply it to elucidating the molecular mechanisms asso...	[ "Both the cost to launch a new drug and the attrition rate during the late stage of the drug discovery and development process are increasing .", "Torcetrapib is a case in point , having been withdrawn from phase III clinical trials after 15 years of development and an estimated cost of US $800 M . Torcetrapib re...	2009
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "carbohydrate metabolism", "chemical compounds", "dna-binding proteins", "vertebrates", "carbohydrates", "glucose metabolism", "organic compounds", "glucose", "animals", "mammals", "cell signaling", "fungi", "model organisms", "glucose signaling", "experimental organism systems", "amni...	Lysine acetyltransferase NuA4 and acetyl-CoA regulate glucose-deprived stress granule formation in Saccharomyces cerevisiae	journal.pgen.1006626	null	[ [ "When eukaryotic cells are exposed to environmental stress such as extreme temperatures , nutrient deprivation , or toxic chemicals , they quickly employ defense mechanisms to promote survival .", "An essential part of the stress response is the formation of stress granules ( SGs ) , cytoplasmic ribonucle...	[ "Eukaryotic cells form stress granules under a variety of stresses , however the signaling pathways regulating their formation remain largely unknown .", "We have determined that the Saccharomyces cerevisiae lysine acetyltransferase complex NuA4 is required for stress granule formation upon glucose deprivation bu...	[ "In response to environmental stress , such as nutrient limitations or toxic chemicals , cells must quickly counteract these threats in order to survive .", "One way cells fight environmental challenges is through the formation of stress granules , which are aggregates of proteins and mRNA within the cytoplasm ."...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	The Integrator Complex Subunit 6 (Ints6) Confines the Dorsal Organizer in Vertebrate Embryogenesis	journal.pgen.1003822	null	[ [ "The vertebrate embryonic dorsal organizer , historically referred to as the Spemann organizer , breaks the symmetry of the blastula by defining its dorsal side and ultimately gives rise to axial mesoderm , which forms the notochord , the defining anatomical feature of the chordate lineage .", "In fish an...	[ "Dorsoventral patterning of the embryonic axis relies upon the mutual antagonism of competing signaling pathways to establish a balance between ventralizing BMP signaling and dorsal cell fate specification mediated by the organizer .", "In zebrafish , the initial embryo-wide domain of BMP signaling is refined int...	[ "A complex integration of signaling pathways establishes the body plan of the vertebrate embryo .", "The dorsal side of the embryo is defined by the organizer , a specialized field of cells that breaks the symmetry of the zebrafish blastula by instructing neighboring cells to adopt dorsal fates based on their pro...	2013
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "infectious diseases/neglected tropical diseases" ]	Role of GP82 in the Selective Binding to Gastric Mucin during Oral Infection with Trypanosoma cruzi	journal.pntd.0000613	null	[ [ "Orally transmitted infection by the protozoan parasite Trypanosoma cruzi has been responsible for frequent outbreaks of acute cases of Chagas' disease in recent years [1] , [2] .", "In Brazil , after the elimination of the domiciliary vector Triatoma infestans in many endemic areas , and the control of t...	[ "Oral infection by Trypanosoma cruzi has been the primary cause of recent outbreaks of acute Chagas' diseases .", "This route of infection may involve selective binding of the metacyclic trypomastigote surface molecule gp82 to gastric mucin as a first step towards invasion of the gastric mucosal epithelium and su...	[ "Frequent outbreaks of acute Chagas' disease by food contamination with T . cruzi , characterized by high mortality , have been reported in recent years .", "In Brazil , oral infection is currently the most important mechanism of T . cruzi transmission .", "Studies on oral T . cruzi infection in mice have shown...	2010
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "medicine and health sciences", "pathology and laboratory medicine", "gene regulation", "pathogens", "endothelial cells", "microbiology", "epithelial cells", "viruses", "protein expression", "dna viruses", "molecular biology techniques", "herpesviruses", "research and analysis methods", "s...	Kaposi’s sarcoma-associated herpesvirus vIRF2 protein utilizes an IFN-dependent pathway to regulate viral early gene expression	journal.ppat.1007743	null	[ [ "Kaposi’s sarcoma-associated herpesvirus ( KSHV ) or human herpesvirus 8 ( HHV8 ) belongs to the genus Rhadinovirus within the subfamily of Gammaherpesvirinae .", "It was identified in 1994 when herpesvirus-like DNA sequences were discovered in AIDS-associated Kaposi's sarcoma ( KS ) tissues [1] .", "...	[ "Kaposi’s sarcoma-associated herpesvirus ( KSHV; human herpesvirus 8 ) belongs to the subfamily of Gammaherpesvirinae and is the etiological agent of Kaposi’s sarcoma as well as of two lymphoproliferative diseases: primary effusion lymphoma and multicentric Castleman disease .", "The KSHV life cycle is divided in...	[ "The life cycle of Kaposi Sarcoma herpesvirus involves both persistence in a latent form and productive replication to generate new viral particles .", "How the virus switches between latency and productive ( ‘lytic’ ) replication is only partially understood .", "Here we show that a viral homologue of interfer...	2019
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "plant growth and development", "plant biology", "developmental biology", "plant science", "model organisms", "plants", "pattern formation", "arabidopsis thaliana", "plant genetics", "biology", "fruits", "plant and algal models", "genetics", "genetics and genomics" ]	Antagonistic Gene Activities Determine the Formation of Pattern Elements along the Mediolateral Axis of the Arabidopsis Fruit	journal.pgen.1003020	null	[ [ "The fruit , a pivotal structure in angiosperms , is the specialized plant organ that develops from the gynoecium after fertilization of the ovules .", "The very term angiosperm comes from the Greek and means “seeds enclosed in a vessel” ( angion , vessel , and sperma , seed ) , describing the main functi...	[ "The Arabidopsis fruit mainly consists of a mature ovary that shows three well defined territories that are pattern elements along the mediolateral axis: the replum , located at the medial plane of the flower , and the valve and the valve margin , both of lateral nature .", "JAG/FIL activity , which includes the ...	[ "There are three main pattern elements in the mediolateral axis of the Arabidopsis fruit .", "Two of them , the valves and the valve margins , are placed in lateral positions , while the third , called replum , is located in the medial plane of the flower .", "The replum expresses meristematic genes ( medial fa...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	The N-terminal Helical Region of the Hepatitis C Virus p7 Ion Channel Protein Is Critical for Infectious Virus Production	journal.ppat.1005297	null	[ [ "Over 130 million people worldwide are at risk for liver fibrosis , cirrhosis , hepatocellular carcinoma , and end stage liver disease as a result of hepatitis C virus ( HCV ) infection [1] .", "These complications of infection have made hepatitis C the most common indication for liver transplantation [2]...	[ "The hepatitis C virus ( HCV ) p7 protein is required for infectious virus production via its role in assembly and ion channel activity .", "Although NMR structures of p7 have been reported , the location of secondary structural elements and orientation of the p7 transmembrane domains differ among models .", "F...	[ "Hepatitis C virus ( HCV ) infection can lead to significant liver disease and , without a vaccine , continues to pose a significant public health threat .", "The viral p7 protein is a multifunctional protein that is required for infectious virus production via its role in orchestrating virion assembly and its ac...	2015
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "skin", "medicine and health sciences", "integumentary system", "immunofluorescence staining", "enzymes", "enzymology", "vertebrates", "dogs", "animals", "mammals", "protein expression", "genome analysis", "epidermis", "mammalian genomics", "molecular biology techniques", "research and...	A de novo variant in the ASPRV1 gene in a dog with ichthyosis	journal.pgen.1006651	null	[ [ "The skin and in particular the epidermis provide both an outward and inward barrier function , which is essential for survival .", "Aberrant skin development or homeostasis can impair this barrier function and may result in skin disorders .", "Ichthyoses are a heterogeneous group of skin disorders ch...	[ "Ichthyoses are a heterogeneous group of inherited cornification disorders characterized by generalized dry skin , scaling and/or hyperkeratosis .", "Ichthyosis vulgaris is the most common form of ichthyosis in humans and caused by genetic variants in the FLG gene encoding filaggrin .", "Filaggrin is a key play...	[ "The skin undergoes a constant process of self-renewing and keratinocytes migrate from the basal layer of the epidermis to the uppermost layer , the stratum corneum , as they differentiate .", "A defect in the differentiation of keratinocytes can lead to cornification disorders such as ichthyosis .", "The most ...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Fibroblast Growth Factor 9 Regulation by MicroRNAs Controls Lung Development and Links DICER1 Loss to the Pathogenesis of Pleuropulmonary Blastoma	journal.pgen.1005242	null	[ [ "Fibroblast Growth Factor 9 ( FGF9 ) is required during lung development for mesenchymal growth and epithelial branching , and inactivation of Fgf9 in mice results in perinatal death due to respiratory insufficiency [1–3] .", "Overexpression of FGF9 in embryonic mouse lung epithelium results in cystic exp...	[ "Pleuropulmonary Blastoma ( PPB ) is the primary neoplastic manifestation of a pediatric cancer predisposition syndrome that is associated with several diseases including cystic nephroma , Wilms tumor , neuroblastoma , rhabdomyosarcoma , medulloblastoma , and ovarian Sertoli-Leydig cell tumor .", "The primary pat...	[ "Pleuropulmonary Blastoma ( PPB ) is a pediatric disease that presents with multifocal cystic lung lesions .", "Familial mutations in DICER1 , an essential gene for microRNA synthesis , predisposes to PPB and other related diseases .", "Loss or mutation of the second copy of DICER1 in developing airway epitheli...	2015
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "medicine and health sciences", "g1 phase", "cell division analysis", "cell cycle and cell division", "cell processes", "population genetics", "simulation and modeling", "physiological processes", "homeostasis", "effective population size", "bioassays and physiological analysis", "population b...	Mathematical modelling reveals unexpected inheritance and variability patterns of cell cycle parameters in mammalian cells	journal.pcbi.1007054	null	[ [ "The cell cycle is a process leading to cell division .", "It plays a critical role in tissue growth , development and regeneration of multicellular organisms .", "It consists of two critical phases: the S phase , in which the cell replicates its DNA , and the M phase where it divides in two progeny c...	[ "The cell cycle is the fundamental process of cell populations , it is regulated by environmental cues and by intracellular checkpoints .", "Cell cycle variability in clonal cell population is caused by stochastic processes such as random partitioning of cellular components to progeny cells at division and random...	[ "All cells in multicellular organisms obey orchestrated sequences of signals to ensure developmental and homeostatic fitness under a variety of external stimuli .", "However , there also exist self-perpetuating stem-cell populations , the function of which is to provide a steady supply of differentiated progenito...	2019
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[]	Resistance of M. leprae to Quinolones: A Question of Relativity?	journal.pntd.0002559	null	[ [ "Mycobacterium leprae is responsible for leprosy , that the World Health Assembly decided , in 1991 , to “eliminate as a public health problem” by the year 2000 .", "But , though a decreasing number of new cases registered each year ( ∼219 , 000 ) during the recent years [1] , [2] , it is generally admitt...	[ "Multidrug resistant leprosy , defined as resistance to rifampin , dapsone and fluoroquinolones ( FQ ) , has been described in Mycobacterium leprae .", "However , the in vivo impact of fluoroquinolone resistance , mainly mediated by mutations in DNA gyrase ( GyrA2GyrB2 ) , has not been precisely assessed .", "O...	[ "Although there is efficient multidrug therapy to cure leprosy , the transmission of M . leprae is still active , leading to 219 , 000 new cases in 2011 .", "Drug resistant leprosy has been described and may prevent eradication of the disease , notably multidrug resistant defined as resistance to rifampin , dapso...	2013
[ "Introduction", "Material and methods", "Results", "Discussion", "Conclusions" ]	[ "medicine and health sciences", "gut bacteria", "microbiome", "body fluids", "microbiology", "parasitic protozoans", "developmental biology", "nymphs", "protozoans", "bacteria", "microbial genomics", "digestive system", "medical microbiology", "life cycles", "actinobacteria", "gastroin...	Field-collected Triatoma sordida from central Brazil display high microbiota diversity that varies with regard to developmental stage and intestinal segmentation	journal.pntd.0006709	null	[ [ "Chagas disease is a potentially life-threatening illness caused by the protozoan Trypanosoma cruzi .", "T . cruzi is a parasite of mammals primarily transmitted through the feces of infected vectors–blood-sucking bugs of the subfamily Triatominae .", "Chagas disease is the fourth most important infec...	[ "Triatomine bugs are the vectors of Trypanosoma cruzi , the agent of Chagas disease .", "Vector control has for decades relied upon insecticide spraying , but insecticide resistance has recently emerged in several triatomine populations .", "One alternative strategy to reduce T . cruzi transmission is paratrans...	[ "Triatomines are blood-sucking bugs that transmit Trypanosoma cruzi , the agent of Chagas disease .", "Insecticide spraying has been very successful at controlling house-infesting bugs , but some triatomines have developed insecticide resistance .", "One alternative disease-control strategy involves modifying t...	2018
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "medicine", "infectious diseases", "leishmaniasis", "neglected tropical diseases" ]	Post-Kala-azar Dermal Leishmaniasis in Nepal: A Retrospective Cohort Study (2000–2010)	journal.pntd.0001433	null	[ [ "Post-kala-azar dermal leishmaniasis ( PKDL ) is a late complication of visceral leishmaniasis ( VL ) , which usually appears several months after treatment of a VL episode .", "PKDL is seen in areas where L . donovani is endemic i . e . in Asia ( India , Nepal and Bangladesh ) and in east Africa ( Ethiop...	[ "Post-kala-azar dermal leishmaniasis ( PKDL ) is a cutaneous complication appearing after treatment of visceral leishmaniasis , and PKDL patients are considered infectious to sand flies and may therefore play a role in the transmission of VL .", "We estimated the risk and risk factors of PKDL in patients with pas...	[ "Post-kala-azar dermal leishmaniasis ( PKDL ) is a skin disorder seen in patients treated for Leishmania donovani visceral leishmaniasis ( VL ) , a neglected tropical disease that is fatal if left untreated .", "In the Indian subcontinent , PKDL is seen in 5–10% of all past VL cases and is also reported in some w...	2011
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "animal types", "medicine and health sciences", "pathology and laboratory medicine", "pathogens", "neighborhoods", "immunology", "tropical diseases", "geographical locations", "vertebrates", "microbiology", "social sciences", "pets and companion animals", "dogs", "animals", "mammals", ...	Socio-spatial heterogeneity in participation in mass dog rabies vaccination campaigns, Arequipa, Peru	journal.pntd.0007600	null	[ [ "The city of Arequipa is in the midst of a sustained dog rabies outbreak .", "The introduction of rabies virus into the city has been ascribed to the unintentional transport of rabid dogs from the rabies-endemic state of Puno during human migration [1–3] , and the persistence of transmission is likely due...	[ "To control and prevent rabies in Latin America , mass dog vaccination campaigns ( MDVC ) are implemented mainly through fixed-location vaccination points: owners have to bring their dogs to the vaccination points where they receive the vaccination free of charge .", "Dog rabies is still endemic in some Latin-Ame...	[ "In Peru and other dog rabies-affected countries , mass dog vaccination campaigns ( MDVC ) are implemented primarily through fixed-location vaccination points: owners have to bring their dogs to the vaccination points where they receive the vaccination .", "To stop rabies virus transmission , a high and even dog ...	2019
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "systems biology", "mathematics", "applied mathematics", "regulatory networks", "biology", "computational biology", "signaling networks" ]	Modelling Cell Polarization Driven by Synthetic Spatially Graded Rac Activation	journal.pcbi.1002366	null	[ [ "Many types of eukaryotic cells undergo directed motion in response to external spatial signals in a process known as chemotaxis .", "Before starting to move , a given cell polarizes according to directional cues in the environment , forming nascent “front” and “back” regions .", "At the front , actin...	[ "The small GTPase Rac is known to be an important regulator of cell polarization , cytoskeletal reorganization , and motility of mammalian cells .", "In recent microfluidic experiments , HeLa cells endowed with appropriate constructs were subjected to gradients of the small molecule rapamycin leading to synthetic...	[ "Cell polarization is associated with intracellular gradients of signaling proteins such as Rho GTPases that organize the cytoskeleton in cell motility .", "We previously observed cells in microfluidic channels and studied their polarization and motility in a simplified ( nearly 1 dimensional ) geometry .", "Th...	2012
[ "Introduction", "Results and discussion", "Methods" ]	[ "open science", "open access publishing", "employment", "publication practices", "engineering and technology", "bibliometrics", "sexual and gender issues", "sociology", "social sciences", "careers", "research and analysis methods", "meta-research article", "computer and information sciences"...	The gender gap in science: How long until women are equally represented?	journal.pbio.2004956	null	[ [ "Although women are increasingly studying Science , Technology , Engineering , Mathematics , and Medicine ( STEMM ) subjects at university , women comprise a minority of senior staff , are less often trained in elite research groups , are promoted more slowly , and are more likely to leave STEMM careers [1–3]...	[ "Women comprise a minority of the Science , Technology , Engineering , Mathematics , and Medicine ( STEMM ) workforce .", "Quantifying the gender gap may identify fields that will not reach parity without intervention , reveal underappreciated biases , and inform benchmarks for gender balance among conference spe...	[ "In most fields of science , medicine , and technology research , men comprise more than half of the workforce , particularly at senior levels .", "Most previous work has concluded that the gender gap is smaller today than it was in the past , giving the impression that there will soon be equal numbers of men and...	2018
[ "Introduction", "Methods", "Results", "Discussion" ]	[]	Primary Motor Cortex Representation of Handgrip Muscles in Patients with Leprosy	journal.pntd.0003944	null	[ [ "Leprosy , also known as Hansen's disease , is a chronic human granulomatous bacilliferous infection caused by the obligate intracellular organism Mycobacterium leprae [1] .", "Leprosy continues to be an important health problem worldwide , particularly in India , Brazil , Democratic Republic of Congo , T...	[ "Leprosy is an endemic infectious disease caused by Mycobacterium leprae that predominantly attacks the skin and peripheral nerves , leading to progressive impairment of motor , sensory and autonomic function .", "Little is known about how this peripheral neuropathy affects corticospinal excitability of handgrip ...	[ "Leprosy is an endemic disease caused by Mycobacterium leprae that predominantly attacks both skin and peripheral nerves , resulting in persistent distal hand atrophy and the loss of sensory and autonomic functions .", "In this study , we employ a noninvasive tool named transcranial magnetic stimulation ( TMS ) t...	2015
[ "Introduction", "Methodology", "Results", "Discussion" ]	[ "schistosoma", "invertebrates", "ecology and environmental sciences", "medicine and health sciences", "ecological niches", "helminths", "china", "atmospheric science", "geographical locations", "tropical diseases", "parasitic diseases", "animals", "oncomelania", "gastropods", "neglected ...	Schistosoma japonicum transmission risk maps at present and under climate change in mainland China	journal.pntd.0006021	null	[ [ "Schistosomiasis is a neglected tropical disease that is known to have affected people in China for more than 2100 years , with presently ~800 , 000 infected and ~65 million people at risk of infection [1] .", "The challenge of combatting this disease lies in the wide distribution of its snail hosts and t...	[ "The South-to-North Water Diversion ( SNWD ) project is designed to channel fresh water from the Yangtze River north to more industrialized parts of China .", "An important question is whether future climate change and dispersal via the SNWD may synergistically favor a northward expansion of species involved in h...	[ "The South-to-North Water Diversion ( SNWD ) project is designed to channel fresh water from the Yangtze River north to more industrialized parts of China .", "An important question is whether future climate change and dispersal via the SNWD may synergistically favor northward expansion of schistosomiasis in Chin...	2017
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "medicine and health sciences", "ecology and environmental sciences", "surface water", "water resources", "pathology and laboratory medicine", "rivers", "pathogens", "vibrio", "tropical diseases", "microbiology", "geographical locations", "diet", "diarrhea", "bacterial diseases", "vibrio...	Cholera returns to southern Vietnam in an outbreak associated with consuming unsafe water through iced tea: A matched case-control study	journal.pntd.0005490	null	[ [ "Cholera is a highly contagious diarrheal disease , caused by infection of the Gram-negative bacterium Vibrio cholerae [1] .", "Areas with poverty , high population-density , poor sanitation , poor education levels , and lack of potable water are at risk for cholera outbreaks [2–4] .", "An estimated 1...	[ "After more than a decade of steadily declining notifications , the number of reported cholera cases has recently increased in Vietnam .", "We conducted a matched case-control study to investigate transmission of cholera during an outbreak in Ben Tre , southern Vietnam , and to explore the associated risk factors...	[ "Cholera is a highly contagious , acute diarrheal illness , which poses a profound health threat in many parts of the less developed world .", "The majority of cases are reported from Sub-Saharan Africa , South-East Asia , and the Americas ( i . e . , Haiti ) where infections are primarily transmitted through ing...	2017
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "sequencing techniques", "medicine and health sciences", "toxins", "pathology and laboratory medicine", "split-decomposition method", "vertebrates", "animals", "toxicology", "toxic agents", "multiple alignment calculation", "reptiles", "forms of dna", "rna isolation", "molecular biology te...	Full-Length Venom Protein cDNA Sequences from Venom-Derived mRNA: Exploring Compositional Variation and Adaptive Multigene Evolution	journal.pntd.0004587	null	[ [ "The evolution of venoms among the advanced colubroid snakes has had tremendous adaptive significance and has allowed this clade to diversify rapidly and occupy a diversity of niches globally [1] .", "Snake venoms are complex glandular secretions that may contain 2–100+ protein/peptide components with a m...	[ "Envenomation of humans by snakes is a complex and continuously evolving medical emergency , and treatment is made that much more difficult by the diverse biochemical composition of many venoms .", "Venomous snakes and their venoms also provide models for the study of molecular evolutionary processes leading to a...	[ "This work demonstrates that full-length venom protein messenger RNAs are present in secreted venoms and can be used to acquire full-length protein sequences of toxins from both front-fanged ( Elapidae , Viperidae ) and rear-fanged ( Colubridae ) snake venoms , eliminating the need to use venom glands .", "Full-l...	2016
[ "Introduction", "Results", "Discussion", "Material and Methods" ]	[ "molecular biology/dna replication", "molecular biology/recombination", "biochemistry/protein chemistry", "genetics and genomics/chromosome biology", "biochemistry/replication and repair", "genetics and genomics/gene function", "microbiology/microbial growth and development", "molecular biology/dna re...	ruvA Mutants That Resolve Holliday Junctions but Do Not Reverse Replication Forks	journal.pgen.1000012	null	[ [ "DNA replication and recombination are two processes that are now recognized as more closely connected than originally suspected .", "It is well documented that replication defects induce the formation of recombination substrates , such as double-stranded DNA ends or single-stranded DNA regions ( ssDNA ) ...	[ "RuvAB and RuvABC complexes catalyze branch migration and resolution of Holliday junctions ( HJs ) respectively .", "In addition to their action in the last steps of homologous recombination , they process HJs made by replication fork reversal , a reaction which occurs at inactivated replication forks by the anne...	[ "DNA replication is the process by which DNA strands are copied to ensure the transmission of the genetic material to daughter cells .", "Chromosome replication is not a continuous process but is subjected to accidental arrests , owing to the encounter of obstacles or to the dysfunctioning of a replication protei...	2008
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biophysics", "cell biology", "mammals", "computational biology" ]	How Force Might Activate Talin's Vinculin Binding Sites: SMD Reveals a Structural Mechanism	journal.pcbi.0040024	null	[ [ "Talin physically links integrins to the contractile cytoskeleton [1 , 2] .", "The talin head ( TH ) , residues 1–432 , has binding sites for integrin β-tails [3] , PIP kinase γ [4] , focal adhesion kinase ( FAK ) [5] , layilin [5] and actin [6] ( Figure 1B ) .", "Binding of the talin head to the cyto...	[ "Upon cell adhesion , talin physically couples the cytoskeleton via integrins to the extracellular matrix , and subsequent vinculin recruitment is enhanced by locally applied tensile force .", "Since the vinculin binding ( VB ) sites are buried in the talin rod under equilibrium conditions , the structural mechan...	[ "For cell survival , most eukaryotic cells need to be mechanically anchored to their environment .", "This is done by transmembrane proteins , including integrins , which externally bind to the extracellular matrix and on the cell interior to the contractile cytoskeleton via scaffolding proteins .", "One essent...	2008
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "ecology and environmental sciences", "messenger rna", "electromagnetic radiation", "circadian oscillators", "chronobiology", "ecological metrics", "gene expression", "luminescence", "physics", "circadian rhythms", "biochemistry", "genetic oscillators", "rna", "bioluminescence", "ecology...	Temperature–amplitude coupling for stable biological rhythms at different temperatures	journal.pcbi.1005501	null	[ [ "Many physiological processes are sensitive to temperature .", "At the biochemical level , the speed of the reactions tends to increase two- to three-fold with a 10°C temperature rise [1] .", "At the system level , cell growth accelerates with temperature , and the cell cycle period of NIH3T3 cells de...	[ "Most biological processes accelerate with temperature , for example cell division .", "In contrast , the circadian rhythm period is robust to temperature fluctuation , termed temperature compensation .", "Temperature compensation is peculiar because a system-level property ( i . e . , the circadian period ) is...	[ "Circadian rhythms govern the timing of many physiological events .", "Mysteriously , the period of the rhythm is robust to temperature although the underlying biochemical reactions usually accelerate with temperature , a paradox that has remained unsolved for more than 60 years .", "Experiments conducted over ...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "molecular biology/dna replication", "genetics and genomics/chromosome biology", "genetics and genomics/cancer genetics", "molecular biology/chromatin structure", "molecular biology/dna repair" ]	Cdc7p-Dbf4p Regulates Mitotic Exit by Inhibiting Polo Kinase	journal.pgen.1000498	null	[ [ "Accurate ordering of cell cycle events is an important requirement for the viability of all eukaryotic organisms .", "Once cells commit to duplicate their genome they must restrain mitosis until replication is complete and then accurately coordinate mitosis with cytokinesis to ensure the faithful transmi...	[ "Cdc7p-Dbf4p is a conserved protein kinase required for the initiation of DNA replication .", "The Dbf4p regulatory subunit binds Cdc7p and is essential for Cdc7p kinase activation , however , the N-terminal third of Dbf4p is dispensable for its essential replication activities .", "Here , we define a short N-t...	[ "Cdc7p-Dbf4p is a two-subunit enzyme required to copy the genetic material present on every chromosome in a process termed DNA replication .", "Dbf4p is an essential regulatory subunit of this enzyme that likely directs the Cdc7p subunit to its targets within the cell .", "We found that Dbf4p physically interac...	2009
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "cognitive science", "engineering and technology", "demography", "population genetics", "neuroscience", "simulation and modeling", "decision analysis", "management engineering", "artificial intelligence", "population biology", "research and analysis methods", "computer and information sciences...	S/HIC: Robust Identification of Soft and Hard Sweeps Using Machine Learning	journal.pgen.1005928	null	[ [ "The availability of population genomic data has empowered efforts to uncover the selective , demographic , and stochastic forces driving patterns of genetic variation within species .", "Chief among these are attempts to uncover the genetic basis of recent adaptation [1] .", "Indeed , recent advances...	[ "Detecting the targets of adaptive natural selection from whole genome sequencing data is a central problem for population genetics .", "However , to date most methods have shown sub-optimal performance under realistic demographic scenarios .", "Moreover , over the past decade there has been a renewed interest ...	[ "The genetic basis of recent adaptation can be uncovered from genomic patterns of variation , which are perturbed in predictable ways when a beneficial mutation “sweeps” through a population .", "However , the detection of such “selective sweeps” is complicated by demographic events , such as population expansion...	2016
[ "Introduction", "Methods", "Results", "Discussion" ]	[]	Regulation of Life Cycle Checkpoints and Developmental Activation of Infective Larvae in Strongyloides stercoralis by Dafachronic Acid	journal.ppat.1005358	null	[ [ "Strongyloides stercoralis is a parasitic nematode that infects both humans and dogs and is the causative agent of strongyloidiasis , which predominately afflicts socio-economically disadvantaged people in developing countries [1–3] .", "While chronic strongyloidiasis is often asymptomatic or accompanied ...	[ "The complex life cycle of the parasitic nematode Strongyloides stercoralis leads to either developmental arrest of infectious third-stage larvae ( iL3 ) or growth to reproductive adults .", "In the free-living nematode Caenorhabditis elegans , analogous determination between dauer arrest and reproductive growth ...	[ "Strongyloides stercoralis is a parasitic nematode that infects hundreds of millions of people worldwide .", "The infectious form of S . stercoralis is a developmentally arrested third-stage larva ( iL3 ) ; once inside the host , the iL3 activates and develops into an adult parasitic female .", "First-stage lar...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "action potentials", "medicine and health sciences", "nervous system", "sleep", "membrane potential", "brain", "electrophysiology", "neuroscience", "learning and memory", "physiological processes", "ganglion cells", "cognition", "memory", "interneurons", "animal cells", "memory consoli...	Hippocampal CA1 Ripples as Inhibitory Transients	journal.pcbi.1004880	null	[ [ "Sleep , which consumes about a third of our lives , is thought to play a critical role in memory consolidation .", "Specifically , sleep influences unconscious post-encoding processes that result in long term memory consolidation and reconsolidation .", "Behavioral studies show that performance in va...	[ "Memories are stored and consolidated as a result of a dialogue between the hippocampus and cortex during sleep .", "Neurons active during behavior reactivate in both structures during sleep , in conjunction with characteristic brain oscillations that may form the neural substrate of memory consolidation .", "I...	[ "Our memories are consolidated while we sleep through a bidirectional exchange of information between two brain areas called cortex and hippocampus .", "Neurons that were active in behavioral tasks reactivate again in both structures during sleep in a process of linking and modifying memories from the short term ...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "oncology", "medicine", "neurological disorders", "neurology", "surgery", "biology", "molecular cell biology" ]	Regulation of Brain Tumor Dispersal by NKCC1 Through a Novel Role in Focal Adhesion Regulation	journal.pbio.1001320	The ion transporter NKCC1 determines brain tumor cell migration by regulating the interplay between cell adhesion and growth factor signaling, and is a potential therapeutic target to treat brain cancer.	[ [ "Glioblastoma ( GB ) is the most common malignant primary brain tumor .", "GBs are aggressive and display key features of invasion and infiltration of healthy brain tissue [1] .", "Due to its invasive nature , GB is not curable through surgical resection [2] , [3] .", "The surgical and medical tre...	[ "Glioblastoma ( GB ) is a highly invasive and lethal brain tumor due to its universal recurrence .", "Although it has been suggested that the electroneutral Na+-K+-Cl− cotransporter 1 ( NKCC1 ) can play a role in glioma cell migration , the precise mechanism by which this ion transporter contributes to GB aggress...	[ "Treatment of many cancers has been hampered by the invasive ability of tumor cells .", "A notable example is brain cancer , which is incurable due to its invasiveness and resulting high tumor recurrence after surgical resection .", "Here , we analyze further the function of NKCC1 , an ion transporter that is k...	2012
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "neuroanatomy", "neural networks", "computational neuroscience", "biology", "neuroscience" ]	Neurobiologically Realistic Determinants of Self-Organized Criticality in Networks of Spiking Neurons	journal.pcbi.1002038	null	[ [ "Self-organized criticality is increasingly postulated to underlie the organization of brain activity [1]–[2] .", "The notion of self-organized criticality describes an unsupervised emergence of critical dynamics in complex systems dominated by internal interactions [3]–[4] .", "Critical dynamics emer...	[ "Self-organized criticality refers to the spontaneous emergence of self-similar dynamics in complex systems poised between order and randomness .", "The presence of self-organized critical dynamics in the brain is theoretically appealing and is supported by recent neurophysiological studies .", "Despite this , ...	[ "The intricate relationship between structural brain connectivity and functional brain activity is an important and intriguing research area .", "Brain structure ( the pattern of neuroanatomical connections ) is thought to strongly influence and constrain brain function ( the pattern of neuronal activations ) .",...	2011
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "immunology/immunity to infections", "virology/vaccines" ]	Synthetic Double-Stranded RNAs Are Adjuvants for the Induction of T Helper 1 and Humoral Immune Responses to Human Papillomavirus in Rhesus Macaques	journal.ppat.1000373	null	[ [ "Effective vaccines against infections caused by intracellular pathogens including HIV infection , malaria , or tuberculosis most likely will need to induce strong cellular and humoral immune responses [1] .", "Current vaccine strategies under development are based on prime-boost immunizations , such as v...	[ "Toll-like receptor ( TLR ) ligands are being considered as adjuvants for the induction of antigen-specific immune responses , as in the design of vaccines .", "Polyriboinosinic-polyribocytoidylic acid ( poly I:C ) , a synthetic double-stranded RNA ( dsRNA ) , is recognized by TLR3 and other intracellular recepto...	[ "Novel adjuvants that facilitate the induction of strong cellular immunity could be of help in the design of vaccine strategies to combat infections such as HIV or tuberculosis .", "Our immune cells possess archaic receptors recognizing structures of infectious pathogens , and the interaction of these receptors w...	2009
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "medicine", "disease mapping", "infectious diseases", "veterinary diseases", "zoonoses", "rabies", "veterinary epidemiology", "infectious disease epidemiology", "epidemiology", "zoonotic diseases", "spatial epidemiology", "population biology", "biology", "animal management", "veterinary ...	Designing Programs for Eliminating Canine Rabies from Islands: Bali, Indonesia as a Case Study	journal.pntd.0002372	null	[ [ "Rabies transmitted by domestic dogs is a re–emerging public health problem in Asia .", "In recent years incidence has increased dramatically in China [1] , [2]; multiple incursions have been reported from Bhutan [3] , [4]; and the disease has spread across several previously rabies–free islands in Indone...	[ "Canine rabies is one of the most important and feared zoonotic diseases in the world .", "In some regions rabies elimination is being successfully coordinated , whereas in others rabies is endemic and continues to spread to uninfected areas .", "As epidemics emerge , both accepted and contentious control metho...	[ "Canine rabies continues to cause tens of thousands of horrific deaths worldwide , primarily in Asia and Africa .", "Momentum is building towards development of a global elimination strategy for canine rabies , but questions remain over how best to eliminate rabies epidemics .", "This paper uses data generated ...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "viruses", "biochemistry", "virology", "biophysics", "molecular biology" ]	Experimental Test of Connector Rotation during DNA Packaging into Bacteriophage φ29 Capsids	journal.pbio.0050059	dsDNA compaction into bacteriophage capsids is observed in packaging complexes. Unlike in previous models, this compaction is found not to be driven by a rotating motor complex.	[ [ "As part of its viral infection cycle , the Bacillus subtilis bacteriophage φ29 packages its double-stranded DNA genome into a preformed capsid shell , or prohead , by means of a powerful molecular motor [1 , 2] .", "The DNA-packaging motor is situated at a unique 5-fold vertex of the prohead and is a com...	[ "The bacteriophage φ29 generates large forces to compact its double-stranded DNA genome into a protein capsid by means of a portal motor complex .", "Several mechanical models for the generation of these high forces by the motor complex predict coupling of DNA translocation to rotation of the head-tail connector ...	[ "The life cycles of many viruses include a self-assembly stage in which a powerful molecular motor packs the DNA genome into the virus's preformed shell ( the capsid ) .", "Biochemical and biophysical studies have identified essential components of the packaging machinery and measured various characteristics of t...	2007
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genome-wide association studies", "genetics", "biology", "computational biology", "genetics and genomics" ]	Statistical Analysis Reveals Co-Expression Patterns of Many Pairs of Genes in Yeast Are Jointly Regulated by Interacting Loci	journal.pgen.1003414	null	[ [ "eQTL studies aim to uncover the genetic architecture underlying expression regulation .", "In the past decade , they have been conducted in many organisms , including yeast , drosophila , mouse , human and many others [1]–[5] .", "A common approach in eQTL data analysis is to consider association bet...	[ "Expression quantitative trait loci ( eQTL ) studies have generated large amounts of data in different organisms .", "The analyses of these data have led to many novel findings and biological insights on expression regulations .", "However , the role of epistasis in the joint regulation of multiple genes has no...	[ "eQTL studies collect both gene expression and genotype data , and they are highly informative as to how genes regulate expressions .", "Although much progress has been made in the analysis of such data , most studies have considered one marker at a time .", "As a result , those markers with weak marginal yet s...	2013
[ "Introduction", "Results/Discussion", "Materials and Methods" ]	[ "sequencing techniques", "organismal evolution", "medicine and health sciences", "genome evolution", "pathology and laboratory medicine", "microbiology", "genome sequencing", "genomic databases", "phylogenetics", "fungi", "fungal evolution", "genome analysis", "microbial evolution", "molec...	Gene Expansion Shapes Genome Architecture in the Human Pathogen Lichtheimia corymbifera: An Evolutionary Genomics Analysis in the Ancient Terrestrial Mucorales (Mucoromycotina)	journal.pgen.1004496	null	[ [ "The basal lineages of terrestrial fungi , formerly Zygomycota , were recently shown to be polyphyletic and were therefore separated into four separate subphyla [1] .", "Especially the order Mucorales of the Mucoromycotina encompasses several human pathogenic species .", "Although infections with muco...	[ "Lichtheimia species are the second most important cause of mucormycosis in Europe .", "To provide broader insights into the molecular basis of the pathogenicity-associated traits of the basal Mucorales , we report the full genome sequence of L . corymbifera and compared it to the genome of Rhizopus oryzae , the ...	[ "Lichtheimia species are ubiquitous saprophytic fungi , which cause life-threating infections in humans .", "In contrast to the mucoralean pathogen R . oryzae , Lichtheimia species belong to the ancient mucoralean lineages .", "We determined the genome of L . corymbifera ( formerly Mycocladus corymbifer ex Absi...	2014
[ "Introduction", "Materials and methods", "Results", "Discussion" ]	[ "bacteriology", "blood cells", "innate immune system", "medicine and health sciences", "luciferase", "body fluids", "immune physiology", "cytokines", "immune cells", "enzymes", "melioidosis", "immunology", "microbiology", "enzymology", "immune receptor signaling", "bacterial diseases",...	Flagellin-independent effects of a Toll-like receptor 5 polymorphism in the inflammatory response to Burkholderia pseudomallei	journal.pntd.0007354	null	[ [ "Melioidosis is a tropical infection caused by the flagellated Gram-negative bacterium Burkholderia pseudomallei [1] .", "The disease commonly presents as pneumonia and sepsis in Southeast Asia and northern Australia .", "The mortality rate from infection with this bacterium can exceed 40% [2] .", ...	[ "Toll-like receptors ( TLRs ) are sentinel receptors of the innate immune system .", "TLR4 detects bacterial lipopolysaccharide ( LPS ) and TLR5 detects bacterial flagellin .", "A common human nonsense polymorphism , TLR5:c . 1174C>T , results in a non-functional TLR5 protein .", "Individuals carrying this va...	[ "Toll-like receptors ( TLRs ) are important receptors of the innate immune system .", "TLR4 detects bacterial lipopolysaccharide ( LPS ) and TLR5 detects bacterial flagellin .", "A common human polymorphism in TLR5 encodes a shortened protein and blunts the immune response to flagellin .", "Individuals carryi...	2019
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "blood cells", "flow cytometry", "innate immune system", "medicine and health sciences", "immune physiology", "cytokines", "immune cells", "immunology", "tropical diseases", "diabetes mellitus", "animal models", "bacterial diseases", "developmental biology", "endocrine disorders", "model...	NK-CD11c+ Cell Crosstalk in Diabetes Enhances IL-6-Mediated Inflammation during Mycobacterium tuberculosis Infection	journal.ppat.1005972	null	[ [ "Mycobacterium tuberculosis ( Mtb ) infects one-third of the world’s population and causes almost 1 . 3 million deaths per year [1] .", "Approximately 90% of those infected have a latent tuberculosis infection and develop protective immunity to contain it; however , but 10% progressive to active tuberculo...	[ "In this study , we developed a mouse model of type 2 diabetes mellitus ( T2DM ) using streptozotocin and nicotinamide and identified factors that increase susceptibility of T2DM mice to infection by Mycobacterium tuberculosis ( Mtb ) .", "All Mtb-infected T2DM mice and 40% of uninfected T2DM mice died within 10 ...	[ "In the current study , we employed an experimentally induced type 2 diabetes mellitus ( T2DM ) model in wild type C57BL/6 mice and investigated the immune response to Mycobacterium tuberculosis ( Mtb ) infection .", "We found that natural killer ( NK ) and CD11c+ cell interactions in Mtb-infected T2DM mice led t...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Crystal Structure of the Pre-fusion Nipah Virus Fusion Glycoprotein Reveals a Novel Hexamer-of-Trimers Assembly	journal.ppat.1005322	null	[ [ "Henipavirus , a relatively recently recognized viral genus in the family Paramyxoviridae , comprises likely over 20 species , including three established species: Hendra ( HeV ) , Nipah ( NiV ) and Cedar ( CedPV ) viruses , with HeV and NiV well-recognized as highly pathogenic agents for both humans and anim...	[ "Nipah virus ( NiV ) is a paramyxovirus that infects host cells through the coordinated efforts of two envelope glycoproteins .", "The G glycoprotein attaches to cell receptors , triggering the fusion ( F ) glycoprotein to execute membrane fusion .", "Here we report the first crystal structure of the pre-fusion...	[ "Paramyxoviruses infect host cells through the coordinated functions of two envelope glycoproteins .", "The G glycoprotein attaches to cell receptors triggering the fusion ( F ) glycoprotein to execute membrane fusion .", "The crystal structure of the NiV-F protein has not been reported .", "Additionally , ma...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "neuroscience", "neuroscience/theoretical neuroscience" ]	Structure of Spontaneous UP and DOWN Transitions Self-Organizing in a Cortical Network Model	journal.pcbi.1000022	null	[ [ "Cortical networks show complex dynamics of intrinsic activity when sensory inputs are absent .", "Whether this spontaneous activity is a mere idling state of the brain or , rather , an internal state that actively engages in brain functions remains unclear .", "Recent experimental studies have reveal...	[ "Synaptic plasticity is considered to play a crucial role in the experience-dependent self-organization of local cortical networks .", "In the absence of sensory stimuli , cerebral cortex exhibits spontaneous membrane potential transitions between an UP and a DOWN state .", "To reveal how cortical networks deve...	[ "Information processing by the brain relies crucially on neuronal circuits .", "Therefore , clarifying the structure of the brain circuitry is a crucial step towards understanding how the brain processes information .", "In particular , the cerebral cortex occupies a large portion of the brain in primates and h...	2008
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biochemistry", "genomics", "functional genomics", "entomology", "proteins", "genome analysis", "transcriptome analysis", "genetics", "biology and life sciences", "proteomics", "computational biology", "zoology", "parasitology" ]	A Novel Highly Divergent Protein Family Identified from a Viviparous Insect by RNA-seq Analysis: A Potential Target for Tsetse Fly-Specific Abortifacients	journal.pgen.1003874	null	[ [ "Tsetse reproductive biology is unusual among insects .", "Female tsetse give birth to a fully mature third instar larva ( viviparity ) after an extended intrauterine gestation .", "This reproductive strategy limits the capacity of tsetse mothers to only 8–10 offspring per lifetime [1] .", "To acc...	[ "In tsetse flies , nutrients for intrauterine larval development are synthesized by the modified accessory gland ( milk gland ) and provided in mother's milk during lactation .", "Interference with at least two milk proteins has been shown to extend larval development and reduce fecundity .", "The goal of this ...	[ "Tsetse flies are the sole vector for African trypanosomes , causative agents of sleeping sickness in humans and nagana in cattle .", "Transcriptome and proteome analyses were utilized to examine the underlying mechanisms of tsetse lactation that occur during each reproductive cycle .", "These analyses revealed...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "chromosome structure and function", "mathematics", "statistics (mathematics)", "protein structure", "epigenetics", "structural genomics", "chromatin", "research and analysis methods", "sex chromosomes", "chromosome biology", "proteins", "mathematical and statistical techniques", "gene expre...	Inferential Structure Determination of Chromosomes from Single-Cell Hi-C Data	journal.pcbi.1005292	null	[ [ "The rapid development of chromosome conformation capture techniques such as 3C [1] , chromosome conformation capture-on-chip [2] , the closely related circular chromosome conformation capture [3] ( both named 4C ) and 5C [4] culminated in a genome-wide variant , Hi-C [5] , which provides all-against-all cont...	[ "Chromosome conformation capture ( 3C ) techniques have revealed many fascinating insights into the spatial organization of genomes .", "3C methods typically provide information about chromosomal contacts in a large population of cells , which makes it difficult to draw conclusions about the three-dimensional org...	[ "Spatial interactions between distant genomic regions are of fundamental importance in gene regulation and other nuclear processes .", "Recent chromatin crosslinking ( “Hi-C” ) experiments probe the spatial organization of chromosomes on a genome-wide scale to an extent that was previously unattainable .", "The...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "molecular biology/transcription elongation", "molecular biology/histone modification", "molecular biology/chromatin structure" ]	14-3-3 Mediates Histone Cross-Talk during Transcription Elongation in Drosophila	journal.pgen.1000975	null	[ [ "The ability of cells to modulate their transcriptional program in response to physiological stimuli is vital for the proper development of eukaryotic organisms .", "This is partly achieved by post-translational modification of histone proteins that associate with the DNA to form nucleosomes , the basic u...	[ "Post-translational modifications of histone proteins modulate the binding of transcription regulators to chromatin .", "Studies in Drosophila have shown that the phosphorylation of histone H3 at Ser10 ( H3S10ph ) by JIL-1 is required specifically during early transcription elongation .", "14-3-3 proteins bind ...	[ "Activation of gene expression is thought to be regulated mainly at the level of transcription initiation .", "Nevertheless , many genes in Drosophila and vertebrates contain RNA polymerase that has started transcription but is paused 30–40 bp from the initiation site .", "Activation of these genes may thus be ...	2010
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "plant biology/plant growth and development", "plant biology/plant genetics and gene expression", "plant biology/plant biochemistry and physiology" ]	The APETALA-2-Like Transcription Factor OsAP2-39 Controls Key Interactions between Abscisic Acid and Gibberellin in Rice	journal.pgen.1001098	null	[ [ "Plant hormones have synergistic or antagonistic effects on the physiological processes associated with growth and development .", "ABA and GA are hormone partners and act through a complicated network of antagonistic interactions .", "The coordination and interaction between phytohormone is essential...	[ "The interaction between phytohormones is an important mechanism which controls growth and developmental processes in plants .", "Deciphering these interactions is a crucial step in helping to develop crops with enhanced yield and resistance to environmental stresses .", "Controlling the expression level of OsA...	[ "Hormones play an important role in controlling plant growth and development through a dynamic and complicated set of interactions .", "ABA and GA are well-known as antagonistic partners although the mechanism through which this occurs still needs further elucidation .", "In this project , we found that a trans...	2010
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "community ecology", "ecological metrics", "ecology and environmental sciences", "ecological niches", "species diversity", "ecology", "species delimitation", "phenotypes", "speciation", "genetics", "biology and life sciences", "theoretical ecology", "evolutionary biology", "biodiversity", ...	Eco-evolutionary Model of Rapid Phenotypic Diversification in Species-Rich Communities	journal.pcbi.1005139	null	[ [ "Community ecology studies how the relationships among species and their environments affect biological diversity and its distribution , usually neglecting phenotypic , genetic and evolutionary changes [1–3] .", "In contrast , evolutionary biology focuses on genetic shifts , variation , differentiation , ...	[ "Evolutionary and ecosystem dynamics are often treated as different processes –operating at separate timescales– even if evidence reveals that rapid evolutionary changes can feed back into ecological interactions .", "A recent long-term field experiment has explicitly shown that communities of competing plant spe...	[ "Population ecology and evolutionary biology have been traditionally studied as separate disciplines , even if feedbacks between community and evolutionary processes are known to exist , having been empirically characterized in recent years in different types of communities ( from microbes to plants and vertebrates...	2016
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "transposons", "genomics", "molecular cell biology", "plant science", "genome evolution", "plant evolution", "plant biology", "plant genomics", "biology", "computational biology", "epigenomics", "molecular biology", "genetics and genomics" ]	Transposon Variants and Their Effects on Gene Expression in Arabidopsis	journal.pgen.1003255	null	[ [ "While transposable elements ( TEs ) constitute a large fraction of plant , animal and human genomes [1]–[3] , their contribution to genome size can change rapidly during evolutionary time .", "In some taxa , TEs have been responsible for two-fold differences in genome size that arose over a few million y...	[ "Transposable elements ( TEs ) make up the majority of many plant genomes .", "Their transcription and transposition is controlled through siRNAs and epigenetic marks including DNA methylation .", "To dissect the interplay of siRNA–mediated regulation and TE evolution , and to examine how TE differences affect ...	[ "Transposable elements ( TEs ) are selfish DNA sequences .", "Together with their immobilized derivatives , they account for a large fraction of eukaryotic genomes .", "TEs can affect nearby gene activity , either directly by disrupting regulatory sequences or indirectly through the host mechanisms used to prev...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "molecular biology/histone modification", "molecular biology/rna-protein interactions", "molecular biology/centromeres", "molecular biology/chromosome structure", "genetics and genomics/chromosome biology", "genetics and genomics/epigenetics", "molecular biology/chromatin structure" ]	Continuous Requirement for the Clr4 Complex But Not RNAi for Centromeric Heterochromatin Assembly in Fission Yeast Harboring a Disrupted RITS Complex	journal.pgen.1001174	null	[ [ "Eukaryotic genomes are characterized by domains of transcriptionally permissive euchromatin and relatively transcriptionally inert heterochromatin .", "In addition to its important role in transcriptional regulation , heterochromatin plays a critical role in the regulation of genomic stability .", "I...	[ "Formation of centromeric heterochromatin in fission yeast requires the combined action of chromatin modifying enzymes and small RNAs derived from centromeric transcripts .", "Positive feedback mechanisms that link the RNAi pathway and the Clr4/Suv39h1 histone H3K9 methyltransferase complex ( Clr-C ) result in re...	[ "Centromeres are the chromosomal regions that promote chromosome movement during cell division .", "They consist of repetitive DNA sequences that are packaged into heterochromatin .", "Disruption of centromeric heterochromatin leads to chromosome loss that can result in miscarriages and genetic disorders .", ...	2010
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "model organisms", "cell biology", "evolutionary biology", "genetics", "biology and life sciences", "immunology", "microbiology", "molecular cell biology", "research and analysis methods" ]	Toxoplasma Effector MAF1 Mediates Recruitment of Host Mitochondria and Impacts the Host Response	journal.pbio.1001845	The intracellular human protozoan parasite Toxoplasma gondii uses a novel secreted protein to recruit host mitochondria and alter the host's response to infection.	[ [ "Mitochondria are highly dynamic organelles that , besides producing energy and regulating apoptotic and Ca2+ signals , play a key role in orchestrating several aspects of cell function and behavior including autophagy , apoptosis , and immune signaling [1]–[3] .", "Interestingly , recent evidence indicat...	[ "Recent information has revealed the functional diversity and importance of mitochondria in many cellular processes including orchestrating the innate immune response .", "Intriguingly , several infectious agents , such as Toxoplasma , Legionella , and Chlamydia , have been reported to grow within vacuoles surrou...	[ "Recent discoveries have revealed the remarkable functional diversity of mitochondria in roles other than energy production , including an integral role for mitochondria and their dynamics in the regulation of the innate immune response .", "Interestingly , host mitochondria are recruited to the membranes that su...	2014
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "medicine and health sciences", "pathology and laboratory medicine", "statistics", "laryngology", "metaanalysis", "tropical diseases", "parasitic diseases", "headaches", "dysphagia", "physiological processes", "mathematics", "signs and symptoms", "pharmaceutics", "neglected tropical diseas...	Isosorbide and nifedipine for Chagas' megaesophagus: A systematic review and meta-analysis	journal.pntd.0006836	null	[ [ "Chagas disease , also known as American trypanosomiasis , is an infectious zoonosis caused by the protozoan parasite Trypanosoma cruzi .", "Once confined to Latin America , it has now spread to other continents .", "It is estimated that about 6 to 8 million people are infected worldwide .", "Infe...	[ "Chagas disease is a neglected tropical disease .", "About 6 to 8 million people are chronically infected and 10% to 15% develop irreversible gastrointestinal disorders , including megaesophagus .", "Treatment focuses on improving symptoms , and isosorbide and nifedipine may be used for this purpose .", "We c...	[ "Chagas disease is a chronic neglected tropical disease that has increased in prevalence in the last decade .", "About 10% of chronically infected patients develop the digestive form of the disease .", "Megaesophagus is a common manifestation , and symptoms include difficulty or discomfort in swallowing and reg...	2018
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "united states", "livestock", "medicine and health sciences", "immunology", "tropical diseases", "geographical locations", "india", "brucellosis", "north america", "preventive medicine", "bacterial diseases", "vaccines", "neglected tropical diseases", "infectious disease control", "vacci...	Cost-benefit analysis of intervention policies for prevention and control of brucellosis in India	journal.pntd.0006488	null	[ [ "Brucellosis is an important zoonotic disease causing infertility , repeat breeding , retention of placenta and abortion in cattle .", "Humans in contact with animals usually get infected by coming in direct or indirect contact with reproductive secretions and excretions from infected animals .", "The...	[ "Brucellosis is endemic in the bovine population in India and causes a loss of US$ 3·4 billion to the livestock industry besides having a significant human health impact .", "We developed a stochastic simulation model to estimate the impact of three alternative vaccination strategies on the prevalence of Brucella...	[ "Brucellosis is an endemic zoonosis in India and recent studies demonstrate that the disease results in a median loss of US$ 3 . 43 billion in livestock populations .", "Lack of resources to compensate farmers and a ban on cow slaughter means that test and slaughter policy to control brucellosis cannot be impleme...	2018
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "death rates", "neonatology", "children", "medicine and health sciences", "maternal health", "immunology", "tropical diseases", "health care", "pediatrics", "preventive medicine", "bacterial diseases", "age groups", "women's health", "infants", "neglected tropical diseases", "populatio...	Risk factors for diagnosed noma in northwest Nigeria: A case-control study, 2017	journal.pntd.0006631	null	[ [ "Noma or cancrum oris , is a poorly understood , rapidly progressing gangrenous infection of the oral cavity , associated with a high mortality rate [1] .", "It mostly affects children under the age of five years [2] .", "It is estimated that up to 90% of noma cases die [3] , and those who survive hav...	[ "Noma ( cancrum oris ) , a neglected tropical disease , rapidly disintegrates the hard and soft tissue of the face and leads to severe disfiguration and high mortality .", "The disease is poorly understood .", "We aimed to estimate risk factors for diagnosed noma to better guide existing prevention and treatmen...	[ "Noma or cancrum oris is an orofacial gangrene that rapidly disintegrates the hard and soft tissue of the face .", "Little is known about noma as most cases live in underserved , difficult to reach locations .", "There is a dearth of literature on the risk factors for the development of noma .", "Médecins San...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "immunology/antigen processing and recognition", "immunology/immunomodulation", "virology/animal models of infection", "virology", "virology/immune evasion", "molecular biology/translational regulation" ]	Signal Peptide-Dependent Inhibition of MHC Class I Heavy Chain Translation by Rhesus Cytomegalovirus	journal.ppat.1000150	null	[ [ "Human cytomegalovirus ( HCMV ) is a widespread pathogen which is mostly asymptomatic in immune competent individuals , but pathogenic in the immune compromised such as post-transplant or AIDS patients [1] .", "Following primary infection , HCMV establishes a latent infection for life which is largely con...	[ "The US2-11 region of human and rhesus cytomegalovirus encodes a conserved family of glycoproteins that inhibit MHC-I assembly with viral peptides , thus preventing cytotoxic T cell recognition .", "Since HCMV lacking US2-11 is no longer able to block assembly and transport of MHC-I , we examined whether this is ...	[ "To avoid immune detection by cytotoxic T lymphocytes , viruses interfere with antigen presentation by major histocompatibility complex class I ( MHC-I ) molecules .", "We have discovered a unique cytomegaloviral protein that interferes with the biosynthesis of MHC-I heavy chains and was thus termed viral inhibit...	2008
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "genome-wide association studies", "plant anatomy", "ecology and environmental sciences", "medicine and health sciences", "integumentary system", "quantitative trait loci", "plant physiology", "genetic mapping", "plant science", "genome analysis", "crops", "plant pathology", "plant ecology",...	A cation diffusion facilitator, GmCDF1, negatively regulates salt tolerance in soybean	journal.pgen.1007798	null	[ [ "Soil salinity is a global ecological issue that has severely affected plant growth and development and decreased agricultural production .", "A high-salt environment causes various damages to crops , such as plant water loss , high osmotic stress , and homeostasis and ion imbalances in plant cells [1 , 2...	[ "Salt stress is one of the major abiotic factors that affect the metabolism , growth and development of plants , and soybean [Glycine max ( L . ) Merr . ] germination is sensitive to salt stress .", "Thus , to ensure the successful establishment and productivity of soybeans in saline soil , the genetic mechanisms...	[ "Soil salinity can seriously threaten soybean growth and development and seed germination is a key phase in the soybean growth cycle .", "Thus , understanding the genetic mechanism of salt tolerance at the germination stage is very important for improving the salt tolerance of soybean at the germination stage .",...	2019
[ "Introduction", "Results and discussion", "Materials and methods" ]	[ "geologic time", "population genetics", "geographical locations", "social sciences", "ethnicities", "archaeology", "effective population size", "geology", "genome analysis", "mesolithic period", "paleontology", "paleogenetics", "population biology", "europe", "genomic libraries", "geno...	Population genomics of Mesolithic Scandinavia: Investigating early postglacial migration routes and high-latitude adaptation	journal.pbio.2003703	null	[ [ "As the ice sheet retracted from northern Europe after the Last Glacial Maximum ( LGM ) , around 23 , 000 years ago , new habitable areas emerged [1] , allowing plants [2 , 3] and animals [4 , 5] to recolonize the Scandinavian peninsula ( hereafter referred to as Scandinavia ) .", "There is consistent evi...	[ "Scandinavia was one of the last geographic areas in Europe to become habitable for humans after the Last Glacial Maximum ( LGM ) .", "However , the routes and genetic composition of these postglacial migrants remain unclear .", "We sequenced the genomes , up to 57× coverage , of seven hunter-gatherers excavate...	[ "The Scandinavian peninsula was the last part of Europe to be colonized after the Last Glacial Maximum .", "The migration routes , cultural networks , and the genetic makeup of the first Scandinavians remain elusive and several hypotheses exist based on archaeology , climate modeling , and genetics .", "By anal...	2018
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "medicine and health sciences", "microbial mutation", "immune physiology", "pathology and laboratory medicine", "hepacivirus", "pathogens", "immunology", "microbiology", "viral structure", "viruses", "mutation", "substitution mutation", "rna viruses", "immunoprecipitation", "mutation dat...	Applying antibody-sensitive hypervariable region 1-deleted hepatitis C virus to the study of escape pathways of neutralizing human monoclonal antibody AR5A	journal.ppat.1006214	null	[ [ "About 150 million people are chronically infected with hepatitis C virus ( HCV ) with an increased risk of developing end-stage liver diseases , including cirrhosis and hepatocellular carcinoma [1–3] .", "Until recently , the treatment against HCV consisted of interferon and ribavirin but its efficacy wa...	[ "Hepatitis C virus ( HCV ) is a major cause of end-stage liver diseases .", "With 3–4 million new HCV infections yearly , a vaccine is urgently needed .", "A better understanding of virus escape from neutralizing antibodies and their corresponding epitopes are important for this effort .", "However , for vira...	[ "Worldwide hepatitis C virus ( HCV ) is one of the leading causes of chronic liver diseases , including cirrhosis and cancer .", "Treatment accessibility is limited and development of a preventive vaccine has proven difficult , partly due to the high mutation rate of the virus .", "Recent studies of HCV antibod...	2017
[ "Introduction", "Methods", "Results", "Discussion" ]	[]	On-Chip Imaging of Schistosoma haematobium Eggs in Urine for Diagnosis by Computer Vision	journal.pntd.0002547	null	[ [ "Microbiological diagnostics at the basic levels of the health care system has to meet the challenges of harsh environmental conditions , inadequately trained personnel and difficulties to maintain routines for quality assurance .", "There is a widespread failure to understand that diagnosis is essential ...	[ "Microscopy , being relatively easy to perform at low cost , is the universal diagnostic method for detection of most globally important parasitic infections .", "As quality control is hard to maintain , misdiagnosis is common , which affects both estimates of parasite burdens and patient care .", "Novel techni...	[ "There is a need to develop diagnostic methods for parasitic infections specifically designed for use in resource-deficient situations .", "Worm infections are common in many poor countries and even if repeated treatment can be arranged at low cost , diagnostics and identification of treatment failures demand res...	2013
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "genomics", "genome evolution", "biology", "computational biology" ]	Global Patterns of Protein Domain Gain and Loss in Superkingdoms	journal.pcbi.1003452	null	[ [ "Proteins are biologically active molecules that perform a wide variety of functions in cells .", "They are involved in catalytic activities ( e . g . enzymes ) , cell-to-cell signaling ( hormones ) , immune response initiation against invading pathogens ( antibodies ) , decoding genetic information ( tra...	[ "Domains are modules within proteins that can fold and function independently and are evolutionarily conserved .", "Here we compared the usage and distribution of protein domain families in the free-living proteomes of Archaea , Bacteria and Eukarya and reconstructed species phylogenies while tracing the history ...	[ "Proteins are made up of well-packed structural units referred to as domains .", "Domain structure in proteins is responsible for protein function and is evolutionarily conserved .", "Here we report global patterns of protein domain gain and loss in the three superkingdoms of life .", "We reconstructed phylog...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genome-wide association studies", "animal genetics", "genetic mutation", "gene function", "animal models", "genome sequencing", "developmental biology", "model organisms", "mutation types", "skeletal development", "morphogenesis", "biology", "zebrafish", "genetics", "genomics", "genet...	Variation of BMP3 Contributes to Dog Breed Skull Diversity	journal.pgen.1002849	null	[ [ "Canine skull shape variation among dog breeds is in large part a human-created phenomenon , occurring through artificial selection and consolidation of desired traits .", "Morphological distinction between wolves and dogs dates as far back as 31 , 000 years ago [1] , [2] .", "Changes in skull shape a...	[ "Since the beginnings of domestication , the craniofacial architecture of the domestic dog has morphed and radiated to human whims .", "By beginning to define the genetic underpinnings of breed skull shapes , we can elucidate mechanisms of morphological diversification while presenting a framework for understandi...	[ "As a result of selective breeding practices , modern dogs display a multitude of head shapes .", "Breeds such as the Pug and Bulldog popularize one of these morphologies , termed “brachycephaly . ”", "A short , upward-pointing snout , a massive and rounded head , and an underbite typify brachycephalic breeds ....	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "action potentials", "medicine and health sciences", "neural networks", "prefrontal cortex", "membrane potential", "brain", "electrophysiology", "neuroscience", "ganglion cells", "network analysis", "interneurons", "computer and information sciences", "animal cells", "cellular neuroscience...	A Detailed Data-Driven Network Model of Prefrontal Cortex Reproduces Key Features of In Vivo Activity	journal.pcbi.1004930	null	[ [ "The prefrontal cortex ( PFC ) is a key structure in higher-level cognitive functions , including working memory , rule and concept representation and behavioral flexibility [1–6] , and has been linked to impairments of these functions in psychiatric disorders like schizophrenia [7–10] or attention-deficit/hy...	[ "The prefrontal cortex is centrally involved in a wide range of cognitive functions and their impairment in psychiatric disorders .", "Yet , the computational principles that govern the dynamics of prefrontal neural networks , and link their physiological , biochemical and anatomical properties to cognitive funct...	[ "Computational network models are an important tool for linking physiological and neuro-dynamical processes to cognition .", "However , harvesting network models for this purpose may less depend on how much biophysical detail is included , but more on how well the model can capture the functional network physiolo...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Systems Modeling of Anti-apoptotic Pathways in Prostate Cancer: Psychological Stress Triggers a Synergism Pattern Switch in Drug Combination Therapy	journal.pcbi.1003358	null	[ [ "Psychological stress has been implicated in cancer for almost 2 millennia .", "It has been observed that psychological stress may contribute to cancer initiation and progression [1] , [2] .", "However , the causal relationship between stress and cancer remains poorly understood [3] , largely because ...	[ "Prostate cancer patients often have increased levels of psychological stress or anxiety , but the molecular mechanisms underlying the interaction between psychological stress and prostate cancer as well as therapy resistance have been rarely studied and remain poorly understood .", "Recent reports show that stre...	[ "Psychological stress and anxiety are often experienced by prostate cancer patients , but the underlying mechanisms of interactions between psychological stress and cancer development , as well as drug resistance , are unclear .", "Here , we employed a systems biology approach to study interactions between stress...	2013
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "cancer genomics", "medicine and health sciences", "cancer genetics", "cell cycle and cell division", "cell processes", "basic cancer research", "oncology", "mutation", "probability distribution", "mathematics", "computer and information sciences", "probability theory", "carcinogenesis", "...	On measuring selection in cancer from subclonal mutation frequencies	journal.pcbi.1007368	null	[ [ "Darwinian evolution in cancer has been the subject of intense research in the past decade .", "In particular , the problem of distinguishing driver mutations that carry a selective advantage from passenger mutations , and their role in shaping intra-tumor genetic heterogeneity has come to the fore [1–5] ...	[ "Recently available cancer sequencing data have revealed a complex view of the cancer genome containing a multitude of mutations , including drivers responsible for cancer progression and neutral passengers .", "Measuring selection in cancer and distinguishing drivers from passengers have important implications f...	[ "Darwinian evolution in cancer is responsible for the emergence of malignant traits in initially benign tumors .", "As tumor cells divide , they accumulate new mutations and while most of them are “passengers” which do not confer any selective growth advantage , “driver” mutations endow cells with traits that con...	2019
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "public health", "medicine", "infectious diseases", "schistosomiasis", "public health and epidemiology", "mathematics", "statistics", "biostatistics", "child health", "parasitic diseases" ]	Multiple Category-Lot Quality Assurance Sampling: A New Classification System with Application to Schistosomiasis Control	journal.pntd.0001806	null	[ [ "Schistosomiasis is a tropical disease caused by infection with Schistosoma parasitic worms .", "The disease burden of schistosomiasis is greatest in sub-Saharan Africa ( SSA ) which shoulders 85% of the global burden [1] , [2] , with school-age children as well as adolescent girls and women of childbeari...	[ "Originally a binary classifier , Lot Quality Assurance Sampling ( LQAS ) has proven to be a useful tool for classification of the prevalence of Schistosoma mansoni into multiple categories ( ≤10% , >10 and <50% , ≥50% ) , and semi-curtailed sampling has been shown to effectively reduce the number of observations n...	[ "The control of schistosomiasis calls for rapid and reliable classification tools .", "This study evaluates the performance of one such tool , Lot Quality Assurance Sampling ( LQAS ) for assessing the prevalence of S . mansoni in African schoolchildren .", "We outline the design considerations and introduce nov...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine", "infectious diseases" ]	Functional Analysis of Host Factors that Mediate the Intracellular Lifestyle of Cryptococcus neoformans	journal.ppat.1002078	null	[ [ "Over the past half-century , Cryptococcus neoformans ( Cn ) , an opportunistic encapsulated yeast , has emerged as the major causative agent of fungal meningoencephalitis in humans and animals worldwide [1] , [2] .", "The pathogen is found in a variety of environmental niches , including soil , vegetatio...	[ "Cryptococcus neoformans ( Cn ) , the major causative agent of human fungal meningoencephalitis , replicates within phagolysosomes of infected host cells .", "Despite more than a half-century of investigation into host-Cn interactions , host factors that mediate infection by this fungal pathogen remain obscure ."...	[ "Cryptococcus neoformans is a facultative intracellular fungal pathogen that causes cryptococcosis in both immunocompromised and immunocompetent individuals worldwide .", "Initial infection usually occurs in the lungs , but the fungus can disseminate to other organs .", "The pathogen shows a predilection to the...	2011
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Discovery of Transcription Factors and Regulatory Regions Driving In Vivo Tumor Development by ATAC-seq and FAIRE-seq Open Chromatin Profiling	journal.pgen.1004994	null	[ [ "Gene expression in higher eukaryotes is tightly controlled by complex cis-regulatory systems consisting of multiple enhancers modulating the transcription levels of a target gene .", "Mapping all active promoters and enhancers in a cell type provides an entry point to reverse engineer the functional gene...	[ "Genomic enhancers regulate spatio-temporal gene expression by recruiting specific combinations of transcription factors ( TFs ) .", "When TFs are bound to active regulatory regions , they displace canonical nucleosomes , making these regions biochemically detectable as nucleosome-depleted regions or accessible/o...	[ "The functional expression of all genes is regulated by proteins , namely transcription factors that bind to specific areas of DNA known as regulatory regions .", "Whereas most DNA in our genome is normally bound by other proteins ( histones ) and packaged into units called nucleosomes , a specific subset of tiss...	2015
[ "Introduction", "Results and discussion", "Methods" ]	[ "biotechnology", "taxonomy", "population genetics", "brassica", "mutation", "phylogenetics", "data management", "model organisms", "substitution mutation", "plant science", "methylation", "phylogenetic analysis", "experimental organism systems", "genome analysis", "plant genomics", "ge...	The rate and potential relevance of new mutations in a colonizing plant lineage	journal.pgen.1007155	null	[ [ "Colonizing or invasive populations sampled through time [1 , 2] constitute “natural experiments” where it is possible to study evolutionary processes in action [3] .", "Colonizations , which are dramatically increasing in number [4 , 5] , sometimes are characterized by strong bottlenecks and genetic isol...	[ "By following the evolution of populations that are initially genetically homogeneous , much can be learned about core biological principles .", "For example , it allows for detailed studies of the rate of emergence of de novo mutations and their change in frequency due to drift and selection .", "Unfortunately...	[ "A consequence of an increasingly interconnected world is the spread of species outside their native range—a phenomenon with potentially dramatic impacts on ecosystem services .", "Using population genomics , we can robustly infer dynamics of colonization and successful population establishment .", "We have com...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Bank Vole Prion Protein As an Apparently Universal Substrate for RT-QuIC-Based Detection and Discrimination of Prion Strains	journal.ppat.1004983	null	[ [ "Prion diseases , or transmissible spongiform encephalopathies , are neurodegenerative disorders that include Creutzfeldt-Jakob disease ( CJD ) , Gerstmann-Straussler-Scheincker syndrome ( GSS ) , fatal familial insomnia ( FFI ) and sporadic fatal insomnia ( sFI ) in humans , bovine spongiform encephalopathy ...	[ "Prions propagate as multiple strains in a wide variety of mammalian species .", "The detection of all such strains by a single ultrasensitive assay such as Real Time Quaking-induced Conversion ( RT-QuIC ) would facilitate prion disease diagnosis , surveillance and research .", "Previous studies have shown that...	[ "Prion diseases are neurodegenerative disorders that propagate as multiple strains in a variety of mammalian species .", "The detection of all such prion types by a single ultrasensitive assay , such as the Real Time Quaking-induced Conversion ( RT-QuIC ) assay , would facilitate prion disease diagnosis , surveil...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "neuroscience", "physiology" ]	Complex Events Initiated by Individual Spikes in the Human Cerebral Cortex	journal.pbio.0060222	A novel study on connections between human neurons reveals that single spikes in pyramidal cells can activate synchronously timed assemblies through strong connections linking pyramidal cells with inhibitory and excitatory GABAergic neurons.	[ [ "Functional characterization of microcircuits of the cerebral cortex of rodents , carnivores , and to some extent , monkeys has been propelled by simultaneous multiple recordings from synaptically connected neurons combined with anatomical and molecular analysis of the recorded cells providing direct experime...	[ "Synaptic interactions between neurons of the human cerebral cortex were not directly studied to date .", "We recorded the first dataset , to our knowledge , on the synaptic effect of identified human pyramidal cells on various types of postsynaptic neurons and reveal complex events triggered by individual action...	[ "We recorded the first connections , to our knowledge , between human nerve cells and reveal that a subset of interactions is so strong that some presynaptic cells are capable of eliciting action potentials in the postsynaptic target neurons .", "Interestingly , these strong connections selectively link pyramidal...	2008
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "antimicrobials", "medicine and health sciences", "body fluids", "pathology and laboratory medicine", "cell cycle and cell division", "drugs", "immunology", "bile", "cell processes", "light microscopy", "microbiology", "salmonellosis", "animal models", "bacterial diseases", "mutation", ...	Tat-exported peptidoglycan amidase-dependent cell division contributes to Salmonella Typhimurium fitness in the inflamed gut	journal.ppat.1007391	null	[ [ "Protein translocation constitutes an essential cell function in all types of prokaryotic or eukaryotic cells .", "Accordingly , bacteria have evolved several sophisticated translocation systems to transport proteins into , or across , the cytoplasmic membrane .", "In particular , for bacterial pathog...	[ "Salmonella enterica serovar Typhimurium ( S . Tm ) is a cause of food poisoning accompanied with gut inflammation .", "Although mucosal inflammation is generally thought to be protective against bacterial infection , S . Tm exploits the inflammation to compete with commensal microbiota , thereby growing up to hi...	[ "For proteins residing outside the bacterial cytoplasm , transport is an essential step for adequate function .", "The twin-arginine translocation ( Tat ) system enables the transport of folded proteins across the cytoplasmic membrane in prokaryotes .", "It has recently become clear that this system plays a piv...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "computational biology/molecular dynamics", "biochemistry/membrane proteins and energy transduction", "cardiovascular disorders", "biophysics/membrane proteins and energy transduction" ]	A Structural Model of the Pore-Forming Region of the Skeletal Muscle Ryanodine Receptor (RyR1)	journal.pcbi.1000367	null	[ [ "Muscle contraction upon excitation by nerve impulse is initiated by a rapid rise in cytoplasmic Ca2+ .", "In skeletal muscle , the rise in cytoplasmic Ca2+ is brought about by the opening of the ryanodine receptor ( RyR1 ) , which releases Ca2+ from intracellular stores [1] , [2] .", "RyRs are large ...	[ "Ryanodine receptors ( RyRs ) are ion channels that regulate muscle contraction by releasing calcium ions from intracellular stores into the cytoplasm .", "Mutations in skeletal muscle RyR ( RyR1 ) give rise to congenital diseases such as central core disease .", "The absence of high-resolution structures of Ry...	[ "Ryanodine receptors ( RyRs ) are ion channels present in the membranes of an intracellular calcium storage organelle , the sarcoplasmic reticulum .", "Nerve impulse triggers the opening of RyR channels , thus increasing the cytoplasmic calcium levels , which subsequently leads to muscle contraction .", "Congen...	2009
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "medicine", "protein interactions", "influenza", "signaling pathways", "alzheimer disease", "infectious diseases", "proteins", "regulatory networks", "biology", "dementia", "systems biology", "biochemistry", "signal transduction", "neurological disorders", "neurology", "viral diseases"...	Adding Protein Context to the Human Protein-Protein Interaction Network to Reveal Meaningful Interactions	journal.pcbi.1002860	null	[ [ "The advent of high-throughput techniques to measure and perturb molecular species in a systematic way has enabled researchers to assess the different layers of cellular metabolism under different experimental conditions .", "Protein-protein interaction ( PPI ) networks created by a variety of methods inc...	[ "Interactions of proteins regulate signaling , catalysis , gene expression and many other cellular functions .", "Therefore , characterizing the entire human interactome is a key effort in current proteomics research .", "This challenge is complicated by the dynamic nature of protein-protein interactions ( PPIs...	[ "Protein-protein-interactions ( PPIs ) participate in virtually all biological processes .", "However , the PPI map is not static but the pairs of proteins that interact depends on the type of cell , the subcellular localization and modifications of the participating proteins , among many other factors .", "The...	2013
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "plant biology/plant-biotic interactions", "virology/host antiviral responses" ]	Structural and Functional Analysis of Viral siRNAs	journal.ppat.1000838	null	[ [ "The RNA silencing based antiviral plant response is one of the best studied antiviral strategies in plants .", "The key element of RNA silencing based antiviral strategies is the virus derived small interfering RNA ( vsiRNA ) , which guides the RNA induced silencing complex ( RISC ) to target viral genom...	[ "A large amount of short interfering RNA ( vsiRNA ) is generated from plant viruses during infection , but the function , structure and biogenesis of these is not understood .", "We profiled vsiRNAs using two different high-throughput sequencing platforms and also developed a hybridisation based array approach ."...	[ "Viral RNA is processed into short RNAs in plants , which guide a complex to the viral RNA and cause cleavage of the viral RNA .", "We profiled Cymbidium ringspot virus ( CymRSV ) derived short RNAs using three different methods .", "Profiling of viral short interfering RNAs revealed a different sequence bias f...	2010
[ "Introduction", "Results", "Discussion", "" ]	[ "animal models", "molecular neuroscience", "neurobiology of disease and regeneration", "drosophila melanogaster", "model organisms", "genetics", "signaling pathways", "biology", "neuroscience", "learning and memory", "genetics and genomics" ]	The Receptor Tyrosine Kinase Alk Controls Neurofibromin Functions in Drosophila Growth and Learning	journal.pgen.1002281	null	[ [ "Receptor Tyrosine Kinases ( RTKs ) are transmembrane proteins with intrinsic kinase activity directed in part towards tyrosine residues within their own carboxy-terminal tails .", "They play pivotal roles in most tissues , including the central nervous system ( CNS ) , by transducing extracellular ligand...	[ "Anaplastic Lymphoma Kinase ( Alk ) is a Receptor Tyrosine Kinase ( RTK ) activated in several cancers , but with largely unknown physiological functions .", "We report two unexpected roles for the Drosophila ortholog dAlk , in body size determination and associative learning .", "Remarkably , reducing neuronal...	[ "Neurofibromatosis-1 ( NF1 ) syndrome is a common ( 1/3 , 000 births ) genetic disorder affecting multiple organ systems , including the nervous system .", "Its clinical features include short stature , learning disabilities , and several types of benign and malignant tumors .", "NF1 is caused by mutations that...	2011
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "developmental biology/cell differentiation", "cell biology/cell growth and division" ]	Daughter-Specific Transcription Factors Regulate Cell Size Control in Budding Yeast	journal.pbio.1000221	The asymmetric localization of cell fate determinants results in asymmetric cell cycle control in budding yeast.	[ [ "At the Start transition in G1 , budding yeast cells integrate internal and external cues into an all-or-none commitment to a new round of cell division [1] , [2] .", "Cell division is asymmetric , producing a smaller daughter cell and a larger mother cell [3] .", "Mother cells progress through Start ...	[ "In budding yeast , asymmetric cell division yields a larger mother and a smaller daughter cell , which transcribe different genes due to the daughter-specific transcription factors Ace2 and Ash1 .", "Cell size control at the Start checkpoint has long been considered to be a main regulator of the length of the G1...	[ "Asymmetric cell division is a universal mechanism for generating differentiated cells .", "The progeny of such divisions can often display differential cell cycle regulation .", "This study addresses how differential regulation of gene expression in the progeny of a single division can alter cell cycle control...	2009
[ "Introduction", "Results and Discussion", "Materials and Methods" ]	[]	Super-Resolution Imaging of ESCRT-Proteins at HIV-1 Assembly Sites	journal.ppat.1004677	null	[ [ "The budding of HIV-1 at the plasma membrane of a virus-producing cell relies on recruitment of , and interaction with , various host cell factors .", "Initial viral bud formation is primarily induced by assembly of plasma membrane associated Gag molecules into a hexagonal lattice that attains an outward ...	[ "The cellular endosomal sorting complex required for transport ( ESCRT ) machinery is involved in membrane budding processes , such as multivesicular biogenesis and cytokinesis .", "In HIV-infected cells , HIV-1 hijacks the ESCRT machinery to drive HIV release .", "Early in the HIV-1 assembly process , the ESCR...	[ "Viruses hijack the cellular machinery to complete their life cycle .", "In the case of HIV-1 , the endosomal sorting complex required for transport ( ESCRT ) is recruited by nascent viruses to release themselves from infected cells .", "Currently , there has been an intense amount of research on how the ESCRT ...	2015
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[]	Expression of Trypanosoma brucei gambiense Antigens in Leishmania tarentolae. Potential for Use in Rapid Serodiagnostic Tests (RDTs)	journal.pntd.0004271	null	[ [ "Human African Trypanosomiasis ( HAT ) , also known as African sleeping sickness , is usually a fatal disease caused by the parasites Trypanosoma brucei gambiense ( T . b . gambiense ) or T . b . rhodesiense [1–3] .", "The parasite is transmitted by the bite of infected tsetse flies in sub-Saharan Africa ...	[ "The development of rapid serodiagnostic tests for sleeping sickness and other diseases caused by kinetoplastids relies on the affordable production of parasite-specific recombinant antigens .", "Here , we describe the production of recombinant antigens from Trypanosoma brucei gambiense ( T . b . gambiense ) in t...	[ "The development of rapid serodiagnostic tests for African sleeping sickness and other diseases caused by kinetoplastids relies in part on the affordable production of parasite-specific recombinant antigens .", "The majority of cases of sleeping sickness are caused by the parasite Trypanosoma brucei gambiense ( T...	2015
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "medicine and health sciences", "neutron scattering", "pathology and laboratory medicine", "particle physics", "pathogens", "bacillus", "microbiology", "prokaryotic models", "experimental organism systems", "lipid structure", "molecular biology techniques", "cellular structures and organelles"...	The in vivo structure of biological membranes and evidence for lipid domains	journal.pbio.2002214	null	[ [ "Because of the inherent complexity of living cells , high-resolution analytical methods are generally used ex vivo , and many depend on labels to differentiate the species of interest .", "In the case of cellular membranes , their nanoscopic structure ( ultrastructure ) has been elucidated primarily thro...	[ "Examining the fundamental structure and processes of living cells at the nanoscale poses a unique analytical challenge , as cells are dynamic , chemically diverse , and fragile .", "A case in point is the cell membrane , which is too small to be seen directly with optical microscopy and provides little observati...	[ "The structure and organization of the cell membrane are central to many biological functions , and although they have been extensively studied , there is still much that we don’t understand .", "A wealth of detailed information has been obtained from studies of model lipid membranes .", "However , these system...	2017
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "blood cells", "hiv infections", "medicine and health sciences", "immune cells", "pathology and laboratory medicine", "pathogens", "immunology", "microbiology", "retroviruses", "viruses", "immunodeficiency viruses", "lymph nodes", "rna viruses", "lymphatic system", "cytotoxic t cells", ...	Low levels of SIV-specific CD8+ T cells in germinal centers characterizes acute SIV infection	journal.ppat.1007311	null	[ [ "Most human immunodeficiency virus ( HIV ) -infected individuals fail to adequately control persistent high-level viral replication that results in gradual loss of CD4 T cells and ultimately AIDS in the absence of antiretroviral therapy ( ART ) .", "B cell follicles in secondary lymphoid tissues have been...	[ "CD8+ T cells play an important role in controlling of HIV and SIV infections .", "However , these cells are largely excluded from B cell follicles where HIV and SIV producing cells concentrate during chronic infection .", "It is not known , however , if antigen-specific CD8+ T cells are excluded gradually as p...	[ "A paucity of SIV-specific CD8+ T cells in lymphoid follicles and complete absence within most follicular germinal centers during early infection may set the stage for the establishment of persistent chronic infection ." ]	2019
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genome-wide association studies", "genetic polymorphism", "genetics", "population genetics", "biology", "human genetics", "genetics and genomics" ]	Predicting Signatures of “Synthetic Associations” and “Natural Associations” from Empirical Patterns of Human Genetic Variation	journal.pcbi.1002600	null	[ [ "Recent years have seen a plethora of genome-wide association studies ( GWAS ) finding thousands of common markers that are associated with hundreds of diseases and other traits .", "GWAS were initially founded on the Common Disease-Common Variant hypothesis [1]–[3] , which predicted that common complex d...	[ "Genome-wide association studies ( GWAS ) have in recent years discovered thousands of associated markers for hundreds of phenotypes .", "However , associated loci often only explain a relatively small fraction of heritability and the link between association and causality has yet to be uncovered for most loci ."...	[ "Genome-wide association studies ( GWAS ) , based on the hypothesis that common genetic variation underlies complex diseases , have found many sites in the genome associated with complex diseases .", "However , both the fraction of variation explained by these sites and the number of studies identifying causal va...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	GITR Intrinsically Sustains Early Type 1 and Late Follicular Helper CD4 T Cell Accumulation to Control a Chronic Viral Infection	journal.ppat.1004517	null	[ [ "During chronic viral infections , exemplified by the clone 13 variant of lymphocytic choriomeningitis virus ( LCMV cl 13 ) , persistent antigen presentation results in the functional exhaustion of the T cell response , characterized by persistent upregulation of inhibitory molecules and a progressive loss of...	[ "CD4 T cells are critical for control of persistent infections; however , the key signals that regulate CD4 T help during chronic infection remain incompletely defined .", "While several studies have addressed the role of inhibitory receptors and soluble factors such as PD-1 and IL-10 , significantly less work ha...	[ "The natural rodent pathogen LCMV clone 13 causes a persistent viral infection in mice and has successfully predicted several immunological factors that are relevant to human chronic viral infection such as HIV .", "LCMV clone 13 infection is ultimately controlled by cell-mediated and humoral immune responses by ...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "computational biology/systems biology" ]	Why Do Hubs in the Yeast Protein Interaction Network Tend To Be Essential: Reexamining the Connection between the Network Topology and Essentiality	journal.pcbi.1000140	null	[ [ "An intriguing question in the analysis of biological networks is whether biological characteristics of a protein , such as essentiality , can be explained by its placement in the network , i . e . , whether topological prominence implies biological importance .", "One of the first connections between the...	[ "The centrality-lethality rule , which notes that high-degree nodes in a protein interaction network tend to correspond to proteins that are essential , suggests that the topological prominence of a protein in a protein interaction network may be a good predictor of its biological importance .", "Even though the ...	[ "Analysis of protein interaction networks in the budding yeast Saccharomyces cerevisiae has revealed that a small number of proteins , the so-called hubs , interact with a disproportionately large number of other proteins .", "Furthermore , many hub proteins have been shown to be essential for survival of the cel...	2008

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