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headings list	keywords list	title stringlengths 20 281	id stringlengths 20 20	toc stringlengths 57 522 ⌀	sections list	abstract list	summary list	year stringclasses 13 values
[ "Introduction", "Methods", "Results", "Discussion" ]	[]	Parasitism in Children Aged Three Years and Under: Relationship between Infection and Growth in Rural Coastal Kenya	journal.pntd.0003721	null	[ [ "Parasitic infections , which are among the most common infections worldwide , disproportionately affect children [1] .", "It is increasingly recognized that both protozoan and helminthic diseases are common among children under the age of five years .", "Of particular concern , their associated disea...	[ "Parasitic infections , which are among the most common infections worldwide , disproportionately affect children; however , little is known about the impact of parasitic disease on growth in very early childhood .", "Our objective was to document the prevalence of parasitic infections and examine their associati...	[ "Parasitic infections are extremely common worldwide and children are especially vulnerable to these infections during critical periods of growth and development .", "There is a paucity of information about how frequently very young children ( under the age of five years ) are infected with parasites and the effe...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods", "Supporting Information" ]	[ "none", "plant biology", "zea", "eukaryotes", "plants" ]	Laser Microdissection of Narrow Sheath Mutant Maize Uncovers Novel Gene Expression in the Shoot Apical Meristem	journal.pgen.0030101	null	[ [ "The paralogous WUSCHEL1-like homeobox ( WOX ) genes narrow sheath1 ( ns1 ) and narrow sheath2 ( ns2 ) function from two , lateral foci within the maize shoot apical meristem ( SAM ) ( Figure", "1 ) [1 , 2] , which comprises a pool of over 1 , 200 pluripotent cells that ultimately generates all lateral or...	[ "Microarrays enable comparative analyses of gene expression on a genomic scale , however these experiments frequently identify an abundance of differentially expressed genes such that it may be difficult to identify discrete functional networks that are hidden within large microarray datasets .", "Microarray anal...	[ "Unlike animals , plants exhibit a prolonged period of organogenesis , generating new leaves throughout their life cycle .", "This ability to maintain an embryo-like state is dependent upon the activity of shoot meristems , whose dual functions are to supply an inner core of pluripotent cells that sustain the sho...	2007
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[]	The histone chaperone HIRA promotes the induction of host innate immune defences in response to HSV-1 infection	journal.ppat.1007667	null	[ [ "The intrinsic , innate , and adaptive arms of host immunity cooperatively supress the replication and spread of invading viral pathogens .", "Conferred by constitutively expressed host factors , intrinsic immunity ( also known as intrinsic antiviral resistance and cell autonomous immunity ) restricts vir...	[ "Host innate immune defences play a critical role in restricting the intracellular propagation and pathogenesis of invading viral pathogens .", "Here we show that the histone H3 . 3 chaperone HIRA ( histone cell cycle regulator ) associates with promyelocytic leukaemia nuclear bodies ( PML-NBs ) to stimulate the ...	[ "Host innate immune defences play critical roles in the cellular restriction of invading viral pathogens and the stimulation of adaptive immune responses .", "A key component in the regulation of this arm of host immunity is the rapid induction of cytokine signalling and the expression of interferon stimulated ge...	2019
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "cell physiology", "medicine and health sciences", "body fluids", "pathology and laboratory medicine", "multiple sclerosis", "nervous system", "neurodegenerative diseases", "pathogens", "immunology", "tropical diseases", "microbiology", "cell metabolism", "viruses", "rabies", "demyelinat...	NMR metabolomics of cerebrospinal fluid differentiates inflammatory diseases of the central nervous system	journal.pntd.0007045	null	[ [ "Encephalomyelitis ( EM ) is a condition characterized by inflammation of the brain ( encephalitis ) and spinal cord ( myelitis ) that frequently causes permanent disability .", "There are myriad causes of EM syndromes , which are in aggregate relatively common [1–4] and include viral , bacterial , fungal...	[ "Myriad infectious and noninfectious causes of encephalomyelitis ( EM ) have similar clinical manifestations , presenting serious challenges to diagnosis and treatment .", "Metabolomics of cerebrospinal fluid ( CSF ) was explored as a method of differentiating among neurological diseases causing EM using a single...	[ "Inflammation of the brain and spinal cord , known as encephalomyelitis , is a dangerous condition that can be caused by a wide range of pathogens , such as viruses and bacteria , and other medical conditions including autoimmunity or drug intoxications .", "Given the many possible causes , it is often difficult ...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "primates", "viruses", "virology", "vertebrates", "animals", "mammals" ]	Functional Genomics Highlights Differential Induction of Antiviral Pathways in the Lungs of SARS-CoV–Infected Macaques	journal.ppat.0030112	null	[ [ "Infection with SARS-CoV causes lower respiratory tract disease with clinical symptoms that include fever , malaise , and lymphopenia [1] .", "Approximately 20%–30% of SARS patients require management in intensive care units , and the overall fatality rate has approached 10% .", "Interestingly , child...	[ "The pathogenesis of severe acute respiratory syndrome coronavirus ( SARS-CoV ) is likely mediated by disproportional immune responses and the ability of the virus to circumvent innate immunity .", "Using functional genomics , we analyzed early host responses to SARS-CoV infection in the lungs of adolescent cynom...	[ "Severe acute respiratory syndrome coronavirus ( SARS-CoV ) infection causes a progressive atypical pneumonia .", "In typical cases , largely confined to adult and elderly individuals , acute respiratory distress syndrome develops , and admission to an intensive care unit is required .", "Although these complic...	2007
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "nuclear import", "innate immune system", "medicine and health sciences", "coronaviruses", "immune physiology", "cytokines", "pathology and laboratory medicine", "respiratory infections", "pathogens", "cell processes", "immunology", "microbiology", "pulmonology", "viruses", "developmenta...	MERS-CoV 4b protein interferes with the NF-κB-dependent innate immune response during infection	journal.ppat.1006838	null	[ [ "Middle East respiratory syndrome coronavirus ( MERS-CoV ) is a human coronavirus that emerged in the Middle East in 2012 .", "Since then , 2100 confirmed cases and 730 deaths have been reported , with an estimated mortality rate of ~36% ( http://www . who . int/csr/don/10-november-2017-mers-oman/en/ ) ."...	[ "Middle East respiratory syndrome coronavirus ( MERS-CoV ) is a novel human coronavirus that emerged in 2012 , causing severe pneumonia and acute respiratory distress syndrome ( ARDS ) , with a case fatality rate of ~36% .", "When expressed in isolation , CoV accessory proteins have been shown to interfere with i...	[ "Middle East respiratory syndrome coronavirus ( MERS-CoV ) is a highly pathogenic human CoV that continues to cause lethal human infections , primarily in the Middle East .", "Virus accessory genes are potential contributors to pathology , possibly by interfering with the innate immune response .", "However , u...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "plant growth and development", "plant biology", "population genetics", "gene function", "plant science", "model organisms", "molecular genetics", "arabidopsis thaliana", "genetic polymorphism", "plant genetics", "biology", "evolutionary genetics", "plant and algal models", "plant evolutio...	Complex Evolutionary Events at a Tandem Cluster of Arabidopsis thaliana Genes Resulting in a Single-Locus Genetic Incompatibility	journal.pgen.1002164	null	[ [ "Both evolutionary biologists and breeders have long been interested in non-additive interactions among alleles at the same locus .", "For example , explanations for heterosis or hybrid vigor , a staple of modern agriculture , share many conceptual formalities with models proposed by Bateson , Dobzhansky ...	[ "Non-additive interactions between genomes have important implications , not only for practical applications such as breeding , but also for understanding evolution .", "In extreme cases , genes from different genomic backgrounds may be incompatible and compromise normal development or physiology .", "Of partic...	[ "While intraspecific hybrids are vitally important in modern agriculture because they often perform better than their inbred parents , certain hybrid combinations fail to develop normally and are inferior to their parents .", "We have identified an Arabidopsis thaliana hybrid with several aberrant growth phenotyp...	2011
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "sequencing techniques", "invertebrates", "parasite groups", "medicine and health sciences", "plasmodium", "population genetics", "tropical diseases", "geographical locations", "parasitic diseases", "animals", "parasitic protozoans", "parasitology", "apicomplexa", "protozoans", "molecula...	Evolution of the Transmission-Blocking Vaccine Candidates Pvs28 and Pvs25 in Plasmodium vivax: Geographic Differentiation and Evidence of Positive Selection	journal.pntd.0004786	null	[ [ "Transmission-blocking ( TB ) vaccines are considered an important tool for malaria control and elimination [1] .", "TB vaccines aim to disrupt malaria transmission by eliciting antibody mediated responses against antigens expressed during sexual or sporogonic stages of the parasite thereby inhibiting its...	[ "Transmission-blocking ( TB ) vaccines are considered an important tool for malaria control and elimination .", "Among all the antigens characterized as TB vaccines against Plasmodium vivax , the ookinete surface proteins Pvs28 and Pvs25 are leading candidates .", "These proteins likely originated by a gene dup...	[ "Plasmodium vivax is the most prevalent human malarial parasite outside Africa .", "The fact that patients can relapse due to the parasite dormant liver stages , among other biologic and epidemiologic characteristics of vivax malaria , facilitates the persistence of the disease in many endemic areas .", "These ...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Peptidoglycan Branched Stem Peptides Contribute to Streptococcus pneumoniae Virulence by Inhibiting Pneumolysin Release	journal.ppat.1004996	null	[ [ "Streptococcus pneumoniae ( the pneumococcus ) is a Gram-positive commensal of the human nasopharynx .", "Though asymptomatic , nasal carriage is considered a prerequisite for the establishment of invasive pneumococcal disease [1] .", "The pneumococcus is an extracellular pathogen that elaborates a mu...	[ "Streptococcus pneumoniae ( the pneumococcus ) colonizes the human nasopharynx and is a significant pathogen worldwide .", "Pneumolysin ( Ply ) is a multi-functional , extracellular virulence factor produced by this organism that is critical for pathogenesis .", "Despite the absence of any apparent secretion or...	[ "Pneumolysin ( Ply ) is a protein toxin produced by Streptococcus pneumoniae that contributes to the ability of this organism to cause invasive disease .", "Release of this protein from the bacterial cell is necessary for many of its functions but the underlying mechanisms driving this process are not well charac...	2015
[ "Introduction", "Materials and methods", "Results", "Discussion" ]	[ "taxonomy", "biogeography", "ecology and environmental sciences", "population genetics", "geographical locations", "biodiversity", "phylogenetics", "data management", "phylogenetic analysis", "population biology", "computer and information sciences", "geography", "south america", "ecosyste...	Dissecting the phyloepidemiology of Trypanosoma cruzi I (TcI) in Brazil by the use of high resolution genetic markers	journal.pntd.0006466	null	[ [ "Trypanosoma cruzi , a protozoan parasite ( Kinetoplastidea: Trypanosomatidae ) , is known to possess a complex epidemiology and is widely distributed from the southern states of the United States of America to the Argentinian Patagonia .", "T . cruzi is a pervasive zoonosis capable of affecting more than...	[ "Trypanosoma cruzi , the causal agent of Chagas disease , is monophyletic but genetically heterogeneous .", "It is currently represented by six genetic lineages ( Discrete Typing Units , DTUs ) designated TcI-TcVI .", "TcI is the most geographically widespread and genetically heterogeneous lineage , this as is ...	[ "T . cruzi is a zoonotic protozoan parasite infecting mammals and widely dispersed throughout endemic Latin America .", "It is known to possess considerable genetic diversity , comprising six discrete genetic lineages designated Discrete Typing Units ( DTUs ) TcI-TcVI .", "TcI is the most genetically diverse DT...	2018
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "chemical bonding", "medicine and health sciences", "chemical characterization", "body fluids", "crystal structure", "pathology and laboratory medicine", "engineering and technology", "pathogens", "immunology", "condensed matter physics", "microbiology", "saliva", "viruses", "rna viruses",...	Nanobodies targeting norovirus capsid reveal functional epitopes and potential mechanisms of neutralization	journal.ppat.1006636	null	[ [ "Human norovirus is recognized as the most important cause of outbreaks of acute gastroenteritis [1] .", "The virus is a non-enveloped single-stranded RNA virus within the Caliciviridae family .", "The human norovirus genome contains three open reading frames ( ORFs ) , where ORF1 encodes non-structur...	[ "Norovirus is the leading cause of gastroenteritis worldwide .", "Despite recent developments in norovirus propagation in cell culture , these viruses are still challenging to grow routinely .", "Moreover , little is known on how norovirus infects the host cells , except that histo-blood group antigens ( HBGAs ...	[ "We determined the binding sites of six novel human norovirus specific Nanobodies ( Nano-4 , Nano-14 , Nano-26 , Nano-27 , Nano-32 , and Nano-42 ) using X-ray crystallography .", "The unique Nanobody recognition epitopes were correlated with their potential neutralizing capacities .", "We showed that one Nanobo...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biochemistry", "immune system proteins", "pattern recognition receptors", "developmental biology", "innate immune system", "cytokines", "proteins", "molecular development", "biology and life sciences", "immune receptors", "immunology", "immune system" ]	A Novel Function of Human Pumilio Proteins in Cytoplasmic Sensing of Viral Infection	journal.ppat.1004417	null	[ [ "The host innate immune system is the first line of defense against invading pathogens .", "Pattern-recognition receptors ( PRRs ) detect pathogen molecules , termed pathogen-associated molecular patterns ( PAMPs ) , to initiate innate immune responses [1] , [2] , [3] , [4] , [5] .", "Viruses invade h...	[ "RIG-I-like receptor ( RLR ) plays a pivotal role in the detection of invading pathogens to initiate type I interferon ( IFN ) gene transcription .", "Since aberrant IFN production is harmful , RLR signaling is strictly regulated .", "However , the regulatory mechanisms are not fully understood .", "By expres...	[ "Mammals utilize innate immune system to counteract viral infections .", "The host pattern-recognition receptors , such as RIG-I-like receptors ( RLRs ) , sense invading pathogens and initiate innate immune responses .", "RLRs are composed of three RNA helicases , RIG-I , MDA5 and LGP2 , and detect a series of ...	2014
[ "Introduction", "Results", "Discussion", "Conclusions", "Materials and Methods" ]	[ "psychology", "cognitive psychology", "social sciences", "cognition", "computational neuroscience", "memory", "biology and life sciences", "computational biology", "cognitive science", "neuroscience", "learning and memory" ]	Statistical Computations Underlying the Dynamics of Memory Updating	journal.pcbi.1003939	null	[ [ "Recent psychophysical studies have explored the dynamics of memory updating by presenting participants with sequences of stimuli and then probing their ability to discriminate between different stimuli in the sequence .", "The logic of these studies is that if the stimuli are assimilated into the same dy...	[ "Psychophysical and neurophysiological studies have suggested that memory is not simply a carbon copy of our experience: Memories are modified or new memories are formed depending on the dynamic structure of our experience , and specifically , on how gradually or abruptly the world changes .", "We present a stati...	[ "When do we modify old memories , and when do we create new ones ?", "We suggest that this question can be answered statistically: The parsing of experience into distinct memory traces corresponds to inferences about the underlying structure of the environment .", "When sensory data change gradually over time ,...	2014
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "africans", "root structure", "plant anatomy", "medicine and health sciences", "body fluids", "tropical diseases", "ethnicities", "bacterial diseases", "plant science", "geology", "molecular biology techniques", "genotyping", "bacteria", "extraction techniques", "petrology", "research ...	Genotypic characterization directly applied to sputum improves the detection of Mycobacterium africanum West African 1, under-represented in positive cultures	journal.pntd.0005900	null	[ [ "Tuberculosis ( TB ) , caused by bacteria of the Mycobacterium tuberculosis complex ( MTBc ) , remains a public health problem .", "Globally , over 8 million new patients with TB disease arise each year , including 2 million deaths .", "The vast majority ( 95% ) of global TB is detected in limited-res...	[ "This study aimed to compare the prevalence of Mycobacterium tuberculosis complex ( MTBc ) lineages between direct genotyping ( on sputum ) and indirect genotyping ( on culture ) , to characterize potential culture bias against difficult growers .", "Smear-positive sputa from consecutive new tuberculosis patients...	[ "The vast majority ( 95% ) of tuberculosis ( TB ) patients worldwide live in low-income countries , including in West-Africa .", "Typing the bacteria responsible for TB ( tuberculosis; Mycobacterium tuberculosis complex ) is important for targeted TB control .", "Typing is usually performed on isolates obtained...	2017
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "genome-wide association studies", "invertebrates", "body weight", "medicine and health sciences", "rna interference", "animals", "animal models", "drosophila melanogaster", "model organisms", "physiological parameters", "experimental organism systems", "genome analysis", "obesity", "epige...	A high throughput, functional screen of human Body Mass Index GWAS loci using tissue-specific RNAi Drosophila melanogaster crosses	journal.pgen.1007222	null	[ [ "Human Genome-Wide Association Scans ( GWAS ) have been successful in discovering many genetic loci that are significantly associated with Body Mass Index ( BMI ) .", "These associations have been replicated across consortia consisting of many large and independent studies , sometimes numbering into hundr...	[ "Human GWAS of obesity have been successful in identifying loci associated with adiposity , but for the most part , these are non-coding SNPs whose function , or even whose gene of action , is unknown .", "To help identify the genes on which these human BMI loci may be operating , we conducted a high throughput s...	[ "Human Genome Wide Association Studies have successfully found thousands of novel genetic variants associated with many diseases .", "While these undoubtedly point to new biology , the field has been slowed in exploiting these new findings to reach a better understanding of exactly how they confer increased risk ...	2018
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "medicine and health sciences", "pathology and laboratory medicine", "chikungunya infection", "pathogens", "immunology", "geographical locations", "microbiology", "tropical diseases", "viruses", "north america", "clinical medicine", "rna viruses", "neglected tropical diseases", "caribbean"...	Incidence of Guillain-Barré Syndrome (GBS) in Latin America and the Caribbean before and during the 2015–2016 Zika virus epidemic: A systematic review and meta-analysis	journal.pntd.0007622	null	[ [ "A rare but severe autoimmune neuropathy , Guillain-Barré syndrome ( GBS ) is the most common type of acute flaccid paralysis ( AFP ) [1] .", "Often preceded by infections such as Campylobacter jejuni , about 25% of patients require mechanical ventilation [2] .", "Prognosis varies greatly based on GBS...	[ "A severe neurological disorder , Guillain-Barré syndrome ( GBS ) is the leading cause of acute flaccid paralysis .", "Enhanced surveillance of GBS in Latin America and the Caribbean ( LAC ) following the 2015–2016 Zika virus ( ZIKV ) epidemic presents an opportunity to estimate , for the first time , the regiona...	[ "A severe neurological disorder , Guillain-Barré syndrome ( GBS ) is the leading cause of acute flaccid paralysis .", "This is the first systematic review on GBS incidence in Latin America and the Caribbean before and during arboviral disease outbreaks .", "There is a large sub-regional and annual fluctuation i...	2019
[ "Introduction", "Results/Discussion", "Methods" ]	[ "evolutionary biology/genomics", "evolutionary biology/evolutionary and comparative genetics" ]	An Approximate Bayesian Estimator Suggests Strong, Recurrent Selective Sweeps in Drosophila	journal.pgen.1000198	null	[ [ "The fixation of beneficial mutations can strongly reduce levels of closely linked neutral variation – the so-called genetic hitchhiking effect [1] .", "This prediction has been used to search for positive selection by looking for regions of the genome with reduced variability [e . g . , 2] .", "The h...	[ "The recurrent fixation of newly arising , beneficial mutations in a species reduces levels of linked neutral variability .", "Models positing frequent weakly beneficial substitutions or , alternatively , rare , strongly selected substitutions predict similar average effects on linked neutral variability , if the...	[ "Understanding the process of adaptive evolution requires quantifying the extent to which beneficial mutations contribute to differences between species .", "However , fundamental parameters of adaptation , such as the rate and strength of beneficial mutations , are poorly understood and have historically been di...	2008
[ "Introduction", "Model", "Results", "Discussion" ]	[ "computer science", "psychology", "reasoning", "social and behavioral sciences", "cognitive psychology", "psychophysics", "sensory perception", "computerized simulations", "neuroscience" ]	How Haptic Size Sensations Improve Distance Perception	journal.pcbi.1002080	null	[ [ "The perception of distances by monocular vision is fundamentally ambiguous: an object that is small and near may create the same image as an object that is large and far ( Figure 1A ) .", "More precisely , the monocular image size of the object ( , visual angle ) does not uniquely specify the physical di...	[ "Determining distances to objects is one of the most ubiquitous perceptual tasks in everyday life .", "Nevertheless , it is challenging because the information from a single image confounds object size and distance .", "Though our brains frequently judge distances accurately , the underlying computations employ...	[ "Perceiving the distance to an object can be difficult because a monocular visual image is influenced by the object's distance and size , so the object's image size alone cannot uniquely determine the distance .", "However , because object distance is so important in everyday life , our brains have developed vari...	2011
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine", "pathology", "immunology", "microbiology", "host-pathogen interaction", "gastroenterology and hepatology", "veterinary science", "infectious diseases", "veterinary diseases", "veterinary parasitology", "veterinary microbiology", "biology", "microbial ecology", "immune response"...	Therapeutic Helminth Infection of Macaques with Idiopathic Chronic Diarrhea Alters the Inflammatory Signature and Mucosal Microbiota of the Colon	journal.ppat.1003000	null	[ [ "The incidence of inflammatory bowel diseases ( IBD ) is highest in industrialized regions wherein helminth infections have been largely eliminated , raising the hypothesis that helminths may protect against intestinal inflammation underlying the disease [1] .", "Indeed , there is evidence that experiment...	[ "Idiopathic chronic diarrhea ( ICD ) is a leading cause of morbidity amongst rhesus monkeys kept in captivity .", "Here , we show that exposure of affected animals to the whipworm Trichuris trichiura led to clinical improvement in fecal consistency , accompanied by weight gain , in four out of the five treated mo...	[ "Young macaques kept in captivity at Primate Research Centers often develop chronic diarrhea , which is difficult to treat because it is poorly understood .", "This disease shares many features with ulcerative colitis , which is an autoimmune disease affecting the intestinal tract of humans .", "Recently , para...	2012
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "computational biology/protein structure prediction", "computational biology/macromolecular structure analysis", "computational biology" ]	Four Distances between Pairs of Amino Acids Provide a Precise Description of their Interaction	journal.pcbi.1000470	null	[ [ "Most biological activities of the living cell are directed or regulated by proteins .", "These diverse functions are due to proteins three-dimensional structures consequent of the physical interactions of their amino acid residues [1] .", "As the backbone of all amino acids is identical , side chains...	[ "The three-dimensional structures of proteins are stabilized by the interactions between amino acid residues .", "Here we report a method where four distances are calculated between any two side chains to provide an exact spatial definition of their bonds .", "The data were binned into a four-dimensional grid a...	[ "Knowledge of high-resolution structures of proteins is an invaluable source of information for molecular biologists .", "Since obtaining structures experimentally is a laborious process , using computational methods to model correctly protein structure is highly beneficial .", "As protein structures are stabil...	2009
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "statistical noise", "ellipses", "decision making", "statistics", "social sciences", "geometry", "neuroscience", "cognitive psychology", "mathematics", "probability distribution", "cognition", "research and analysis methods", "gaussian noise", "animal cells", "behavior", "research asse...	Comparing Bayesian and non-Bayesian accounts of human confidence reports	journal.pcbi.1006572	null	[ [ "People often have a sense of a level of confidence about their decisions .", "Such a “feeling of knowing” [1 , 2] may serve to improve performance in subsequent decisions [3] , learning [1] , and group decision-making [4] .", "Much recent work has focused on identifying brain regions and neural mecha...	[ "Humans can meaningfully report their confidence in a perceptual or cognitive decision .", "It is widely believed that these reports reflect the Bayesian probability that the decision is correct , but this hypothesis has not been rigorously tested against non-Bayesian alternatives .", "We use two perceptual cat...	[ "Humans are able to report a sense of confidence in decisions that we make .", "It is widely hypothesized that confidence reflects the computed probability that a decision is accurate; however , this hypothesis has not been fully explored .", "We use several human behavioral experiments to test a variety of mod...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "cellular structures", "subcellular organelles", "cellular stress responses", "mechanisms of signal transduction", "dictyosteliomycota", "microbiology", "signaling in selected disciplines", "adenylyl cyclase signaling cascade", "cell differentiation", "gene function", "camp signaling cascade", ...	Deficiency of Huntingtin Has Pleiotropic Effects in the Social Amoeba Dictyostelium discoideum	journal.pgen.1002052	null	[ [ "Huntington's disease ( HD ) is an autosomal dominant neurodegenerative disorder whose clinical manifestations include psychiatric disturbances , cognitive decline and characteristic involuntary movements , typically diagnosed in mid-life [1] , [2] .", "HD is caused by a CAG trinucleotide repeat expansion...	[ "Huntingtin is a large HEAT repeat protein first identified in humans , where a polyglutamine tract expansion near the amino terminus causes a gain-of-function mechanism that leads to selective neuronal loss in Huntington's disease ( HD ) .", "Genetic evidence in humans and knock-in mouse models suggests that thi...	[ "Genetic evidence in humans and mouse models of Huntington's disease suggests that the disease mutation confers a deleterious gain-of-function on huntingtin that acts through the deregulation of some aspect of the protein's normal function ( s ) .", "While huntingtin's function is poorly understood , its evolutio...	2011
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "systems biology", "mathematics", "theoretical biology", "biology", "genetics and genomics" ]	A Density-Dependent Switch Drives Stochastic Clustering and Polarization of Signaling Molecules	journal.pcbi.1002271	null	[ [ "The formation of local , high density regions of signaling molecules ( referred to below as “clusters” ) can switch cellular pathways between “off” and “on” states and direct downstream processes [1] .", "This transition may require careful regulation , particularly when an “on” state initiates large-sca...	[ "Positive feedback plays a key role in the ability of signaling molecules to form highly localized clusters in the membrane or cytosol of cells .", "Such clustering can occur in the absence of localizing mechanisms such as pre-existing spatial cues , diffusional barriers , or molecular cross-linking .", "What p...	[ "A large body of work has focused on the ability of positive feedback in biological networks to create either switches in time ( i . e . , cells are either in an “on” or an “off” state ) or form patterns in space ( i . e . , spatial organization in cells and tissues ) .", "Here , we propose a stochastic “neutral ...	2011
[ "Introduction", "Materials and Methods", "Results/Discussion" ]	[ "computational biology/molecular dynamics", "computer science/systems and control theory", "computational biology/systems biology", "computational biology/signaling networks" ]	Analysis of Stochastic Strategies in Bacterial Competence: A Master Equation Approach	journal.pcbi.1000985	null	[ [ "Competence is the ability of a cell , usually a bacterium , to bind and internalize transforming exogenous DNA .", "Under stressful environments , such as nutrient limitations , some cells enter competence while other cells commit irreversibly to sporulation .", "Entry in competence is a transient pr...	[ "Competence is a transiently differentiated state that certain bacterial cells reach when faced with a stressful environment .", "Entrance into competence can be attributed to the excitability of the dynamics governing the genetic circuit that regulates this cellular behavior .", "Like many biological behaviors...	[ "When exposed to stress , organisms react by taking actions that help them protect their DNA .", "ComK protein is a key regulator which activates hundreds of genes , including the genes encoding the DNA-uptake and recombination systems .", "In Bacillus subtilis , stress in the environment activates a sequence o...	2010
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "pest control", "biology", "microbiology", "evolutionary biology", "agriculture" ]	The Baculovirus Uses a Captured Host Phosphatase to Induce Enhanced Locomotory Activity in Host Caterpillars	journal.ppat.1002644	null	[ [ "Viruses and other parasites are known to usurp or alter the behavior of their hosts for their own benefit .", "This type of behavior modification by animal and even plant viruses is widely observed in arthropod hosts [1] , [2] .", "One of the earliest documented examples of such behavior modification...	[ "The baculovirus is a classic example of a parasite that alters the behavior or physiology of its host so that progeny transmission is maximized .", "Baculoviruses do this by inducing enhanced locomotory activity ( ELA ) that causes the host caterpillars to climb to the upper foliage of plants .", "We previousl...	[ "Pathogens are known to usurp or alter the behavior of their hosts for their own benefit .", "Such behavior modification by animal and even plant viruses is widely observed in insect hosts .", "One of the earliest documented examples of such behavior modification is Wipfelkrankheit , a baculovirus-induced disea...	2012
[ "Introduction", "Results and discussion", "Materials and methods" ]	[ "medicine and health sciences", "parasite replication", "tropical diseases", "parasitic diseases", "parasitic protozoans", "biological locomotion", "parasitology", "circadian oscillators", "protozoans", "physiological parameters", "body temperature", "chronobiology", "malarial parasites", ...	Timing of host feeding drives rhythms in parasite replication	journal.ppat.1006900	null	[ [ "The discovery of daily rhythms in parasites dates back to the Hippocratic era and a taxonomically diverse range of parasites ( including fungi , helminths , Coccidia , nematodes , trypanosomes , and malaria parasites [1–6] ) display rhythms in development and several behaviours .", "Yet , how rhythms in ...	[ "Circadian rhythms enable organisms to synchronise the processes underpinning survival and reproduction to anticipate daily changes in the external environment .", "Recent work shows that daily ( circadian ) rhythms also enable parasites to maximise fitness in the context of ecological interactions with their hos...	[ "How cycles of asexual replication by malaria parasites are coordinated to occur in synchrony with the circadian rhythms of the host is a long-standing mystery .", "We reveal that rhythms associated with the time-of-day that hosts feed are responsible for the timing of rhythms in parasite development .", "Speci...	2018
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "genome-wide association studies", "medicine and health sciences", "quantitative trait loci", "sociology", "social sciences", "physical activity", "mathematics", "statistics (mathematics)", "genome analysis", "research and analysis methods", "public and occupational health", "genomic signal pr...	Ranking and characterization of established BMI and lipid associated loci as candidates for gene-environment interactions	journal.pgen.1006812	null	[ [ "Gene-environment ( G×E ) interactions may contribute to complex diseases , but their detection has proven challenging; hence , a variety of approaches have been developed to enhance power .", "Most G×E analyses focus on loci that are strong biological candidates [1] or those with highly significant margi...	[ "Phenotypic variance heterogeneity across genotypes at a single nucleotide polymorphism ( SNP ) may reflect underlying gene-environment ( G×E ) or gene-gene interactions .", "We modeled variance heterogeneity for blood lipids and BMI in up to 44 , 211 participants and investigated relationships between variance e...	[ "Most contemporary studies of gene-environment interactions focus on gene variants that are known to bear strong and reliable associations with the traits of interest .", "The strategy is intuitive because it helps limit the number of tests performed by focusing on a relatively small number of gene variants .", ...	2017
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "infectious diseases/neglected tropical diseases", "biochemistry/cell signaling and trafficking structures", "infectious diseases/protozoal infections", "immunology/immunity to infections" ]	Trypanosoma cruzi Utilizes the Host Low Density Lipoprotein Receptor in Invasion	journal.pntd.0000953	null	[ [ "The Low-Density Lipoprotein receptor ( LDLr ) ( UniProtKB: P01130 ) is a cell surface glycoprotein that plays a critical role in cholesterol homeostasis [1] .", "LDLr is the patriarch of an entire class of receptors called LDL receptor related proteins ( LRPs ) that contain similar structural modules [2]...	[ "Trypanosoma cruzi , an intracellular protozoan parasite that infects humans and other mammalian hosts , is the etiologic agent in Chagas disease .", "This parasite can invade a wide variety of mammalian cells .", "The mechanism ( s ) by which T . cruzi invades its host cell is not completely understood .", "...	[ "Trypanosoma cruzi , an intracellular protozoan parasite that causes Chagas disease in humans and results in the development of cardiomyopathy , is a major health problem in endemic areas .", "This parasite can invade a wide variety of mammalian cells .", "The mechanisms by which these parasites invade their ho...	2011
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biochemistry", "lipids", "metabolism", "kinetoplastids", "biology and life sciences", "protozoology", "microbiology", "sterols", "lipid metabolism", "parasitology", "parasite physiology" ]	Sterol Biosynthesis Is Required for Heat Resistance but Not Extracellular Survival in Leishmania	journal.ppat.1004427	null	[ [ "Leishmaniasis is a group of parasitic diseases infecting 10–12 million people in 88 countries [1] .", "It is caused by protozoan parasites of the genus Leishmania and transmitted through the bite of sandflies .", "During their life cycle , Leishmania parasites alternate between motile promastigotes w...	[ "Sterol biosynthesis is a crucial pathway in eukaryotes leading to the production of cholesterol in animals and various C24-alkyl sterols ( ergostane-based sterols ) in fungi , plants , and trypanosomatid protozoa .", "Sterols are important membrane components and precursors for the synthesis of powerful bioactiv...	[ "Leishmania parasites are transmitted through the bite of sandflies causing a spectrum of serious diseases in humans .", "Current drugs are inadequate and no safe vaccine is available .", "These parasites produce different types of sterols from humans , making the sterol synthesis pathway a valuable target of s...	2014
[ "Introduction", "Results and discussion", "Materials and methods" ]	[ "blood cells", "medicine and health sciences", "immune cells", "vesicles", "pathology and laboratory medicine", "electrophoretic mobility shift assay", "pathogens", "immunology", "membrane potential", "microbiology", "electrophysiology", "tuberculosis drug discovery", "physiological processe...	Potassium response and homeostasis in Mycobacterium tuberculosis modulates environmental adaptation and is important for host colonization	journal.ppat.1007591	null	[ [ "Ions are a fundamental component of organisms , playing roles in myriad biological processes .", "The ionic milieu surrounding a bacterium during infection varies with location and the immune response [1–7] , and successful host colonization thus requires proper sensing and response to the local ionic mi...	[ "Successful host colonization by bacteria requires sensing and response to the local ionic milieu , and coordination of responses with the maintenance of ionic homeostasis in the face of changing conditions .", "We previously discovered that Mycobacterium tuberculosis ( Mtb ) responds synergistically to chloride ...	[ "Tuberculosis is the leading cause of death from infectious diseases globally , and knowledge of the fundamental biology underlying successful host colonization by Mycobacterium tuberculosis ( Mtb ) is critical for understanding its pathogenicity .", "Our study focuses on one such important facet—the ability of M...	2019
[ "Introduction", "Methods", "Results", "Discussion" ]	[]	Associations between Schistosomiasis and the Use of Human Waste as an Agricultural Fertilizer in China	journal.pntd.0003444	null	[ [ "For centuries , people have collected human waste and used the material , called night soil , to fertilize agricultural crops [1 , 2] .", "The use of human fecal waste as an agricultural fertilizer has the potential to improve crop yields without the expense , environmental risk or transportation infrast...	[ "Human waste is used as an agricultural fertilizer in China and elsewhere .", "Because the eggs of many helminth species can survive in environmental media , reuse of untreated or partially treated human waste , commonly called night soil , may promote transmission of human helminthiases .", "We conducted an op...	[ "Many people use human waste as an agricultural fertilizer , often called “night soil . ”", "If the waste is not properly treated , the use of night soil may promote the spread of infectious diseases .", "We suspected that night soil use may facilitate the spread of the water-borne disease , schistosomiasis , a...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "microbial mutation", "genetic mutation", "microbiology", "host-pathogen interaction", "gene function", "mutation", "molecular cell biology", "mutation types", "fungal evolution", "microbial evolution", "cell growth", "molecular genetics", "mycology", "medical microbiology", "biology", ...	DNA Mutations Mediate Microevolution between Host-Adapted Forms of the Pathogenic Fungus Cryptococcus neoformans	journal.ppat.1002936	null	[ [ "Pathogens across all major microbial groups – viruses , bacteria , fungi and protists – have representative species that owe their success to rapid change during infection or within a population .", "Microevolution is thus essential to pathogenesis , yet due to its stochastic nature it can be difficult t...	[ "The disease cryptococcosis , caused by the fungus Cryptococcus neoformans , is acquired directly from environmental exposure rather than transmitted person-to-person .", "One explanation for the pathogenicity of this species is that interactions with environmental predators select for virulence .", "However , ...	[ "Many diseases are contracted from the environment , rather than from sick people .", "It is unclear why those species are able to cause disease , since the selective pressures in the environment are presumed to be very different from those found within the host .", "Cryptococcus neoformans is a fungus that cau...	2012
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "biology and life sciences", "ecology and environmental sciences", "medicine and health sciences" ]	QTL Mapping of Genome Regions Controlling Temephos Resistance in Larvae of the Mosquito Aedes aegypti	journal.pntd.0003177	null	[ [ "Aedes aegypti is the principal vector of Dengue Fever ( DENV ) and Yellow Fever ( YFV ) flaviviruses throughout tropical and subtropical regions of the world and 2 . 5 billion people are at risk for DENV infection [1] .", "Currently DENV vaccines have low efficacy [2] , [3] so that vector control remains...	[ "The mosquito Aedes aegypti is the principal vector of dengue and yellow fever flaviviruses .", "Temephos is an organophosphate insecticide used globally to suppress Ae .", "aegypti larval populations but resistance has evolved in many locations .", "Quantitative Trait Loci ( QTL ) controlling temephos surviv...	[ "The mosquito Aedes aegypti is the principal vector of dengue and yellow fever flaviviruses .", "Due to a lack of effective drugs or vaccines , if an epidemic of dengue fever occurs in the near future , the first line of defense will involve the use of insecticides to suppress adult populations of Ae .", "aegyp...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "immunology/immunity to infections", "immunology/innate immunity" ]	Inhibition of Macrophage Migration Inhibitory Factor Ameliorates Ocular Pseudomonas aeruginosa-Induced Keratitis	journal.ppat.1000826	null	[ [ "Eye trauma and contact lens wear are the main factors that predispose to the development of infectious keratitis associated with vision loss and blindness [1] , [2] .", "The organism most often isolated from contact lens associated corneal ulcers is Pseudomonas aeruginosa [3] , [4] .", "Existing ther...	[ "Pseudomonas aeruginosa causes severe sight-threatening corneal infections , with the inflammatory response to the pathogen being the major factor resulting in damage to the cornea that leads to loss of visual acuity .", "We found that mice deficient for macrophage migration inhibitory factor ( MIF ) , a key regu...	[ "Pseudomonas aeruginosa can induce infections that lead to a rapid loss of visual function .", "The current therapy includes antibiotic treatment which reduces the bacterial burden; nevertheless , tissue damage occurs as a result of an uncontrolled inflammation .", "Therefore , new therapeutic approaches are ne...	2010
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "computational biology/protein structure prediction", "biophysics/biomacromolecule-ligand interactions" ]	Computation of Conformational Coupling in Allosteric Proteins	journal.pcbi.1000484	null	[ [ "Allosteric transitions , in which binding of an effector molecule to one site of a protein is coupled to a conformational change at a distant site , are fundamental to biological regulation .", "Although the first models were proposed more than 40 years ago [1] , [2] , developing a mechanistic understand...	[ "In allosteric regulation , an effector molecule binding a protein at one site induces conformational changes , which alter structure and function at a distant active site .", "Two key challenges in the computational modeling of allostery are the prediction of the structure of one allosteric state starting from t...	[ "A common means of biological regulation is allostery , in which an effector molecule binds to one site on a protein and induces a conformational change which changes activity at a distant active site .", "Frequently high resolution structures are determined for one state of an allosteric protein but not the othe...	2009
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "evolutionary ecology", "adaptation", "population genetics", "biology", "evolutionary biology", "evolutionary processes" ]	The Evolution of Sex Is Favoured During Adaptation to New Environments	journal.pbio.1001317	In experiments with a facultatively sexual rotifer, populations adapting to novel environments evolve higher rates of sex because sexual mixing quickly assembles well-adapted genotypes.	[ [ "The pervasiveness of sex , given its varied and potentially large costs , is highly perplexing [1]–[10] .", "Numerous hypotheses have been proposed and sophisticated theoretical analyses have helped to define the conditions under which particular hypotheses may apply [3] , [11]–[14] .", "Despite the ...	[ "Both theory and experiments have demonstrated that sex can facilitate adaptation , potentially yielding a group-level advantage to sex .", "However , it is unclear whether this process can help solve the more difficult problem of the maintenance of sex within populations .", "Using experimental populations of ...	[ "For well over a century , biologists have wondered why sex is such a common mode of reproduction , given the immediate 2-fold fitness cost entailed by the reduced number of offspring per parent .", "The most classic explanation is that sex is favoured because it helps to generate the variation necessary for adap...	2012
[ "Introduction", "Results/Discussion", "Methods" ]	[ "biophysics/protein folding", "biophysics/theory and simulation", "pharmacology/drug development", "biophysics/biomacromolecule-ligand interactions", "computational biology", "computational biology/molecular dynamics" ]	Modeling Signal Propagation Mechanisms and Ligand-Based Conformational Dynamics of the Hsp90 Molecular Chaperone Full-Length Dimer	journal.pcbi.1000323	null	[ [ "Heat Shock Protein 90 ( Hsp90 ) is an essential ATPase directed molecular chaperone required for folding quality control , maturation and trafficking of client proteins [1]–[4] .", "Hsp90 represents a fundamental hub in protein interaction networks [5] , [6] , with key roles in many cellular functions ."...	[ "Hsp90 is a molecular chaperone essential for protein folding and activation in normal homeostasis and stress response .", "ATP binding and hydrolysis facilitate Hsp90 conformational changes required for client activation .", "Hsp90 plays an important role in disease states , particularly in cancer , where chap...	[ "Dynamic processes underlie the functions of all proteins .", "Hence , to understand , control , and design protein functions in the cell , we need to unravel the basic principles of protein dynamics .", "This is fundamental in studying the mechanisms of a specific class of proteins known as molecular chaperone...	2009
[ "Introduction", "Results and Discussion", "Materials and Methods" ]	[ "biochemistry", "computational biology" ]	An Enzymatic Atavist Revealed in Dual Pathways for Water Activation	journal.pbio.0060206	How does nature construct complex catalysts? Molecular simulations revealed two sets of catalytic residues in the enzyme IMPDH, one of which seems to represent a primitive catalytic machinery that may be a vestige of evolution.	[ [ "Textbooks extol the extraordinary catalytic power and specificity of enzymes , yet the ability of many enzymes to promote several different chemical transformations is even more remarkable .", "In examples such as the polyketide synthases , the substrate is tethered to a flexible linker and swings gymnas...	[ "Inosine monophosphate dehydrogenase ( IMPDH ) catalyzes an essential step in the biosynthesis of guanine nucleotides .", "This reaction involves two different chemical transformations , an NAD-linked redox reaction and a hydrolase reaction , that utilize mutually exclusive protein conformations with distinct cat...	[ "Many enzymes have the remarkable ability to catalyze several different chemical transformations .", "For example , IMP dehydrogenase catalyzes both an NAD-linked redox reaction and a hydrolase reaction .", "These reactions utilize distinct catalytic residues and protein conformations .", "How did Nature cons...	2008
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "medicine", "infectious diseases", "emerging infectious diseases", "virology", "emerging viral diseases", "dengue fever", "neglected tropical diseases", "travel-associated diseases", "biology", "microbiology" ]	First Report of Sylvatic DENV-2-Associated Dengue Hemorrhagic Fever in West Africa	journal.pntd.0001251	null	[ [ "Dengue viruses ( DENV ) are the most widely distributed arboviruses in the world .", "The four distinct serotypes belong to the family Flaviviridae and are some of the most important vector-borne pathogens of humans [1] .", "DENV circulation occurs in two cycles: an endemic/epidemic cycle between hum...	[ "Dengue virus ( DENV ) circulates in human and sylvatic cycles .", "Sylvatic strains are both ecologically and evolutionarily distinct from endemic viruses .", "Although sylvatic dengue cycles occur in West African countries and Malaysia , only a few cases of mild human disease caused by sylvatic strains and on...	[ "Dengue viruses are mosquito borne pathogens that cause up to 100 million infections annually .", "Dengue viruses circulate in either humans or non-human primates in two separate cycles: human and sylvatic .", "All four different serotypes infect humans causing frequent epidemics and severe disease , including ...	2011
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "phosphorylation", "medicine and health sciences", "neurochemistry", "chemical compounds", "signaling networks", "brain", "neuroscience", "organic compounds", "adenylyl cyclase signaling cascade", "hormones", "network analysis", "amines", "neurotransmitters", "catecholamines", "calcium s...	Role of DARPP-32 and ARPP-21 in the Emergence of Temporal Constraints on Striatal Calcium and Dopamine Integration	journal.pcbi.1005080	null	[ [ "Reinforcement learning plays an important role in building the learned-behavioral repertoire of an organism .", "It operates by updating the salience of an environmental cue or a cue-response association which has elicited a reward in the past .", "Basal ganglia are critical for reward learning and t...	[ "In reward learning , the integration of NMDA-dependent calcium and dopamine by striatal projection neurons leads to potentiation of corticostriatal synapses through CaMKII/PP1 signaling .", "In order to elicit the CaMKII/PP1-dependent response , the calcium and dopamine inputs should arrive in temporal proximity...	[ "A response towards an environmental stimulus could be reinforced if it elicits a reward .", "On the subcellular level , the environmental stimulus and the reward signal lead to a transient increase in striatal calcium- and dopamine-signaling , respectively .", "The integration of calcium and dopamine signals ,...	2016
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "dengue virus", "medicine and health sciences", "pathology and laboratory medicine", "demography", "pathogens", "geographical locations", "tropical diseases", "microbiology", "indonesia", "viruses", "age groups", "rna viruses", "neglected tropical diseases", "infectious disease control", ...	Dengue seroprevalence and force of primary infection in a representative population of urban dwelling Indonesian children	journal.pntd.0005621	null	[ [ "Dengue is an arbovirus transmitted to humans via the bites of infected Aedes mosquitoes .", "It is the most rapidly spreading mosquito-borne viral disease with a global incidence that has increased 30-fold over the last 50 years [1] .", "While reliable burden estimates remain elusive , two studies ha...	[ "Indonesia reports the second highest dengue disease burden in the world; these data are from passive surveillance reports and are likely to be significant underestimates .", "Age-stratified seroprevalence data are relatively unbiased indicators of past exposure and allow understanding of transmission dynamics ."...	[ "Indonesia reported to the WHO the world’s second highest average number of dengue cases and the highest in Asia from 2004 to 2010 .", "These passive surveillance reports vary widely within the country and are likely to be a severe under-estimation of the full disease burden as frequently only dengue haemorrhagic...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Ribosomal Protein Mutations Result in Constitutive p53 Protein Degradation through Impairment of the AKT Pathway	journal.pgen.1005326	null	[ [ "The stabilization of the p53 tumor suppressor is a pivotal event in the programmed cell death response .", "Levels of p53 protein are normally kept very low through its physical association with the MDM2 protein , an E3 ubiquitin ligase that constitutively ubiquitinates p53 and targets it for proteasomal...	[ "Mutations in ribosomal protein ( RP ) genes can result in the loss of erythrocyte progenitor cells and cause severe anemia .", "This is seen in patients with Diamond-Blackfan anemia ( DBA ) , a pure red cell aplasia and bone marrow failure syndrome that is almost exclusively linked to RP gene haploinsufficiency ...	[ "The p53 tumor suppressor is the most commonly mutated gene in human cancers .", "However , cancer cells exploit multiple mechanisms to silence the p53 pathway in addition to inactivation of the p53 gene .", "We previously reported that one of these mechanisms is found in tumor cells with ribosomal protein ( RP...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "mutation", "model organisms", "molecular cell biology", "genetic polymorphism", "chromosome biology", "population genetics", "yeast and fungal models", "biology", "evolutionary theory", "evolutionary biology", "saccharomyces cerevisiae", "evolutionary genetics", "chromatin" ]	Histone Variant HTZ1 Shows Extensive Epistasis with, but Does Not Increase Robustness to, New Mutations	journal.pgen.1003733	null	[ [ "Biological systems produce phenotypes that appear to be robust to genetic and non-genetic sources of variation [1] , [2] .", "It has been proposed that understanding robustness is crucial for understanding healthy and diseased states [3]–[5] , as well as the potential for populations to adapt to evolutio...	[ "Biological systems produce phenotypes that appear to be robust to perturbation by mutations and environmental variation .", "Prior studies identified genes that , when impaired , reveal previously cryptic genetic variation .", "This result is typically interpreted as evidence that the disrupted gene normally i...	[ "Natural populations typically harbor much genetic variation .", "Some of this variation is cryptic — it does not affect observed traits except if the organism is exposed to a major environmental or genetic perturbation .", "One often-proposed explanation for the revelation of cryptic genetic variation is that ...	2013
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "medicine and health sciences", "diagnostic radiology", "functional magnetic resonance imaging", "brain", "social sciences", "neuroscience", "magnetic resonance imaging", "perception", "simulation and modeling", "cognitive psychology", "brain mapping", "computational neuroscience", "vision",...	A predictive coding account of bistable perception - a model-based fMRI study	journal.pcbi.1005536	null	[ [ "During bistable perception , observers experience fluctuations between two mutually exclusive interpretations of a constant ambiguous input .", "Remarkably , percepts evoked by ambiguous stimuli usually closely resemble the experience of unambiguous objects and thus illustrate the constructive nature of ...	[ "In bistable vision , subjective perception wavers between two interpretations of a constant ambiguous stimulus .", "This dissociation between conscious perception and sensory stimulation has motivated various empirical studies on the neural correlates of bistable perception , but the neurocomputational mechanism...	[ "In bistable vision , perception spontaneously alternates between two different interpretations of a constant ambiguous stimulus .", "Here , we show that such spontaneous perceptual transitions can be parsimoniously described by a Bayesian predictive coding model .", "Using simulated , behavioural and fMRI data...	2017
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "molecular biology/bioinformatics", "molecular biology/chromatin structure", "computational biology/genomics", "computational biology" ]	Learning a Weighted Sequence Model of the Nucleosome Core and Linker Yields More Accurate Predictions in Saccharomyces cerevisiae and Homo sapiens	journal.pcbi.1000834	null	[ [ "DNA in eukaryotes is packaged with histone and other proteins into a chromatin complex .", "The most basic element of chromatin is the nucleosome , which consists of a core of eight histone proteins around which is wound approximately 147 bp of double-stranded DNA .", "The precise positioning of the ...	[ "DNA in eukaryotes is packaged into a chromatin complex , the most basic element of which is the nucleosome .", "The precise positioning of the nucleosome cores allows for selective access to the DNA , and the mechanisms that control this positioning are important pieces of the gene expression puzzle .", "We de...	[ "DNA in eukaryotes is packaged into a chromatin complex , the most basic element of which is the nucleosome .", "The precise positioning of the nucleosome cores allows for selective access to the DNA , and the mechanisms that control this positioning are important pieces of the gene expression puzzle .", "In th...	2010
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine", "neuropsychiatric disorders", "neurochemistry", "mental health", "anatomy and physiology", "neuroscience", "motor systems", "neurotransmitters", "neurological system", "neuroimaging", "nervous system physiology", "biology", "psychiatry", "neuromodulation", "central nervous sy...	Elimination of the Vesicular Acetylcholine Transporter in the Striatum Reveals Regulation of Behaviour by Cholinergic-Glutamatergic Co-Transmission	journal.pbio.1001194	A novel mouse model that eliminates cholinergic neurotransmission in the striatum while leaving glutamate release intact reveals differential effects on cocaine-induced behavior and dopaminergic responses.	[ [ "The striatum is the major input gateway to the basal ganglia .", "Striatal activity plays important roles in controlling motor functions and goal-directed and reward-related behaviours [1]–[4] .", "The striatum is the brain region mostly affected in motor diseases , such as Parkinson's disease ( PD )...	[ "Cholinergic neurons in the striatum are thought to play major regulatory functions in motor behaviour and reward .", "These neurons express two vesicular transporters that can load either acetylcholine or glutamate into synaptic vesicles .", "Consequently cholinergic neurons can release both neurotransmitters ...	[ "The neurotransmitters dopamine and acetylcholine play opposite roles in the striatum ( a brain region involved in motor control and reward-related behaviour ) , and their balance is thought to be critical for striatal function .", "Acetylcholine in the striatum has been linked to a number of functions , includin...	2011
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "developmental biology", "biology" ]	Par-1 Regulates Tissue Growth by Influencing Hippo Phosphorylation Status and Hippo-Salvador Association	journal.pbio.1001620	Par-1 regulates the Hippo signaling pathway in Drosophila melanogaster by modifying the phosphorylation status of Hippo and also by inhibiting the interaction of Hippo and Salvador.	[ [ "The control of organ size , which requires the delicate coordination of cell growth , cell proliferation , and cell death , is a fascinating biological process .", "The identification of the Hippo ( Hpo ) signaling pathway has shed some light on this biological phenomenon .", "The Hpo pathway has eme...	[ "The evolutionarily conserved Hippo ( Hpo ) signaling pathway plays a pivotal role in organ size control by balancing cell proliferation and cell death .", "Here , we reported the identification of Par-1 as a regulator of the Hpo signaling pathway using a gain-of-function EP screen in Drosophila melanogaster .", ...	[ "An organism's organ size is determined by cell number , the size of each cell , and the distance between cells .", "All of these factors are controlled by the coordination of different cell signaling pathways and other mechanisms .", "The Hippo signaling pathway controls organ size by restricting the number of...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "molecular biology/translation mechanisms", "molecular biology/translational regulation", "microbiology/parasitology" ]	snoRNA, a Novel Precursor of microRNA in Giardia lamblia	journal.ppat.1000224	null	[ [ "The role of small non-coding RNAs in gene regulation has been extensively studied in recent years [1] .", "MicroRNAs ( miRNA ) are a major class of small RNAs that are involved in gene regulation via a translational repression mechanism .", "They play important roles in regulation of genes involved i...	[ "An Argonaute homolog and a functional Dicer have been identified in the ancient eukaryote Giardia lamblia , which apparently lacks the ability to perform RNA interference ( RNAi ) .", "The Giardia Argonaute plays an essential role in growth and is capable of binding specifically to the m7G-cap , suggesting a pot...	[ "Gene regulation in Giardia lamblia , a primitive parasitic protozoan responsible for the diarrheal disease giardiasis , is poorly understood .", "There is no consensus promoter sequence .", "A simple eight–base pair AT-rich region is sufficient to initiate gene transcription in this organism .", "Thus , the ...	2008
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "medicine", "infectious diseases", "public health and epidemiology", "diagnostic medicine", "clinical immunology", "drugs and devices", "endocrinology", "global health", "immunology", "biology", "microbiology", "molecular cell biology", "diabetes and endocrinology", "public health" ]	Inflammatory Cytokine Expression Is Associated with Chikungunya Virus Resolution and Symptom Severity	journal.pntd.0001279	null	[ [ "The Chikungunya virus ( CHIKV ) , an arthropod-borne virus ( arbovirus ) , is a single-stranded positive-sense RNA virus with three genotypes .", "The virus is of the Alphavirus genus in the Togaviridae family [1] , [2] .", "CHIKV has been shown to infect and be transmitted by Ae .", "aegyptii an...	[ "The Chikungunya virus infection zones have now quickly spread from Africa to parts of Asia , North America and Europe .", "Originally thought to trigger a disease of only mild symptoms , recently Chikungunya virus caused large-scale fatalities and widespread economic loss that was linked to recent virus genetic ...	[ "Chikungunya virus ( CHIKV ) is transmitted by mosquitoes and causes a human disease clinically characterized by sudden appearance of high fever , rash , headache , nausea , and severe joint pain ( the defining symptom ) .", "Chikungunya was identified in Africa and the word Chikungunya means that which bends up ...	2011
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "invertebrates", "medicine and health sciences", "body fluids", "pathology and laboratory medicine", "viral transmission and infection", "pathogens", "geographical locations", "microbiology", "australia", "rna extraction", "saliva", "animals", "viral vectors", "viruses", "rna viruses", ...	Assessment of Local Mosquito Species Incriminates Aedes aegypti as the Potential Vector of Zika Virus in Australia	journal.pntd.0004959	null	[ [ "Zika virus ( ZIKV ) was first isolated from a rhesus monkey in the Zika Forest of Uganda in 1947 during studies investigating the ecology of yellow fever virus [1] .", "It was subsequently isolated from Aedes africanus , indicating a mosquito-borne transmission cycle .", "It was not until almost 20 y...	[ "Within the last 10 years Zika virus ( ZIKV ) has caused unprecedented epidemics of human disease in the nations and territories of the western Pacific and South America , and continues to escalate in both endemic and non-endemic regions .", "We evaluated the vector competence of Australian mosquitoes for ZIKV to...	[ "Zika virus was first isolated in Uganda in 1947 and exists in a transmission cycle between mosquitoes and non-human primates or humans .", "Whilst most clinical infections result in a self-limiting febrile illness , Zika virus has recently been linked to neurological syndromes , such as Guillain-Barré syndrome a...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "immunity", "gene expression", "genetics", "molecular genetics", "biology", "immunology", "genetics and genomics" ]	A Shared Role for RBF1 and dCAP-D3 in the Regulation of Transcription with Consequences for Innate Immunity	journal.pgen.1002618	null	[ [ "The RB family proteins ( pRB , p130 and p107 in humans; RBF1 and RBF2 in Drosophila ) co-ordinate changes in gene expression .", "Understanding the types of programs that these proteins regulate is important because of the unequivocal link between the inactivation of RB proteins and human cancer .", ...	[ "Previously , we discovered a conserved interaction between RB proteins and the Condensin II protein CAP-D3 that is important for ensuring uniform chromatin condensation during mitotic prophase .", "The Drosophila melanogaster homologs RBF1 and dCAP-D3 co-localize on non-dividing polytene chromatin , suggesting t...	[ "The retinoblastoma protein ( pRB ) is a tumor suppressor protein known for its ability to repress transcription of E2F-dependent genes and induce cell cycle arrest .", "We have previously shown that RB proteins in Drosophila and human cells interact with the Condensin II subunit , CAP-D3 , in an E2F-independent ...	2012
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "mechanisms of resistance and susceptibility", "virology", "biology", "microbiology" ]	Coronaviruses Lacking Exoribonuclease Activity Are Susceptible to Lethal Mutagenesis: Evidence for Proofreading and Potential Therapeutics	journal.ppat.1003565	null	[ [ "The potential for CoVs to cause significant human disease is well demonstrated , with six known HCoVs—HKU1 , OC43 , NL63 , 229E , SARS-CoV and MERS-CoV—causing colds , pneumonia , systemic infection , and severe or lethal disease [1]–[5] .", "Four of these viruses have been identified in just the last 10...	[ "No therapeutics or vaccines currently exist for human coronaviruses ( HCoVs ) .", "The Severe Acute Respiratory Syndrome-associated coronavirus ( SARS-CoV ) epidemic in 2002–2003 , and the recent emergence of Middle East Respiratory Syndrome coronavirus ( MERS-CoV ) in April 2012 , emphasize the high probability...	[ "RNA viruses have high mutation rates ( 10−3 to 10−5 mutations/nucleotide/round of replication ) , allowing for rapid viral adaptation in response to selective pressure .", "While RNA viruses have long been considered unable to correct mistakes during replication , CoVs such as SARS-CoV and the recently emerged M...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biotechnology", "infectious diseases", "cell biology", "mammals", "microbiology", "computational biology", "mus (mouse)", "molecular biology", "genetics and genomics", "eubacteria", "saccharomyces" ]	Yeast Functional Genomic Screens Lead to Identification of a Role for a Bacterial Effector in Innate Immunity Regulation	journal.ppat.0030021	null	[ [ "Bacterial pathogens have evolved numerous mechanisms to evade host cell defenses and promote infection .", "One strategy common to many pathogens is the manipulation of host cell processes by bacterial effector proteins that are directly delivered into host cells by specialized secretion systems [1] .", ...	[ "Numerous bacterial pathogens manipulate host cell processes to promote infection and ultimately cause disease through the action of proteins that they directly inject into host cells .", "Identification of the targets and molecular mechanisms of action used by these bacterial effector proteins is critical to und...	[ "Many bacterial pathogens use specialized secretion systems to deliver effector proteins directly into host cells .", "The effector proteins mediate the subversion or inhibition of host cell processes to promote survival of the pathogens .", "Although these proteins are critical elements of pathogenesis , relat...	2007
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "hematology/lymphomas and chronic lymphoblastic leukemia", "oncology", "genetics and genomics/gene discovery", "genetics and genomics/gene expression", "genetics and genomics/complex traits", "genetics and genomics/genetics of disease", "hematology", "oncology/hematological malignancies", "oncology/...	GWAS of Follicular Lymphoma Reveals Allelic Heterogeneity at 6p21.32 and Suggests Shared Genetic Susceptibility with Diffuse Large B-cell Lymphoma	journal.pgen.1001378	null	[ [ "Non-Hodgkin lymphoma ( NHL ) represents a diverse group of B- and T-cell malignancies", "of lymphatic origin .", "The most common subtypes are of B-cell origin and are further", "classified on the basis of their resemblance to normal stages of B-cell", "differentiation [1] .", "Epidemiolo...	[ "Non-Hodgkin lymphoma ( NHL ) represents a diverse group of hematological", "malignancies , of which follicular lymphoma ( FL ) is a prevalent subtype .", "A", "previous genome-wide association study has established a marker , rs10484561 in", "the human leukocyte antigen ( HLA ) class II region on 6p21 . 32...	[ "Earlier studies have established a marker rs10484561 , in the HLA class II region", "on 6p21 . 32 , associated with increased follicular lymphoma ( FL ) risk .", "Here , in a", "three-stage genome-wide association study of 1 , 428 FL cases and 6 , 581 controls ,", "we identified a second independent FL–ass...	2011
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "molecular cell biology", "genetics", "biology", "genomics", "evolutionary biology", "microbiology", "genetics and genomics" ]	Dynamic Large-Scale Chromosomal Rearrangements Fuel Rapid Adaptation in Yeast Populations	journal.pgen.1003232	null	[ [ "Organisms have different ways to respond to environmental stresses and evolve corresponding adaptive functions [1] .", "At the genic level , adaptation can be achieved by subtle , small-scale nucleotide changes ( base insertions , deletions or substitutions ) that alter gene expression , protein structur...	[ "Large-scale genome rearrangements have been observed in cells adapting to various selective conditions during laboratory evolution experiments .", "However , it remains unclear whether these types of mutations can be stably maintained in populations and how they impact the evolutionary trajectories .", "Here w...	[ "Large-scale chromosomal rearrangements are often associated with dramatic phenotypic changes such as cancer cell formation .", "It has been speculated that large-scale chromosomal rearrangements may play a crucial role at the early stages of adaptation , since they can quickly change the expression level of mult...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Elevated In Vivo Levels of a Single Transcription Factor Directly Convert Satellite Glia into Oligodendrocyte-like Cells	journal.pgen.1005008	null	[ [ "Transcription factor-mediated reprogramming is currently the method of choice for the generation of induced pluripotent stem ( iPS ) cells [1] .", "It is also used to directly convert one cell type into another .", "Successful conversion depends on the choice of transcription factors , but is also in...	[ "Oligodendrocytes are the myelinating glia of the central nervous system and ensure rapid saltatory conduction .", "Shortage or loss of these cells leads to severe malfunctions as observed in human leukodystrophies and multiple sclerosis , and their replenishment by reprogramming or cell conversion strategies is ...	[ "Developmental or acquired defects of oligodendrocytes or their myelin sheaths impairs saltatory nerve conduction in the central nervous system and thus leads to severe neurological diseases .", "Strategies to regenerate or replace these cells require a deeper understanding of the regulatory processes that underl...	2015
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "quantitative traits", "lipids", "proteins", "lipoproteins", "biology", "biochemistry", "phenotypes", "heredity", "genetics", "apolipoprotein genes", "genetics of disease", "genetics and genomics", "complex traits" ]	Population-Based Resequencing of APOA1 in 10,330 Individuals: Spectrum of Genetic Variation, Phenotype, and Comparison with Extreme Phenotype Approach	journal.pgen.1003063	null	[ [ "Genome-wide association studies have identified multiple loci associated with complex traits and diseases , but until now common genetic variants ( minor allele frequency >5% ) at these loci only explain small proportions of the heritability [1] , [2] .", "For example , the estimated heritability of high...	[ "Rare genetic variants , identified by in-detail resequencing of loci , may contribute to complex traits .", "We used the apolipoprotein A-I gene ( APOA1 ) , a major high-density lipoprotein ( HDL ) gene , and population-based resequencing to determine the spectrum of genetic variants , the phenotypic characteris...	[ "Rare genetic variants , identified by in-detail resequencing of loci , may contribute to complex traits .", "We used the apolipoprotein A-I gene ( APOA1 ) , a major high-density lipoprotein ( HDL ) gene , and population-based resequencing to determine the spectrum of genetic variants , the phenotypic characteris...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "ecology", "mammals" ]	Forest Elephant Crisis in the Congo Basin	journal.pbio.0050111	A systematic survey of 68,000 km2 throughout Central Africa reveals that the forest elephant--distinct from the savannah elephant--is severely threatened by poaching, despite a near universal ban of trade in ivory.	[ [ "Between 1970 and 1989 , half of Africa's elephants ( Loxodonta africana ) , perhaps 700 , 000 individuals , were killed , mostly to supply the international ivory trade [1] .", "This catastrophic decline prompted the Conference of the Parties ( CoP ) to the Convention on the International Trade in Endang...	[ "Debate over repealing the ivory trade ban dominates conferences of the Convention on International Trade in Endangered Species of Wild Fauna and Flora ( CITES ) .", "Resolving this controversy requires accurate estimates of elephant population trends and rates of illegal killing .", "Most African savannah elep...	[ "Forest elephants , perhaps a distinct species of African elephant , occur in the forests of West and Central Africa .", "Compared to the more familiar savannah elephant of Eastern and Southern Africa , forest elephant biology and their conservation status are poorly known .", "To provide robust scientific data...	2007
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "medicine", "infectious diseases", "rabies", "public health and epidemiology", "molecular epidemiology", "epidemiology", "neglected tropical diseases", "public health" ]	Genetic Diversity and Geographic Distribution of Genetically Distinct Rabies Viruses in the Philippines	journal.pntd.0002144	null	[ [ "Rabies is a fatal viral disease that causes an estimated 55 , 000 human deaths globally ever year , of which 57% occur in Asia [1] .", "Although effective measures to control rabies , such as dog vaccination , are available , rabies still is a major public health problem in many countries such as the Phi...	[ "Rabies continues to be a major public health problem in the Philippines , where 200–300 human cases were reported annually between 2001 and 2011 .", "Understanding the phylogeography of rabies viruses is important for establishing a more effective and feasible control strategy .", "We performed a molecular ana...	[ "Rabies continues to be a major public health problem in the Philippines .", "We conducted a molecular epidemiological study of rabies using the complete glycoprotein ( G ) gene from 235 animal brain samples collected in the Philippines between 2004 and 2010 .", "We identified three major clades and two distinc...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Manipulating or Superseding Host Recombination Functions: A Dilemma That Shapes Phage Evolvability	journal.pgen.1003825	null	[ [ "Genetic recombination plays key roles in biology .", "Recombinases are required for essential cellular functions such as repair of stalled or collapsed replication forks , DNA repair and chromosome segregation [1] , [2] .", "Recombination also drives genetic diversification and increases the efficien...	[ "Phages , like many parasites , tend to have small genomes and may encode autonomous functions or manipulate those of their hosts' .", "Recombination functions are essential for phage replication and diversification .", "They are also nearly ubiquitous in bacteria .", "The E . coli genome encodes many copies ...	[ "Bacterial viruses , called bacteriophages , are extremely abundant in the biosphere .", "They have key roles in the regulation of bacterial populations and in the diversification of bacterial genomes .", "Among these viruses , lambdoid phages are very abundant in enterobacteria and exchange genetic material ve...	2013
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "cell binding", "flow cytometry", "cell physiology", "bacteriology", "phosphorylation", "medicine and health sciences", "pathology and laboratory medicine", "viral transmission and infection", "molecular probe techniques", "pathogens", "microbiology", "immunoblotting", "epithelial cells", ...	Integrin but not CEACAM receptors are dispensable for Helicobacter pylori CagA translocation	journal.ppat.1007359	null	[ [ "Secretion systems of Gram-negative bacteria have evolved to mediate the passage of macromolecules across two or more cellular membranes , either into the extracellular space , or directly into selected host target cells [1] .", "A highly versatile group represents the bacterial Type IV secretion systems ...	[ "Translocation of the Helicobacter pylori ( Hp ) cytotoxin-associated gene A ( CagA ) effector protein via the cag-Type IV Secretion System ( cag-T4SS ) into host cells is a hallmark of infection with Hp and a major risk factor for severe gastric diseases , including gastric cancer .", "To mediate the injection o...	[ "The Cag Type IV secretion system of Helicobacter pylori ( Hp ) interacts with host cell integrins and injects the bacterial oncoprotein CagA into host cells thereby contributing to inflammation and carcinogenesis during chronic infection .", "Binding of β1 integrin receptors by the CagA protein and the type IV s...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biotechnology", "plant biology", "immunology", "plant science", "crops", "plant pathology", "genetically modified organisms", "crop diseases", "biology", "agriculture", "immunity", "innate immunity", "plant pathogens", "agricultural biotechnology" ]	Intramolecular Interaction Influences Binding of the Flax L5 and L6 Resistance Proteins to their AvrL567 Ligands	journal.ppat.1003004	null	[ [ "The plant immune system is based upon the ability to accurately perceive and appropriately respond to potential threats .", "In general , plants use membrane-spanning proteins with extracellular receptor domains to recognize common features of plant pathogens ( pathogen associated molecular patterns , PA...	[ "L locus resistance ( R ) proteins are nucleotide binding ( NB-ARC ) leucine-rich repeat ( LRR ) proteins from flax ( Linum usitatissimum ) that provide race-specific resistance to the causal agent of flax rust disease , Melampsora lini .", "L5 and L6 are two alleles of the L locus that directly recognize variant...	[ "The biotrophic fungus Melampsora lini is the causal agent of flax rust disease .", "Flax produces immune-receptor proteins that recognize fungal effector proteins , and subsequently signal the activation of plant defense responses .", "Here we report the molecular details of interactions between L-locus immune...	2012
[ "Introduction", "Methods", "Results", "Discussion" ]	[]	Insensitivity to the Spatial Repellent Action of Transfluthrin in Aedes aegypti: A Heritable Trait Associated with Decreased Insecticide Susceptibility	journal.pntd.0003726	null	[ [ "New vector control tools and paradigms are desperately needed to complement existing approaches [1–3] , and there is growing evidence to support the expanded use of spatial repellents to help address this need [4–9] .", "The ultimate goal of public health interventions utilizing repellents is to exploit ...	[ "New vector control paradigms expanding the use of spatial repellents are promising , but there are many gaps in our knowledge about how repellents work and how their long-term use might affect vector populations over time .", "Reported here are findings from a series of in vitro studies that investigated the pla...	[ "There is growing evidence to support the expanded use of spatial repellents for vector control , but there are still many uncertainties about how repellents work and how their long term use may impact vector populations over time .", "Here , we conducted a series of in vitro experiments that investigated spatial...	2015
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "evolutionary biology", "evolutionary biology/paleontology", "evolutionary biology/genomics" ]	Genomic DNA Sequences from Mastodon and Woolly Mammoth Reveal Deep Speciation of Forest and Savanna Elephants	journal.pbio.1000564	This study compares three extant elephants species - forest, savanna, and Asian - to extinct mammoth and mastodon. Surprisingly, forest and savanna elephants in Africa today are as distinct from each other as mammoth and Asian elephants.	[ [ "The technology for sequencing DNA from extinct species such as mastodons ( genus Mammut ) and mammoths ( genus Mammuthus ) provides a powerful tool for elucidating the phylogeny of the Elephantidae , a family that originated in the Miocene and that includes Asian elephants ( genus Elephas ) , African elephan...	[ "To elucidate the history of living and extinct elephantids , we generated 39 , 763 bp of aligned nuclear DNA sequence across 375 loci for African savanna elephant , African forest elephant , Asian elephant , the extinct American mastodon , and the woolly mammoth .", "Our data establish that the Asian elephant is...	[ "The living elephants are the last survivors of a once highly successful mammalian order , the Proboscidea , which includes extinct species such as the iconic woolly mammoth ( Mammuthus primigenius ) and the American mastodon ( Mammut americanum ) .", "Despite numerous studies , the phylogenetic relationships of ...	2010
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine", "infectious diseases", "hepatitis", "hepatitis b", "immune cells", "gastroenterology and hepatology", "virology", "t cells", "immunology", "biology", "microbiology", "viral diseases", "liver diseases" ]	CD40 Activation Rescues Antiviral CD8+ T Cells from PD-1-Mediated Exhaustion	journal.ppat.1003490	null	[ [ "Rapid clonal expansion of CD8+ T cells in response to antigenic challenge is a hallmark of adaptive immunity and a crucial element of host defense .", "Activation and differentiation of T cells are largely determined by their initial encounter with antigen-presenting cells ( APCs ) , and the resultant re...	[ "The intrahepatic immune environment is normally biased towards tolerance .", "Nonetheless , effective antiviral immune responses can be induced against hepatotropic pathogens .", "To examine the immunological basis of this paradox we studied the ability of hepatocellularly expressed hepatitis B virus ( HBV ) t...	[ "Hepatitis B virus ( HBV ) infection is responsible for more than 500 , 000 deaths annually as a result of the immune-mediated chronic liver damage it induces .", "The HBV specific CD8+ T cell response contributes to the pathogenesis of liver disease and viral clearance , and the failure to induce and/or sustain ...	2013
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "japanese encephalitis virus", "dengue virus", "invertebrates", "medicine and health sciences", "pathology and laboratory medicine", "togaviruses", "pathogens", "biological cultures", "microbiology", "animals", "alphaviruses", "viruses", "chikungunya virus", "rna viruses", "cell cultures...	Working with Zika and Usutu Viruses In Vitro	journal.pntd.0004931	null	[ [ "Usutu virus ( USUV ) , first identified in South Africa in 1959 , is a flavivirus belonging to the Japanese encephalitis complex [1 , 2] .", "In 2001 , USUV emerged in Austria and spread throughout the European and Asian continents [3–10] .", "Unlike USUV circulating in Africa , the new emergent stra...	[ "Usutu ( USUV ) and Zika ( ZIKV ) viruses are emerging arboviruses of significant medical and veterinary importance .", "These viruses have not been studied as well as other medically important arboviruses such as West Nile ( WNV ) , dengue ( DENV ) , or chikungunya ( CHIKV ) viruses .", "As such , information ...	[ "Usutu and Zika viruses are arboviruses of significant medical and veterinary outbreaks in recent years .", "Currently , standard laboratory methods for these viruses are limited to 2–3 cell lines .", "Here , our studies demonstrate that Zika and Usutu viruses are able to replicate in cells from a wide range of...	2016
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "computer science", "mathematics", "applied mathematics", "biology", "computerized simulations", "neuroscience" ]	STDP Allows Fast Rate-Modulated Coding with Poisson-Like Spike Trains	journal.pcbi.1002231	null	[ [ "STDP is now a well-established physiological mechanism of activity-driven synaptic regulation [1] , which can capture spiking information at a short timescale , down to milliseconds [2] , [3] .", "Although the relationship between the stimulating input structure and the resulting weight specialization ha...	[ "Spike timing-dependent plasticity ( STDP ) has been shown to enable single neurons to detect repeatedly presented spatiotemporal spike patterns .", "This holds even when such patterns are embedded in equally dense random spiking activity , that is , in the absence of external reference times such as a stimulus o...	[ "In vivo neural responses to stimuli are known to have a lot of variability across trials .", "If the same number of spikes is emitted from trial to trial , the neuron is said to be reliable .", "If the timing of such spikes is roughly preserved across trials , the neuron is said to be precise .", "Here we de...	2011
[ "Introduction", "Results and Discussion", "Methods" ]	[ "computational chemistry", "molecular dynamics", "biology and life sciences", "chemistry", "physical sciences", "computational biology", "molecular mechanics", "biophysics", "biophysical simulations" ]	Correlated Inter-Domain Motions in Adenylate Kinase	journal.pcbi.1003721	null	[ [ "Conformational heterogeneity as a consequence of dynamics is an intrinsic feature of proteins linked to biological function . [1]", "An important aspect for our understanding of protein dynamics is a molecular characterization of the structural states that are populated and of how correlated conformation...	[ "Correlated inter-domain motions in proteins can mediate fundamental biochemical processes such as signal transduction and allostery .", "Here we characterize at structural level the inter-domain coupling in a multidomain enzyme , Adenylate Kinase ( AK ) , using computational methods that exploit the shape inform...	[ "Most proteins contain several domains , and inter-domain motions play important roles in their biological functions .", "Describing the various inter-domain orientations that multi-domain proteins adopt at equilibrium is challenging , but key for understanding the relationship between protein structure and funct...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "molecular cell biology", "virology", "membranes and sorting", "viral replication complex", "biology", "microbiology", "viral replication" ]	Increased Long Chain acyl-Coa Synthetase Activity and Fatty Acid Import Is Linked to Membrane Synthesis for Development of Picornavirus Replication Organelles	journal.ppat.1003401	null	[ [ "( + ) RNA viruses of eukaryotes are a very successful group of pathogens infecting organisms from unicellular algae to humans .", "In spite of adaptation to diverse hosts the basic processes of genome expression and replication are highly conserved among these viruses .", "One such feature shared amo...	[ "All positive strand ( +RNA ) viruses of eukaryotes replicate their genomes in association with membranes .", "The mechanisms of membrane remodeling in infected cells represent attractive targets for designing future therapeutics , but our understanding of this process is very limited .", "Elements of autophagy...	[ "Eukaryotic cells feature astonishing complexity of regulatory networks , yet control over this fine-tuned machinery is easily overrun by viruses with expression of just a handful of proteins .", "One of the striking examples of such hostile take-over is the rewiring of normal cellular membrane metabolism by ( + ...	2013
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "medicine and health sciences", "tropical diseases", "database searching", "parasitic diseases", "bacterial diseases", "filariasis", "eye diseases", "neglected tropical diseases", "onchocerciasis", "lymphatic filariasis", "blindness", "research and analysis methods", "infectious diseases", ...	Productivity Loss Related to Neglected Tropical Diseases Eligible for Preventive Chemotherapy: A Systematic Literature Review	journal.pntd.0004397	null	[ [ "Most of the people affected by Neglected Tropical Diseases ( NTDs ) are impoverished and marginalized populations , with low visibility and little political voice .", "They are not considered a priority market for pharmaceutical manufacturers or a health risk for the wealthier parts of the world .", ...	[ "Neglected Tropical Diseases ( NTDs ) not only cause health and life expectancy loss , but can also lead to economic consequences including reduced ability to work .", "This article describes a systematic literature review of the effect on the economic productivity of individuals affected by one of the five world...	[ "Neglected Tropical Diseases ( NTDs ) not only have impact on health and life expectancy of mostly disadvantaged populations , but can also lead to economic consequences , including reduced ability to work .", "Investments in health improvement of the populations affected by NTDs would also help to increase econo...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genetics and genomics/genetics of disease", "molecular biology/recombination", "molecular biology/dna repair", "infectious diseases/neglected tropical diseases" ]	TOPO3α Influences Antigenic Variation by Monitoring Expression-Site-Associated VSG Switching in Trypanosoma brucei	journal.ppat.1000992	null	[ [ "Trypanosoma brucei proliferates in the bloodstream of its mammalian host and periodically escapes the antibody-mediated immune response .", "A single species of variant surface glycoprotein ( VSG ) is expressed at a given time , from among >1 , 000 VSG genes and pseudogenes [1] , [2] , and ∼10 million VS...	[ "Homologous recombination ( HR ) mediates one of the major mechanisms of trypanosome antigenic variation by placing a different variant surface glycoprotein ( VSG ) gene under the control of the active expression site ( ES ) .", "It is believed that the majority of VSG switching events occur by duplicative gene c...	[ "Trypanosoma brucei , the causative agent of African sleeping sickness , escapes the host immune response through a mechanism known as the antigenic variation .", "Each individual trypanosome expresses a single species of surface antigenic protein at any time yet possesses an infinite potential to express differe...	2010
[ "Introduction", "Methods", "Results and Discussion" ]	[ "public health", "medicine", "preventive medicine", "infectious diseases", "global health", "leishmaniasis", "parasitic diseases" ]	A Review of Preventative Methods against Human Leishmaniasis Infection	journal.pntd.0002278	null	[ [ "Leishmania is of the protozoan genus trypanosomatida .", "The parasite resides intracellularly causing the disease leishmaniasis , and is transmitted between hosts by the bite of the female sandfly ( genus Phlebotomus in the Old World localities of Europe , Africa and Asia , and Lutzomyia in the New Worl...	[ "Leishmaniasis is an intracellular parasitic infection transmitted to humans via the sandfly .", "Approximately 350 million people are at risk of contracting the disease and an estimated 1 . 6 million new cases occur annually .", "Of the two main forms , visceral and cutaneous , the visceral form is fatal in 85...	[ "Leishmaniasis is a vector-borne parasite infection , transmitted to humans by sandflies .", "It is estimated to cause 1 . 6 million new cases of disease annually .", "Of the two main forms , so-called “visceral” and “cutaneous” , the visceral form is fatal in 85–90% of untreated cases .", "This literature re...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biology" ]	FANCJ/BACH1 Acetylation at Lysine 1249 Regulates the DNA Damage Response	journal.pgen.1002786	null	[ [ "The hereditary breast cancer associated gene product , BRCA1 is an essential tumor suppressor .", "To promote genomic stability , BRCA1 interacts with multiple protein partners .", "In particular , through its C-terminal BRCT repeats , BRCA1 directly interacts with Abraxas , CtIP and FANCJ ( also kno...	[ "BRCA1 promotes DNA repair through interactions with multiple proteins , including CtIP and FANCJ ( also known as BRIP1/BACH1 ) .", "While CtIP facilitates DNA end resection when de-acetylated , the function of FANCJ in repair processing is less well defined .", "Here , we report that FANCJ is also acetylated ....	[ "The BRCA1–Fanconi anemia ( FA ) pathway is required for both tumor suppression and cell survival , particularly following treatment with DNA damaging agents that induce DNA interstrand crosslinks ( ICLs ) .", "ICL processing by the BRCA–FA pathway includes promotion of homologous recombination ( HR ) and DNA dam...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine", "viral transmission and infection", "immunology", "microbiology", "cancers and neoplasms", "epstein-barr virus infectious mononucleosis", "oncology", "hiv opportunistic infections", "infectious diseases", "bone and soft tissue sarcomas", "hiv", "biology", "kaposi sarcoma", "hos...	Kaposi's Sarcoma Associated Herpesvirus Tegument Protein ORF75 Is Essential for Viral Lytic Replication and Plays a Critical Role in the Antagonization of ND10-Instituted Intrinsic Immunity	journal.ppat.1003863	null	[ [ "Human Herpesvirus 8 ( HHV8 ) , or Kaposi's Sarcoma-Associated Herpesvirus ( KSHV ) , belongs to the subfamily Gammaherpesvirinae and is grouped together with the closely related prototypic Saimiriine herpesvirus 2 , or Herpesvirus saimiri ( HVS ) , into the genus Rhadinovirus .", "KSHV was first discover...	[ "Nuclear domain 10 ( ND10 ) components are restriction factors that inhibit herpesviral replication .", "Effector proteins of different herpesviruses can antagonize this restriction by a variety of strategies , including degradation or relocalization of ND10 proteins .", "We investigated the interplay of Kaposi...	[ "Kaposi's Sarcoma-Associated Herpesvirus ( KSHV ) establishes a lifelong persistent infection in humans and is associated with tumors and lymphoproliferative disease , particularly upon immunosuppression .", "The virus has to overcome cellular intrinsic immunity in order to initiate viral protein expression and g...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Ectodysplasin/NF-κB Promotes Mammary Cell Fate via Wnt/β-catenin Pathway	journal.pgen.1005676	null	[ [ "The murine mammary gland development initiates at around embryonic day 10 . 5 ( E10 . 5 ) with the establishment of bilateral milk or mammary lines [1] .", "Between E11-E12 , five pairs of mammary placodes , local thickenings of the epithelium , emerge at conserved positions .", "By E13 . 5 , the pla...	[ "Mammary gland development commences during embryogenesis with the establishment of a species typical number of mammary primordia on each flank of the embryo .", "It is thought that mammary cell fate can only be induced along the mammary line , a narrow region of the ventro-lateral skin running from the axilla to...	[ "Mammary glands are the most characteristic feature of all mammals .", "The successful growth and function of the mammary glands is vital for the survival of offspring since the secreted milk is the main nutritional source of a new-born .", "Ectodysplasin ( Eda ) is a signaling molecule that regulates the forma...	2015
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "oncology", "genome-wide association studies", "medicine", "genetic causes of cancer", "cancer genetics", "gastroenterology and hepatology", "genetics", "cancer risk factors", "biology", "gastrointestinal cancers", "genetics of disease", "genetics and genomics" ]	Multiple Common Susceptibility Variants near BMP Pathway Loci GREM1, BMP4, and BMP2 Explain Part of the Missing Heritability of Colorectal Cancer	journal.pgen.1002105	null	[ [ "Genome-wide association ( GWA ) studies of colorectal cancer ( CRC ) have so far identified 14 common , low-risk susceptibility variants [1] .", "Of these 14 variants , 3 are close to loci that are secreted members of the bone morphogenetic protein ( BMP ) signalling pathway: GREM1 ( rs4779584 ) ; BMP4 (...	[ "Genome-wide association studies ( GWAS ) have identified 14 tagging single nucleotide polymorphisms ( tagSNPs ) that are associated with the risk of colorectal cancer ( CRC ) , and several of these tagSNPs are near bone morphogenetic protein ( BMP ) pathway loci .", "The penalty of multiple testing implicit in G...	[ "Genome-wide association studies ( GWAS ) have identified several colorectal cancer ( CRC ) susceptibility polymorphisms near genes that encode proteins in the bone morphogenetic protein ( BMP ) pathway .", "However , most of the inherited susceptibility to CRC remains unexplained .", "We investigated three of ...	2011
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	The Serum Resistome of a Globally Disseminated Multidrug Resistant Uropathogenic Escherichia coli Clone	journal.pgen.1003834	null	[ [ "Escherichia coli O25b:H4-ST131 ( E . coli ST131 ) is a recently emerged , globally disseminated clone that is often multidrug resistant and is responsible for a high proportion of community- and nosocomially-acquired urinary tract and bloodstream infections [1]–[6] .", "E . coli ST131 strains are also ca...	[ "Escherichia coli ST131 is a globally disseminated , multidrug resistant clone responsible for a high proportion of urinary tract and bloodstream infections .", "The rapid emergence and successful spread of E . coli ST131 is strongly associated with antibiotic resistance; however , this phenotype alone is unlikel...	[ "The emergence and rapid dissemination of new bacterial pathogens presents multiple challenges to healthcare systems , including the need for rapid detection , precise diagnostics , effective transmission control and effective treatment .", "E . coli ST131 is an example of a recently emerged multidrug resistant p...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Integration of the Unfolded Protein and Oxidative Stress Responses through SKN-1/Nrf	journal.pgen.1003701	null	[ [ "The endoplasmic reticulum ( ER ) is responsible for multiple functions in protein synthesis and processing , lipid metabolism , xeno/endobiotic detoxification , and Ca2+ storage ( reviewed in [1] , [2] ) .", "The ER forms a continuous structure with the nuclear envelope and maintains extensive contact wi...	[ "The Unfolded Protein Response ( UPR ) maintains homeostasis in the endoplasmic reticulum ( ER ) and defends against ER stress , an underlying factor in various human diseases .", "During the UPR , numerous genes are activated that sustain and protect the ER .", "These responses are known to involve the canonic...	[ "Proteins that are placed in membranes or secreted are produced in a cellular structure called the endoplasmic reticulum ( ER ) .", "An accumulation of misfolded proteins in the ER contributes to many disease states , including diabetes and neurodegeneration .", "The ER protects against a toxic buildup of misfo...	2013
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "medicine", "infectious diseases", "public health and epidemiology", "epidemiology", "immunology", "biology" ]	IFN-γ Production to Leishmania Antigen Supplements the Leishmania Skin Test in Identifying Exposure to L. braziliensis Infection	journal.pntd.0001947	null	[ [ "American tegumentary leishmaniasis ( ATL ) is caused predominantly by Leishmania braziliensis , L . guaynensis , L . mexicana and L . amazonensis [1] , [2] .", "It is endemic in South and Central America and cutaneous leishmaniasis ( CL ) , characterized by well delimited ulcers with raised borders , is ...	[ "Cutaneous leishmaniasis due to L . braziliensis ( CL ) is characterized by a positive delayed type hypersensitivity test ( DTH ) leishmania skin test ( LST ) and high IFN-γ production to soluble leishmania antigen ( SLA ) .", "The LST is used for diagnosis of CL and for identification of individuals exposed to l...	[ "Both control of L . braziliensis infection and development of cutaneous leishmaniasis ( CL ) are dependent on the host immunological response .", "Due to the difficulty of finding parasites in leishmanial lesions , a delayed type hypersensitivity reaction - leishmania skin test ( LST ) , is widely used to diagno...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biochemistry", "dermatology/pediatric skin diseases, including genetic diseases", "dermatology/photodermatology and skin aging", "immunology/immune response", "gastroenterology and hepatology/inflammatory bowel disease", "genetics and genomics/disease models", "genetics and genomics/genetics of disease...	Loss of Kindlin-1 Causes Skin Atrophy and Lethal Neonatal Intestinal Epithelial Dysfunction	journal.pgen.1000289	null	[ [ "Kindler Syndrome ( KS; OMIM:173650 ) is a rare , recessive genodermatosis caused by mutations in the FERMT1 gene ( C20ORF42/KIND1 ) [1] , [2] .", "KS patients suffer from varying skin abnormalities that occur at distinct phases of their life [3] .", "Skin blisters develop and disappear after birth , ...	[ "Kindler Syndrome ( KS ) , characterized by transient skin blistering followed by abnormal pigmentation , skin atrophy , and skin cancer , is caused by mutations in the FERMT1 gene .", "Although a few KS patients have been reported to also develop ulcerative colitis ( UC ) , a causal link to the FERMT1 gene mutat...	[ "Mutations in FERMT1 , coding for the Kindlin-1 protein , cause Kindler Syndrome in humans , characterized by skin blistering , atrophy , and cancer .", "Recent reports showed that some Kindler Syndrome patients additionally suffer from ulcerative colitis .", "However , it is unknown whether this is caused by l...	2008
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "physics/interdisciplinary physics", "evolutionary biology/sexual behavior", "mathematics", "biophysics/theory and simulation", "computational biology/evolutionary modeling", "infectious diseases/hiv infection and aids", "public health and epidemiology/epidemiology", "public health and epidemiology/in...	Untangling the Interplay between Epidemic Spread and Transmission Network Dynamics	journal.pcbi.1000984	null	[ [ "Despite huge efforts to improve public health , the spread of infectious diseases is still ubiquitous at the beginning of the 21st century , and there is considerable variability in epidemic patterns between locations .", "Although the recent influenza pandemic has been a global challenge , there have no...	[ "The epidemic spread of infectious diseases is ubiquitous and often has a considerable impact on public health and economic wealth .", "The large variability in the spatio-temporal patterns of epidemics prohibits simple interventions and requires a detailed analysis of each epidemic with respect to its infectious...	[ "The way potentially infectious contacts are made strongly influences how fast and how widely epidemics spread in their host population .", "Therefore , it is important to assess changes in contact behavior throughout an epidemic; these may occur due to external factors , such as demographic change , or as a side...	2010
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "blood cells", "medicine and health sciences", "immune cells", "forkhead box", "natural antisense transcripts", "gene regulation", "immunology", "micrornas", "stem cells", "tcr signaling cascade", "immune system proteins", "white blood cells", "animal cells", "proteins", "gene expression...	miR-181a/b-1 controls thymic selection of Treg cells and tunes their suppressive capacity	journal.pbio.2006716	null	[ [ "Regulatory T cells ( Treg cells ) expressing the lineage-defining transcription factor forkhead box protein P3 ( Foxp3 ) form an integral part of the adaptive immune system and function to prevent unwanted immune responses [1 , 2] .", "Treg cells are generated during T-cell development in the thymus ( th...	[ "The interdependence of selective cues during development of regulatory T cells ( Treg cells ) in the thymus and their suppressive function remains incompletely understood .", "Here , we analyzed this interdependence by taking advantage of highly dynamic changes in expression of microRNA 181 family members miR-18...	[ "T cells are pivotal in orchestrating an adaptive immune response .", "They are produced in the thymus and undergo selection processes resulting in elimination of nonfunctional and self-reactive cells in order to prevent autoimmune disease .", "One type of T cells , called regulatory T cells ( Treg cells ) , is...	2019
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "invertebrates", "medicine and health sciences", "pathology and laboratory medicine", "animals", "research design", "developmental biology", "pupae", "surveys", "infectious disease control", "insect vectors", "zoology", "research and analysis methods", "infectious diseases", "serology", ...	The relationship between entomological indicators of Aedes aegypti abundance and dengue virus infection	journal.pntd.0005429	null	[ [ "Dengue virus ( DENV ) , which is transmitted by the bite of female Aedes aegypti mosquitoes , causes more human morbidity and mortality than any other arthropod-borne virus [1] .", "Since the 1950s , dengue has spread via the globalization of trade and travel , rapid urbanization and expansion of vector ...	[ "Routine entomological monitoring data are used to quantify the abundance of Ae .", "aegypti .", "The public health utility of these indicators is based on the assumption that greater mosquito abundance increases the risk of human DENV transmission , and therefore reducing exposure to the vector decreases incid...	[ "In this study , we compared measures of entomological risk collected through routine household entomological monitoring by estimating an association with human DENV infection .", "Longitudinal entomological and human serology data from Iquitos , Peru , were used to test associations between Ae .", "aegypti ind...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "complex systems", "physics", "computer and information sciences", "systems science", "mathematics", "neural networks", "applied mathematics", "biophysics theory", "biology and life sciences", "physical sciences", "computational biology", "biophysics", "neuroscience", "biophysical simulati...	Emergence of Assortative Mixing between Clusters of Cultured Neurons	journal.pcbi.1003796	null	[ [ "The theory of complex networks [1]–[5] has proven to be a useful framework for the study of the interplay between structure and functionality in social , technological , and biological systems .", "A complex network is no more than a specific representation of the interactions between the elements of the...	[ "The analysis of the activity of neuronal cultures is considered to be a good proxy of the functional connectivity of in vivo neuronal tissues .", "Thus , the functional complex network inferred from activity patterns is a promising way to unravel the interplay between structure and functionality of neuronal syst...	[ "The architecture of neuronal cultures is the result of an intricate self-organization process that balances structural and dynamical demands .", "We observe that when the motility of neurons is allowed , these neurons organize into compact clusters .", "These neuronal assemblies have an intrinsic synchronous a...	2014
[ "Introduction", "Methods", "Results", "Discussion" ]	[]	Sensitivity and Specificity of a Urine Circulating Anodic Antigen Test for the Diagnosis of Schistosoma haematobium in Low Endemic Settings	journal.pntd.0003752	null	[ [ "After many years of neglect , schistosomiasis and other parasitic worm infections are given considerable attention by the research community , non-governmental organizations , funding bodies , international organizations , policy makers , and disease control managers [1 , 2] .", "Indeed , drug donations ...	[ "Elimination of schistosomiasis as a public health problem and interruption of transmission in selected areas are key goals of the World Health Organization for 2025 .", "Conventional parasitological methods are insensitive for the detection of light-intensity infections .", "Techniques with high sensitivity an...	[ "The World Health Organization aspires to eliminate snail fever ( schistosomiasis ) as a public health problem and to interrupt the transmission of this disease in selected areas by 2025 .", "Efforts to achieve these goals are currently being intensified .", "As a result , the prevalence and intensity of infect...	2015
[ "Introduction", "Results", "Discussion", "Materials & Methods" ]	[ "sequencing techniques", "taxonomy", "organismal evolution", "microbiology", "vertebrates", "animals", "mammals", "dogs", "animal phylogenetics", "phylogenetics", "data management", "phylogenetic analysis", "microbial evolution", "molecular biology techniques", "mammalian genomics", "z...	Large-Scale Phylogenomic Analysis Reveals the Complex Evolutionary History of Rabies Virus in Multiple Carnivore Hosts	journal.ppat.1006041	null	[ [ "Revealing how viruses jump species boundaries and establish productive infections in new hosts is key to understanding disease emergence .", "As most recent emerging and re-emerging viruses have RNA genomes [1] , it is of central importance to understand the drivers of RNA virus evolution , diversificati...	[ "The natural evolution of rabies virus ( RABV ) provides a potent example of multiple host shifts and an important opportunity to determine the mechanisms that underpin viral emergence .", "Using 321 genome sequences spanning an unprecedented diversity of RABV , we compared evolutionary rates and selection pressu...	[ "Zoonoses account for most recently emerged infectious diseases of humans , although little is known about the evolutionary mechanisms involved in cross-species virus transmission .", "Understanding the evolutionary patterns and processes that underpin such cross-species transmission is of importance for predicti...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "virology/virion structure, assembly, and egress", "virology/host invasion and cell entry", "virology" ]	Cellular Proteins in Influenza Virus Particles	journal.ppat.1000085	null	[ [ "Knowledge of the protein composition of a virus particle often serves as an initial guide in determining functional roles for viral proteins .", "Virion proteins are commonly termed “structural proteins” and broadly-speaking , include proteins that either form an integral part of the virus architecture o...	[ "Virions are thought to contain all the essential proteins that govern virus egress from the host cell and initiation of replication in the target cell .", "It has been known for some time that influenza virions contain nine viral proteins; however , analyses of other enveloped viruses have revealed that proteins...	[ "Viruses are released from infected cells in the form of virions , which contain all the essential factors necessary for initiating infection in a new target cell .", "For influenza virus , it is known that virions contain the viral genome , a lipid envelope , and at least nine viral proteins .", "We performed ...	2008
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "meiosis", "chromosome staining", "medicine and health sciences", "reproductive system", "spermatocytes", "cell cycle and cell division", "cell processes", "germ cells", "animal models", "fungi", "model organisms", "experimental organism systems", "dna", "sperm", "homologous recombinatio...	CXXC1 is not essential for normal DNA double-strand break formation and meiotic recombination in mouse	journal.pgen.1007657	null	[ [ "Meiotic recombination ensures production of fertile gametes with a correct haploid chromosome number and genetic diversity [1] .", "In most of mammals , the meiotic recombination sites are restricted to 1–2 kb regions , termed recombination hotspots , locations of which are determined by the DNA binding ...	[ "In most mammals , including mice and humans , meiotic recombination is determined by the meiosis specific histone methytransferase PRDM9 , which binds to specific DNA sequences and trimethylates histone 3 at lysine-4 and lysine-36 at the adjacent nucleosomes .", "These actions ensure successful DNA double strand...	[ "Meiotic recombination increases genetic diversity by ensuring novel combination of alleles passing correctly to the next generation .", "In most mammals , the meiotic recombination sites are determined by histone methyltransferase PRDM9 .", "These sites are proposed to become associated with the chromosome axi...	2018
[ "Introduction", "Materials and methods", "Results", "Discussion" ]	[ "enzymes", "enzymology", "collagens", "serine proteases", "developmental biology", "muscle proteins", "proteins", "gene expression", "life cycles", "recombinant proteins", "biochemistry", "signal transduction", "cell biology", "genetics", "tgf-beta signaling cascade", "biology and life...	Identification of a host collagen inducing factor from the excretory secretory proteins of Trichinella spiralis	journal.pntd.0006516	null	[ [ "Trichinella spiralis can make collagen capsules in host muscles during their life cycle that surround muscle stage larvae and might protect the larvae from the host immune system .", "This phenomenon can be understood as the parasite creating a simple structure to protect itself , but when examined close...	[ "In a previous study , we found that Trichinella spiralis muscle larva excretory and secretory proteins ( ES-P ) most likely activate collagen synthesis via TGF-β/Smad signaling , and this event could influence collagen capsule formation .", "In order to identify the specific collagen inducing factor , ES-P was f...	[ "Trichinella spiralis can make collagen capsules in host muscle cells during its life cycle , which encapsulates muscle stage larvae .", "Many investigators have tried to reveal the complex mechanism behind this collagen capsule architecture , and it has been suggested that several serine proteases in excretory-s...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "immunology/antigen processing and recognition", "microbiology/immunity to infections", "respiratory medicine/respiratory infections", "immunology/immune response", "microbiology/innate immunity", "immunology/innate immunity", "immunology", "infectious diseases/respiratory infections", "infectious d...	Human Mucosal Associated Invariant T Cells Detect Bacterially Infected Cells	journal.pbio.1000407	A first indication of the biological role of mucosal associated invariant T (MAIT) cells reveals that this discrete T cell subset is broadly reactive to bacterial infection. In particular MAIT cells recognize Mycobacterium tuberculosis-infected lung airway epithelial cells via the most evolutionarily conserved major hi...	[ [ "Mycobacterium tuberculosis ( Mtb ) , which causes tuberculosis ( TB ) , remains a leading cause of infectious disease mortality worldwide [1] .", "The majority of TB cases are exclusively pulmonary , suggesting a need for mucosal immunity in the control of Mtb .", "Th1-type immunity , including stron...	[ "Control of infection with Mycobacterium tuberculosis ( Mtb ) requires Th1-type immunity , of which CD8+ T cells play a unique role .", "High frequency Mtb-reactive CD8+ T cells are present in both Mtb-infected and uninfected humans .", "We show by limiting dilution analysis that nonclassically restricted CD8+ ...	[ "About one-third of the world's population is infected with Mycobacterium tuberculosis ( Mtb ) , yet thanks to a robust immune response most infected people remain healthy .", "CD8 T cells are unique in detecting intracellular infections .", "Surprisingly , Mtb-reactive CD8 T cells are found in humans with no p...	2010
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "humoral immunity", "medicine", "infectious diseases", "immunity", "virology", "emerging viral diseases", "immunity to infections", "immunology", "dengue", "biology", "microbiology", "viral diseases", "immune response" ]	Correlation between Dengue-Specific Neutralizing Antibodies and Serum Avidity in Primary and Secondary Dengue Virus 3 Natural Infections in Humans	journal.pntd.0002274	null	[ [ "The four serotypes of the flavivirus dengue virus ( DENV1–4 ) cause the most common mosquito-borne viral disease in humans worldwide , with 50–100 million people infected annually and over 3 billion people at risk [1] .", "DENV infection can be asymptomatic or cause a spectrum of disease ranging from cla...	[ "Although heterotypic secondary infection with dengue virus ( DENV ) is associated with severe disease , the majority of secondary infections are mild or asymptomatic .", "The mechanisms of antibody-mediated protection are poorly understood .", "In 2010 , 108 DENV3-positive cases were enrolled in a pediatric ho...	[ "Dengue is the most common mosquito-borne viral illness in humans , with 3 billion people at risk for infection .", "Four different dengue virus serotypes ( DENV1–4 ) cause the disease , which can be either inapparent or present with flu-like symptoms ( Dengue Fever , aka “breakbone fever” ) .", "The disease ca...	2013
[ "General introduction", "In vivo models in TB research", "Human-based in vitro models in TB research", "Organoids as infection models", "Lung organoids in TB research", "Conclusions" ]	[ "organoids", "medicine and health sciences", "animal models of disease", "biological cultures", "tropical diseases", "microbiology", "animal models", "bacterial diseases", "developmental biology", "review", "model organisms", "organism development", "experimental organism systems", "lung d...	Experimental study of tuberculosis: From animal models to complex cell systems and organoids	journal.ppat.1006421	null	[ [ "Tuberculosis ( TB ) kills over 1 . 8 million people every year and thus remains the leading cause of death by an infectious agent [1] .", "Additionally , TB afflicts over 10 . 4 million new individuals per year and is estimated to exist in a latent form in nearly 2 billion people worldwide [1] .", "I...	[ "Tuberculosis ( TB ) is a devastating disease to mankind that has killed more people than any other infectious disease .", "Despite many efforts and successes from the scientific and health communities , the prospect of TB elimination remains distant .", "On the one hand , sustainable public health programs wit...	[ "Tuberculosis ( TB ) is the number 1 killer in the world due to a bacterial infection .", "The study of this disease through clinical and epidemiological data and through the use of different experimental models has provided important knowledge on the role of the immune response generated during infection .", "...	2017
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[]	Target Inhibition Networks: Predicting Selective Combinations of Druggable Targets to Block Cancer Survival Pathways	journal.pcbi.1003226	null	[ [ "Over the past decade , there has been a significant increase in the R&D cost when translating new cancer drug candidates into effective therapies in the clinic .", "The two single most important reasons are", "( i ) lack of efficacy and", "( ii ) clinical safety of the candidate drug compounds [1...	[ "A recent trend in drug development is to identify drug combinations or multi-target agents that effectively modify multiple nodes of disease-associated networks .", "Such polypharmacological effects may reduce the risk of emerging drug resistance by means of attacking the disease networks through synergistic and...	[ "Selective inhibition of specific panels of multiple protein targets provides an unprecedented potential for improving therapeutic efficacy of anticancer agents .", "We introduce a computational systems pharmacology strategy , which uses the concept of target inhibition networks to predict effective multi-target ...	2013
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "medicine", "infectious diseases", "public health and epidemiology", "epidemiology", "infectious disease epidemiology", "neglected tropical diseases", "leprosy", "infectious disease control", "public health" ]	Interruption and Defaulting of Multidrug Therapy against Leprosy: Population-Based Study in Brazil's Savannah Region	journal.pntd.0001031	null	[ [ "Leprosy control is based on early diagnosis , treatment , and cure , aiming at the elimination of sources of infection and of sequels in affected individuals .", "Similar to other countries , in Brazil leprosy control measures are integrated into general public health care , thus facilitating access to a...	[ "Low adherence to multidrug therapy against leprosy ( MDT ) is still an important obstacle of disease control , and may lead to remaining sources of infection , incomplete cure , irreversible complications , and multidrug resistance .", "We performed a population-based study in 78 municipalities in Tocantins Stat...	[ "Leprosy is still a public health problem in Brazil , and low adherence to multidrug therapy against leprosy ( MDT ) is an important obstacle of disease control .", "This may lead to remaining sources of infection , incomplete cure , complications , and multidrug resistance .", "We performed a study in 78 munic...	2011
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "virology/vaccines", "virology/animal models of infection", "virology/emerging viral diseases", "infectious diseases/viral infections", "public health and epidemiology/infectious diseases", "infectious diseases/epidemiology and control of infectious diseases" ]	Estimation of Transmission Parameters of H5N1 Avian Influenza Virus in Chickens	journal.ppat.1000281	null	[ [ "Highly pathogenic avian influenza virus strains of the H5 or H7 subtypes are noted for being highly contagious among various bird species and inducing high mortality rates in poultry .", "Although outbreaks of highly pathogenic avian influenza have been reported since the 1950s the current focus is on th...	[ "Despite considerable research efforts , little is yet known about key epidemiological parameters of H5N1 highly pathogenic influenza viruses in their avian hosts .", "Here we show how these parameters can be estimated using a limited number of birds in experimental transmission studies .", "Our quantitative es...	[ "Outbreaks of highly pathogenic H5N1 avian influenza in poultry first occurred in China in 1996 .", "Since that time , the virus has become endemic in Asia , and has been the cause of outbreaks in Africa and Europe .", "Although many aspects of H5N1 virus biology have been studied in detail , surprisingly littl...	2009
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biology and life sciences", "computational biology" ]	The Structural Basis of ATP as an Allosteric Modulator	journal.pcbi.1003831	null	[ [ "Adenosine-5’-triphosphate ( ATP ) , the naturally occurring nucleotide used in cells as a coenzyme , serves as the “energy currency of the cell” in intracellular energy metabolism [1] .", "In eukaryotes , the majority of ATP is manufactured in the chloroplasts ( for plants ) or in the mitochondria ( for ...	[ "Adenosine-5’-triphosphate ( ATP ) is generally regarded as a substrate for energy currency and protein modification .", "Recent findings uncovered the allosteric function of ATP in cellular signal transduction but little is understood about this critical behavior of ATP .", "Through extensive analysis of ATP i...	[ "The endogenous ATP can be regarded as a substrate and an allosteric modulator in cellular signal transduction .", "We analyzed the properties of allosteric and substrate ATP-binding sites and found that the allosteric ATP-binding sites are less conserved than the substrate ATP-binding sites .", "Allosteric ATP...	2014
[ "Introduction", "Materials and methods", "Results", "Discussion" ]	[ "medicine and health sciences", "diagnostic radiology", "functional magnetic resonance imaging", "neural networks", "particle physics", "random variables", "neuroscience", "covariance", "colliders", "magnetic resonance imaging", "simulation and modeling", "mathematics", "algebra", "network...	From correlation to causation: Estimating effective connectivity from zero-lag covariances of brain signals	journal.pcbi.1006056	null	[ [ "The networks of the brain are key to understanding its function and dysfunction [1] .", "Depending on the methods employed to assess structure and to record activity , networks may be defined at different levels of resolution .", "Their nodes may be individual neurons , linked by chemical or electric...	[ "Knowing brain connectivity is of great importance both in basic research and for clinical applications .", "We are proposing a method to infer directed connectivity from zero-lag covariances of neuronal activity recorded at multiple sites .", "This allows us to identify causal relations that are reflected in n...	[ "Changes in brain connectivity are considered an important biomarker for certain brain diseases .", "This directly raises the question of accessibility of connectivity from measured brain signals .", "Here we show how directed effective connectivity can be inferred from continuous brain signals , like fMRI .", ...	2018
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "molecular biology/bioinformatics", "genetics and genomics/animal genetics", "genetics and genomics/bioinformatics", "molecular biology/dna repair" ]	Delayed and Accelerated Aging Share Common Longevity Assurance Mechanisms	journal.pgen.1000161	null	[ [ "The complexity of the aging process , as well as the conspicuous lack of tools to study it , has hindered hypothesis-driven reductionist approaches to identifying the molecular mechanism of aging in mammals .", "In mice , recent progress has revealed that several aspects of aging could be accelerated or ...	[ "Mutant dwarf and calorie-restricted mice benefit from healthy aging and unusually long lifespan .", "In contrast , mouse models for DNA repair-deficient progeroid syndromes age and die prematurely .", "To identify mechanisms that regulate mammalian longevity , we quantified the parallels between the genome-wid...	[ "To identify mechanisms that regulate mammalian longevity , we have quantified the expression parallels of a number of long-lived mice that show delayed aging and DNA repair mutants that age and die prematurely .", "Unexpectedly , we found significant , genome-wide similarities and a widespread overlap of over-re...	2008
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "blood cells", "medicine and health sciences", "immune cells", "granulomas", "immunology", "vertebrates", "light microscopy", "animals", "animal models", "osteichthyes", "developmental biology", "model organisms", "microscopy", "confocal microscopy", "embryos", "neutrophils", "resear...	Mycobacterium abscessus-Induced Granuloma Formation Is Strictly Dependent on TNF Signaling and Neutrophil Trafficking	journal.ppat.1005986	null	[ [ "The rapidly-growing non-tuberculous mycobacteria ( NTM ) , Mycobacterium abscessus ( Mabs ) , is an emerging pathogen that causes a wide clinical spectrum of syndromes , including skin and soft tissues infections and pseudotuberculous pulmonary infections , especially in patients with underlying lung disorde...	[ "Mycobacterium abscessus is considered the most common respiratory pathogen among the rapidly growing non-tuberculous mycobacteria .", "Infections with M . abscessus are increasingly found in patients with chronic lung diseases , especially cystic fibrosis , and are often refractory to antibiotic therapy .", "M...	[ "The incidence of non-tuberculous mycobacterial infections has recently increased and has even surpassed tuberculosis as a public health concern in many developed countries .", "These infections require long treatment regimens that are often unsuccessful .", "Among these , Mycobacterium abscessus has emerged as...	2016
[ "Introduction", "Methods", "Results", "Discussion", "Conclusions" ]	[ "learning", "medicine and health sciences", "statistics", "applied mathematics", "social sciences", "neuroscience", "learning and memory", "simulation and modeling", "algorithms", "cognitive psychology", "mathematics", "systems science", "evolutionary adaptation", "eyes", "research and a...	A generative learning model for saccade adaptation	journal.pcbi.1006695	null	[ [ "The accuracy of saccadic eye movement is maintained through mechanisms of saccade adaptation , which adjust the amplitude [1–3] or direction [4–6] of subsequent movements in response to targeting errors .", "As online visual feedback cannot be used to correct the ongoing movement , saccadic eye movements...	[ "Plasticity in the oculomotor system ensures that saccadic eye movements reliably meet their visual goals—to bring regions of interest into foveal , high-acuity vision .", "Here , we present a comprehensive description of sensorimotor learning in saccades .", "We induced continuous adaptation of saccade amplitu...	[ "Constant adjustments of saccade metrics maintain oculomotor accuracy under changing environments .", "This error-driven learning can be induced experimentally by manipulating the targeting error of eye movements .", "Here , we investigate oculomotor learning in healthy participants in response to a sinusoidall...	2019

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