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headings list	keywords list	title stringlengths 20 281	id stringlengths 20 20	toc stringlengths 57 522 ⌀	sections list	abstract list	summary list	year stringclasses 13 values
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "recreation", "learning", "machine learning algorithms", "medicine and health sciences", "engineering and technology", "sports", "applied mathematics", "pilots", "brain electrophysiology", "social sciences", "electrophysiology", "neuroscience", "learning and memory", "simulation and modeli...	The Cybathlon BCI race: Successful longitudinal mutual learning with two tetraplegic users	journal.pbio.2003787	null	[ [ "Since the first demonstration of the profound clinical potential of brain–computer interfaces ( BCIs ) [1] , the vast majority of studies have pertained to methodological and technical challenges involving experimentation with able-bodied individuals .", "While these works can be largely credited with th...	[ "This work aims at corroborating the importance and efficacy of mutual learning in motor imagery ( MI ) brain–computer interface ( BCI ) by leveraging the insights obtained through our participation in the BCI race of the Cybathlon event .", "We hypothesized that , contrary to the popular trend of focusing mostly...	[ "Noninvasive brain–computer interface ( BCI ) based on imagined movements can restore functions lost to disability by enabling spontaneous , direct brain control of external devices without risks associated with surgical implantation of neural interfaces .", "We hypothesized that , contrary to the popular trend o...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "animal physiology", "entomology", "pest control", "biology", "zoology", "agriculture" ]	Juvenile Hormone and Insulin Regulate Trehalose Homeostasis in the Red Flour Beetle, Tribolium castaneum	journal.pgen.1003535	null	[ [ "Many biological functions of juvenile hormone ( JH ) in regulation of almost every aspect of an insect's life have been reported since its discovery in 1965 [1] , [2] .", "To maintain the larval state , JH induces the expression of the genes coding for transcription factors such as Kr-h1 to prevent metam...	[ "Insulin/IGF-1 signaling ( IIS ) has been well studied for its role in the control of life span extension and resistance to a variety of stresses .", "The Drosophila melanogaster insulin-like receptor ( InR ) mutant showed extended life span due to reduced juvenile hormone ( JH ) levels .", "However , little is...	[ "Both juvenile hormone ( JH ) and Insulin/IGF-1 signaling ( IIS ) regulate life span and starvation resistance in insects .", "Regulation of longevity and starvation resistance by IIS has been well studied , yet little is known about the underlying mechanisms and cross talk between these two hormones .", "The r...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	The Functional Connectome of Speech Control	journal.pbio.1002209	This study uses graph theory to analyze functional MRI data recorded from speakers as they produce single syllables or whole sentences, revealing the complexity of the brain network machinery that controls speech and language.	[ [ "Extensive neuroimaging research over the past two decades installed the notion that speech and language require an orchestration between several brain regions for comprehension , planning , and integration of a heard sound with a spoken word [1–6] .", "However , studies investigating brain networks of sp...	[ "In the past few years , several studies have been directed to understanding the complexity of functional interactions between different brain regions during various human behaviors .", "Among these , neuroimaging research installed the notion that speech and language require an orchestration of brain regions for...	[ "Speech production is a complex process that requires the orchestration of multiple brain regions .", "However , our current understanding of the large-scale neural architecture during speaking remains scant , as research has mostly focused on examining distinct brain circuits involved in distinct aspects of spee...	2015
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "genomics", "genome evolution", "evolutionary modeling", "biology", "computational biology" ]	A Universal Trend among Proteomes Indicates an Oily Last Common Ancestor	journal.pcbi.1002839	null	[ [ "What did the proteome of the first successful lifeform look like ?", "This question is critical to the understanding of how life as we know it first began on earth .", "Despite the progresses in ancestral sequence reconstruction methods [1]–[3] , predicting the proteome of the Last Common Ancestor ( ...	[ "Despite progresses in ancestral protein sequence reconstruction , much needs to be unraveled about the nature of the putative last common ancestral proteome that served as the prototype of all extant lifeforms .", "Here , we present data that indicate a steady decline ( oil escape ) in proteome hydrophobicity ov...	[ "Although of importance to both evolution and protein design , the manner in which the first proteome came to be , and the actual features of the earliest ancestral proteomes are both unknown .", "Through the analysis of diverse proteomes , we provide glimpses into the composition of the last common ancestor ( LU...	2012
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "medicine and health sciences", "pathology and laboratory medicine", "electrophoretic mobility shift assay", "gene regulation", "pathogens", "rna extraction", "dna-binding proteins", "microbiology", "membrane proteins", "regulator genes", "outer membrane proteins", "gene types", "molecular b...	The AraC Negative Regulator family modulates the activity of histone-like proteins in pathogenic bacteria	journal.ppat.1006545	null	[ [ "Pathogenic bacteria utilize elaborate regulatory mechanisms to effect appropriate expression of virulence-associated traits .", "The availability of genomic data sets and new high-throughput methods have illuminated not only a large number of new virulence loci , but also exposed previously unappreciated...	[ "The AraC Negative Regulators ( ANR ) comprise a large family of virulence regulators distributed among diverse clinically important Gram-negative pathogens , including Vibrio spp .", ", Salmonella spp .", ", Shigella spp .", ", Yersinia spp .", ", Citrobacter spp .", ", and pathogenic E . coli strains ."...	[ "The AraC Negative Regulators ( ANR ) is a large family of negative regulators distributed in several clinically relevant Gram-negative pathogens , including Vibrio spp .", ", Salmonella spp .", ", Shigella spp .", ", Yersinia spp .", ", Citrobacter spp .", ", pathogenic E . coli , and members of the Past...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "evolutionary biology", "none", "computational biology" ]	Automated Protein Subfamily Identification and Classification	journal.pcbi.0030160	null	[ [ "De novo subfamily identification—partitioning of sequences in a dataset into subtypes—provides two advantages for high-throughput systems of functional classification .", "First , assuming at least one subfamily member has been experimentally characterized , it becomes possible to infer function for othe...	[ "Function prediction by homology is widely used to provide preliminary functional annotations for genes for which experimental evidence of function is unavailable or limited .", "This approach has been shown to be prone to systematic error , including percolation of annotation errors through sequence databases ."...	[ "Predicting the function of a gene or protein ( gene product ) from its primary sequence is a major focus of many bioinformatics methods .", "In this paper , the authors present a three-stage computational pipeline for gene functional annotation in an evolutionary framework to reduce the systematic errors associa...	2007
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Alkaline Ceramidase 3 Deficiency Results in Purkinje Cell Degeneration and Cerebellar Ataxia Due to Dyshomeostasis of Sphingolipids in the Brain	journal.pgen.1005591	null	[ [ "Ceramides consisting of a sphingoid base moiety and an amide-linked acyl chain are the precursors of all complex sphingolipids that are essential for brain development , maturation , and proper functioning in mammals [1 , 2] .", "Ceramides are also essential precursors of sphingosine-1-phosphate ( S1P ) ...	[ "Dyshomeostasis of both ceramides and sphingosine-1-phosphate ( S1P ) in the brain has been implicated in aging-associated neurodegenerative disorders in humans .", "However , mechanisms that maintain the homeostasis of these bioactive sphingolipids in the brain remain unclear .", "Mouse alkaline ceramidase 3 (...	[ "Bioactive sphingolipids , such as ceramides and sphingosine-1-phosphates , have been implicated in neurodegenerative diseases .", "However , it remains unclear as to how the homeostasis of these bioactive lipids is sustained .", "Alkaline ceramidase 3 ( ACER3 ) catalyzes the hydrolysis of saturated long-chain ...	2015
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "medicine and health sciences", "immune physiology", "pathology and laboratory medicine", "niger", "immunology", "tropical diseases", "geographical locations", "bacterial diseases", "signs and symptoms", "eye diseases", "sexually transmitted diseases", "neglected tropical diseases", "antibod...	Community-level chlamydial serology for assessing trachoma elimination in trachoma-endemic Niger	journal.pntd.0007127	null	[ [ "Trachoma , caused by repeated ocular infection with Chlamydia trachomatis ( Ct ) , has been targeted by the World Health Organization ( WHO ) for elimination as a public health problem by the year 2020 .", "As part of the strategy to achieve elimination , WHO recommends annual mass drug administration ( ...	[ "Program decision-making for trachoma elimination currently relies on conjunctival clinical signs .", "Antibody tests may provide additional information on the epidemiology of trachoma , particularly in regions where it is disappearing or elimination targets have been met .", "A cluster-randomized trial of mass...	[ "Trachoma programs currently use the clinical sign of trachomatous inflammation-follicular ( TF ) to guide community treatment decisions and evaluate response to mass drug administration with azithromycin .", "These programs rely on clinical grading that poorly correlates with infection with the causative agent o...	2019
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "cell biology", "genetics", "biology and life sciences", "epigenetics", "molecular cell biology", "molecular biology", "parasitology" ]	SUMOylation by the E3 Ligase TbSIZ1/PIAS1 Positively Regulates VSG Expression in Trypanosoma brucei	journal.ppat.1004545	null	[ [ "Trypanosoma brucei displays a sophisticated mechanism of antigenic variation of the Variant Surface Glycoprotein ( VSG ) that allows the parasite to elude the host immune antibody response , ensuring a persistent infection [1] , [2] .", "Antigenic variation is achieved by mutually exclusive expression of...	[ "Bloodstream form trypanosomes avoid the host immune response by switching the expression of their surface proteins between Variant Surface Glycoproteins ( VSG ) , only one of which is expressed at any given time .", "Monoallelic transcription of the telomeric VSG Expression Site ( ES ) by RNA polymerase I ( RNA ...	[ "African trypanosomes have evolved one of the most complex strategies of immune evasion by routinely switching the expression of surface proteins called Variant Surface Glycoproteins ( VSG ) , only one of which is expressed at any given time .", "Previous work has suggested that the recruitment of a single VSG te...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine", "infectious diseases", "public health and epidemiology", "epidemiology", "genetics", "immunology", "biology", "microbiology", "evolutionary biology", "genetics and genomics" ]	Significant Association of KIR2DL3-HLA-C1 Combination with Cerebral Malaria and Implications for Co-evolution of KIR and HLA	journal.ppat.1002565	null	[ [ "Malaria is a serious infectious disease , affecting over 300 million people and causing more than 1 million deaths annually worldwide [1] .", "Cerebral malaria is a major , life-threatening complication of Plasmodium falciparum malaria , and has a high mortality rate [2] .", "Host immune system and g...	[ "Cerebral malaria is a major , life-threatening complication of Plasmodium falciparum malaria , and has very high mortality rate .", "In murine malaria models , natural killer ( NK ) cell responses have been shown to play a crucial role in the pathogenesis of cerebral malaria .", "To investigate the role of NK ...	[ "NK cells play an important role in early defense against pathogens .", "Killer immunoglobulin-like receptors ( KIR ) are a diverse family of activating and inhibitory receptors expressed on human NK cells .", "Some inhibitory KIRs recognize human leukocyte antigen ( HLA ) class I molecules as their ligands .",...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "evolutionary biology", "ecology" ]	Density-Dependent Cladogenesis in Birds	journal.pbio.0060071	Molecular evidence provides strong evidence that speciation rates slow down through time.	[ [ "Patterns of speciation vary across both time and space .", "The changing time course of speciation has been emphasized in the context of adaptive radiations , where it is proposed that a diversity of unexploited resources stimulates a burst of speciation , with speciation slowing down as niches become fi...	[ "A characteristic signature of adaptive radiation is a slowing of the rate of speciation toward the present .", "On the basis of molecular phylogenies , studies of single clades have frequently found evidence for a slowdown in diversification rate and have interpreted this as evidence for density dependent specia...	[ "It is probable that the number of species that a given region can support is limited; however , it is unclear whether the limit is approached sufficiently in nature such that the rate at which new species form slows down .", "Using the pattern of phylogenetic branching , a technique that estimates evolutionary r...	2008
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "computer applications", "computer science", "biology", "computational biology" ]	Automatic Morphological Subtyping Reveals New Roles of Caspases in Mitochondrial Dynamics	journal.pcbi.1002212	null	[ [ "Recent studies have shown that the fusion-fission dynamics of mitochondria are essential to many cellular processes , including ATP-level maintenance , redox signaling , oxidative stress generation , and cell death [1]–[4] .", "Meanwhile , it is also known that dysfunctional mitochondrial dynamics ushers...	[ "Morphological dynamics of mitochondria is associated with key cellular processes related to aging and neuronal degenerative diseases , but the lack of standard quantification of mitochondrial morphology impedes systematic investigation .", "This paper presents an automated system for the quantification and class...	[ "Mitochondria are “cellular power plants” that synthesize adenosine triphosphate ( ATP ) from degradation of nutrients , providing chemical energy for cellular activities .", "In addition , mitochondria are involved in a range of other cellular processes , such as signaling , cell differentiation , cell death , c...	2011
[ "Introduction", "Methods", "Results", "Discussion" ]	[]	Geographic Variation in Access to Dog-Bite Care in Pakistan and Risk of Dog-Bite Exposure in Karachi: Prospective Surveillance Using a Low-Cost Mobile Phone System	journal.pntd.0002574	null	[ [ "Infectious disease surveillance continues to remain challenging in developing countries with resource constraints , weak health systems and poor reporting mechanisms [1] , [2] .", "Existing limitations in achieving these core capacities of the International Health Regulations ( IHR ) have been further co...	[ "Dog-bites and rabies are under-reported in developing countries such as Pakistan and there is a poor understanding of the disease burden .", "We prospectively collected data utilizing mobile phones for dog-bite and rabies surveillance across nine emergency rooms ( ER ) in Pakistan , recording patient health-seek...	[ "Resource constraints prevent adequate surveillance of neglected infectious diseases such as rabies in developing countries leading to a poor understanding of the disease burden and limited evidence with which to design effective control measures .", "We utilized a low cost mobile-phone based system to carry out ...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "molecular biology/bioinformatics", "microbiology/microbial evolution and genomics", "infectious diseases/gastrointestinal infections" ]	The Defective Prophage Pool of Escherichia coli O157: Prophage–Prophage Interactions Potentiate Horizontal Transfer of Virulence Determinants	journal.ppat.1000408	null	[ [ "Horizontal gene transfer ( HGT ) is a major mechanism involved in bacterial evolution .", "In HGT between bacteria , viruses known as bacteriophages ( or phages ) play particularly important roles as gene transfer vehicles [1] , [2] .", "Incoming temperate bacteriophages parasitize their hosts by int...	[ "Bacteriophages are major genetic factors promoting horizontal gene transfer ( HGT ) between bacteria .", "Their roles in dynamic bacterial genome evolution have been increasingly highlighted by the fact that many sequenced bacterial genomes contain multiple prophages carrying a wide range of genes .", "Enteroh...	[ "Bacterial viruses , known as bacteriophages or phages , are major factors promoting horizontal gene transfer ( HGT ) between bacteria , and this activity has sparked new interest in light of the discovery that many sequenced bacterial genomes harbor multiple prophages carrying a wide range of genes , including tho...	2009
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Decoding a Signature-Based Model of Transcription Cofactor Recruitment Dictated by Cardinal Cis-Regulatory Elements in Proximal Promoter Regions	journal.pgen.1003906	null	[ [ "DNase I hypersensitive sites ( DHSs ) mark ‘open’ chromatin regions in the human genome [1] .", "When profiled at genome-wide scale in many different tissues and cell types , DHS profiles reveal that most human promoters ( at the transcriptional start site , TSS ) remain in an ‘open’ chromatin state [2]–...	[ "Genome-wide maps of DNase I hypersensitive sites ( DHSs ) reveal that most human promoters contain perpetually active cis-regulatory elements between −150 bp and +50 bp ( −150/+50 bp ) relative to the transcription start site ( TSS ) .", "Transcription factors ( TFs ) recruit cofactors ( chromatin remodelers , h...	[ "Human cells exploit different mechanisms to coordinate the expression of both protein-coding and non-coding RNAs .", "Elucidating these mechanisms is essential to understanding normal physiology and disease .", "In our attempt to identify new regulatory layers acting particularly at proximal promoters , we hav...	2013
[ "Introduction", "Materials and Methods", "Results and Discussion" ]	[ "genomics", "trypanosoma", "protozoans", "genome evolution", "parasite evolution", "genetics", "parasitology", "biology and life sciences", "comparative genomics", "microbiology", "computational biology", "protozoology", "parasitic protozoans", "organisms" ]	A Genome-Wide Analysis of Genetic Diversity in Trypanosoma cruzi Intergenic Regions	journal.pntd.0002839	null	[ [ "Understanding the functional significance of noncoding DNA is one of the major challenges of current genomics research .", "Although a number of early studies suggested that noncoding DNA evolve largely free from selective constraints , recent genome-wide comparative studies in higher eukaryotes showed t...	[ "Trypanosoma cruzi is the causal agent of Chagas Disease .", "Recently , the genomes of representative strains from two major evolutionary lineages were sequenced , allowing the construction of a detailed genetic diversity map for this important parasite .", "However this map is focused on coding regions of the...	[ "Chagas disease is caused by the protozoan parasite Trypanosoma cruzi , and poses a serious public health problem in the America , with approximately 8 million people infected and 200 , 000 new cases reported annually .", "The disease has different clinical manifestations .", "The fact that infections by the sa...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "cell physiology", "invertebrates", "mechanisms of signal transduction", "caenorhabditis", "animals", "animal models", "organisms", "developmental biology", "caenorhabditis elegans", "model organisms", "tyrosine kinase signaling cascade", "developmental signaling", "crosstalk (biology)", "...	An In Vivo EGF Receptor Localization Screen in C. elegans Identifies the Ezrin Homolog ERM-1 as a Temporal Regulator of Signaling	journal.pgen.1004341	null	[ [ "The formation of epithelial tissues involves the polarized distribution of growth factor receptors that determine cell proliferation and differentiation .", "Notably , changes in EGFR localization have a major impact on signaling and organogenesis [1]–[3] .", "In C . elegans , the let-23 gene encodes...	[ "The subcellular localization of the epidermal growth factor receptor ( EGFR ) in polarized epithelial cells profoundly affects the activity of the intracellular signaling pathways activated after EGF ligand binding .", "Therefore , changes in EGFR localization and signaling are implicated in various human diseas...	[ "Abnormal signaling by the epidermal growth factor receptor ( EGFR ) contributes to the development of various human diseases , including different cancer types .", "One important mechanism that controls intracellular signal transduction is by regulation of the subcellular receptor localization in the signal-rece...	2014
[ "Introduction", "Results" ]	[]	Transcriptional Bursting in Gene Expression: Analytical Results for General Stochastic Models	journal.pcbi.1004292	null	[ [ "The cellular response to fluctuating environments requires adjustments to cellular phenotypes driven by underlying changes in gene expression .", "Given the inherent stochasticity of cellular reactions , biological circuits controlling gene expression have to operate in the presence of significant noise ...	[ "Gene expression in individual cells is highly variable and sporadic , often resulting in the synthesis of mRNAs and proteins in bursts .", "Such bursting has important consequences for cell-fate decisions in diverse processes ranging from HIV-1 viral infections to stem-cell differentiation .", "It is generally...	[ "One of the fundamental problems in biology is understanding how phenotypic variations arise among individuals in a population .", "Recent research has shown that phenotypic variations can arise due to probabilistic cell-fate decisions driven by inherent randomness ( noise ) in the process of gene expression .", ...	2015
[ "Introduction", "Methods", "Results", "Discussion" ]	[]	Modeling the Afferent Dynamics of the Baroreflex Control System	journal.pcbi.1003384	null	[ [ "The main role of the cardiovascular ( CV ) system is to provide adequate oxygenation of all tissues , a function which is achieved by maintaining homeostasis of blood flow and pressure .", "When a mammal is subjected to an orthostatic maneuver ( e . g . , running , jumping , etc . ) , its blood volume is...	[ "In this study we develop a modeling framework for predicting baroreceptor firing rate as a function of blood pressure .", "We test models within this framework both quantitatively and qualitatively using data from rats .", "The models describe three components: arterial wall deformation , stimulation of mechan...	[ "Many people have experienced lightheadedness when standing up , yet the exact cause of this phenomenon remains unknown .", "For some people , lightheadedness occurs because of anomalies in the blood pressure control system , which keeps blood flow and pressure at homeostasis .", "One way to explore this system...	2013
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "ecology/global change ecology", "virology/virus evolution and symbiosis", "virology/emerging viral diseases" ]	Temperature, Viral Genetics, and the Transmission of West Nile Virus by Culex pipiens Mosquitoes	journal.ppat.1000092	null	[ [ "The interaction between pathogens , their vectors , and vertebrate hosts is a dynamic one , and evolution in any one of the three can significantly alter transmission dynamics .", "Theory suggests that pathogens will evolve to maximize their fitness , which is a function of transmissibility and virulence...	[ "The distribution and intensity of transmission of vector-borne pathogens can be strongly influenced by the competence of vectors .", "Vector competence , in turn , can be influenced by temperature and viral genetics .", "West Nile virus ( WNV ) was introduced into the United States of America in 1999 and subse...	[ "West Nile virus ( WNV ) was introduced into New York in 1999 and subsequently expanded its range to include much of North , Central , and South America .", "Previously , we have shown that a new strain of WNV ( referred to as WN02 ) that was first detected in 2001 and subsequently spread across North America was...	2008
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "biotechnology", "cell death", "plant anatomy", "medicine and health sciences", "pathology and laboratory medicine", "engineering and technology", "enzymes", "cell processes", "immunology", "enzymology", "immune suppression", "parasitic diseases", "ubiquitin ligases", "nematode infections"...	The potato cyst nematode effector RHA1B is a ubiquitin ligase and uses two distinct mechanisms to suppress plant immune signaling	journal.ppat.1007720	null	[ [ "Globodera pallida , a plant-parasitic cyst nematode , is a global threat to agronomically important crops such as potato and tomato .", "This sedentary plant endoparasite penetrates plant root systems to reach the inner cortex where it establishes a permanent feeding site , a multi-nucleate structure ter...	[ "Plant pathogens , such as bacteria , fungi , oomycetes and nematodes , rely on wide range of virulent effectors delivered into host cells to suppress plant immunity .", "Although phytobacterial effectors have been intensively investigated , little is known about the function of effectors of plant-parasitic nemat...	[ "Globodera pallida is a plant-parasitic cyst nematode that causes vast losses in economically important crops such as potato and tomato .", "To successfully parasitize host plants , G . pallida produces proteins called effectors to overcome plant defenses .", "Here , we report identification of a novel G . pall...	2019
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "medicine and health sciences", "immune physiology", "pathology and laboratory medicine", "togaviruses", "chikungunya infection", "pathogens", "immunology", "tropical diseases", "microbiology", "alphaviruses", "viruses", "muscle regeneration", "developmental biology", "chikungunya virus", ...	Molecular Mimicry between Chikungunya Virus and Host Components: A Possible Mechanism for the Arthritic Manifestations	journal.pntd.0005238	null	[ [ "Chikungunya fever is caused by a arbovirus belonging to Family Togaviridae and Genus Alphavirus .", "CHIKV is positive sense RNA virus with about 11 . 8 kb long genome .", "The prevalence of CHIKV has increased globally .", "It caused massive outbreaks when it re- emerged in 2005 in French Reunio...	[ "Chikungunya virus ( CHIKV ) , a reemerging pathogen causes a self limited illness characterized by fever , headache , myalgia and arthralgia .", "However , 10–20% affected individuals develop persistent arthralgia which contributes to considerable morbidity .", "The exact molecular mechanisms underlying these ...	[ "The outcome of Chikungunya virus infection is usually benign but persistent arthritis has been reported in 10–20% of patients after Chikungunya fever .", "However , some reports have suggested that similarity between host proteins and viral proteins ( molecular mimicry ) leads to immune mediated damage .", "Ho...	2017
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "medicine and health sciences", "biopsy", "neurodegenerative diseases", "protein interaction networks", "topographic maps", "surgical and invasive medical procedures", "multivariate analysis", "mathematics", "statistics (mathematics)", "network analysis", "genome analysis", "research and analy...	A systematic atlas of chaperome deregulation topologies across the human cancer landscape	journal.pcbi.1005890	null	[ [ "Eukaryotic proteomes comprise a complex repertoire of diverse protein species that are organized in a modular interactome network in order to execute native function in support of proteostasis and a healthy cellular phenotype .", "Proteome balance is safeguarded by the proteostasis network ( PN ) , an in...	[ "Proteome balance is safeguarded by the proteostasis network ( PN ) , an intricately regulated network of conserved processes that evolved to maintain native function of the diverse ensemble of protein species , ensuring cellular and organismal health .", "Proteostasis imbalances and collapse are implicated in a ...	[ "Protein homeostasis , or proteostasis , is maintained by the proteostasis network ( PN ) , an intricately regulated modular network of interacting processes that evolved to balance the native proteome , supporting cellular and organismal health throughout lifespan .", "Imbalances and collapse of cellular proteos...	2018
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "medicine and health sciences", "pathology and laboratory medicine", "biopsy", "pathogens", "microbiology", "surgical and invasive medical procedures", "viruses", "dna viruses", "genome analysis", "herpesviruses", "research and analysis methods", "sequence analysis", "genomic libraries", "...	Quantitative RNAseq analysis of Ugandan KS tumors reveals KSHV gene expression dominated by transcription from the LTd downstream latency promoter	journal.ppat.1007441	null	[ [ "Since its discovery in 1994 , the Kaposi sarcoma-associated herpesvirus ( KSHV ) , also known as human herpesvirus-8 ( HHV-8 ) , has been identified as the etiologic cause of all types of Kaposi sarcoma ( KS ) , and is etiologically associated with primary effusion lymphoma ( PEL ) and multicentric Castleman...	[ "KSHV is endemic in Uganda and the HIV epidemic has dramatically increased the incidence of Kaposi sarcoma ( KS ) .", "To investigate the role of KSHV in the development of KS , we obtained KS biopsies from ART-naïve , HIV-positive individuals in Uganda and analyzed the tumors using RNAseq to globally characteriz...	[ "Kaposi’s sarcoma ( KS ) is among the world’s most common AIDS-associated malignancies .", "The Kaposi sarcoma-associated herpesvirus ( KSHV ) was first identified in KS tumors and is now known to be the causative agent of all forms of KS , including classical , endemic , iatrogenic and HIV-associated .", "KSHV...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Lysine Acetyltransferase GCN5b Interacts with AP2 Factors and Is Required for Toxoplasma gondii Proliferation	journal.ppat.1003830	null	[ [ "Lysine acetylation of histones is a well-characterized post-translational modification linked to the activation of gene expression .", "Initially identified in the free-living protozoan Tetrahymena thermophila , the first histone acetyltransferase ( HAT ) was homologous to a transcriptional adaptor prote...	[ "Histone acetylation has been linked to developmental changes in gene expression and is a validated drug target of apicomplexan parasites , but little is known about the roles of individual histone modifying enzymes and how they are recruited to target genes .", "The protozoan parasite Toxoplasma gondii ( phylum ...	[ "Toxoplasma gondii is a protozoan parasite that causes significant opportunistic infection in AIDS and other immunocompromised patients .", "Acute episodes of toxoplasmosis stem from tissue destruction caused by the rapidly growing form of the parasite , the tachyzoite .", "In this study , we identify a lysine ...	2014
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "medicine", "infectious diseases", "neglected tropical diseases", "parasitic diseases" ]	Efficacy and Safety of Nitazoxanide, Albendazole, and Nitazoxanide-Albendazole against Trichuris trichiura Infection: A Randomized Controlled Trial	journal.pntd.0001685	null	[ [ "Infections with the soil-transmitted helminths , Ascaris lumbricoides , Trichuris trichiura , and the two hookworm species Ancylostoma duodenale and Necator americanus , are the most common infections of humans , causing an estimated global burden of 39 million disability-adjusted life years lost ( DALYs ) [...	[ "The currently used anthelmintic drugs , in single oral application , have low efficacy against Trichuris trichiura infection , and hence novel anthelmintic drugs are needed .", "Nitazoxanide has been suggested as potential drug candidate .", "The efficacy and safety of a single oral dose of nitazoxanide ( 1 , ...	[ "More than 5 billion people are at risk of infection with one of the three most common intestinal worms , the roundworm Ascaris lumbricoides , the whipworm Trichuris trichiura , and two different kinds of hookworms .", "The global strategy to control these intestinal worm infections is through the regular adminis...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine and health sciences", "breast tumors", "morphogenic segmentation", "cancers and neoplasms", "dna-binding proteins", "oncology", "mutation", "developmental biology", "gene types", "pharmacology", "frameshift mutation", "morphogenesis", "tumor suppressor genes", "proteins", "gene...	Gain- and Loss-of-Function Mutations in the Breast Cancer Gene GATA3 Result in Differential Drug Sensitivity	journal.pgen.1006279	null	[ [ "High-throughput genome sequencing has allowed the systematic analysis of the complex mutational landscape of tumours and has provided key insights into tumour evolution and cancer etiology [1–3] .", "Mutation patterns in individual genes also reveal important insights into their role in tumourigenesis an...	[ "Patterns of somatic mutations in cancer genes provide information about their functional role in tumourigenesis , and thus indicate their potential for therapeutic exploitation .", "Yet , the classical distinction between oncogene and tumour suppressor may not always apply .", "For instance , TP53 has been sim...	[ "Cancer is a disease caused by genetic mutations .", "Mutation patterns are often indicative of a gene’s function as either tumour promoting or tumour suppressive .", "Here we describe the frequently mutated , but poorly studied , breast cancer gene GATA3 as a rare exception: We discover that two different func...	2016
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[]	Infectiousness of Sylvatic and Synanthropic Small Rodents Implicates a Multi-host Reservoir of Leishmania (Viannia) braziliensis	journal.pntd.0004137	null	[ [ "Transmission of zoonotic pathogens may involve one , or typically more than one , reservoir host .", "Compared to pathogens with single reservoir hosts , those involving multi-host communities usually show reduced transmission rates through a process of zooprophylaxis or “dilution effect” due to heteroge...	[ "The possibility that a multi-host wildlife reservoir is responsible for maintaining transmission of Leishmania ( Viannia ) braziliensis causing human cutaneous and mucocutaneous leishmaniasis is tested by comparative analysis of infection progression and infectiousness to sandflies in rodent host species previousl...	[ "Across the Americas , Leishmania ( V . ) braziliensis is the predominant Leishmania species causing cutaneous and mucocutaneous leishmaniasis in humans .", "Transmitted by Phlebotomine sandflies , questions remain about the epidemiological contributions of the numerous zoonotic and more domestic host species .",...	2015
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "infographics", "chemical characterization", "protein interactions", "social sciences", "archaeology", "protein structure", "research and analysis methods", "sequence analysis", "computer and information sciences", "sequence alignment", "bioinformatics", "proteins", "biological databases", ...	A benchmark driven guide to binding site comparison: An exhaustive evaluation using tailor-made data sets (ProSPECCTs)	journal.pcbi.1006483	null	[ [ "Due to the huge number of available binding site comparison algorithms[5] , a large-scale analysis of all methods is beyond the scope of this article .", "We have therefore restricted the evaluation to a small , but still diverse subset of promising algorithms .", "These were derived from an analysis...	[ "The automated comparison of protein-ligand binding sites provides useful insights into yet unexplored site similarities .", "Various stages of computational and chemical biology research can benefit from this knowledge .", "The search for putative off-targets and the establishment of polypharmacological effect...	[ "Binding site similarities are useful in the context of promiscuity prediction , drug repurposing , the analysis of protein-ligand and protein-protein complexes , function prediction , and further fields of general interest in chemical biology and biochemistry .", "Many years of research have led to the developme...	2018
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "physiology/neuronal signaling mechanisms", "biophysics/theory and simulation", "physiology", "biophysics", "neuroscience", "neuroscience/theoretical neuroscience" ]	Ion Channel Density Regulates Switches between Regular and Fast Spiking in Soma but Not in Axons	journal.pcbi.1000753	null	[ [ "It is now more than 60 years since Alan Hodgkin categorized the firing behaviour in his classical study of isolated axons from the crab Carcinus maenas [1] .", "In many respects his experiments still form the basis for analysis of firing patterns in nervous systems .", "Using threshold dynamics and m...	[ "The threshold firing frequency of a neuron is a characterizing feature of its dynamical behaviour , in turn determining its role in the oscillatory activity of the brain .", "Two main types of dynamics have been identified in brain neurons .", "Type 1 dynamics ( regular spiking ) shows a continuous relationshi...	[ "All activity of the brain is manifested in electrical oscillatory patterns , shaped by the firing dynamics of the many neurons forming the brain networks .", "The underlying mechanisms of the firing pattern in the single neurons are still not fully understood .", "The distribution and identity of different cha...	2010
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	9-cis-13,14-Dihydroretinoic Acid Is an Endogenous Retinoid Acting as RXR Ligand in Mice	journal.pgen.1005213	null	[ [ "Micronutrients such as vitamin A and polyunsaturated fatty acids are essential ingredients of mammalian diet and can act as bioactive molecules .", "Nuclear hormone receptors sense such molecular signals and accordingly regulate gene expression , thus functioning as ligand-controlled transcription factor...	[ "The retinoid X receptors ( RXRs ) are ligand-activated transcription factors which heterodimerize with a number of nuclear hormone receptors , thereby controlling a variety of ( patho ) -physiological processes .", "Although synthetic RXR ligands are developed for the treatment of various diseases , endogenous l...	[ "Daily nutrition , in addition to being a source of energy , contains micronutrients , a class of nutrients including vitamins which are essential for life and which act by orchestrating a vast number of developmental and physiological processes .", "During metabolism , micronutrients are frequently transformed i...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "growth plate", "sequencing techniques", "medicine and health sciences", "chondrocytes", "twins", "mutation", "developmental biology", "bone", "connective tissue cells", "sequence motif analysis", "molecular biology techniques", "frameshift mutation", "cartilage", "research and analysis me...	Altered mRNA Splicing, Chondrocyte Gene Expression and Abnormal Skeletal Development due to SF3B4 Mutations in Rodriguez Acrofacial Dysostosis	journal.pgen.1006307	null	[ [ "The acrofacial dysostoses ( AFD ) are a genetically heterogeneous group of inherited disorders unified by craniofacial and limb abnormalities .", "At least 18 types of AFD have been characterized and , depending on the specific patterns of limb abnormalities , they have been further classified into those...	[ "The acrofacial dysostoses ( AFD ) are a genetically heterogeneous group of inherited disorders with craniofacial and limb abnormalities .", "Rodriguez syndrome is a severe , usually perinatal lethal AFD , characterized by severe retrognathia , oligodactyly and lower limb abnormalities .", "Rodriguez syndrome h...	[ "The acrofacial dysostoses ( AFD ) are inherited disorders with abnormalities of the facial and limb bones .", "Rodriguez syndrome is a severe type of AFD that is usually lethal in the immediate perinatal period .", "Rodriguez syndrome has been proposed to be a severe form of Nager syndrome , a non-lethal AFD t...	2016
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "nucleic acid synthesis", "mitochondrial dna", "dna-binding proteins", "fungi", "model organisms", "polymerases", "dna replication", "experimental organism systems", "forms of dna", "mitochondria", "dna", "bioenergetics", "cellular structures and organelles", "gel electrophoresis", "dna ...	The presence of rNTPs decreases the speed of mitochondrial DNA replication	journal.pgen.1007315	null	[ [ "The replication of DNA is a highly accurate process where free deoxyribonucleoside triphosphates ( dNTPs ) are incorporated opposite their complementary base .", "In general , DNA polymerases are good at discriminating between ribonucleoside triphosphates ( rNTPs; the units that constitute RNA ) and dNTP...	[ "Ribonucleotides ( rNMPs ) are frequently incorporated during replication or repair by DNA polymerases and failure to remove them leads to instability of nuclear DNA ( nDNA ) .", "Conversely , rNMPs appear to be relatively well-tolerated in mitochondrial DNA ( mtDNA ) , although the mechanisms behind the toleranc...	[ "Mitochondria are essential for energy production , and defects in the maintenance of mitochondrial DNA ( mtDNA ) lead to a variety of human diseases including mtDNA depletion syndrome ( MDS ) .", "Certain forms of MDS are caused by imbalances in the mitochondrial deoxyribonucleoside triphosphate ( dNTP ) pool , ...	2018
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[]	Spot the Difference—Development of a Syndrome Based Protein Microarray for Specific Serological Detection of Multiple Flavivirus Infections in Travelers	journal.pntd.0003580	null	[ [ "The family Flaviviridae , genus Flavivirus , holds many of the world’s most prevalent arboviral diseases that are also considered the most important travel related arboviral infections . [1]", "As the geographic distribution and symptoms caused by these viruses overlap , detection requires differential d...	[ "The family Flaviviridae , genus Flavivirus , holds many of the world’s most prevalent arboviral diseases that are also considered the most important travel related arboviral infections .", "In most cases , flavivirus diagnosis in travelers is primarily based on serology as viremia is often low and typically has ...	[ "The number of international travelers has increased dramatically in recent decades .", "This has contributed to the increase in infectious diseases in travelers which are not present in their countries of origin and so may cause a threat to the public health .", "Viruses transmitted by biting insects ( vector-...	2015
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "molecular cell biology", "virology", "biology", "microbiology" ]	Intracellular Vesicle Acidification Promotes Maturation of Infectious Poliovirus Particles	journal.ppat.1003046	null	[ [ "The Picornaviridae , a family of non-enveloped viruses with a small positive strand RNA genome , includes numerous known and emerging pathogens of medical , veterinary and agricultural importance [1] .", "Poliovirus ( PV ) is the most extensively studied virus in this family in terms of our collective un...	[ "The autophagic pathway acts as part of the immune response against a variety of pathogens .", "However , several pathogens subvert autophagic signaling to promote their own replication .", "In many cases it has been demonstrated that these pathogens inhibit or delay the degradative aspect of autophagy .", "H...	[ "The autophagic degradation pathway is a well-known agent of innate immunity .", "Several pathogens , including poliovirus ( PV ) , a model for several medically important RNA viruses , subvert this pathway for their own benefit .", "In doing so , pathogens often inhibit the degradative portion of the pathway ,...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods", "Supporting Information" ]	[ "aging", "developmental biology", "caenorhabditis", "indy", "wolbachia", "drosophila", "genetics and genomics" ]	No Influence of Indy on Lifespan in Drosophila after Correction for Genetic and Cytoplasmic Background Effects	journal.pgen.0030095	null	[ [ "Mutations in single genes in invertebrate model organisms have been used with great success to discover developmental mechanisms that are evolutionarily conserved in mammals .", "More recently , it has become apparent that the aging process , too , can be investigated by analysis of single gene mutations...	[ "To investigate whether alterations in mitochondrial metabolism affect longevity in Drosophila melanogaster , we studied lifespan in various single gene mutants , using inbred and outbred genetic backgrounds .", "As positive controls we included the two most intensively studied mutants of Indy , which encodes a D...	[ "Human life expectancy is increasing in many populations .", "Research on aging has gained great attention recently by discoveries of mutations that slow down aging in relatively short-lived models .", "Studies carried out in yeast , worms , and flies have revealed evolutionarily conserved mechanisms of aging ,...	2007
[ "Introduction", "Results and Discussion", "Materials and Methods" ]	[ "sequencing techniques", "cell motility", "medicine and health sciences", "pathology and laboratory medicine", "pathogens", "split-decomposition method", "microbiology", "genomic databases", "bacterial diseases", "multiple alignment calculation", "enterobacteriaceae", "genome analysis", "mol...	Evolutionary Genomics Suggests That CheV Is an Additional Adaptor for Accommodating Specific Chemoreceptors within the Chemotaxis Signaling Complex	journal.pcbi.1004723	null	[ [ "Bacteria navigate in chemical gradients by regulating their flagellar motility .", "This behavior , known as chemotaxis , is characterized by high sensitivity and precise adaptation that are attributed to the underlying molecular machinery , which is best understood in the model organism Escherichia coli...	[ "Escherichia coli and Salmonella enterica are models for many experiments in molecular biology including chemotaxis , and most of the results obtained with one organism have been generalized to another .", "While most components of the chemotaxis pathway are strongly conserved between the two species , Salmonella...	[ "Due to the overwhelming complexity and diversity of biological systems , the functional roles of the majority of proteins encoded in sequenced genomes remain unknown or poorly understood .", "The multi-protein pathway controlling chemotaxis in bacteria and archaea is an example of such complexity and diversity ....	2016
[ "Introduction", "Methods", "Results", "Discussion" ]	[]	Inhibition of Tityus serrulatus venom hyaluronidase affects venom biodistribution	journal.pntd.0007048	null	[ [ "Scorpionism is considered a serious public health threat and was officially recognized as a neglected tropical disease by the Brazilian Academy of Sciences [1] .", "In Brazil , scorpion sting reports have been increasing over the years , reaching 90 , 000 accidents in 2016 , and outnumbering the accident...	[ "The hyaluronidase enzyme is generally known as a spreading factor in animal venoms .", "Although its activity has been demonstrated in several organisms , a deeper knowledge about hyaluronidase and the venom spreading process from the bite/sting site until its elimination from the victim's body is still in need ...	[ "Hyaluronidases are known as the venom components responsible for disseminating toxins from the injection site to the victim’s organism .", "Therefore , understanding how the venom distribution occurs and the role of hyaluronidases in this process is crucial in the field of toxinology .", "In this study , we in...	2019
[ "Introduction", "Methods", "Results", "Discussion" ]	[]	Identification of avian flapping motion from non-volant winged dinosaurs based on modal effective mass analysis	journal.pcbi.1006846	null	[ [ "The origin of avian flight has been debated for over 150 years , ever since the discovery of the first fossil of Archaeopteryx in 1861 [1–35] .", "Being widely considered as the oldest and most basal-known avian taxon , Archaeopteryx is characterized by a long boney tail , three clawed digits forming the...	[ "The origin of avian flight is one of the most controversial debates in Paleontology .", "This paper investigates the wing performance of Caudipteryx , the most basal non-volant dinosaur with pennaceous feathered forelimbs by using modal effective mass theory .", "From a mechanical standpoint , the forced vibra...	[ "The origin of avian flight in the perspective of mechanics has been investigated for the first time .", "We reported the first evidence for flapping hypothesis based on principle of physical modeling .", "This is significant because using modal effective mass method and reconstructed Caudipteryx , the most bas...	2019
[ "Introduction", "Methods", "Results", "Discussion" ]	[]	Temephos Resistance in Aedes aegypti in Colombia Compromises Dengue Vector Control	journal.pntd.0002438	null	[ [ "Dengue fever is the most rapidly expanding arboviral disease in the world .", "Approximately 50 million infections occur in 100 countries annually [1] , [2] , and 60% of those are estimated to occur in the Americas [3] .", "In Colombia , dengue is considered a major public health problem , with appro...	[ "Control and prevention of dengue relies heavily on the application of insecticides to control dengue vector mosquitoes .", "In Colombia , application of the larvicide temephos to the aquatic breeding sites of Aedes aegypti is a key part of the dengue control strategy .", "Resistance to temephos was recently de...	[ "Dengue fever , caused by viruses transmitted by the Aedes aegypti mosquito , is an important threat to public health in many tropical and subtropical countries .", "In the absence of a vaccine or specific drug treatment , prevention and control of dengue transmission relies on interventions targeting vector mosq...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	dbl-1/TGF-β and daf-12/NHR Signaling Mediate Cell-Nonautonomous Effects of daf-16/FOXO on Starvation-Induced Developmental Arrest	journal.pgen.1005731	null	[ [ "C . elegans L1-stage larvae must feed upon hatching in order to exit developmental arrest .", "Larvae in L1 arrest have increased stress resistance and can survive for weeks , initiating postembryonic development when food is available [1] .", "C . elegans larvae can also arrest development during th...	[ "Nutrient availability has profound influence on development .", "In the nematode C . elegans , nutrient availability governs post-embryonic development .", "L1-stage larvae remain in a state of developmental arrest after hatching until they feed .", "This “L1 arrest” ( or \"L1 diapause\" ) is associated with...	[ "Animals must cope with feast and famine in the wild .", "Environmental fluctuations require a balancing act between development in favorable conditions and survival during starvation .", "Disruption of the pathways that govern this balance can lead to cancer , where cells proliferate when they should not , and...	2015
[ "Introduction", "Results", "Discussion" ]	[ "medicine and health sciences", "pathology and laboratory medicine", "evolutionary biology", "pathogens", "population genetics", "bladder", "microbiology", "gene pool", "genetic elements", "population biology", "kidneys", "proteus mirabilis", "bacterial pathogens", "infectious diseases", ...	Genome-wide transposon mutagenesis of Proteus mirabilis: Essential genes, fitness factors for catheter-associated urinary tract infection, and the impact of polymicrobial infection on fitness requirements	journal.ppat.1006434	null	[ [ "The Gram-negative bacterium Proteus mirabilis thrives in a wide variety of environments , including soil , water sources , sewage , and as a commensal in the intestinal tract of humans and animals [1 , 2] .", "P . mirabilis has also been identified as the causative agent of numerous human illnesses inclu...	[ "The Gram-negative bacterium Proteus mirabilis is a leading cause of catheter-associated urinary tract infections ( CAUTIs ) , which are often polymicrobial .", "Numerous prior studies have uncovered virulence factors for P . mirabilis pathogenicity in a murine model of ascending UTI , but little is known concern...	[ "Proteus mirabilis is a common cause of single-species and polymicrobial catheter-associated urinary tract infections ( CAUTIs ) .", "Prior studies have uncovered P . mirabilis virulence factors for single-species ascending UTI , but little is known concerning pathogenesis during CAUTI or polymicrobial infection ...	2017
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "computational biology/molecular dynamics", "biophysics/theory and simulation", "biophysics/membrane proteins and energy transduction" ]	Asymmetric Switching in a Homodimeric ABC Transporter: A Simulation Study	journal.pcbi.1000762	null	[ [ "ATP-binding cassette ( ABC ) transporters are a large family of membrane proteins that use MgATP hydrolysis to drive the import or export of solutes to or from the cytoplasm .", "They undertake a number of physiological roles , for example bacterial nutrient uptake , bacterial drug resistance , tumor dru...	[ "ABC transporters are a large family of membrane proteins involved in a variety of cellular processes , including multidrug and tumor resistance and ion channel regulation .", "Advances in the structural and functional understanding of ABC transporters have revealed that hydrolysis at the two canonical nucleotide...	[ "ABC transporters are a large family of membrane proteins present in all organisms .", "Typically , they utilize ATP hydrolysis , the most prominent biological energy source , to translocate substrates into cells ( e . g . , bacterial nutritient uptake ) or out of cells ( e . g . , multidrug exporters that contri...	2010
[ "Introduction", "Materials and methods", "Results", "Discussion" ]	[ "geomorphology", "medicine and health sciences", "ecology and environmental sciences", "surface water", "rivers", "landforms", "topography", "tropical diseases", "geographical locations", "argentina", "bacterial diseases", "research design", "aquatic environments", "bodies of water", "fl...	Knowledge, attitudes and practices (KAP) regarding leptospirosis among residents of riverside settlements of Santa Fe, Argentina	journal.pntd.0006470	null	[ [ "Leptospirosis is a zoonotic disease caused by Leptospira spirochetes .", "Pathogenic leptospires are excreted in the urine of mammalian hosts such as rodents , dogs and cattle and can persist in the environment for weeks or months [1–4] .", "Humans serve as incidental hosts , exposure may occur throu...	[ "Leptospirosis is a global and re-emerging zoonotic disease caused by Leptospira spirochetes that are shed into the environment by infected animals .", "Humans can get infected via contact with animal hosts or contaminated environment .", "In Argentina , the highest annual incidences were reported in the provin...	[ "Leptospirosis is a zoonotic bacterial disease that has been recognized as a growing public health problem affecting mainly residents from slum settlements located in floodable areas .", "As such , it is considered a neglected disease that needs greater attention to reduce its global burden .", "A key step towa...	2018
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "dna transcription", "cell biology", "chromosome biology", "genetic interference", "animal genomics", "gene expression", "genetics", "gene regulation", "biology and life sciences", "gene types", "mammalian genomics", "genomics", "reporter genes", "genetic loci", "chromosomes" ]	Three distinct mechanisms of long-distance modulation of gene expression in yeast	journal.pgen.1006736	null	[ [ "Cell proliferation and differentiation depend on rigorously controlled gene activities .", "Gene regulation is best understood at the level of linear organization of the genome , including the primary DNA sequences and arrays of closely associated regulatory proteins .", "The three-dimensional ( 3D )...	[ "Recent Hi-C measurements have revealed numerous intra- and inter-chromosomal interactions in various eukaryotic cells .", "To what extent these interactions regulate gene expression is not clear .", "This question is particularly intriguing in budding yeast because it has extensive long-distance chromosomal in...	[ "Eukaryotic transcription occurs within the nucleus where DNA is packaged into high order chromosome structures .", "Some long-distance chromosomal interactions play an important role in gene regulation in higher eukaryotic species , such as mouse and human .", "In budding yeast , gene expression is traditional...	2017
[ "Introduction", "Results and discussion", "Conclusions", "Materials and methods" ]	[ "amphibian genomics", "taxonomy", "organismal evolution", "medicine and health sciences", "pathology and laboratory medicine", "pathogens", "microbiology", "vertebrates", "animals", "animal phylogenetics", "retroviruses", "viruses", "phylogenetics", "data management", "reptile genomics",...	Endogenous retroviruses of non-avian/mammalian vertebrates illuminate diversity and deep history of retroviruses	journal.ppat.1007072	null	[ [ "Retroviruses ( family Retroviridae ) exclusively infect vertebrates and cause a wide variety of diseases , such as AIDS and cancers [1 , 2] .", "Different from other RNA viruses , the replication of retroviruses requires reverse transcription of viral RNA into DNA and integration of the newly synthesized...	[ "The deep history and early diversification of retroviruses remains elusive , largely because few retroviruses have been characterized in vertebrates other than mammals and birds .", "Endogenous retroviruses ( ERVs ) documented past retroviral infections and thus provide ‘molecular fossils’ for studying the deep ...	[ "Retroviruses infect a wide range of vertebrates and cause many diseases , such as AIDS and cancers .", "To date , retroviruses have been rarely characterized in vertebrates other than mammals and birds , impeding our understanding of the diversity and early evolution of retroviruses .", "Retroviruses can occas...	2018
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "medicine", "infectious diseases", "drugs and devices", "global health", "public health" ]	A Cluster Randomized Study of The Safety of Integrated Treatment of Trachoma and Lymphatic Filariasis in Children and Adults in Sikasso, Mali	journal.pntd.0002221	null	[ [ "Lymphatic filariasis ( LF ) , a leading cause of permanent and long-term disability globally , affects over 120 million people in more than 80 countries in tropical and subtropical areas [1] .", "Trachoma is the main cause of infectious blindness , responsible for around 5% of the world's blind people [2...	[ "Neglected tropical diseases are co-endemic in many areas of the world , including sub Saharan Africa .", "Currently lymphatic filariasis ( albendazole/ivermectin ) and trachoma ( azithromycin ) are treated separately .", "Consequently , financial and logistical benefit can be gained from integration of prevent...	[ "Neglected tropical diseases are co-endemic in many areas of the world .", "Currently lymphatic filariasis ( albendazole+ivermectin ) and trachoma ( azithromycin ) are treated separately .", "Benefits can be gained from integration of preventive chemotherapy programs in such areas .", "To assess the safety of...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biochemistry", "infectious diseases", "cell biology", "microbiology", "neuroscience" ]	SV2 Mediates Entry of Tetanus Neurotoxin into Central Neurons	journal.ppat.1001207	null	[ [ "The Clostridium genus of bacteria are responsible for the production of the clostridial neurotoxins ( CNTs ) , which include both tetanus neurotoxin ( TeNT ) and seven botulinum neurotoxins ( BoNT/A–G ) [1] .", "TeNT is synthesized by Clostridium tetani , and is one of the most toxic substances known to ...	[ "Tetanus neurotoxin causes the disease tetanus , which is characterized by rigid paralysis .", "The toxin acts by inhibiting the release of neurotransmitters from inhibitory neurons in the spinal cord that innervate motor neurons and is unique among the clostridial neurotoxins due to its ability to shuttle from t...	[ "Tetanus neurotoxin is one of the most deadly bacterial toxins known and is the causative agent for the disease tetanus , also known as lockjaw .", "Tetanus neurotoxin utilizes motor neurons as a means of transport in order to enter the spinal cord .", "Once in the spinal cord , the toxin leaves motor neurons a...	2010
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "none", "infectious diseases" ]	Nanobacteria Are Mineralo Fetuin Complexes	journal.ppat.0040041	null	[ [ "“Nanobacteria” are mysterious particles that have spurred one of the biggest controversies in modern microbiology [1–3] .", "First discovered by geologists as 100 nm coccoid particles present on mineral surfaces [4] , such structures were later found in human and cow blood as well as in commercial cell c...	[ "“Nanobacteria” are nanometer-scale spherical and ovoid particles which have spurred one of the biggest controversies in modern microbiology .", "Their biological nature has been severely challenged by both geologists and microbiologists , with opinions ranging from considering them crystal structures to new life...	[ "In the last decade , the exact nature of nanobacteria was one of the most controversial of scientific questions .", "An audacious theory proposed the existence of nanobacteria , initially discovered in Italian hot spring deposits , as a new life form responsible for a wide range of diseases in humans , thus qual...	2008
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biology and life sciences" ]	Enhanced Interaction between Pseudokinase and Kinase Domains in Gcn2 stimulates eIF2α Phosphorylation in Starved Cells	journal.pgen.1004326	null	[ [ "Eukaryotic cells harbor stress-activated protein kinases that down-regulate protein synthesis and simultaneously up-regulate transcriptional activators at the translational level .", "This dual response allows cells to reduce bulk protein synthesis while re-programming transcription to favor expression o...	[ "The stress-activated protein kinase Gcn2 regulates protein synthesis by phosphorylation of translation initiation factor eIF2α , from yeast to mammals .", "The Gcn2 kinase domain ( KD ) is inherently inactive and requires allosteric stimulation by adjoining regulatory domains .", "Gcn2 contains a pseudokinase ...	[ "The survival of all living organisms depends on their capacity to adapt their gene expression program to variations in the environment .", "When subjected to various stresses , eukaryotic cells down-regulate general protein synthesis by phosphorylation of eukaryotic translation initiation factor 2 alpha ( eIF2α ...	2014
[ "Introduction", "Materials and methods", "Results", "Discussion" ]	[ "medicine and health sciences", "chemical compounds", "microbiology", "parasitic diseases", "parasitic protozoans", "organic compounds", "protozoan life cycles", "parasitology", "animal models", "parasitemia", "developmental biology", "trypomastigotes", "model organisms", "protozoans", "...	Anti-parasitic effect of vitamin C alone and in combination with benznidazole against Trypanosoma cruzi	journal.pntd.0006764	null	[ [ "Trypanosoma cruzi is the causative agent of Chagas’ disease , which was declared of worldwide interest by the World Health Organization ( WHO ) [1] .", "To fight this illness that originated in Latin America ( American trypanosomiasis ) , nifurtimox and benznidazole ( Bnz ) are used .", "These drugs ...	[ "Drugs currently used for the treatment of Chagas’ disease , nifurtimox and benznidazole , have a limited effectiveness and toxic side effects .", "With the aim of finding new therapeutic approaches , in vitro and in vivo anti-Trypanosoma cruzi activity of vitamin C alone and combined with benznidazole were inves...	[ "The huge worldwide expansion of Chagas’ disease ( American trypanosomiasis ) that has occurred as a result of the population mobility from Latin America , has caused this parasitic disease to become an important topic for the World Health Organization .", "Cases of Chagas’ disease have been reported in the Unite...	2018
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "sequencing techniques", "invertebrates", "typhus", "medicine and health sciences", "pathology and laboratory medicine", "pathogens", "geographical locations", "microbiology", "vertebrates", "animals", "mammals", "next-generation sequencing", "bacterial diseases", "genome analysis", "mol...	Heterogeneity of Orientia tsutsugamushi genotypes in field-collected trombiculid mites from wild-caught small mammals in Thailand	journal.pntd.0006632	null	[ [ "Scrub typhus is caused by intracellular Gram-negative bacteria belonging to the genus Orientia , although O . tsutsugamushi was thought to be the only causative agent until recently .", "Orientia species have been separated from the genus Rickettsia on the basis of differences in genome arrangement and c...	[ "Trombiculid mites are the vectors of scrub typhus , with infected larval mites ( chiggers ) transmitting the causative agent , Orientia tsutsugamushi , during feeding .", "Co-existence of multiple O . tsutsugamushi strains within infected mites has previously been reported in naturally infected , laboratory-rear...	[ "Scrub typhus is a leading cause of undifferentiated febrile illness , putting 1 billion people at risk of infection .", "Trombiculid mites are the major vectors of the causative agent of scrub typhus , Orientia tsutsugamushi ( OT ) , which is transferred through the bite of an infected mite .", "Previously , w...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "systems biology", "medicine", "drug research and development", "drugs and devices", "pharmacology", "biology", "computational biology", "drug interactions", "drug discovery" ]	Assessing Drug Target Association Using Semantic Linked Data	journal.pcbi.1002574	null	[ [ "Understanding the interaction of drugs with multiple targets can identify potential side effects and toxicities [1]–[3] , as well as possible new applications of existing drugs [4]–[8] .", "Many efforts have been made to integrate drug-target interactions in a large scale [9]–[12] .", "A variety of c...	[ "The rapidly increasing amount of public data in chemistry and biology provides new opportunities for large-scale data mining for drug discovery .", "Systematic integration of these heterogeneous sets and provision of algorithms to data mine the integrated sets would permit investigation of complex mechanisms of ...	[ "Modern drug discovery requires the understanding of chemogenomics , the complex interaction of chemical compounds and drugs with a wide variety of protein target and genes in the body .", "A large amount of data pertaining to such relationships exists in publicly-accessible datasets but it is siloed and thus imp...	2012
[ "Introduction", "Model", "Results", "Discussion", "Materials and Methods" ]	[]	Protein Connectivity in Chemotaxis Receptor Complexes	journal.pcbi.1004650	null	[ [ "Escherichia coli cells are able to sense changes in the chemical environment , allowing the bacteria to move towards higher concentrations of attractants and lower concentrations of repellents .", "The chemotaxis system is remarkable for its high sensitivity , wide dynamic range , and precise adaptation ...	[ "The chemotaxis sensory system allows bacteria such as Escherichia coli to swim towards nutrients and away from repellents .", "The underlying pathway is remarkably sensitive in detecting chemical gradients over a wide range of ambient concentrations .", "Interactions among receptors , which are predominantly c...	[ "Receptor clusters of the bacterial chemotaxis sensory system act as antennae to amplify tiny changes in concentrations in the chemical environment of the cell , ultimately steering the cell towards nutrients and away from toxins .", "Despite bacterial chemotaxis being the most widely studied sensory pathway , th...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genetics and genomics/comparative genomics", "cell biology/cell signaling", "computational biology/transcriptional regulation", "genetics and genomics/functional genomics", "genetics and genomics/gene expression", "biochemistry/chemical biology of the cell", "genetics and genomics/bioinformatics", "g...	Global Transcriptome and Deletome Profiles of Yeast Exposed to Transition Metals	journal.pgen.1000053	null	[ [ "Throughout the world , environmental and human health threats are posed by contamination from transition metals .", "Metals can be introduced into the environment through both natural and anthropogenic routes [1] .", "Human exposure routes include absorption through the skin , ingestion , and inhalat...	[ "A variety of pathologies are associated with exposure to supraphysiological concentrations of essential metals and to non-essential metals and metalloids .", "The molecular mechanisms linking metal exposure to human pathologies have not been clearly defined .", "To address these gaps in our understanding of th...	[ "Environmental and human health threats are posed by contamination from transition metals .", "A variety of pathologies are associated with exposure to supraphysiological concentrations of essential metals and to non-essential metals and metalloids .", "To defend against metal toxicity , sophisticated defense m...	2008
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Lipidomic Analysis Links Mycobactin Synthase K to Iron Uptake and Virulence in M. tuberculosis	journal.ppat.1004792	null	[ [ "Mycobacterium tuberculosis ( M . tb ) , an obligate human pathogen , causes tuberculosis , typically through a decades-long infection .", "Long-term survival in the host necessitated the evolution of mechanisms for scavenging essential nutrients .", "Iron plays crucial roles in bacterial respiration ...	[ "The prolonged survival of Mycobacterium tuberculosis ( M . tb ) in the host fundamentally depends on scavenging essential nutrients from host sources .", "M . tb scavenges non-heme iron using mycobactin and carboxymycobactin siderophores , synthesized by mycobactin synthases ( Mbt ) .", "Although a general mec...	[ "M . tuberculosis ( M . tb ) survives only if it can acquire iron from its human host , so new therapies for tuberculosis might be discovered if the pathways necessary for iron acquisition are identified .", "M . tb scavenges iron in two ways: from free iron , or from the blood in the form of heme .", "To bind ...	2015
[ "Introduction", "Results and discussion", "Materials and methods" ]	[ "membrane proteins", "protein structure comparison", "biochemistry", "peripheral membrane proteins", "protein structure determination", "cell biology", "protein structure prediction", "proteins", "integral membrane proteins", "protein structure", "protein domains", "biology and life sciences",...	A model for hydrophobic protrusions on peripheral membrane proteins	journal.pcbi.1006325	null	[ [ "Biological membranes are ancient and crucial components in the organisation of life .", "Not only do they define the boundaries of cells and organelles , but they are central to a myriad protein-protein and protein-lipid interactions instrumental in numerous pathways [1–5] .", "Besides the embedded t...	[ "With remarkable spatial and temporal specificities , peripheral membrane proteins bind to biological membranes .", "They do this without compromising solubility of the protein , and their binding sites are not easily distinguished .", "Prototypical peripheral membrane binding sites display a combination of pat...	[ "Peripheral membrane proteins bind cellular membranes transiently , and are otherwise soluble proteins .", "As the interaction between proteins and membranes happens at cellular interfaces they are naturally involved in important interfacial processes such as recognition , signaling and trafficking .", "Commonl...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "systemic lupus erythematosus", "medicine", "rheumatology", "genetics of the immune system", "genetic association studies", "genetics", "immunology", "biology", "human genetics", "genetics of disease", "genetics and genomics" ]	Association of NCF2, IKZF1, IRF8, IFIH1, and TYK2 with Systemic Lupus Erythematosus	journal.pgen.1002341	null	[ [ "Systemic lupus erythematosus ( SLE ) is a relapsing-remitting complex trait which most commonly affects women of child-bearing age , with a ratio of 9∶1 in female to males .", "The disease prevalence varies with ethnicity , being more prevalent in non-European populations ( approximately 1∶500 in populat...	[ "Systemic lupus erythematosus ( SLE ) is a complex trait characterised by the production of a range of auto-antibodies and a diverse set of clinical phenotypes .", "Currently , ∼8% of the genetic contribution to SLE in Europeans is known , following publication of several moderate-sized genome-wide ( GW ) associa...	[ "Genome-wide association studies have revolutionised our ability to identify common susceptibility alleles for systemic lupus erythematosus ( SLE ) .", "In complex diseases such as SLE , where many different genes make a modest contribution to disease susceptibility , it is necessary to perform large-scale associ...	2011
[ "Introduction", "Methods", "Results", "Discussion", "Conclusions" ]	[ "invertebrates", "medicine and health sciences", "geographical locations", "india", "parasitic diseases", "animals", "ethnicities", "organisms", "molecular biology techniques", "infectious disease control", "insect vectors", "research and analysis methods", "infectious diseases", "tamil pe...	Application of a household-based molecular xenomonitoring strategy to evaluate the lymphatic filariasis elimination program in Tamil Nadu, India	journal.pntd.0005519	null	[ [ "Lymphatic filariasis ( LF ) is a mosquito-borne parasitic disease caused by the filarial worm species Wuchereria bancrofti , Brugia malayi and Brugia timori .", "LF is a major public health problem with nearly 800 million individuals at risk of infection in 73 tropical and subtropical countries worldwide...	[ "The monitoring and evaluation of lymphatic filariasis ( LF ) has largely relied on the detection of antigenemia and antibodies in human populations .", "Molecular xenomonitoring ( MX ) , the detection of parasite DNA/RNA in mosquitoes , may be an effective complementary method , particularly for detecting signal...	[ "Lymphatic filariasis ( LF ) is one of the world’s foremost debilitating infectious diseases with nearly 800 million people at risk of infection .", "Given that LF is a mosquito-borne disease , the use of molecular xenomonitoring ( MX ) to detect parasite DNA/RNA in mosquitoes can serve as a valuable tool for LF ...	2017
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "bacteriology", "medicine and health sciences", "toxins", "pathology and laboratory medicine", "pathogens", "microbiology", "pili and fimbriae", "toxic agents", "toxicology", "epithelial cells", "cellular structures and organelles", "bacterial pathogens", "digestive system", "adhesins", ...	Highly conserved type 1 pili promote enterotoxigenic E. coli pathogen-host interactions	journal.pntd.0005586	null	[ [ "Among young children under five years of age in developing countries , diarrhea is a leading cause of morbidity and mortality .", "Enterotoxigenic E . coli ( ETEC ) is one of the most common causes of moderate to severe diarrheal illness and deaths due to diarrhea in young children and incidentally is al...	[ "Enterotoxigenic Escherichia coli ( ETEC ) , defined by their elaboration of heat-labile ( LT ) and/or heat-stable ( ST ) enterotoxins , are a common cause of diarrheal illness in developing countries .", "Efficient delivery of these toxins requires ETEC to engage target host enterocytes .", "This engagement is...	[ "Enterotoxigenic Escherichia coli ( ETEC ) infections contribute substantially to death and morbidity due to diarrheal illness and are associated with serious sequelae including malnutrition , stunted growth , and intellectual impairment among young children in developing countries .", "Effective engagement of in...	2017
[ "Results", "Discussion", "Material and methods" ]	[ "body weight", "medicine and health sciences", "brown adipose tissue", "diet", "physiological processes", "adipocytes", "physiological parameters", "nutrition", "connective tissue cells", "obesity", "lipids", "animal cells", "fats", "connective tissue", "biological tissue", "biochemist...	p38α blocks brown adipose tissue thermogenesis through p38δ inhibition	journal.pbio.2004455	null	[ [ "p38α has emerged as one of the main player that could activate the thermogenic capacity of adipose tissue .", "Because the thermogenesis of adipose tissue is reduced in obesity [6 , 7 , 21] , we wondered whether expression of this kinase changes in human WAT during obesity .", "Using 2 cohorts for vi...	[ "Adipose tissue has emerged as an important regulator of whole-body metabolism , and its capacity to dissipate energy in the form of heat has acquired a special relevance in recent years as potential treatment for obesity .", "In this context , the p38MAPK pathway has arisen as a key player in the thermogenic pro...	[ "Accumulation of fat in adipose tissue is essential to store energy and insulate the body; however , excessive body fat leads to obesity .", "Of the 2 existing types of adipose tissue , white adipose tissue ( WAT ) stores energy , whereas brown adipose tissue ( BAT ) can produce heat .", "Activation of BAT and ...	2018
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "blood cells", "cell death", "innate immune system", "medicine and health sciences", "immune cells", "immune physiology", "cytokines", "vacuoles", "vesicles", "immunology", "cell processes", "developmental biology", "phagosomes", "molecular development", "phagocytes", "cellular structu...	B-1 cell-mediated modulation of M1 macrophage profile can ameliorate microbicidal functions and disrupt the evasion mechanisms of Encephalitozoon cuniculi	journal.pntd.0007674	null	[ [ "Microsporidia are obligate intracellular spore-forming microorganisms that can infect a wide range of vertebrate and invertebrate species .", "These fungi have been recognized as human pathogens and are particularly harmful to immunodeficient patients infected with HIV .", "Since then , interest amon...	[ "Here , we have investigated the possible effect of B-1 cells on the activity of peritoneal macrophages in E . cuniculi infection .", "In the presence of B-1 cells , peritoneal macrophages had an M1 profile with showed increased phagocytic capacity and index , associated with the intense microbicidal activity and...	[ "The adaptive immune response plays a key role against Encephalitozoon cuniculi , an opportunistic fungus for T cells immunodeficient patients .", "The role of B cells and antibody play in natural resistance to Encephalitozoon cuniculi remains unknown .", "Previously , we demonstrated that B-1 deficient mice ( ...	2019
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "immune physiology", "lymphatic system", "biology", "anatomy and physiology" ]	Pharmacological Approaches That Slow Lymphatic Flow As a Snakebite First Aid	journal.pntd.0002722	null	[ [ "Snake envenoming worldwide remains a major health problem with 20 , 000–94 , 000 deaths [1] and a morbidity of several 100 , 000 people per year [2] .", "Snake envenoming has been identified as a neglected tropical disease and there is a desperate need for improved treatment .", "First aid procedures...	[ "This study examines the use of topical pharmacological agents as a snakebite first aid where slowing venom reaching the circulation prevents systemic toxicity .", "It is based on the fact that toxin molecules in most snake venoms are large molecules and generally first enter and traverse the lymphatic system bef...	[ "Snakebite remains a major problem worldwide causing death or serious illness in many tens of thousands of victims annually .", "An approach to reduce the burden of envenoming is to provide optimum first aid procedures .", "We have previously shown that topical application of a nitric oxide ( NO ) donor slowed ...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "cellular stress responses", "dna transcription", "histone modification", "epigenetics", "dna", "dna structure", "chromatin", "gene expression", "biology", "dna modification", "molecular biology", "cell biology", "nucleic acids", "genetics", "molecular cell biology", "genetics and geno...	BZLF1 Governs CpG-Methylated Chromatin of Epstein-Barr Virus Reversing Epigenetic Repression	journal.ppat.1002902	null	[ [ "Activity and repression of eukaryotic genes correlate with the level of DNA methylation of promoter regions .", "Prominent models are ß-globin genes .", "Their sequential developmental activation and silencing in embryonic , fetal , and adult erythroid cells depends on the methylation status of DNA s...	[ "Epigenetic mechanisms are essential for the regulation of all genes in mammalian cells but transcriptional repression including DNA methylation are also major epigenetic mechanisms of defense inactivating potentially harmful pathogens .", "Epstein-Barr Virus ( EBV ) , however , has evolved to take advantage of C...	[ "Latency is a fundamental molecular mechanism that is observed in many viruses .", "We reveal that the human herpes virus Epstein-Barr virus ( EBV ) uses cellular functions of epigenetic repression to establish latency in infected B cells and a previously unknown mechanism to escape from it .", "We show that th...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine", "mental health", "neurological disorders", "neurology", "genetics", "biology", "genomics", "evolutionary biology", "neuroscience", "genetics and genomics" ]	Human-Specific Histone Methylation Signatures at Transcription Start Sites in Prefrontal Neurons	journal.pbio.1001427	Mapping histone methylation landscapes in neurons from human, chimpanzee, and macaque brains reveals coordinated, human-specific epigenetic regulation at hundreds of regulatory sequences.	[ [ "Cognitive abilities and psychiatric diseases unique to modern humans could be based on genomic features distinguishing our brain cells , including neurons , from those of other primates .", "Because protein coding sequences for synaptic and other neuron-specific genes are highly conserved across the prim...	[ "Cognitive abilities and disorders unique to humans are thought to result from adaptively driven changes in brain transcriptomes , but little is known about the role of cis-regulatory changes affecting transcription start sites ( TSS ) .", "Here , we mapped in human , chimpanzee , and macaque prefrontal cortex th...	[ "Primate and human genomes comprise billions of base pairs , but we are unlikely to gain a deeper understanding of brain functions unique to human ( including cognitive abilities and psychiatric diseases ) merely by comparing linear DNA sequences .", "Such determinants of species-specific function might instead b...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genetics and genomics/epigenetics", "genetics and genomics/gene expression", "genetics and genomics/functional genomics" ]	The Honey Bee Epigenomes: Differential Methylation of Brain DNA in Queens and Workers	journal.pbio.1000506	Using genome-wide methylation profiles in honey bee queen and worker brains to understand how contrasting organismal outputs are generated from the same genotype.	[ [ "Many animal species have evolved the capacity to generate organisms with contrasting morphological , reproductive , and behavioral phenotypes from the same genome .", "However , the question of how such strikingly different organismal outputs occur with no standard genetic changes remains one of the key ...	[ "In honey bees ( Apis mellifera ) the behaviorally and reproductively distinct queen and worker female castes derive from the same genome as a result of differential intake of royal jelly and are implemented in concert with DNA methylation .", "To determine if these very different diet-controlled phenotypes corre...	[ "The queen honey bee and her worker sisters do not seem to have much in common .", "Workers are active and intelligent , skillfully navigating the outside world in search of food for the colony .", "They never reproduce; that task is left entirely to the much larger and longer-lived queen , who is permanently e...	2010
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "evolutionary biology", "teleost fishes", "neuroscience", "computational biology" ]	Spatial Acuity and Prey Detection in Weakly Electric Fish	journal.pcbi.0030038	null	[ [ "Weakly electric fish are commonly found in the freshwater systems of South America and Africa [1 , 2] .", "These nocturnal fish use a unique sensory modality , called the “electrosense , ” to help them navigate , communicate , and find prey in the absence of strong visual cues [3] .", "The electrosen...	[ "It is well-known that weakly electric fish can exhibit extreme temporal acuity at the behavioral level , discriminating time intervals in the submicrosecond range .", "However , relatively little is known about the spatial acuity of the electrosense .", "Here we use a recently developed model of the electric f...	[ "Extracting and characterizing small signals in a noisy background is a universal problem in sensory processing .", "In human audition , this is referred to as the cocktail party problem .", "Weakly electric knifefish face a similar difficulty .", "Objects in their environment produce distortions in a self-ge...	2007
[ "Introduction", "Materials and methods", "Results", "Discussion" ]	[ "medicine and health sciences", "pathology and laboratory medicine", "infectious disease epidemiology", "population dynamics", "tropical diseases", "bacterial diseases", "age groups", "eye diseases", "neglected tropical diseases", "population biology", "infectious disease control", "infectious...	Optimising sampling regimes and data collection to inform surveillance for trachoma control	journal.pntd.0006531	null	[ [ "Trachoma is targeted for elimination as a public health problem by 2020 by the World Health Organization .", "At the global level there has been a high degree of programmatic success in terms of control [1] , as the established intervention strategies have been highly effective in a large proportion of e...	[ "It is estimated that 190 million individuals are at risk of blindness from trachoma , and that control by mass drug administration ( MDA ) is reducing this risk in many populations .", "Programs are monitored using prevalence of follicular trachoma disease ( TF ) in children .", "However , as programs progress...	[ "Trachoma is a bacterial infection , which , with repeated infections over time , can lead to blindness .", "The WHO is aiming to eliminate trachoma as a public health problem by 2020 , however at low prevalence levels the relationship between infection and disease prevalence is non-linear , making the interpreta...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "developmental biology/pattern formation", "developmental biology/neurodevelopment", "developmental biology" ]	Dynamic Assignment and Maintenance of Positional Identity in the Ventral Neural Tube by the Morphogen Sonic Hedgehog	journal.pbio.1000382	During development of the vertebrate neural tube, cells acquire their positional identity from not only the spatial level of the Sonic Hedgehog signaling gradient, but also the temporal duration.	[ [ "A defining feature of embryogenesis is the specification of a large variety of cell types in stereotypical spatial and temporal patterns .", "A common mechanism by which this is achieved involves the deployment of morphogens [1] , [2] , [3] .", "These secreted molecules are proposed to establish sign...	[ "Morphogens are secreted signalling molecules that act in a graded manner to control the pattern of cellular differentiation in developing tissues .", "An example is Sonic hedgehog ( Shh ) , which acts in several developing vertebrate tissues , including the central nervous system , to provide positional informat...	[ "In many developing tissues , the pattern in which cell types are generated depends on secreted factors called morphogens .", "These signalling molecules are produced in specific locations and at specific concentrations , thereby forming concentration gradients .", "Different target genes are induced at specifi...	2010
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	An O-Methyltransferase Is Required for Infection of Tick Cells by Anaplasma phagocytophilum	journal.ppat.1005248	null	[ [ "Anaplasma phagocytophilum is an obligately intracellular bacterium classified in the order Rickettsiales , and is the causative agent of Human Granulocytic Anaplasmosis ( HGA ) [1] .", "HGA is characterized by high fevers , rigors , generalized myalgias , and severe headache .", "It is a potentially ...	[ "Anaplasma phagocytophilum , the causative agent of Human Granulocytic Anaplasmosis ( HGA ) , is an obligately intracellular α-proteobacterium that is transmitted by Ixodes spp ticks .", "However , the pathogen is not transovarially transmitted between tick generations and therefore needs to survive in both a mam...	[ "Since its discovery in 1994 , Human Granulocytic Anaplasmosis ( HGA ) has become the second most commonly diagnosed tick-borne disease in the US , and it is gaining importance in several countries in Europe .", "HGA is caused by Anaplasma phagocytophilum , a bacterium transmitted by black-legged ticks and their ...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "nucleic acid synthesis", "nuclear staining", "hela cells", "gene regulation", "biological cultures", "rna extraction", "viruses", "rna viruses", "cell cultures", "rna synthesis", "extraction techniques", "chemical synthesis", "research and analysis methods", "small interfering rnas", "s...	Leader-Containing Uncapped Viral Transcript Activates RIG-I in Antiviral Stress Granules	journal.ppat.1005444	null	[ [ "Retinoic acid-inducible gene I ( RIG-I ) , a DExD/H-box RNA helicase family protein , is a crucial cytosolic viral RNA ( vRNA ) sensor that initiates signal transduction to produce antiviral cytokines , namely , type I and III interferons ( IFN-α/β and IFN-λ ) [1–4] .", "RIG-I selectively recognizes rela...	[ "RIG-I triggers antiviral responses by recognizing viral RNA ( vRNA ) in the cytoplasm .", "However , the spatio-temporal dynamics of vRNA sensing and signal transduction remain elusive .", "We investigated the time course of events in cells infected with Newcastle disease virus ( NDV ) , a non-segmented negati...	[ "RIG-I plays a critical role in sensing cytoplasmic vRNA and triggering a downstream signaling cascade to produce the antiviral cytokine IFN .", "Over the past decade , a number of in vitro studies have been undertaken to address the nature of the ligands for RIG-I , and it was demonstrated that RNA species formi...	2016
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[]	Laboratory-Based Prospective Surveillance for Community Outbreaks of Shigella spp. in Argentina	journal.pntd.0002521	null	[ [ "In view of the increasing movement of people , animals , and food products around the globe , new strategies and collaborations are urgently needed to detect the emergence of microbial threats and implement effective control measures .", "National and regional electronic laboratory-based surveillance col...	[ "To implement effective control measures , timely outbreak detection is essential .", "Shigella is the most common cause of bacterial diarrhea in Argentina .", "Highly resistant clones of Shigella have emerged , and outbreaks have been recognized in closed settings and in whole communities .", "We hereby repo...	[ "Shigellosis causes dysentery and kills an estimated 1 . 1 million people per year worldwide , 60% of them children under the age of 5 .", "The infectious agent is Shigella spp , transmitted from person to person by fecal-oral route or via ingestion of contaminated food or water .", "Having a system for early d...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genome-wide association studies", "invertebrates", "animals", "wolbachia", "animal models", "drosophila melanogaster", "model organisms", "genome analysis", "karyotypes", "dna", "bacteria", "drosophila", "homologous recombination", "research and analysis methods", "genomics", "chromos...	The Genetic Architecture of Natural Variation in Recombination Rate in Drosophila melanogaster	journal.pgen.1005951	null	[ [ "Meiotic recombination , the reciprocal exchange of genetic information between homologous chromosomes during meiosis , is necessary for proper chromosome segregation in many organisms [1] .", "Interestingly , the distribution of meiotic recombination events , or crossovers , varies dramatically in almost...	[ "Meiotic recombination ensures proper chromosome segregation in many sexually reproducing organisms .", "Despite this crucial function , rates of recombination are highly variable within and between taxa , and the genetic basis of this variation remains poorly understood .", "Here , we exploit natural variation...	[ "During meiosis , homologous chromosomes exchange genetic material through recombination .", "In most sexually reproducing species , recombination is necessary for chromosomes to properly segregate .", "Recombination defects can generate gametes with an incorrect number of chromosomes , which is devastating for...	2016
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "medicine and health sciences", "liver", "diabetic endocrinology", "paracrine signaling", "messenger rna", "cell differentiation", "hormones", "endocrine physiology", "developmental biology", "insulin resistance", "growth factors", "fibroblast growth factor", "insulin", "animal cells", "...	Insulin resistance disrupts epithelial repair and niche-progenitor Fgf signaling during chronic liver injury	journal.pbio.2006972	null	[ [ "Successful wound healing requires coordination between stromal and epithelial cell compartments .", "Stromal activation lays the groundwork for epithelial repair , producing the appropriate microenvironment and growth factors to facilitate proliferation and remodeling of epithelia [1] .", "Metabolic ...	[ "Insulin provides important information to tissues about feeding behavior and energy status .", "Defective insulin signaling is associated with ageing , tissue dysfunction , and impaired wound healing .", "In the liver , insulin resistance leads to chronic damage and fibrosis , but it is unclear how tissue-repa...	[ "“Insulin resistance” is a chronic state of reduced sensitivity to the effects of circulating insulin .", "It is one of the hallmarks of metabolic disease and a consequence of ageing , but insulin resistance is also observed in otherwise healthy individuals after severe trauma/hemorrhage/sepsis , suggesting that ...	2019
[ "Introduction", "Results and Discussion", "Materials and Methods" ]	[]	Cationic Peptides Facilitate Iron-induced Mutagenesis in Bacteria	journal.pgen.1005546	null	[ [ "Pseudomonas aeruginosa is an important opportunistic pathogen involved in chronic respiratory and hospital-acquired infections [1] .", "In cystic fibrosis ( CF ) patients , one of the most common genetic diseases in humans , this bacterium causes chronic lung infections that result in significant morbidi...	[ "Pseudomonas aeruginosa is the causative agent of chronic respiratory infections and is an important pathogen of cystic fibrosis patients .", "Adaptive mutations play an essential role for antimicrobial resistance and persistence .", "The factors that contribute to bacterial mutagenesis in this environment are ...	[ "Cationic antimicrobial peptides ( cAMPs ) are small proteins naturally produced by the immune system to limit bacterial growth mainly through pore formation in the membrane .", "It has recently been suggested that sub-inhibitory concentrations of cAMPs promote bacterial mutagenesis , similarly to antibiotics .",...	2015
[ "Introduction", "Model", "Results", "Discussion" ]	[ "photosynthetic efficiency", "ecology and environmental sciences", "c3 photosynthesis", "chemical compounds", "particle physics", "atmospheric science", "plant cell biology", "permeability", "chloroplasts", "photons", "plant science", "materials science", "c4 photosynthesis", "photosynthes...	Computational modelling predicts substantial carbon assimilation gains for C3 plants with a single-celled C4 biochemical pump	journal.pcbi.1007373	null	[ [ "Global food consumption is estimated to increase by over 70% by 2050 [1 , 2] .", "To ensure global food security within the context of detrimental climate change it will be essential to achieve a substantial increase in agricultural productivity per hectare over the next couple of decades , combined with...	[ "Achieving global food security for the estimated 9 billion people by 2050 is a major scientific challenge .", "Crop productivity is fundamentally restricted by the rate of fixation of atmospheric carbon .", "The dedicated enzyme , RubisCO , has a low turnover and poor specificity for CO2 .", "This limitation...	[ "Feeding the estimated world population of 9 billion people by 2050 presents a major challenge .", "Crop yields currently increase by about 1% each year .", "They would need to grow almost twice as fast to ensure global food security .", "New technologies that boost plant productivity are needed .", "A fund...	2019
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "united states", "invertebrates", "medicine and health sciences", "pathology and laboratory medicine", "pathogens", "geographical locations", "microbiology", "animals", "north america", "viruses", "seasons", "developmental biology", "rna viruses", "pupae", "insect vectors", "connecticu...	Northern range expansion of the Asian tiger mosquito (Aedes albopictus): Analysis of mosquito data from Connecticut, USA	journal.pntd.0005623	null	[ [ "The Asian tiger mosquito , Aedes albopictus ( Skuse ) , is an invasive species that has spread from East Asia to the Americas , Africa , Europe , and the Middle East primarily by the global tire trade [1 , 2] .", "This mosquito inhabits urbanized environments [3] , develops in artificial , water-holding ...	[ "The Asian tiger mosquito ( Aedes albopictus ) is an invasive species and important arbovirus vector that was introduced into the U . S . in the 1980's where it continues to expand its range .", "Winter temperature is an important constraint to its northward expansion , with potential range limits located between...	[ "The Asian tiger mosquito ( Aedes albopictus ) is a highly invasive species and an important disease vector that is undergoing rapid range expansion in many countries including the U . S . Winter temperature is an important limit to its northward expansion with Connecticut situated near the northern boundary of its...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "humoral immunity", "immunodeficiency viruses", "viral vaccines", "immunity", "virology", "microbial evolution", "biology", "microbiology", "viral evolution" ]	Increased Functional Stability and Homogeneity of Viral Envelope Spikes through Directed Evolution	journal.ppat.1003184	null	[ [ "For an HIV/AIDS vaccine to be effective , it is widely thought that it should elicit high titers of broadly neutralizing antibody ( Ab ) [1] , [2] .", "HIV-1 neutralizing Abs target the envelope glycoprotein ( Env ) spike , which is a trimer containing three copies each of the surface subunit , gp120 , a...	[ "The functional HIV-1 envelope glycoprotein ( Env ) trimer , the target of anti-HIV-1 neutralizing antibodies ( Abs ) , is innately labile and coexists with non-native forms of Env .", "This lability and heterogeneity in Env has been associated with its tendency to elicit non-neutralizing Abs .", "Here , we use...	[ "A vaccine is needed to prevent HIV/AIDS but eliciting potent neutralizing antibodies ( Abs ) against primary isolates has been a major stumbling block .", "The target of HIV-1 neutralizing antibodies is the native envelope glycoprotein ( Env ) trimer that is displayed on the surface of the virus .", "Virion as...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods", "Supporting Information" ]	[ "mus (mouse)", "infectious diseases", "microbiology", "eubacteria" ]	Brucella Control of Dendritic Cell Maturation Is Dependent on the TIR-Containing Protein Btp1	journal.ppat.0040021	null	[ [ "The immune response to bacterial infection relies on the combined action of both the innate and adaptive immune systems .", "Dendritic cells ( DCs ) are known as mediators of pathogen recognition and are strategically located at the typical sites of bacterial entry and have the ability to migrate from pe...	[ "Brucella is an intracellular pathogen able to persist for long periods of time within the host and establish a chronic disease .", "We show that soon after Brucella inoculation in intestinal loops , dendritic cells from ileal Peyer's patches become infected and constitute a cell target for this pathogen .", "I...	[ "A key determinant for intracellular pathogenic bacteria to induce infectious diseases is their ability to avoid recognition by the host immune system .", "Although most microorganisms internalized by host cells are efficiently cleared , Brucella behave as a Trojan horse causing a zoonosis called brucellosis that...	2008
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "medicine and health sciences", "face", "gene regulation", "cell processes", "mandible", "incisors", "developmental biology", "embryos", "digestive system", "embryology", "cell proliferation", "gene expression", "biological tissue", "head", "teeth", "mouth", "anatomy", "cell biolog...	FoxO6 regulates Hippo signaling and growth of the craniofacial complex	journal.pgen.1007675	null	[ [ "Hippo signaling is a major determinant in regulating organ size and tissue regeneration .", "Several lines of evidence indicate that developing organs possess intrinsic mechanisms that modulate their final size [1 , 2] .", "Genetic studies have established that the Hippo pathway plays a crucial role ...	[ "The mechanisms that regulate post-natal growth of the craniofacial complex and that ultimately determine the size and shape of our faces are not well understood .", "Hippo signaling is a general mechanism to control tissue growth and organ size , and although it is known that Hippo signaling functions in neural ...	[ "The basic question of how human faces develop , undergo morphogenesis and grow after birth to define our final characteristic shape has been studied from the earliest days of comparative vertebrate developmental research .", "While many studies have shown the factors and mechanisms that contribute to the cells a...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine", "biology" ]	Nrf2, a PPARγ Alternative Pathway to Promote CD36 Expression on Inflammatory Macrophages: Implication for Malaria	journal.ppat.1002254	null	[ [ "Mononuclear phagocytes represent the first line of innate immune defense against pathogens through mechanisms involving recognition by pattern-recognition receptors ( PRRs ) of highly structurally conserved microbial structures , known as pathogen-associated molecular patterns [1] .", "Among the PRRs fam...	[ "CD36 is the major receptor mediating nonopsonic phagocytosis of Plasmodium falciparum-parasitized erythrocytes by macrophages .", "Its expression on macrophages is mainly controlled by the nuclear receptor PPARγ .", "Here , we demonstrate that inflammatory processes negatively regulate CD36 expression on human...	[ "Severe and fatal malaria is still increasing both in incidence and in its resistance to antimalarial agents .", "The improved understanding of immune mechanisms mediating Plasmodium elimination might therefore offer a complementary way to conventional therapeutic interventions .", "The main host innate immune ...	2011
[ "Introduction", "Results", "Discussion", "Material and Methods" ]	[ "medicine", "biology" ]	The NF1 Gene Contains Hotspots for L1 Endonuclease-Dependent De Novo Insertion	journal.pgen.1002371	null	[ [ "Long interspersed nuclear elements ( LINE-1 or L1 elements ) and Alu sequences belonging to the family of short interspersed nuclear elements ( SINEs ) still actively amplify in the human genome , by a process called retrotransposition .", "L1 elements comprise ∼17% of the human genome sequence [1] but o...	[ "Long interspersed ( L1 ) and Alu elements are actively amplified in the human genome through retrotransposition of their RNA intermediates by the ∼100 still retrotranspositionally fully competent L1 elements .", "Retrotransposition can cause inherited disease if such an element is inserted near or within a funct...	[ "Repetitive retrotransposable elements , including LINE1 and Alu elements accounting for more than one fourth of the human genome , are still actively amplifying .", "It is widely believed that retroelements insert randomly in the genome .", "Retroelements newly inserted in the germ line may cause genetic disea...	2011
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "manifolds", "experimental design", "egfr signaling", "mathematical models", "eigenvalues", "research design", "systems science", "mathematics", "algebra", "dna", "research and analysis methods", "complex systems", "computer and information sciences", "mathematical and statistical techniqu...	The Limitations of Model-Based Experimental Design and Parameter Estimation in Sloppy Systems	journal.pcbi.1005227	null	[ [ "Mathematical models play an important role in understanding complex biological systems .", "Mathematical models often synthesize a large amount of information about a system into a single representation that can be used to give both conceptual insights into mechanisms and to make predictions about differ...	[ "We explore the relationship among experimental design , parameter estimation , and systematic error in sloppy models .", "We show that the approximate nature of mathematical models poses challenges for experimental design in sloppy models .", "In many models of complex biological processes it is unknown what a...	[ "Sloppy models are often unidentifiable , i . e . , characterized by many parameters that are poorly constrained by experimental data .", "Many models of complex biological systems are sloppy , which has prompted considerable debate about the identifiability of parameters and methods of selecting optimal experime...	2016
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "geomorphology", "united states", "medicine and health sciences", "landforms", "toxoplasma gondii", "california", "topography", "geographical locations", "vertebrates", "parasitic protozoans", "mammals", "animals", "north america", "protozoans", "toxoplasma", "medical risk factors", ...	Potential public health benefits from cat eradications on islands	journal.pntd.0007040	null	[ [ "Cats ( Felis catus ) are reservoirs of many pathogens that affect humans , including the parasite Toxoplasma gondii [1] .", "Cats are also the second most widespread introduced predator found on islands [2 , 3] , and have contributed to 14% of global bird , reptile and mammal extinctions on islands [2] ....	[ "Cats ( Felis catus ) are reservoirs of several pathogens that affect humans , including Toxoplasma gondii .", "Infection of pregnant women with T . gondii can cause ocular and neurological lesions in newborns , and congenital toxoplasmosis has been associated with schizophrenia , epilepsy , movement disorders , ...	[ "Infection with T . gondii can cause miscarriage or severe ocular and neurological lesions in newborns , systemic disease in immunocompromised individuals , and has been linked to mental disorders and neurodegenerative diseases such as schizophrenia , Alzheimer’s and movement disorders in adults .", "On the major...	2019
[ "Introduction", "Materials and methods", "Results", "Discussion" ]	[ "genome-wide association studies", "body weight", "medicine and health sciences", "computational biology", "diet", "physical activity", "biological locomotion", "health care", "regression analysis", "nutrition", "mathematics", "statistics (mathematics)", "physiological parameters", "genome...	Gene-environment interaction study for BMI reveals interactions between genetic factors and physical activity, alcohol consumption and socioeconomic status	journal.pgen.1006977	null	[ [ "Gene-environment interactions result from individuals responding differently to environmental stimuli depending on their genotype , or from genetic effects that vary between groups of individuals depending on their lifestyles .", "In humans , the most famous examples include skin color and risk of melano...	[ "Previous genome-wide association studies ( GWAS ) have identified hundreds of genetic loci to be associated with body mass index ( BMI ) and risk of obesity .", "Genetic effects can differ between individuals depending on lifestyle or environmental factors due to gene-environment interactions .", "In this stud...	[ "Genome-wide association studies ( GWAS ) have identified hundreds of genes as being associated with body mass index ( BMI ) .", "How these genetic effects are modulated by lifestyle factors has not been extensively investigated previously .", "Here we utilise data from approximately 360 , 000 participants from...	2017
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "circuit models", "mathematics", "neural networks", "computational neuroscience", "biology", "computational biology", "neuroscience", "nonlinear dynamics" ]	Sparse Gamma Rhythms Arising through Clustering in Adapting Neuronal Networks	journal.pcbi.1002281	null	[ [ "Synchronous rhythmic spiking is ubiquitous in networks of the brain [1] .", "Extensive experimental evidence suggests such activity is useful for coordinating spatially disparate locations in sensory [2] , motor [3] , attentional [4] , and memory tasks [5] .", "In particular , network spiking in the ...	[ "Gamma rhythms ( 30–100 Hz ) are an extensively studied synchronous brain state responsible for a number of sensory , memory , and motor processes .", "Experimental evidence suggests that fast-spiking interneurons are responsible for carrying the high frequency components of the rhythm , while regular-spiking pyr...	[ "Fast periodic synchronized neural spiking corresponds to a variety of functions in many different areas of the brain .", "Most theories and experiments suggest inhibitory neurons carry the regular rhythm while being driven by excitatory neurons that spike more sparsely in time .", "We suggest a simple mechanis...	2011
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "medicine and health sciences", "neural networks", "nervous system", "vertebrates", "neuroscience", "animals", "mammals", "primates", "optimization", "mathematics", "brain mapping", "network analysis", "old world monkeys", "research and analysis methods", "computer and information scienc...	Features of spatial and functional segregation and integration of the primate connectome revealed by trade-off between wiring cost and efficiency	journal.pcbi.1005776	null	[ [ "The large-scale network of cortical areas in the brain supports and integrates brain functions that are distributed across spatially segregated regions [1] .", "It has been known for a long time that different regions have specialized roles in brain function [2 , 3] and such segregated functions also nee...	[ "The primate connectome , possessing a characteristic global topology and specific regional connectivity profiles , is well organized to support both segregated and integrated brain function .", "However , the organization mechanisms shaping the characteristic connectivity and its relationship to functional requi...	[ "The intricate primate structural connectome , as the network substrate for distributed and integrated brain function , is shaped by fundamental physical factors and functional requirements .", "We addressed a trade-off between two competing basic factors of wiring cost and processing efficiency as well as additi...	2017
[ "Introduction", "Materials and methods", "Results", "Discussion" ]	[ "invertebrates", "medicine and health sciences", "pathology and laboratory medicine", "tropical diseases", "geographical locations", "animals", "health care", "signs and symptoms", "neglected tropical diseases", "infectious disease control", "insect vectors", "zoology", "public and occupatio...	Dengue knowledge, attitudes and practices and their impact on community-based vector control in rural Cambodia	journal.pntd.0006268	null	[ [ "With up to 3 . 9 billion people in 128 countries at risk of the disease , dengue affects most of the world’s tropical and sub-tropical regions and has become the most rapidly spreading mosquito-borne viral disease[1 , 2] .", "There are an estimated 390 million infections per year , of which 96 million ar...	[ "Globally there are an estimated 390 million dengue infections per year , of which 96 million are clinically apparent .", "In Cambodia , estimates suggest as many as 185 , 850 cases annually .", "The World Health Organization global strategy for dengue prevention aims to reduce mortality rates by 50% and morbid...	[ "The global incidence of dengue has grown dramatically over the last few decades and has become the most rapidly spreading mosquito-borne disease .", "To date , there is no specific treatment .", "A vaccine came on the market in 2015 , but it will be several years before it becomes widely available and its effi...	2018
[ "Introduction", "Results", "Discussion", "Methods" ]	[]	Identification of Effective Subdominant Anti-HIV-1 CD8+ T Cells Within Entire Post-infection and Post-vaccination Immune Responses	journal.ppat.1004658	null	[ [ "Only two HIV vaccines designed to elicit protective T cell responses have reached clinical efficacy testing , both with disappointing results [1][2][3] .", "The reasons for this are not completely understood , despite much accumulated knowledge regarding the characteristics of cell-mediated immune respon...	[ "Defining the components of an HIV immunogen that could induce effective CD8+ T cell responses is critical to vaccine development .", "We addressed this question by investigating the viral targets of CD8+ T cells that potently inhibit HIV replication in vitro , as this is highly predictive of virus control in viv...	[ "Attempts to develop an HIV vaccine that elicits potent cell-mediated immunity have so far been unsuccessful .", "This is due in part to the use of immunogens that appear to recapitulate responses induced naturally by HIV that are , at best , partially effective .", "We previously showed that the capacity of CD...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "cell biology", "ophthalmology/retinal disorders" ]	Ablation of Whirlin Long Isoform Disrupts the USH2 Protein Complex and Causes Vision and Hearing Loss	journal.pgen.1000955	null	[ [ "Usher syndrome manifests as both retinal degeneration and hearing loss [1] , [2] .", "It is classified into type I , II , and III based on clinical features of the hearing defects [3]–[8] .", "Usher syndrome type I ( USH1 ) presents with profound congenital deafness and vestibular dysfunction .", ...	[ "Mutations in whirlin cause either Usher syndrome type II ( USH2 ) , a deafness-blindness disorder , or nonsyndromic deafness .", "The molecular basis for the variable disease expression is unknown .", "We show here that only the whirlin long isoform , distinct from a short isoform by virtue of having two N-ter...	[ "Usher syndrome is a devastating genetic disorder affecting both vision and hearing .", "It is classified into three clinical types .", "Among them , type II ( USH2 ) is the predominant form accounting for about 70% of all Usher syndrome cases .", "Three genes , USH2A , USH2C , and USH2D , underlie the develo...	2010
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "medicine", "protein interactions", "protein folding", "protein structure", "sequence analysis", "infectious diseases", "proteins", "hiv", "biology", "biophysics", "physics", "biochemistry", "protein chemistry", "viral diseases", "computational biology", "macromolecular structure analy...	Correlated Electrostatic Mutations Provide a Reservoir of Stability in HIV Protease	journal.pcbi.1002675	null	[ [ "Proteins evolve through random mutagenesis and their evolutionary selection is constrained by structural , functional and environmental factors [1] .", "Thermodynamic stability is by far the most important structural factor , as most proteins need to be folded in order to function .", "The stability ...	[ "HIV protease , an aspartyl protease crucial to the life cycle of HIV , is the target of many drug development programs .", "Though many protease inhibitors are on the market , protease eventually evades these drugs by mutating at a rapid pace and building drug resistance .", "The drug resistance mutations , ca...	[ "HIV is incurable because its enzymes evolve rapidly by developing resistance mutations to retroviral inhibitors .", "Most of these mutations work synergistically , but the biophysical basis behind their cooperation is not well understood .", "Our work addresses these important issues by bridging the gap betwee...	2012
[ "Introduction", "Results", "Discussion", "Methods" ]	[]	Asymmetric Evolutionary Games	journal.pcbi.1004349	null	[ [ "Evolutionary game theory has been used extensively to study the evolution of cooperation in social dilemmas [1–3] .", "A social dilemma is typically modeled as a game with two strategies , cooperate ( C ) and defect ( D ) , whose payoffs for pairwise interactions are defined by a matrix of the form", ...	[ "Evolutionary game theory is a powerful framework for studying evolution in populations of interacting individuals .", "A common assumption in evolutionary game theory is that interactions are symmetric , which means that the players are distinguished by only their strategies .", "In nature , however , the micr...	[ "Biological interactions , even between members of the same species , are almost always asymmetric due to differences in size , access to resources , or past interactions .", "However , classical game-theoretical models of evolution fail to account for sources of asymmetry in a comprehensive manner .", "Here , ...	2015
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "infographics", "medicine and health sciences", "action potentials", "neural networks", "nervous system", "membrane potential", "electrophysiology", "neuroscience", "synaptic plasticity", "network analysis", "neuronal plasticity", "developmental neuroscience", "computer and information scien...	Plasticity-Driven Self-Organization under Topological Constraints Accounts for Non-random Features of Cortical Synaptic Wiring	journal.pcbi.1004759	null	[ [ "The patterns of synaptic connectivity in our brains are thought to be the neurophysiological substrate of our memories , and framework upon which our cognitive functions are computed .", "Understanding the development of micro-structure in the cortex has significant implications for the understanding of ...	[ "Understanding the structure and dynamics of cortical connectivity is vital to understanding cortical function .", "Experimental data strongly suggest that local recurrent connectivity in the cortex is significantly non-random , exhibiting , for example , above-chance bidirectionality and an overrepresentation of...	[ "The problem of how the brain wires itself up has important implications for the understanding of both brain development and cognition .", "The microscopic structure of the circuits of the adult neocortex , often considered the seat of our highest cognitive abilities , is still poorly understood .", "Recent exp...	2016
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "livestock", "medicine and health sciences", "diagnostic radiology", "ultrasound imaging", "pathology and laboratory medicine", "tropical diseases", "vertebrates", "parasitic diseases", "animals", "mammals", "tongue", "neglected tropical diseases", "digestive system", "research and analysi...	Assessing Ultrasonography as a Diagnostic Tool for Porcine Cysticercosis	journal.pntd.0005282	null	[ [ "Ultrasonography is a noninvasive diagnostic tool that can detect soft-tissue larval cestode infections .", "It is considered a primary method for identifying hepatic cystic hydatidosis and subcutaneous cysticercosis in humans [1–5] , and has proved useful for mass screening of hydatidosis in sheep and go...	[ "Taenia solium inflicts substantial neurologic disease and economic losses on rural communities in many developing nations .", "“Ring-strategy” is a control intervention that targets treatment of humans and pigs among clusters of households ( rings ) that surround pigs heavily infected with cysticerci .", "Thes...	[ "Taenia solium is a cestode that infects humans and pigs .", "The parasite causes up to one-third of epilepsy in Latin America , Asia and Africa and results in economic harm to smallholder farmers who cannot sell the contaminated pork of their infected pigs .", "“Ring-strategy” is an intervention being evaluate...	2017
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "genetics and genomics/animal genetics", "developmental biology", "diabetes and endocrinology/endocrinology", "nephrology/renal physiology", "pathology/pathophysiology", "developmental biology/aging", "genetics and genomics/disease models", "genetics and genomics/genetics of disease", "physiology/en...	Genetic Evidence of Serum Phosphate-Independent Functions of FGF-23 on Bone	journal.pgen.1000154	null	[ [ "Maintaining physiological phosphate balance is essential , not only for skeletal mineralization but also for various important biological activities that include cellular signaling , and biochemical reactions [1] .", "Acute hypophosphatemia can cause myopathy , cardiac dysfunction , and hematological abn...	[ "Maintenance of physiologic phosphate balance is of crucial biological importance , as it is fundamental to cellular function , energy metabolism , and skeletal mineralization .", "Fibroblast growth factor-23 ( FGF-23 ) is a master regulator of phosphate homeostasis , but the molecular mechanism of such regulatio...	[ "Regulation of phosphate homeostasis is a tightly controlled hormonal process involving the intestine , kidneys , and bone , and imbalance of this homeostasis may influence overall mineralization .", "Fibroblast growth factor-23 ( FGF-23 ) is a circulating hormone produced in the bone that mainly targets the kidn...	2008
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine", "biochemistry", "infectious diseases", "immunology", "biology", "microbiology" ]	c-di-AMP Is a New Second Messenger in Staphylococcus aureus with a Role in Controlling Cell Size and Envelope Stress	journal.ppat.1002217	null	[ [ "Staphylococcus aureus is a very prevalent human pathogen that permanently colonizes the nares and skin of approximately 20% of the population , while another 60% are colonized transiently [1] .", "Infections caused by this pathogen are becoming increasingly more difficult to treat due to its resistance t...	[ "The cell wall is a vital and multi-functional part of bacterial cells .", "For Staphylococcus aureus , an important human bacterial pathogen , surface proteins and cell wall polymers are essential for adhesion , colonization and during the infection process .", "One such cell wall polymer , lipoteichoic acid (...	[ "Staphylococcus aureus is an important human pathogen that colonizes the nares and skin of both sick and healthy individuals and causes a variety of infections ranging from superficial skin to invasive infections .", "The ability of this bacterium to cause disease depends on many factors and is , in part , due to...	2011
[ "Introduction", "Methods", "Discussion" ]	[ "public health", "medicine", "infectious diseases", "global health" ]	Where Does Human Plague Still Persist in Latin America?	journal.pntd.0002680	null	[ [ "Plague is a historic disease that is responsible for some of the most devastating epidemics in human history .", "Despite its low and decreasing incidence , it continues to be endemic in some countries of the world and remains a public health threat .", "Plague is an epidemic-prone disease with a hig...	[ "Plague is an epidemic-prone disease with a potential impact on public health , international trade , and tourism .", "It may emerge and re-emerge after decades of epidemiological silence .", "Today , in Latin America , human cases and foci are present in Bolivia , Brazil , Ecuador , and Peru .", "The objecti...	[ "Plague is a disease of epidemic potential that could emerge and re-emerge after decades of epidemiological silence .", "Today , in Latin America , human cases and natural foci are present in Bolivia , Brazil , Ecuador , and Peru .", "We searched for official information of where cases of human plague still per...	2014
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "medicine and health sciences", "liver", "pathology and laboratory medicine", "hepacivirus", "pathogens", "protein interaction networks", "microbiology", "viruses", "oncology", "rna viruses", "network analysis", "research and analysis methods", "sequence analysis", "computer and informatio...	Identification of Entry Factors Involved in Hepatitis C Virus Infection Based on Host-Mimicking Short Linear Motifs	journal.pcbi.1005368	null	[ [ "The conventional approach to countering viral infections has been to develop drugs that target viral genetic material or proteins .", "However , two major roadblocks to this strategy exist:", "1 ) the limited number of druggable viral proteins owing to small viral genomes , and", "2 ) drug resist...	[ "Host factors that facilitate viral entry into cells can , in principle , be identified from a virus-host protein interaction network , but for most viruses information for such a network is limited .", "To help fill this void , we developed a bioinformatics approach and applied it to hepatitis C virus ( HCV ) in...	[ "Viruses recruit host proteins , called entry factors , to help gain entry to host cells .", "Identification of entry factors can provide targets for developing antiviral drugs .", "By exploring the concept that short linear peptide motifs involved in human protein-protein interactions may be mimicked by viruse...	2017
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "medicine" ]	Clinical Forms of Chikungunya in Gabon, 2010	journal.pntd.0001517	null	[ [ "Chikungunya fever ( CHIK ) is a neglected tropical disease caused by the Chikungunya virus ( CHIKV ) , an arthropod-borne virus belonging to the genus Alphavirus of the Togaviridae family .", "This virus is transmitted to humans via the bite of infected Aedes mosquitoes ( Aedes aegypti , Aedes albopictus...	[ "Chikungunya virus ( CHIKV ) has caused multiple outbreaks in tropical and temperate areas worldwide , but the clinical and biological features of this disease are poorly described , particularly in Africa .", "We report a prospective study of clinical and biological features during an outbreak that occurred in F...	[ "Chikungunya fever ( CHIK ) is a disease caused by a virus transmitted to humans by infected mosquitos .", "The virus is responsible for multiple outbreaks in tropical and temperate areas worldwide , and is now a global concern .", "Clinical and biological features of the disease are poorly described , especial...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "ecology/evolutionary ecology", "evolutionary biology/evolutionary ecology", "evolutionary biology", "ecology", "ecology/community ecology and biodiversity", "ecology/theoretical ecology" ]	Inferring the Dynamics of Diversification: A Coalescent Approach	journal.pbio.1000493	A novel approach to infer diversification dynamics shows that biodiversity is still expanding but at a slower rate than in the past.	[ [ "We considered nine diversification scenarios , illustrated in Figure 1 ( see also Table 1 ) .", "In each of these scenarios , every lineage is equally likely to diversify or go extinct .", "Two of the scenarios ( Models 1 and", "2 ) correspond to the hypothesis that diversity is saturated .", ...	[ "Recent analyses of the fossil record and molecular phylogenies suggest that there are fundamental limits to biodiversity , possibly arising from constraints in the availability of space , resources , or ecological niches .", "Under this hypothesis , speciation rates decay over time and biodiversity eventually sa...	[ "Is species diversity in equilibrium , or is it still expanding ?", "Are there ecological limits on diversity , or will evolution always find new niches for further specialization ?", "These are all long-standing questions about the dynamics of macro-evolution , which have been examined using the fossil record ...	2010

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