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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" ]	[ "molecular biology" ]	Two Modes of Transcriptional Activation at Native Promoters by NF-κB p65	journal.pbio.1000073	The p65 subunit of NF-κB drives expression of target genes not only as a classical activator, via direct interactions with the basic transcriptional machinery, but also independently by controlling the recruitment of secondary transcription factors to target promoters.	[ [ "The goal of understanding transcriptional activation encompasses the description of an unbroken chain of events leading from the binding of a transcription factor to its natural target promoters in an intact cell , until the initiation of mRNA synthesis by RNA polymerase II ( pol-II ) .", "In the case of...	[ "The NF-κB family of transcription factors is crucial for the expression of multiple genes involved in cell survival , proliferation , differentiation , and inflammation .", "The molecular basis by which NF-κB activates endogenous promoters is largely unknown , but it seems likely that it should include the means...	[ "Transcriptional activation by the NF-κB family of transcription factors is crucial for the expression of multiple genes involved in cell survival , proliferation , differentiation , and inflammation .", "The activation domain of the p65 subunit of NF-κB has been extensively studied in vitro and on artificial rep...	2009
[ "Introduction", "Methods", "Results", "Discussion" ]	[]	Whole Genome Sequencing of Field Isolates Reveals Extensive Genetic Diversity in Plasmodium vivax from Colombia	journal.pntd.0004252	null	[ [ "Despite significant advancements toward malaria control and elimination , about 40% of the world’s population remains at risk of infection by one of the four protozoan species that commonly cause the disease [1] .", "Among the human malarias , P . vivax is the parasite with the most morbidity outside Afr...	[ "Plasmodium vivax is the most prevalent malarial species in South America and exerts a substantial burden on the populations it affects .", "The control and eventual elimination of P . vivax are global health priorities .", "Genomic research contributes to this objective by improving our understanding of the bi...	[ "Although P . vivax is not as deadly as the more widely studied P . falciparum , it remains a pressing global health problem .", "Here we report the results of a whole-genome study of P . vivax from Cordóba , Colombia , in South America .", "This parasite is the most prevalent in this region .", "We show that...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	An RNA-Binding Complex Involved in Ribosome Biogenesis Contains a Protein with Homology to tRNA CCA-Adding Enzyme	journal.pbio.1001669	The structure of a complex of two ribosome synthesis factors and identification of their ribosomal binding sites provides insights into early stages of ribosome biogenesis.	[ [ "Ribosomes , the protein factory , are large RNA–protein complexes composed of small and large subunits ( SSUs and LSUs ) .", "The core structure and function of ribosomes are universally conserved , but eukaryotic ribosomes are 40% larger than their bacterial counterparts mainly due to the presence of ad...	[ "A multitude of proteins and small nucleolar RNAs transiently associate with eukaryotic ribosomal RNAs to direct their modification and processing and the assembly of ribosomal proteins .", "Utp22 and Rrp7 , two interacting proteins with no recognizable domain , are components of the 90S preribosome or the small ...	[ "Ribosomes are large RNA–protein complexes that manufacture proteins in all living organisms .", "Synthesis of large and small ribosomal subunits is a fundamental and enormous task that requires activities of approximately 200 assembly factors in eukaryotic cells .", "These factors transiently associate with th...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "infectious diseases/protozoal infections", "computational biology/systems biology", "genetics and genomics/gene expression" ]	Proteomic Profiling of Plasmodium Sporozoite Maturation Identifies New Proteins Essential for Parasite Development and Infectivity	journal.ppat.1000195	null	[ [ "The life cycle of human malaria parasite Plasmodium falciparum within the mosquito vector begins when gametocytes are taken up in an infected blood meal; after forming gametes and fertilisation , the resulting zygote differentiates into a motile ookinete that traverses the midgut epithelium and transforms wi...	[ "Plasmodium falciparum sporozoites that develop and mature inside an Anopheles mosquito initiate a malaria infection in humans .", "Here we report the first proteomic comparison of different parasite stages from the mosquito—early and late oocysts containing midgut sporozoites , and the mature , infectious saliva...	[ "Human malaria is caused by Plasmodium falciparum , a unicellular protozoan parasite that is transmitted by Anopheles mosquitoes .", "An infectious mosquito injects saliva containing sporozoite forms of the parasite and these then migrate from the skin to the liver , where they establish an infection .", "Many ...	2008
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Requirement of Stat3 Signaling in the Postnatal Development of Thymic Medullary Epithelial Cells	journal.pgen.1005776	null	[ [ "Throughout life , the thymus serves as a primary lymphoid organ for the production of T cells .", "The thymic environment comprises two distinct domains , the cortex and the medulla , which are mainly composed of thymic epithelial cells ( TECs ) organized in a three dimensional architecture [1 , 2] .", ...	[ "Thymic medullary regions are formed in neonatal mice as islet-like structures , which increase in size over time and eventually fuse a few weeks after birth into a continuous structure .", "The development of medullary thymic epithelial cells ( TEC ) is dependent on NF-κB associated signaling though other signal...	[ "Thymic medulla is known to be an essential site for the deletion of auto-reactive T cells .", "Whereas it has been well documented that the development of medullary thymic epithelial cells ( mTECs ) depends on NF-κB associated signaling , it remained unclear whether other signaling pathways are also involved .",...	2016
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "action potentials", "medicine and health sciences", "neural networks", "membrane potential", "brain", "vertebrates", "electrophysiology", "neuroscience", "animals", "mammals", "primates", "neuronal tuning", "computer and information sciences", "monkeys", "cerebral cortex", "animal cel...	A case study in the functional consequences of scaling the sizes of realistic cortical models	journal.pcbi.1007198	null	[ [ "One of the greatest challenges of science today is to unlock the mysteries of the brain .", "The cerebral cortex is a vast network of neurons the dynamical interaction of which shapes our perception of the external world and controls our behavior .", "Modeling is the key to understanding cortical fun...	[ "Neuroscience models come in a wide range of scales and specificity , from mean-field rate models to large-scale networks of spiking neurons .", "There are potential trade-offs between simplicity and realism , versatility and computational speed .", "This paper is about large-scale cortical network models , and...	[ "With the vast numbers of neurons in the cerebral cortex , models in neuroscience are , for practical reasons , often orders of magnitude smaller than the actual network .", "We examine in this article the scalability of cortical networks .", "We find that function and dynamics in a network depend on network si...	2019
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "cell death", "medicine and health sciences", "luciferase", "gene regulation", "enzymes", "messenger rna", "cell processes", "cancers and neoplasms", "enzymology", "nucleotides", "oncology", "micrornas", "cell growth", "proteins", "lung and intrathoracic tumors", "oxidoreductases", "...	MiR-1254 suppresses HO-1 expression through seed region-dependent silencing and non-seed interaction with TFAP2A transcript to attenuate NSCLC growth	journal.pgen.1006896	null	[ [ "MicroRNAs ( miRNAs ) are a class of small non-coding RNAs , which direct post-transcriptional gene silencing ( PTGS ) and play important regulatory roles in a vast range of cellular processes including cell differentiation , proliferation , apoptosis , and migration [1–3] .", "Aberrant expression of miRN...	[ "MicroRNAs ( miRNAs ) are a class of small non-coding RNAs , which direct post-transcriptional gene silencing ( PTGS ) and function in a vast range of biological events including cancer development .", "Most miRNAs pair to the target sites through seed region near the 5’ end , leading to mRNA cleavage and/or tran...	[ "It is generally accepted that miRNAs bind to 3`UTR of target mRNAs and direct post-transcriptional gene silencing ( PTGS ) via its seed sequence .", "Here we report a new dual regulatory mechanism of miRNA .", "We described that miR-1254 repressed HO-1 at post-transcriptional level by directly targeting HO-1 3...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "blood cells", "cell physiology", "hiv infections", "medicine and health sciences", "immune cells", "pathology and laboratory medicine", "pathogens", "immunology", "microbiology", "viral structure", "retroviruses", "viruses", "immunodeficiency viruses", "luminescent proteins", "rna virus...	HIV Cell-to-Cell Spread Results in Earlier Onset of Viral Gene Expression by Multiple Infections per Cell	journal.ppat.1005964	null	[ [ "Cell-to-cell spread of HIV is a mechanism of viral transmission whereby interaction between an infected donor cell and an infectable target cell leads to the directed transmission of virions to the target cell .", "Such interactions can occur between donor and target cells by various mechanisms [1–12] , ...	[ "Cell-to-cell spread of HIV , a directed mode of viral transmission , has been observed to be more rapid than cell-free infection .", "However , a mechanism for earlier onset of viral gene expression in cell-to-cell spread was previously uncharacterized .", "Here we used time-lapse microscopy combined with auto...	[ "How quickly infection occurs should be an important determinant of viral fitness , but mechanisms which could accelerate the onset of viral gene expression were previously undefined .", "In this work we use time-lapse microscopy to quantify the timing of the HIV viral cycle and show that onset of viral gene expr...	2016
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "mathematics/statistics", "genetics and genomics/population genetics" ]	Linkage Disequilibrium-Based Quality Control for Large-Scale Genetic Studies	journal.pgen.1000147	null	[ [ "Data quality has been implicated as a source of bias and loss of power in both linkage analyses and population-based association studies [1] , [2] , [3] , [4] .", "Quality control ( QC ) is thus a critical step in large-scale studies of genetic variation .", "While , on average , high-throughput sing...	[ "Quality control ( QC ) is a critical step in large-scale studies of genetic variation .", "While , on average , high-throughput single nucleotide polymorphism ( SNP ) genotyping assays are now very accurate , the errors that remain tend to cluster into a small percentage of “problem” SNPs , which exhibit unusual...	[ "In large-scale studies of population genetic data , particularly genome-wide association studies , considerable effort may be spent on quality control ( QC ) to ensure genotype data are accurate .", "Typically , QC steps are applied independently to individual marker loci , with data from suspicious loci being e...	2008
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "circuit models", "complex systems", "physics", "computer and information sciences", "systems science", "mathematics", "interdisciplinary physics", "computational neuroscience", "applied mathematics", "biology and life sciences", "physical sciences", "computational biology", "nonlinear dynam...	Mechanisms of Zero-Lag Synchronization in Cortical Motifs	journal.pcbi.1003548	null	[ [ "The study of large-scale brain dynamics , and the cortical networks on which they unfold , is a very active research area , providing new insights into the mechanisms of functional integration and complementing the traditional focus on functional specialization in the brain [1] , [2] .", "Whilst progress...	[ "Zero-lag synchronization between distant cortical areas has been observed in a diversity of experimental data sets and between many different regions of the brain .", "Several computational mechanisms have been proposed to account for such isochronous synchronization in the presence of long conduction delays: Of...	[ "Understanding large-scale neuronal dynamics – and how they relate to the cortical anatomy – is one of the key areas of neuroscience research .", "Despite a wealth of recent research , the key principles of this relationship have yet to be established .", "Here we employ computational modeling to study neuronal...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genetics and genomics/animal genetics", "cell biology/nuclear structure and function", "genetics and genomics/nuclear structure and function", "genetics and genomics/chromosome biology", "biochemistry/replication and repair" ]	ATM Promotes the Obligate XY Crossover and both Crossover Control and Chromosome Axis Integrity on Autosomes	journal.pgen.1000076	null	[ [ "Crossing-over between homologous chromosomes in conjunction with sister chromatid cohesion provides physical connections necessary for accurate chromosome segregation during the first meiotic division [1] .", "Due to their central role in meiosis , crossovers are tightly controlled in most organisms such...	[ "During meiosis in most sexually reproducing organisms , recombination forms crossovers between homologous maternal and paternal chromosomes and thereby promotes proper chromosome segregation at the first meiotic division .", "The number and distribution of crossovers are tightly controlled , but the factors that...	[ "Meiosis is the specialized cell division that gives rise to reproductive cells such as sperm and eggs .", "During meiosis in most organisms , genetic information is exchanged between homologous maternal and paternal chromosomes through the process of homologous recombination .", "This recombination forms conne...	2008
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biochemistry", "microscopy", "proteins", "virology", "protein structure", "electron microscopy", "biology and life sciences", "microbiology", "computational biology", "viral structure", "research and analysis methods" ]	A Structural Model of the Genome Packaging Process in a Membrane-Containing Double Stranded DNA Virus	journal.pbio.1002024	Modeling how PRD1, a dsDNA membrane-containing virus, packages its genome using electron cryo-microscopy.	[ [ "The functional and structural knowledge of assembly principles of macromolecular complexes , in general , and viruses , in particular , have extended our understanding of viral capsid maturation and genome packaging processes .", "The model systems used are most often double-stranded DNA ( dsDNA ) viruse...	[ "Two crucial steps in the virus life cycle are genome encapsidation to form an infective virion and genome exit to infect the next host cell .", "In most icosahedral double-stranded ( ds ) DNA viruses , the viral genome enters and exits the capsid through a unique vertex .", "Internal membrane-containing viruse...	[ "The life cycle of a virus involves serial coordination of viral molecular machines .", "These machines facilitate functions such as membrane fusion and genome delivery during infection , and capsid formation and genome packaging during replication and shedding .", "Icosahedral dsDNA viruses use one genome-tran...	2014
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "rna interference", "chromosome structure and function", "centromeres", "gene regulation", "fungi", "model organisms", "experimental organism systems", "epigenetics", "chromatin", "schizosaccharomyces", "heterochromatin", "research and analysis methods", "small interfering rnas", "genome c...	The intron in centromeric noncoding RNA facilitates RNAi-mediated formation of heterochromatin	journal.pgen.1006606	null	[ [ "Chromosome segregation is a fundamental process in the transmission of genetic information to the daughter cells in eukaryotic cells .", "During mitosis , formation of heterochromatin at centromeres is essential for correct segregation of chromosomes , because centromeric heterochromatin provides an envi...	[ "In fission yeast , the formation of centromeric heterochromatin is induced through the RNA interference ( RNAi ) -mediated pathway .", "Some pre-mRNA splicing mutants ( prp ) exhibit defective formation of centromeric heterochromatin , suggesting that splicing factors play roles in the formation of heterochromat...	[ "Formation of centromeric heterochromatin is required for correct segregation of sister chromatids during mitosis .", "In fission yeast , formation of heterochromatin at centromeres is performed through the RNA interference ( RNAi ) system , which involves processing of noncoding RNAs transcribed from the centrom...	2017
[ "Introduction", "Materials and methods", "Results", "Discussion" ]	[ "medicine and health sciences", "astrocytes", "vertebrates", "social sciences", "mice", "neuroscience", "macroglial cells", "animals", "mammals", "learning and memory", "biological locomotion", "animal models", "cognitive neuroscience", "model organisms", "animal behavior", "cognition"...	The Noonan Syndrome-linked Raf1L613V mutation drives increased glial number in the mouse cortex and enhanced learning	journal.pgen.1008108	null	[ [ "The canonical RAS/RAF/MEK/ERK ( aka ERK1/2 or MAPK3/MAPK1 ) intracellular signaling cascade is a crucial regulator of specific aspects of neural development and synaptic function [1 , 2 , 3 , 4 , 5 , 6 , 7 , 8] .", "Mutations that lead to altered ERK1/2 signaling give rise to a group of human development...	[ "RASopathies are a family of related syndromes caused by mutations in regulators of the RAS/Extracellular Regulated Kinase 1/2 ( ERK1/2 ) signaling cascade that often result in neurological deficits .", "RASopathy mutations in upstream regulatory components , such as NF1 , PTPN11/SHP2 , and RAS have been well-cha...	[ "The RASopathies are a large and complex family of syndromes caused by mutations in the RAS/MAPK signaling cascade with no known cure .", "Individuals with these syndromes often present with heart defects , craniofacial differences , and neurological abnormalities , such as developmental delay , cognitive changes...	2019
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "microbiology", "model organisms", "forms of dna", "molecular genetics", "dna", "dna amplification", "biology", "molecular biology", "nucleic acids", "genetics", "gene duplication", "yeast and fungal models", "saccharomyces cerevisiae", "dna recombination", "molecular cell biology", "g...	A Mechanism of Gene Amplification Driven by Small DNA Fragments	journal.pgen.1003119	null	[ [ "DNA amplification is defined as a molecular process resulting in copy number increase of a discrete chromosomal DNA region .", "DNA amplification is found in many tumors , it is associated with several neuropathies and it can affect the susceptibility to certain diseases , such as systemic lupus erythema...	[ "DNA amplification is a molecular process that increases the copy number of a chromosomal tract and often causes elevated expression of the amplified gene ( s ) .", "Although gene amplification is frequently observed in cancer and other degenerative disorders , the molecular mechanisms involved in the process of ...	[ "DNA amplification is a copy-number increase of a DNA segment .", "Although DNA amplification is frequently observed in cancer and other degenerative disorders , the molecular mechanisms initiating this process are still largely elusive .", "Here we demonstrate that small DNA fragments with homology to two dist...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "cell biology/morphogenesis and cell biology", "microbiology/parasitology", "cell biology/cell signaling" ]	A Cyclic GMP Signalling Module That Regulates Gliding Motility in a Malaria Parasite	journal.ppat.1000599	null	[ [ "Malaria parasites belong to the subphylum apicomplexa , which comprises a large diversity of often intracellular parasites , including important causative agents of disease in humans and animals .", "Apicomplexa use a unique kind of substrate dependent gliding motility as a key virulence strategy [1]–[3]...	[ "The ookinete is a motile stage in the malaria life cycle which forms in the mosquito blood meal from the zygote .", "Ookinetes use an acto-myosin motor to glide towards and penetrate the midgut wall to establish infection in the vector .", "The regulation of gliding motility is poorly understood .", "Through...	[ "Malaria parasites are single celled organisms , which must alternate between vertebrate and mosquito hosts to survive and spread .", "In both hosts , certain parasite stages can glide through tissues and invade cells .", "Many components of the molecular motor that powers gliding and invasion are known and we ...	2009
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine and health sciences", "muscle tissue", "nervous system", "vertebrates", "neuroscience", "animals", "motor neurons", "animal models", "osteichthyes", "developmental biology", "model organisms", "molecular motors", "actin motors", "nerve fibers", "embryos", "motor proteins", ...	Myosin phosphatase Fine-tunes Zebrafish Motoneuron Position during Axonogenesis	journal.pgen.1006440	null	[ [ "It has been long recognized that during embryonic development of multicellular organisms , differential growth rates and morphogenetic movements of adjacent tissues are highly coordinated [1 , 2] .", "For example , the developing vertebral column and the spinal cord exhibit differential growth rates and ...	[ "During embryogenesis the spinal cord shifts position along the anterior-posterior axis relative to adjacent tissues .", "How motor neurons whose cell bodies are located in the spinal cord while their axons reside in adjacent tissues compensate for such tissue shift is not well understood .", "Using live cell i...	[ "Embryonic development requires tight coordination between tissues as they frequently grow at different rates .", "Such differential growth rates can cause shifts between neighboring tissues , and are a particular challenge for individual cells that span multiple tissues , in part because mechanical tension on su...	2016
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "virology", "biology", "microbiology" ]	Second External Quality Assurance Study for the Serological Diagnosis of Hantaviruses in Europe	journal.pntd.0001607	null	[ [ "Hantaviruses are endemic throughout the world and naturally hosted by rodents and insectivores .", "Humans are mostly infected by inhalation of virus-containing aerosolized excretions ( urine , saliva or feces ) or bites from host rodents , and there is no transmission between humans .", "Two human z...	[ "Hantaviruses are endemic throughout the world and hosted by rodents and insectivores .", "Two human zoonoses , hemorrhagic fever with renal syndrome ( HFRS ) and hantavirus pulmonary syndrome ( HPS ) , are caused by hantaviruses and case fatality rates have reached 12% for HFRS and 50% for HPS in some outbreaks ...	[ "Hantaviruses are endemic throughout the world and naturally hosted by rodents .", "The vast majority of human hantavirus infections are asymptomatic .", "In Europe , symptomatic hantavirus infections are summarised as hemorrhagic fever with renal syndrome ( HFRS ) mainly due to Puumala , Dobrava-Belgrade and S...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "computational biology/systems biology", "cell biology/cell signaling" ]	Fuzzy Logic Analysis of Kinase Pathway Crosstalk in TNF/EGF/Insulin-Induced Signaling	journal.pcbi.1000340	null	[ [ "A variety of modeling methods can be applied to understanding protein signaling", "networks and the links between signals and phenotypes [1] .", "The choice of modeling", "method depends on the question being posed ( e . g . , mechanistic or phenotypic ) , the", "quality and type of experimen...	[ "When modeling cell signaling networks , a balance must be struck between", "mechanistic detail and ease of interpretation .", "In this paper we apply a fuzzy", "logic framework to the analysis of a large , systematic dataset describing the", "dynamics of cell signaling downstream of TNF , EGF , and insulin...	[ "Cells use networks of interacting proteins to interpret intra-cellular state and", "extra-cellular cues and to execute cell-fate decisions .", "Even when individual", "proteins are well understood at a molecular level , the dynamics and behavior of", "networks as a whole are harder to understand .", "How...	2009
[ "Introduction", "Results and Discussion", "Materials and Methods" ]	[]	Genome Analysis of a Transmissible Lineage of Pseudomonas aeruginosa Reveals Pathoadaptive Mutations and Distinct Evolutionary Paths of Hypermutators	journal.pgen.1003741	null	[ [ "A molecular and mechanistic understanding of how bacterial pathogens evolve during infection of their human hosts is important for our ability to fight infections .", "The advent of high-throughput sequencing techniques now offer unprecedented nucleotide resolution to determine the relatedness among infe...	[ "Genome sequencing of bacterial pathogens has advanced our understanding of their evolution , epidemiology , and response to antibiotic therapy .", "However , we still have only a limited knowledge of the molecular changes in in vivo evolving bacterial populations in relation to long-term , chronic infections .",...	[ "Pseudomonas aeruginosa is the dominating pathogen of chronic airway infections in patients with cystic fibrosis ( CF ) .", "Although bacterial long-term persistence in CF hosts involves mutation and selection of genetic variants with increased fitness in the CF lung environment , our understanding of the within-...	2013
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "genetics", "population genetics", "biology", "evolutionary biology", "population biology", "evolutionary processes", "genetics and genomics" ]	The Rate of Beneficial Mutations Surfing on the Wave of a Range Expansion	journal.pcbi.1002447	null	[ [ "Our model is a variant of Kimura's stepping-stone model [18] for a population in a linear habitat , and has been used in Ref .", "[4] to quantify the surfing of neutral mutations .", "In this model , colonization sites ( which are called “demes” ) are regularly distributed along the axis .", "Due...	[ "Many theoretical and experimental studies suggest that range expansions can have severe consequences for the gene pool of the expanding population .", "Due to strongly enhanced genetic drift at the advancing frontier , neutral and weakly deleterious mutations can reach large frequencies in the newly colonized re...	[ "When a life form expands its range , the individuals close to the expanding front are more likely to dominate the gene pool of the newly colonized territory .", "This leads to the sweeping of pioneer genes across the newly colonized , a process which has been named gene surfing .", "We investigate how this eff...	2012
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "taxonomy", "crystal structure", "protein interactions", "enzymes", "split-decomposition method", "condensed matter physics", "enzymology", "multiple alignment calculation", "phylogenetics", "data management", "physicochemical properties", "phylogenetic analysis", "crystallography", "resea...	Recognition of sites of functional specialisation in all known eukaryotic protein kinase families	journal.pcbi.1005975	null	[ [ "Protein kinases , as key regulators of cellular functions , are among the largest and most diverse protein superfamilies known [1 , 2] .", "On account of their phosphotransfer function to a Ser / Thr / Tyr residue in eukaryotes , they are also known as STY kinases .", "Congruent to their function as ...	[ "The conserved function of protein phosphorylation , catalysed by members of protein kinase superfamily , is regulated in different ways in different kinase families .", "Further , differences in activating triggers , cellular localisation , domain architecture and substrate specificity between kinase families ar...	[ "Protein kinases are molecular switches that destine crucial decision points in cell signalling pathways .", "Consequently , they are implicated in the normal functioning of a cell as well as in various cancers if mutated .", "Kinases constitute a large and diverse superfamily with conserved 3-dimensional struc...	2018
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "cell death", "autophagic cell death", "medicine and health sciences", "cell processes", "brain", "vertebrates", "mice", "neuroscience", "animals", "mammals", "fibroblasts", "animal models", "model organisms", "connective tissue cells", "experimental organism systems", "nerve fibers", ...	Altered distribution of ATG9A and accumulation of axonal aggregates in neurons from a mouse model of AP-4 deficiency syndrome	journal.pgen.1007363	null	[ [ "The hereditary spastic paraplegias ( HSPs ) are a clinically and genetically diverse group of neurological disorders characterized by progressive lower limb spasticity [1 , 2 , 3] .", "HSPs are further classified into “pure” and “complicated” depending on the absence or presence of additional clinical fe...	[ "The hereditary spastic paraplegias ( HSP ) are a clinically and genetically heterogeneous group of disorders characterized by progressive lower limb spasticity .", "Mutations in subunits of the heterotetrameric ( ε-β4-μ4-σ4 ) adaptor protein 4 ( AP-4 ) complex cause an autosomal recessive form of complicated HSP...	[ "Hereditary spastic paraplegia ( HSP ) is a genetic disorder characterized by progressive stiffness of the legs .", "To date , mutations in more than 70 genes have been shown to cause HSP .", "Four of these genes encode the subunits of adaptor protein 4 ( AP-4 ) , a heterotetrameric complex involved in intracel...	2018
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "transfection", "gene regulation", "cloning", "plasmid construction", "analysis of variance", "mathematics", "dna replication", "statistics (mathematics)", "dna construction", "molecular biology techniques", "dna", "dna structure", "research and analysis methods", "small interfering rnas",...	Rad51 recruitment and exclusion of non-homologous end joining during homologous recombination at a Tus/Ter mammalian replication fork barrier	journal.pgen.1007486	null	[ [ "The stalling of replication forks at sites of abnormal DNA structure , following collisions with transcription complexes or due to nucleotide pool depletion—collectively termed “replication stress”—is a significant contributor to genomic instability .", "Inherited mutations in genes that regulate the rep...	[ "Classical non-homologous end joining ( C-NHEJ ) and homologous recombination ( HR ) compete to repair mammalian chromosomal double strand breaks ( DSBs ) .", "However , C-NHEJ has no impact on HR induced by DNA nicking enzymes .", "In this case , the replication fork is thought to convert the DNA nick into a o...	[ "Genomic instability is a significant contributor to human disease , ranging from hereditary developmental disorders to cancer predisposition .", "Two major triggers to genomic instability are chromosomal double strand breaks ( DSBs ) and the stalling of replication forks during the DNA synthesis ( S phase ) of t...	2018
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "fish", "molecular dynamics", "chemical compounds", "split-decomposition method", "social sciences", "vertebrates", "neuroscience", "animals", "organic compounds", "animal models", "osteichthyes", "multiple alignment calculation", "model organisms", "experimental organism systems", "amin...	Identifying human diamine sensors for death related putrescine and cadaverine molecules	journal.pcbi.1005945	null	[ [ "Olfaction is the major neurosensory function by which many species explore the chemical composition of their natural environments to locate food , avoid potentially harmful situations , recognize territory , identify members of their own group or predators , and choose a mate .", "Notable among the many ...	[ "Pungent chemical compounds originating from decaying tissue are strong drivers of animal behavior .", "Two of the best-characterized death smell components are putrescine ( PUT ) and cadaverine ( CAD ) , foul-smelling molecules produced by decarboxylation of amino acids during decomposition .", "These volatile...	[ "The distinctive dead smell comes largely from molecules like cadaverine and putrescine that are produced during decomposition of organic tissues .", "These volatile compounds act as powerful chemical signals important for the survival of a wide range of species .", "Previous studies have identified the trace a...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "cognitive neuroscience", "biology", "neuroscience", "neuroimaging" ]	Movement-Related Theta Rhythm in Humans: Coordinating Self-Directed Hippocampal Learning	journal.pbio.1001267	A multimodal neuroimaging study of virtual spatial navigation extends the role of the hippocampal theta rhythm to human memory and self-directed learning.	[ [ "Spatial exploration provides an ecologically valid experimental paradigm to investigate volitional behaviour and cognition across different species .", "In freely behaving rodents , the theta rhythm ( ∼4–12 Hz ) dominates the hippocampal local field potential ( LFP ) during translational motion , particu...	[ "The hippocampus is crucial for episodic or declarative memory and the theta rhythm has been implicated in mnemonic processing , but the functional contribution of theta to memory remains the subject of intense speculation .", "Recent evidence suggests that the hippocampus might function as a network hub for voli...	[ "Neural activity both within and across brain regions can oscillate in different frequency ranges ( such as alpha , gamma , and theta frequencies ) , and these different ranges are associated with distinct functions .", "In behaving rodents , for example , theta rhythms ( 4–12 Hz ) in the hippocampus are prominen...	2012
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "invertebrates", "cell death", "caenorhabditis", "enzymes", "statistics", "cell processes", "enzymology", "neuroscience", "animals", "alleles", "animal models", "caenorhabditis elegans", "statistical data", "model organisms", "mathematics", "experimental organism systems", "nerve fib...	Distinct CED-10/Rac1 domains confer context-specific functions in development	journal.pgen.1007670	null	[ [ "Correct axonal projection is essential for developing a functional nervous system .", "The Caenorhabditis elegans ventral nerve cord ( VNC ) contains two fascicles housing multiple neurons that project axons along the length of the animal [1] .", "During development , the extending tips of VNC axons ...	[ "Rac GTPases act as master switches to coordinate multiple interweaved signaling pathways .", "A major function for Rac GTPases is to control neurite development by influencing downstream effector molecules and pathways .", "In Caenorhabditis elegans , the Rac proteins CED-10 , RAC-2 and MIG-2 act in parallel t...	[ "Brain development requires that neurite outgrowth and guidance are precisely regulated .", "Previous studies have shown that molecular switch proteins called Rac GTPases perform redundant functions in controlling neurite development .", "Using a pair of bilateral neurons in the nematode Caenorhabditis elegans ...	2018
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "systems biology", "computer and information sciences", "mathematics", "theoretical biology", "statistics (mathematics)", "population modeling", "network analysis", "biology and life sciences", "signaling networks", "computational biology", "physical sciences", "probability theory" ]	ODE Constrained Mixture Modelling: A Method for Unraveling Subpopulation Structures and Dynamics	journal.pcbi.1003686	null	[ [ "Multi-cellular organisms are faced with diverse , ever changing environments .", "To ensure survival and evolutionary success , microbial systems exploit cell-to-cell variability originating from bet-hedging strategies which increase the robustness against environmental changes [1] .", "Such bet-hedg...	[ "Functional cell-to-cell variability is ubiquitous in multicellular organisms as well as bacterial populations .", "Even genetically identical cells of the same cell type can respond differently to identical stimuli .", "Methods have been developed to analyse heterogeneous populations , e . g . , mixture models...	[ "In this manuscript , we introduce ODE constrained mixture models for the analysis of population snapshot data of kinetics and dose responses .", "Population snapshot data can for instance be derived from flow cytometry or single-cell microscopy and provide information about the population structure and the dynam...	2014
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "public health and epidemiology/epidemiology" ]	A Rationale for Schistosomiasis Control in Elementary Schools of the Rainforest Zone of Pernambuco, Brazil	journal.pntd.0000395	null	[ [ "Fifty-fourth World Health Assembly , resolution WHA54 . 19 ( WHA-54 . 19 ) [1] , held in May 2001 , recommended Country Members to develop sustainable control activities , ensure access to medication , promote preventive measures and secure resources for the control of schistosomiasis and soil-transmitted he...	[ "Since its beginning in 1999 , the Schistosomiasis Control Program within the Unified Health System ( PCE-SUS ) has registered a cumulative coverage of just 20% of the population from the Rainforest Zone of Pernambuco ( ZMP ) , northeast Brazil .", "This jeopardizes the accomplishment of the minimum goal of the F...	[ "In 2001 , a World Health Assembly resolution urged member states to ensure treatment against schistosomiasis and soil-transmitted helminthiasis in endemic areas with the goal of attaining a minimum target of at least 75% of all school-aged children by 2010 .", "In the highly endemic Rainforest Zone of Pernambuco...	2009
[ "Introduction", "Results and Discussion", "Materials and Methods" ]	[]	Shade Avoidance Components and Pathways in Adult Plants Revealed by Phenotypic Profiling	journal.pgen.1004953	null	[ [ "Plant canopy shade limits available light for photosynthesis .", "Because plants are sessile , this presents a particular challenge .", "Perhaps as a consequence plants developed a light-quality sensory system for canopy shade; perception of foiliar shade and/or reflection from neighbor plants ( “nei...	[ "Shade from neighboring plants limits light for photosynthesis; as a consequence , plants have a variety of strategies to avoid canopy shade and compete with their neighbors for light .", "Collectively the response to foliar shade is called the shade avoidance syndrome ( SAS ) .", "The SAS includes elongation o...	[ "Because plants depend on light for photosynthesis , neighboring plant shade can be detrimental to survival .", "Many plants sense and respond to neighbor shade to compete for light .", "Although shade causes responses throughout the plant ( collectively known as the shade avoidance syndrome or SAS ) , most SAS...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "neuroscience/neurodevelopment", "developmental biology/neurodevelopment", "developmental biology/morphogenesis and cell biology" ]	RACK-1 Acts with Rac GTPase Signaling and UNC-115/abLIM in Caenorhabditis elegans Axon Pathfinding and Cell Migration	journal.pgen.1001215	null	[ [ "The actin cytoskeleton is necessary for the formation of cellular protrusions , lamellipodia and filopodia , that underlie morphogenetic events such as cell migration and axon pathfinding [1]–[4] .", "Unraveling the complex molecular events that regulate actin structure and dynamics in migrating cells an...	[ "Migrating cells and growth cones extend lamellipodial and filopodial protrusions that are required for outgrowth and guidance .", "The mechanisms of cytoskeletal regulation that underlie cell and growth cone migration are of much interest to developmental biologists .", "Previous studies have shown that the Ar...	[ "In the developing nervous system , the growth cone guides axons of neurons to their correct targets in the organism .", "The growth cone is a highly dynamic specialization at the tip of the axon that senses cues and responds by crawling toward its target , leaving the axon behind .", "Key to growth cone motili...	2010
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "public health", "medicine", "infectious diseases", "computer science", "disease ecology", "computer modeling", "neglected tropical diseases", "onchocerciasis", "infectious disease control", "infectious disease modeling", "parasitic diseases", "helminth infection" ]	Uncertainty Surrounding Projections of the Long-Term Impact of Ivermectin Treatment on Human Onchocerciasis	journal.pntd.0002169	null	[ [ "Human onchocerciasis , caused by Onchocerca volvulus and transmitted by Simulium blackflies , is a parasitic disease leading to ocular ( vision loss , blindness ) and cutaneous ( itching , dermatitis , depigmentation ) pathology [1] , [2] , as well as to increased host mortality [3] , [4] , [5] .", "The ...	[ "Recent studies in Mali , Nigeria , and Senegal have indicated that annual ( or biannual ) ivermectin distribution may lead to local elimination of human onchocerciasis in certain African foci .", "Modelling-based projections have been used to estimate the required duration of ivermectin distribution to reach eli...	[ "Studies in Mali , Nigeria , and Senegal suggest that , in some settings , it is possible to eliminate onchocerciasis after 15–17 years of ivermectin distribution .", "Computer models have been used to estimate the required duration of ivermectin distribution to reach elimination .", "Some models assume that an...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "agriculture", "biology" ]	Functional Analysis of the Kinome of the Wheat Scab Fungus Fusarium graminearum	journal.ppat.1002460	null	[ [ "In eukaryotic organisms , reversible protein phosphorylation by protein kinase ( PK ) is involved in the regulation of various growth and developmental processes and responses to environmental stimuli .", "Approximately 30% of cellular proteins are phosphorylated [1] .", "The eukaryotic PK superfamil...	[ "As in other eukaryotes , protein kinases play major regulatory roles in filamentous fungi .", "Although the genomes of many plant pathogenic fungi have been sequenced , systematic characterization of their kinomes has not been reported .", "The wheat scab fungus Fusarium graminearum has 116 protein kinases ( P...	[ "Fusarium head blight caused by Fusarium graminearum is one of the most important diseases on wheat and barley .", "Although protein kinases are known to play major regulatory roles in fungi , systematic characterization of fungal kinomes has not been reported in plant pathogens .", "In this study we generated ...	2011
[ "Introduction", "Results and Discussion", "Methods" ]	[ "biochemistry", "computational chemistry", "molecular dynamics", "nucleic acids", "biology and life sciences", "dna repair", "dna", "physical sciences", "chemistry", "biophysics", "biophysical simulations" ]	Alkylpurine Glycosylase D Employs DNA Sculpting as a Strategy to Extrude and Excise Damaged Bases	journal.pcbi.1003704	null	[ [ "Despite its remarkable stability , DNA is subject to a variety of reactions .", "Left unchecked , these processes could impair the transmission of vital genetic information and threaten the integrity of the genome .", "To cope with genomic instability cells have evolved elaborate DNA repair mechanism...	[ "Alkylpurine glycosylase D ( AlkD ) exhibits a unique base excision strategy .", "Instead of interacting directly with the lesion , the enzyme engages the non-lesion DNA strand .", "AlkD induces flipping of the alkylated and opposing base accompanied by DNA stack compression .", "Since this strategy leaves th...	[ "DNA repair efficiency is critically dependent on the function of DNA glycosylases .", "These versatile enzymes perform a remarkably discriminating search for DNA lesions , followed by damage-specific base extrusion into to the enzyme's active site and removal of the damaged bases .", "Our work elucidates the m...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "reverse transcriptase-polymerase chain reaction", "sequencing techniques", "rna-binding proteins", "medicine and health sciences", "ocular anatomy", "social sciences", "neuroscience", "alternative splicing", "sequence motif analysis", "molecular biology techniques", "research and analysis metho...	The Musashi 1 Controls the Splicing of Photoreceptor-Specific Exons in the Vertebrate Retina	journal.pgen.1006256	null	[ [ "Vertebrate nervous systems contain numerous types of neurons with characteristic morphology , connectivity , electrophysiological properties , and neurotransmitter signatures .", "Single cell transcriptome profiling studies reveal dozens of distinct gene expression profiles in the central nervous system ...	[ "Alternative pre-mRNA splicing expands the coding capacity of eukaryotic genomes , potentially enabling a limited number of genes to govern the development of complex anatomical structures .", "Alternative splicing is particularly prevalent in the vertebrate nervous system , where it is required for neuronal deve...	[ "Vertebrates possess extraordinarily complex nervous systems that are formed by hundreds of different types of neurons .", "This neuronal diversity is achieved in part through the expression of specific sets of genes .", "In addition , neurons use alternative splicing to a much higher degree than other cells to...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "signatures of natural selection", "genetic polymorphism", "natural selection", "symbiosis", "genetics", "biology and life sciences", "population genetics", "species interactions", "evolutionary biology", "evolutionary processes", "evolutionary genetics" ]	The Evolution of Sex Ratio Distorter Suppression Affects a 25 cM Genomic Region in the Butterfly Hypolimnas bolina	journal.pgen.1004822	null	[ [ "In 1930 , Fisher noted that the strength of selection on the sex ratio was frequency dependent , echoing earlier findings of Düsing [1] , [2] .", "As a well-mixed outbreeding population progressively deviates from a 1∶1 sex ratio , selection on individuals to restore the sex ratio to parity becomes stron...	[ "Symbionts that distort their host's sex ratio by favouring the production and survival of females are common in arthropods .", "Their presence produces intense Fisherian selection to return the sex ratio to parity , typified by the rapid spread of host ‘suppressor’ loci that restore male survival/development .",...	[ "The sex ratio of the offspring produced by an individual can be an evolutionary battleground .", "In many arthropod species , maternally inherited microbes selectively kill male hosts , and the host may in turn evolve strategies to restore the production or survival of males .", "When males are rare , the inte...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biology and life sciences", "immunology", "microbiology" ]	Early Mucosal Sensing of SIV Infection by Paneth Cells Induces IL-1β Production and Initiates Gut Epithelial Disruption	journal.ppat.1004311	null	[ [ "Chronic inflammation and disease progression in HIV infection is attributed to dysfunction in the structure of the intestinal epithelial barrier as well as impairment of the mucosal immune response resulting in increased microbial translocation [1]–[3] , dysbiosis of the gut microbiome [4]–[6] , and enteric ...	[ "HIV causes rapid CD4+ T cell depletion in the gut mucosa , resulting in immune deficiency and defects in the intestinal epithelial barrier .", "Breakdown in gut barrier integrity is linked to chronic inflammation and disease progression .", "However , the early effects of HIV on the gut epithelium , prior to t...	[ "The loss of intestinal CD4+ T cells in chronic HIV infection is associated with impaired immune responses to pathogens , aberrant immune activation , and defects in the gut epithelial barrier .", "While much is known about the pathogenesis of HIV in chronic disease , less is known about the defects that occur pr...	2014
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "genetics and genomics/bioinformatics", "genetics and genomics/gene expression" ]	An Abundance of Ubiquitously Expressed Genes Revealed by Tissue Transcriptome Sequence Data	journal.pcbi.1000598	null	[ [ "A fundamental question in molecular biology is how cells and tissues differ in gene expression and how those differences specify biological function .", "A related question is what part of the cellular machinery represents housekeeping functions needed by all cells and how many genes encode such function...	[ "The parts of the genome transcribed by a cell or tissue reflect the biological processes and functions it carries out .", "We characterized the features of mammalian tissue transcriptomes at the gene level through analysis of RNA deep sequencing ( RNA-Seq ) data across human and mouse tissues and cell lines .", ...	[ "A variety of genes are active within the nuclei of our cells .", "Some are needed for the day-to-day maintenance of cell functions , while others have roles that are more specific to certain tissues or particular cell types; for example , only the pancreas produces insulin .", "As a result , every tissue has i...	2009
[ "Introduction", "General Methods", "Experiments and Results", "Discussion" ]	[ "medicine", "infectious diseases" ]	Factors Affecting the Propensity of Tsetse Flies to Enter Houses and Attack Humans Inside: Increased Risk of Sleeping Sickness in Warmer Climates	journal.pntd.0002193	null	[ [ "Tsetse flies ( Glossina spp . ) feed exclusively on vertebrate blood , and in so doing they can transmit species of trypanosome ( Trypanosoma spp . ) that cause the diseases of nagana in domestic animals and sleeping sickness in humans [1] .", "The latter disease , also known as human African trypanosomi...	[ "Sleeping sickness , or human African trypanosomiasis , is caused by two species of Trypanosoma brucei that are transmitted to humans by tsetse flies ( Glossina spp . ) when these insects take a bloodmeal .", "It is commonly assumed that humans must enter the normal woodland habitat of the flies to become infecte...	[ "To identify factors affecting the contact between tsetse and humans in buildings , we caught tsetse that", "( i ) accumulated in a large thatched house in Zimbabwe , and", "( ii ) alighted on humans in the house during the day .", "In accord with earlier work , the numbers accumulating increased about 10-fol...	2013
[ "Introduction", "Methods", "Discussion" ]	[ "statistics", "variant genotypes", "genetic mapping", "kernel functions", "mathematics", "test statistics", "protein structure", "protein structure databases", "research and analysis methods", "operator theory", "proteins", "mathematical and statistical techniques", "biological databases", ...	Identifying individual risk rare variants using protein structure guided local tests (POINT)	journal.pcbi.1006722	null	[ [ "Rare genetic variants , e . g . those which occur in less than 1-3% of a population , play an important role in complex diseases .", "Individual rare variants can be difficult to detect due to low frequencies of the mutant alleles .", "Therefore , associations involving rare variants are typically di...	[ "Rare variants are of increasing interest to genetic association studies because of their etiological contributions to human complex diseases .", "Due to the rarity of the mutant events , rare variants are routinely analyzed on an aggregate level .", "While aggregation analyses improve the detection of global-l...	[ "While it is known that rare variants play an important role in understanding associations between genotype and complex diseases , pinpointing individual rare variants likely to be responsible for association is still a daunting task .", "Due to their low frequency in the population and reduced signal , localizin...	2019
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "cell biology", "genetics", "biology and life sciences", "microbiology", "molecular cell biology" ]	Rad51–Rad52 Mediated Maintenance of Centromeric Chromatin in Candida albicans	journal.pgen.1004344	null	[ [ "The centromere ( CEN ) is a specialized chromosomal locus that recruits a macromolecular multi-protein complex , called the kinetochore that binds to spindle microtubules and helps in equal separation of chromosomes during the anaphase stage of mitosis .", "Despite performing a conserved function , CEN D...	[ "Specification of the centromere location in most eukaryotes is not solely dependent on the DNA sequence .", "However , the non-genetic determinants of centromere identity are not clearly defined .", "While multiple mechanisms , individually or in concert , may specify centromeres epigenetically , most studies ...	[ "The epigenetic mark of centromeres , CENP-A , is deposited in S phase in most yeasts by a mechanism that is not completely understood .", "Here , we identify two CEN7 flanking replication origins , ORI7-L1 and ORI7-RI , proximal to an early replicating centromere ( CEN7 ) in a budding yeast Candida albicans .", ...	2014
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "inflammatory diseases", "urology", "medicine and health sciences", "body fluids", "nervous system", "tropical diseases", "geographical locations", "treponematoses", "bacterial diseases", "sexually transmitted diseases", "neglected tropical diseases", "africa", "infectious diseases", "infe...	Neurosyphilis in Africa: A systematic review	journal.pntd.0005880	null	[ [ "Syphilis , caused by Treponema pallidum subsp .", "pallidum , remains an important sexually transmitted disease worldwide .", "Some studies suggest the natural history , outcomes of treatment , and likelihood of central nervous system involvement are different in HIV-infected compared to uninfected i...	[ "Neurological involvement is one of the most important clinical manifestations of syphilis and neurological disease occurs in both early and late syphilis .", "The impact of HIV co-infection on clinical neurosyphilis remains unclear .", "The highest prevalence of both syphilis and HIV is in Africa .", "Theref...	[ "Involvement of the central nervous system is an important manifestation of syphilis which may be more common in patients co-infected with HIV .", "As most cases of syphilis and HIV are seen in Africa it might be anticipated that neurosyphilis was common there .", "We reviewed all published material on neurosyp...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine and health sciences", "lysosomes", "keratinocytes", "toxins", "pathology and laboratory medicine", "intracellular pathogens", "pathogens", "group a streptococcal infection", "toxicology", "toxic agents", "epithelial cells", "bacterial diseases", "protein synthesis", "cellular str...	NAD+-Glycohydrolase Promotes Intracellular Survival of Group A Streptococcus	journal.ppat.1005468	null	[ [ "Since the 1980’s , there has been a sustained , worldwide increase in the incidence of severe , invasive infections due to group A Streptococcus ( Streptococcus pyogenes or GAS ) , particularly necrotizing fasciitis and streptococcal toxic shock syndrome [1–3] .", "The reasons for the emergence of invasi...	[ "A global increase in invasive infections due to group A Streptococcus ( S . pyogenes or GAS ) has been observed since the 1980s , associated with emergence of a clonal group of strains of the M1T1 serotype .", "Among other virulence attributes , the M1T1 clone secretes NAD+-glycohydrolase ( NADase ) .", "When ...	[ "Invasive infections due to group A Streptococcus ( S . pyogenes or GAS ) have become more frequent since the 1980s due , in part , to the emergence and global spread of closely related strains of the M1T1 serotype .", "A feature of this clonal group is the production of a secreted enzyme , NAD+-glycohydrolase ( ...	2016
[ "Introduction", "Results", "Discussion", "Material and Methods" ]	[ "medicine and health sciences", "molecular complexes", "pathology and laboratory medicine", "microbiology", "basic cancer research", "oncology", "gastroenterology and hepatology", "bacterial pathogens", "infectious diseases", "cell adhesion", "proteins", "medical microbiology", "microbial pa...	Crk Adaptors Negatively Regulate Actin Polymerization in Pedestals Formed by Enteropathogenic Escherichia coli (EPEC) by Binding to Tir Effector	journal.ppat.1004022	null	[ [ "Enteropathogenic Escherichia coli ( EPEC ) causes infant diarrhea worldwide and is a leading cause of death in developing countries .", "EPEC adheres to intestinal epithelial cells , causing local disappearance of microvilli and altering cell permeability , giving rise to what are classically known as at...	[ "Infections by enteropathogenic Escherichia coli ( EPEC ) cause diarrhea linked to high infant mortality in developing countries .", "EPEC adheres to epithelial cells and induces the formation of actin pedestals .", "Actin polymerization is driven fundamentally through signaling mediated by Tir bacterial effect...	[ "Infections by enteropathogenic Escherichia coli are an important cause of diarrhea linked to high infant mortality .", "Such bacteria attach to cells and form actin-rich structures called pedestals , which contain many proteins that play unknown functions during pedestal formation .", "Here we studied two near...	2014
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "neural networks", "engineering and technology", "signal processing", "bifurcation theory", "neuroscience", "signal filtering", "systems science", "mathematics", "algebra", "white noise", "computational neuroscience", "computer and information sciences", "animal cells", "linear filters", ...	Contrasting the effects of adaptation and synaptic filtering on the timescales of dynamics in recurrent networks	journal.pcbi.1006893	null	[ [ "Adaptive behavior requires processing information over a vast span of timescales [1] , ranging from micro-seconds for acoustic localisation [2] , milliseconds for detecting changes in the visual field [3] , seconds for evidence integration [4] and working memory [5] , to hours , days or years in the case of ...	[ "Neural activity in awake behaving animals exhibits a vast range of timescales that can be several fold larger than the membrane time constant of individual neurons .", "Two types of mechanisms have been proposed to explain this conundrum .", "One possibility is that large timescales are generated by a network ...	[ "Brain activity spans a wide range of timescales , as it is required to interact in complex time-varying environments .", "However , individual neurons are primarily fast devices: their membrane time constant is of the order of a few tens of milliseconds .", "Yet , neurons are also subject to additional biophys...	2019
[ "Introduction", "Materials and methods", "Results", "Discussion" ]	[ "schistosoma", "invertebrates", "schistosoma mansoni", "medicine and health sciences", "immune physiology", "helminths", "immunology", "vertebrates", "parasitic diseases", "animals", "mammals", "primates", "animal models", "experimental organism systems", "antibodies", "antibody respon...	Specific anti-glycan antibodies are sustained during and after parasite clearance in Schistosoma japonicum-infected rhesus macaques	journal.pntd.0005339	null	[ [ "Schistosomiasis is a debilitating parasitic disease caused by members of the helminth genus Schistosoma ( S . ) , with S . mansoni , S . japonicum and S . haematobium being the most prevalent human species .", "Once Schistosoma infection establishes , mature worms can live up to 30 years in the host unti...	[ "Human immunity to Schistosoma infection requires many years of exposure , and multiple infections and treatments to develop .", "Unlike humans , rhesus macaques clear an established schistosome infection naturally at the same time acquiring immunity towards re-infection .", "In macaques , schistosome egg produ...	[ "Schistosomes express many glycan antigens to which antibodies are raised by the infected host .", "These glycans may therefore form potential vaccine targets .", "Unlike humans where the disease persists chronically if not treated , schistosome-infected rhesus macaques are able to elicit a self-cure process na...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genomics", "gene regulatory networks", "fungal genetics", "gene expression", "genetics", "biology and life sciences", "molecular genetics", "molecular biology techniques", "computational biology", "molecular biology", "gene function" ]	A Functional Portrait of Med7 and the Mediator Complex in Candida albicans	journal.pgen.1004770	null	[ [ "Mediator is a multi-subunit protein complex that is implicated in the proper expression of most RNA polymerase II ( pol II ) transcripts , including both protein-coding and non-coding genes [1]–[9] .", "Mediator , which contains four modules , termed head , middle , tail and kinase , serves as a central ...	[ "Mediator is a multi-subunit protein complex that regulates gene expression in eukaryotes by integrating physiological and developmental signals and transmitting them to the general RNA polymerase II machinery .", "We examined , in the fungal pathogen Candida albicans , a set of conditional alleles of genes encod...	[ "In this study , we have investigated Mediator function in the human fungal pathogen C . albicans .", "An initial screening of conditionally regulated Mediator subunits showed that the Med7 of C . albicans was not essential , in contrast to the situation noted for S . cerevisiae .", "While loss of CaMed7 did no...	2014
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[]	Multiple Pathogens Including Potential New Species in Tick Vectors in Côte d’Ivoire	journal.pntd.0004367	null	[ [ "Ticks are important vectors of many pathogens and are considered as the second biggest vectors of human and animal diseases after mosquitoes [1 , 2] .", "Many tick-borne bacterial emerging diseases such as spotted fevers , borrelioses , anaplasmoses , ehrlichioses , and Q fever have been described worldw...	[ "Our study aimed to assess the presence of different pathogens in ticks collected in two regions in Côte d’Ivoire .", "Real-time PCR and standard PCR assays coupled to sequencing were used .", "Three hundred and seventy eight ( 378 ) ticks ( 170 Amblyomma variegatum , 161 Rhipicepalus microplus , 3 Rhipicephalu...	[ "The management of febrile illnesses represents a veritable challenge in sub Saharan-Africa .", "Until recently most of them were considered as malaria .", "However , it was showed that a large part of non-malarial febrile diseases in African rural regions ( for instance , in Senegal ) may be caused by tick-bor...	2016
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "algorithms", "systems biology", "computer science", "metabolic networks", "biology", "computational biology" ]	Fast Reconstruction of Compact Context-Specific Metabolic Network Models	journal.pcbi.1003424	null	[ [ "Cell metabolism is known to play a key role in the pathogenesis of various diseases [1] such as Parkinson's disease [2] and cancer [3] .", "The study of human metabolism has been greatly advanced by the development of computational models of metabolism , such as Recon 1 [4] , the Edinburgh human metaboli...	[ "Systemic approaches to the study of a biological cell or tissue rely increasingly on the use of context-specific metabolic network models .", "The reconstruction of such a model from high-throughput data can routinely involve large numbers of tests under different conditions and extensive parameter tuning , whic...	[ "Metabolism comprises all life-sustaining biochemical processes .", "It plays an essential role in various aspects of biology , including the development and progression of many diseases .", "As the metabolism of a living cell involves several thousands of small molecules and their conversion , a full analysis ...	2014
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "medicine and health sciences", "vertebrates", "electrophysiology", "mice", "neuroscience", "animals", "mammals", "social sciences", "ion channels", "animal behavior", "behavioral disorders", "molecular biology techniques", "zoology", "mood disorders", "research and analysis methods", ...	TDAG51 is a crucial regulator of maternal care and depressive-like behavior after parturition	journal.pgen.1008214	null	[ [ "Maternal behavior represents an instinctive pattern of caring for an offspring by a mother [1] .", "The physical and physiological changes that occur in response to pregnancy and parturition may cause maternal depression , which has deleterious effects on maternal behavior [2] .", "Postpartum depress...	[ "Postpartum depression is a severe emotional and mental disorder that involves maternal care defects and psychiatric illness .", "Postpartum depression is closely associated with a combination of physical changes and physiological stress during pregnancy or after parturition in stress-sensitive women .", "Altho...	[ "Postpartum depression is a severe emotional and mental disease that can affect women typically after parturition .", "However , the genetic risk factors associated with the development of postpartum depression are still largely unknown .", "We discovered a novel function of T cell death-associated gene 51 ( TD...	2019
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "computer science", "cell biology", "computational biology", "biophysics", "neuroscience", "rattus (rat)" ]	Coincidence Detection of Place and Temporal Context in a Network Model of Spiking Hippocampal Neurons	journal.pcbi.0030234	null	[ [ "The hippocampal network needs to integrate information about place and temporal context to enable an animal to navigate its environment based on previous experience [1–5] .", "Since the discovery of place cells , which fire selectively when a rat is in a particular location [6] , it has been clear that t...	[ "Recent advances in single-neuron biophysics have enhanced our understanding of information processing on the cellular level , but how the detailed properties of individual neurons give rise to large-scale behavior remains unclear .", "Here , we present a model of the hippocampal network based on observed biophys...	[ "Understanding how behavior is connected to cellular and network processes is one of the most important challenges in neuroscience , and computational modeling allows one to directly formulate hypotheses regarding the interactions between these scales .", "We present a model of the hippocampal network , an area o...	2007
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	β-Catenin Signaling Biases Multipotent Lingual Epithelial Progenitors to Differentiate and Acquire Specific Taste Cell Fates	journal.pgen.1005208	null	[ [ "The sense of taste is indispensable for feeding behavior .", "It informs the body whether food is harmful or nutritious , and thus is critical for regulating the intake of essential nutrients .", "Taste stimuli are detected in the oral cavity by taste buds , which are collections of neuroepithelial c...	[ "Continuous taste bud cell renewal is essential to maintain taste function in adults; however , the molecular mechanisms that regulate taste cell turnover are unknown .", "Using inducible Cre-lox technology , we show that activation of β-catenin signaling in multipotent lingual epithelial progenitors outside of t...	[ "Taste is a fundamental sense that helps the body determine whether food can be ingested .", "Taste dysfunction can be a side effect of cancer therapies , can result from an alteration of the renewal capacities of the taste buds , and is often associated with psychological distress and malnutrition .", "Thus , ...	2015
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "medicine and health sciences", "ecology and environmental sciences", "water resources", "cross-sectional studies", "tropical diseases", "vertebrates", "parasitic diseases", "dogs", "animals", "mammals", "research design", "mathematics", "statistics (mathematics)", "rural areas", "neglec...	Potential Risk Factors Associated with Human Cystic Echinococcosis: Systematic Review and Meta-analysis	journal.pntd.0005114	null	[ [ "Cystic echinococcosis ( CE ) , caused by the metacestode stage of the tapeworm Echinococcus granulosus sensu lato ( s . l . ) , is a neglected zoonotic disease producing economic losses in animals and high morbidity and mortality rates in humans with huge health , social and economic consequences for communi...	[ "Scientific literature on cystic echinococcosis ( CE ) reporting data on risk factors is limited and to the best of our knowledge , no global evaluation of human CE risk factors has to date been performed .", "This systematic review ( SR ) summarizes available data on statistically relevant potential risk factors...	[ "Cystic echinococcosis ( CE ) is a chronic zoonotic disease causing serious global socio-economic losses in human and animal hosts .", "Two main aspects make it extremely difficult to study risk factors associated with human CE , the parasite’s unknown and apparently long incubation period which may last for seve...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "bacteriology", "immunology", "microbiology", "host-pathogen interaction", "bacterial biochemistry", "bacterial pathogens", "microbial physiology", "medical microbiology", "microbial pathogens", "biology", "biochemistry", "gram negative", "immunity", "innate immunity" ]	Helicobacter pylori versus the Host: Remodeling of the Bacterial Outer Membrane Is Required for Survival in the Gastric Mucosa	journal.ppat.1002454	null	[ [ "Helicobacter pylori , a gram-negative bacterium with only one well-defined niche , the human stomach , can persist for several years without manifestation of symptoms .", "However , over time serious complications may appear including peptic ulcer disease and gastric cancer , allowing for classification ...	[ "Modification of bacterial surface structures , such as the lipid A portion of lipopolysaccharide ( LPS ) , is used by many pathogenic bacteria to help evade the host innate immune response .", "Helicobacter pylori , a gram-negative bacterium capable of chronic colonization of the human stomach , modifies its lip...	[ "Since its discovery in 1982 Helicobacter pylori has been identified as the leading cause of gastritis and peptic ulcer disease , infecting around 50% of the world's population .", "Infected patients are at increased risk for gastric cancers , allowing for classification of H . pylori as a class I carcinogen by t...	2011
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[]	Multiplicity of Infection and Disease Severity in Plasmodium vivax	journal.pntd.0004355	null	[ [ "A common observation in many malaria endemic areas is that there are patients concurrently infected by more than one distinct parasite genotype .", "These infections are usually referred to as multiclonal infections .", "In addition to the frequency of multiclonal infections , molecular epidemiologis...	[ "Multiplicity of infection ( MOI ) refers to the average number of distinct parasite genotypes concurrently infecting a patient .", "Although several studies have reported on MOI and the frequency of multiclonal infections in Plasmodium falciparum , there is limited data on Plasmodium vivax .", "Here , MOI and ...	[ "Previous studies on rodent malarias and mathematical models have postulated a link between multiclonal infections and disease severity .", "This association has been tested in Plasmodium falciparum mostly in Africa with limited information on P . vivax .", "Furthermore , there is a paucity of information from ...	2016
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "medicine and health sciences", "dendritic structure", "nervous system", "radii", "electrophysiology", "geometry", "neuroscience", "optimization", "mathematics", "ganglion cells", "neuronal dendrites", "animal cells", "cellular neuroscience", "cell biology", "anatomy", "synapses", "p...	Optimal Current Transfer in Dendrites	journal.pcbi.1004897	null	[ [ "Integration of synaptic inputs relies on the propagation of currents arising from sources across the dendritic tree .", "Whilst active processes strongly contribute to current flow in most neurons [1–3] , understanding the passive backbone to transmission is key to an intuitive grasp of dendritic functio...	[ "Integration of synaptic currents across an extensive dendritic tree is a prerequisite for computation in the brain .", "Dendritic tapering away from the soma has been suggested to both equalise contributions from synapses at different locations and maximise the current transfer to the soma .", "To find out how...	[ "Neurons take a great variety of shapes that allow them to perform their different computational roles across the brain .", "The most distinctive visible feature of many neurons is the extensively branched network of cable-like projections that make up their dendritic tree .", "A neuron receives current-inducin...	2016
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "genetics and genomics/comparative genomics", "evolutionary biology/evolutionary and comparative genetics", "evolutionary biology/human evolution", "genetics and genomics/functional genomics", "evolutionary biology/genomics", "computational biology/evolutionary modeling", "computational biology/genomics...	The Use of Orthologous Sequences to Predict the Impact of Amino Acid Substitutions on Protein Function	journal.pgen.1000968	null	[ [ "Due to continuing advances in DNA sequencing technologies , our knowledge of human genetic variation is rapidly increasing .", "It is currently impractical to assay the biological effect of most genetic variants empirically , so computational predictions of their functional impact must play an important ...	[ "Computational predictions of the functional impact of genetic variation play a critical role in human genetics research .", "For nonsynonymous coding variants , most prediction algorithms make use of patterns of amino acid substitutions observed among homologous proteins at a given site .", "In particular , su...	[ "The rapid pace of technological advances in DNA sequencing methods is leading to the discovery of genetic variants at a remarkable rate .", "Indeed , it is conceivable that entire individual genomes will be sequenced routinely in the near future .", "While these platforms greatly increase our ability to catalo...	2010
[ "Introduction", "Results", "Methods", "Discussion" ]	[ "biochemistry/transcription and translation", "genetics and genomics/gene expression", "genetics and genomics/chromosome biology", "computational biology/transcriptional regulation" ]	Blurring of High-Resolution Data Shows that the Effect of Intrinsic Nucleosome Occupancy on Transcription Factor Binding is Mostly Regional, Not Local	journal.pcbi.1000649	null	[ [ "Genomic DNA is largely covered in proteins , mostly in the form of nucleosomes .", "Much of the remainder consists of chromatin-associated proteins , including enzymes that modify histones or DNA , or catalyze the rearrangement of nucleosomes , and sequence specific DNA binding proteins ( transcription f...	[ "Genome wide maps of nucleosome occupancy in yeast have recently been produced through deep sequencing of nuclease-protected DNA .", "These maps have been obtained from both crosslinked and uncrosslinked chromatin in vivo , and from chromatin assembled from genomic DNA and nucleosomes in vitro .", "Here , we an...	[ "Genomic DNA is largely covered by proteins that compete with one another for binding to regulatory sequences .", "Most of these proteins are in the form of nucleosomes .", "How nucleosomes come to occupy particular sites and thereby compete with sequence specific transcription factors is a central problem in d...	2010
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "biology" ]	Cell Death and Reproductive Regression in Female Schistosoma mansoni	journal.pntd.0001509	null	[ [ "Infection with trematode parasites of the genus Schistosoma causes chronic and debilitating disease in over 200 million people worldwide [1] , [2] .", "Adult S . mansoni worms live within the mesenteric veins laying eggs that are intended to pass into the intestinal lumen for release into the environment...	[ "The vitellarium is a highly proliferative organ , producing cells which are incorporated along with a fertilized ovum into the schistosome egg .", "Vitellarial growth fails to occur in virgin female schistosomes in single sex ( female-only ) infections , and involution of this tissue , which is accompanied by ph...	[ "Schistosomes are parasitic trematode worms that infect more that 200 million people in 76 countries of the tropics and subtropics .", "These parasites are unusual amongst trematodes in having separate sexes .", "Mating of male and female schistosome involves the female residing within a specialized canal on th...	2012
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "biotechnology", "biology", "zoology", "parasitology" ]	In Vitro Silencing of Brugia malayi Trehalose-6-Phosphate Phosphatase Impairs Embryogenesis and In Vivo Development of Infective Larvae in Jirds	journal.pntd.0001770	null	[ [ "Lymphatic filariasis ( LF ) , caused by mosquito transmitted filarial parasites , Wuchereria bancrofti , Brugia malayi and B . timori has been identified as a second leading cause of permanent and long term disability .", "LF control relies on community-wide mass distribution of diethylcarbamazine or ive...	[ "The trehalose metabolic enzymes have been considered as potential targets for drug or vaccine in several organisms such as Mycobacterium , plant nematodes , insects and fungi due to crucial role of sugar trehalose in embryogenesis , glucose uptake and protection from stress .", "Trehalose-6-phosphate phosphatase...	[ "Lymphatic filariasis , one of the neglected tropical diseases , is the second leading cause of permanent and long term disability .", "Control of the disease relies on the mass administration of drugs which mainly act on the microfilariae without substantial effect on adult worms .", "Drugs need to be continue...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Neuronal Reprograming of Protein Homeostasis by Calcium-Dependent Regulation of the Heat Shock Response	journal.pgen.1003711	null	[ [ "Cellular health and organismal lifespan are critically dependent upon the fidelity of the proteome and the proteostasis network [1] .", "What are the molecular events that control proteostasis across tissues to activate protective responses at the cellular level to ensure organismal health ?", "At th...	[ "Protein quality control requires constant surveillance to prevent misfolding , aggregation , and loss of cellular function .", "There is increasing evidence in metazoans that communication between cells has an important role to ensure organismal health and to prevent stressed cells and tissues from compromising ...	[ "The protein quality control machinery is responsible for preventing the accumulation of misfolded and damaged proteins and loss of cellular function .", "The capacity of cellular surveillance is limited however , leading to increased appearance of protein aggregates and risk for age-associated diseases .", "He...	2013
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "sequencing techniques", "medicine and health sciences", "influenza", "population dynamics", "population genetics", "simulation and modeling", "mathematics", "statistics (mathematics)", "effective population size", "molecular biology techniques", "population biology", "research and analysis me...	Quantifying and Mitigating the Effect of Preferential Sampling on Phylodynamic Inference	journal.pcbi.1004789	null	[ [ "Phylodynamics—a set of techniques for estimating population dynamics from genetic data—has proven useful in ecology and epidemiology [1 , 2] .", "Phylodynamics is especially useful in cases where ascertaining population sizes via traditional sampling methods is infeasible; e . g . , in infectious disease...	[ "Phylodynamics seeks to estimate effective population size fluctuations from molecular sequences of individuals sampled from a population of interest .", "One way to accomplish this task formulates an observed sequence data likelihood exploiting a coalescent model for the sampled individuals’ genealogy and then i...	[ "Phylodynamics seeks to estimate changes in population size from genetic data sampled from individuals across a particular population .", "One approach to accomplish this task uses a model called the coalescent , which relates the shape of the individuals’ shared ancestral tree to genetic diversity , which is in ...	2016
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "neuroscience/neuronal signaling mechanisms", "neuroscience/theoretical neuroscience", "computational biology/computational neuroscience" ]	Relating Neuronal Firing Patterns to Functional Differentiation of Cerebral Cortex	journal.pcbi.1000433	null	[ [ "Neurons transmit stereotypical electrical pulses called spikes .", "The in vivo spike firing of cortical neurons is often regarded as a series of simple random events that conveys no information other than the frequency , or rate , of occurrences .", "However , it is possible that neuronal firing pat...	[ "It has been empirically established that the cerebral cortical areas defined by Brodmann one hundred years ago solely on the basis of cellular organization are closely correlated to their function , such as sensation , association , and motion .", "Cytoarchitectonically distinct cortical areas have different den...	[ "Neurons , or nerve cells in the brain , communicate with each other using stereotyped electric pulses , called spikes .", "It is believed that neurons convey information mainly through the frequency of the transmitted spikes , called the firing rate .", "In addition , neurons may communicate some information t...	2009
[ "Introduction", "Results and Discussion", "Materials and Methods" ]	[ "biomacromolecule-ligand interactions", "biochemistry", "enzyme structure", "hydrolysis", "biocatalysis", "thermodynamics", "enzymes", "catalysis", "chemistry", "chemical reactions", "biology", "enzyme kinetics", "biophysics", "physical chemistry" ]	Ground State Destabilization by Anionic Nucleophiles Contributes to the Activity of Phosphoryl Transfer Enzymes	journal.pbio.1001599	Enhanced phosphate binding by phosphatases upon removal of their anionic nucleophiles suggests that these enzymes use ground state destabilization by anionic active site nucleophiles as part of their catalytic arsenal.	[ [ "Enzymes are central to biology , allowing chemical processes to be carried out rapidly and specifically .", "A range of enzymatic catalytic efficiencies of 106–1029 fold have been observed [1] , [2] , with the more difficult chemical reactions generally exhibiting higher rate enhancements such that kcat/...	[ "Enzymes stabilize transition states of reactions while limiting binding to ground states , as is generally required for any catalyst .", "Alkaline Phosphatase ( AP ) and other nonspecific phosphatases are some of Nature's most impressive catalysts , achieving preferential transition state over ground state stabi...	[ "Enzymes use a variety of tools and strategies to enhance ( catalyze ) biological reactions; these include the use of general acids and bases , cofactors , and the employment of remote binding interactions to position substrates near reactive chemical groups .", "Phosphatases are some of Nature's best enzymes , a...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "animal models", "mitosis", "meiosis", "drosophila melanogaster", "model organisms", "molecular cell biology", "cell division", "cell biology", "chromosome biology", "centromeres", "biology" ]	The Cell Cycle Timing of Centromeric Chromatin Assembly in Drosophila Meiosis Is Distinct from Mitosis Yet Requires CAL1 and CENP-C	journal.pbio.1001460	The centromeric histone CENP-A is incorporated at different cell cycle phases during somatic mitosis, meiosis I and meiosis II in Drosophila melanogaster.	[ [ "Centromeres are key regions of eukaryotic chromosomes that ensure proper chromosome segregation during cell divisions .", "In most eukaryotes , centromere identity is defined epigenetically by the presence of a centromere-specific histone H3 variant CENP-A ( CID in flies , CENH3 in some organisms ) [1] ....	[ "CENP-A ( CID in flies ) is the histone H3 variant essential for centromere specification , kinetochore formation , and chromosome segregation during cell division .", "Recent studies have elucidated major cell cycle mechanisms and factors critical for CENP-A incorporation in mitosis , predominantly in cultured c...	[ "Centromeres are regions of eukaryotic chromosomes that recruit the kinetochores and are essential for faithful segregation of DNA during all cell divisions .", "The centromere-specific histone H3 variant CENP-A accumulates at the centromere , defining this region , and is maintained throughout cellular generatio...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "immune cells", "protein interactions", "viruses and cancer", "immunology", "microbiology", "c-jun n-terminal kinase signaling cascade", "cell growth", "biology", "proteomics", "pathogenesis", "biochemistry", "signal transduction", "b cells", "viral persistence and latency", "cell biolog...	The Germinal Center Kinase TNIK Is Required for Canonical NF-κB and JNK Signaling in B-Cells by the EBV Oncoprotein LMP1 and the CD40 Receptor	journal.pbio.1001376	TNIK has an important function in physiological activation and viral transformation of human B-cells by interacting with the TRAF6 adapter complex and mediating NF-κB and JNK signal transduction.	[ [ "TNIK was discovered in a yeast-two-hybrid screen for interaction partners of the adapter proteins TRAF2 and Nck [1] .", "The serine/threonine kinase TNIK is a member of the germinal center kinase ( GCK ) family , which belongs to the Ste20 group of kinases [2] .", "GCKs share high sequence homology i...	[ "The tumor necrosis factor-receptor-associated factor 2 ( TRAF2 ) - and Nck-interacting kinase ( TNIK ) is a ubiquitously expressed member of the germinal center kinase family .", "The TNIK functions in hematopoietic cells and the role of TNIK-TRAF interaction remain largely unknown .", "By functional proteomic...	[ "The germinal center kinase family member TNIK was discovered in a yeast-two-hybrid screen for interaction partners of the adapter proteins TRAF2 and Nck , and here we show it is one of the missing molecular players in two key signaling pathways in B-lymphocytes .", "We found that TNIK is crucial for the activiti...	2012
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "computational neuroscience", "biology", "computational biology" ]	Modeling of Pharmacokinetics of Cocaine in Human Reveals the Feasibility for Development of Enzyme Therapies for Drugs of Abuse	journal.pcbi.1002610	null	[ [ "Substance abuse and addiction are a major medical and social problem in the world [1] .", "Most of substances of abuse are psychoactive drugs , such as cocaine , illicit opiates , amphetamine-type stimulants , ecstasy-group substances , and cannabinoids .", "All psychoactive compounds have the abuse ...	[ "A promising strategy for drug abuse treatment is to accelerate the drug metabolism by administration of a drug-metabolizing enzyme .", "The question is how effectively an enzyme can actually prevent the drug from entering brain and producing physiological effects .", "In the present study , we have developed a...	[ "In this computational study , we have examined , for the first time , the potential effects of a drug-metabolizing enzyme on drug pharmacokinetics in human , showing that a high-activity drug-metabolizing enzyme can completely/effectively prevent the drug of abuse from entering brain to produce physiological effec...	2012
[ "Introduction", "Materials and methods", "Results", "Discussion" ]	[ "medicine and health sciences", "decision making", "engineering and technology", "electronics", "neurodegenerative diseases", "signal processing", "integrators", "social sciences", "neuroscience", "noise reduction", "systems science", "mathematics", "cognitive psychology", "cognition", "...	Myopic control of neural dynamics	journal.pcbi.1006854	null	[ [ "Advances in recording technology are making it possible to gain real-time access to neural dynamics at different length and time scales [1 , 2] , allowing us to consider the structure of the brain’s operation in ways that were previously inaccessible .", "Central to that understanding of neural dynamics ...	[ "Manipulating the dynamics of neural systems through targeted stimulation is a frontier of research and clinical neuroscience; however , the control schemes considered for neural systems are mismatched for the unique needs of manipulating neural dynamics .", "An appropriate control method should respect the varia...	[ "Stimulating a neural system and observing its effect through simultaneous observation offers the promise to better understand how neural systems perform computations , as well as for the treatment of neurological disorders .", "A powerful perspective for understanding a neural system’s behavior undergoing stimul...	2019
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "developmental biology", "biology", "morphogenesis", "pattern formation", "cell differentiation" ]	Interactions with Iridophores and the Tissue Environment Required for Patterning Melanophores and Xanthophores during Zebrafish Adult Pigment Stripe Formation	journal.pgen.1003561	null	[ [ "The pigment patterns of teleost fishes are extraordinarily diverse and have important functions in mate choice , shoaling and predation avoidance [1]–[4] .", "These patterns result from the spatial arrangements of several classes of pigment cells including black melanophores that contain melanin , yellow...	[ "Skin pigment patterns of vertebrates are a classic system for understanding fundamental mechanisms of morphogenesis , differentiation , and pattern formation , and recent studies of zebrafish have started to elucidate the cellular interactions and molecular mechanisms underlying these processes .", "In this spec...	[ "Pigment patterns are some of the most distinctive , diverse and aesthetically pleasing traits of vertebrates .", "In turn , these patterns offer an outstanding opportunity to understand the mechanisms underlying the development of adult form and how such mechanisms change evolutionarily .", "Among the especial...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "viral components", "viral core", "viruslike particles", "encapsidation", "virology", "biology and life sciences", "capsids", "microbiology", "viral replication complex", "viral structure", "viral replication" ]	The N-Terminus of Murine Leukaemia Virus p12 Protein Is Required for Mature Core Stability	journal.ppat.1004474	null	[ [ "Retroviruses initially assemble as immature viruses containing a core of Gag and Gag-Pol polyproteins .", "During maturation these are cleaved into mature proteins by the virally encoded protease ( PR ) .", "Cleavage of the gammaretrovirus Gag polyprotein produces four mature proteins: matrix ( MA ) ...	[ "The murine leukaemia virus ( MLV ) gag gene encodes a small protein called p12 that is essential for the early steps of viral replication .", "The N- and C-terminal regions of p12 are sequentially acting domains , both required for p12 function .", "Defects in the C-terminal domain can be overcome by introduci...	[ "All retroviral genomes contain a gag gene that codes for the Gag polyprotein .", "Gag is cleaved upon viral maturation to release individual proteins , including matrix , capsid and nucleocapsid , providing the structural components of the virion .", "In murine leukaemia virus ( MLV ) , Gag cleavage releases a...	2014
[ "Introduction", "Results/Discussion", "Materials and Methods" ]	[ "viral core", "virology", "biology", "microbiology", "viral structure" ]	Atomic Model of Rabbit Hemorrhagic Disease Virus by Cryo-Electron Microscopy and Crystallography	journal.ppat.1003132	null	[ [ "Rabbit hemorrhagic disease ( RHD ) is extremely contagious in adult rabbits and is often associated with liver necrosis , hemorrhaging , and high mortality [1] .", "It was first described in China in 1984 [2] , and within a few years had spread worldwide [3] .", "RHD outbreaks still occur on almost e...	[ "Rabbit hemorrhagic disease , first described in China in 1984 , causes hemorrhagic necrosis of the liver .", "Its etiological agent , rabbit hemorrhagic disease virus ( RHDV ) , belongs to the Lagovirus genus in the family Caliciviridae .", "The detailed molecular structure of any lagovirus capsid has yet to b...	[ "Rabbit hemorrhagic disease ( RHD ) , first described in China in 1984 , causes hemorrhagic necrosis of the liver within three days after infection and with a mortality rate that exceeds 90% .", "RHD has spread to large parts of the world and threatens the rabbit industry and related ecology .", "Its etiologica...	2013
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "animal types", "quantitative trait loci", "population genetics", "domestic animals", "animals", "model organisms", "experimental organism systems", "evolutionary adaptation", "population biology", "plants", "zoology", "research and analysis methods", "grasses", "genetic polymorphism", "...	Genetic architecture and selective sweeps after polygenic adaptation to distant trait optima	journal.pgen.1007794	null	[ [ "Understanding molecular adaptation is essential for the study of evolutionary processes , genetic diseases , and plant and animal breeding .", "The process of adaptation is often divided into three separate modes: hard selective sweeps , soft selective sweeps and polygenic adaptation [1] .", "In rece...	[ "Understanding the genetic basis of phenotypic adaptation to changing environments is an essential goal of population and quantitative genetics .", "While technological advances now allow interrogation of genome-wide genotyping data in large panels , our understanding of the process of polygenic adaptation is sti...	[ "Many traits are controlled by a large number of genes , and environmental changes can lead to shifts in trait optima .", "How populations adapt to these shifts depends on a number of parameters including the genetic basis of the trait as well as population demography .", "We simulate a number of trait architec...	2018
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "computational biology/metabolic networks", "computational biology/systems biology", "computational biology/computational neuroscience" ]	Organization of Excitable Dynamics in Hierarchical Biological Networks	journal.pcbi.1000190	null	[ [ "The analysis of biological networks presents an intriguing challenge , due to the complex , non-random organization of these systems and the diverse dynamic behaviors that they express .", "The topology of several biological networks has been shown to be based on a scale-free degree distribution , which ...	[ "This study investigates the contributions of network topology features to the dynamic behavior of hierarchically organized excitable networks .", "Representatives of different types of hierarchical networks as well as two biological neural networks are explored with a three-state model of node activation for sys...	[ "Many complex biological networks are characterized by the coexistence of topological features such as modules and central hub nodes .", "What are the relative contributions of these structural features to the networks' dynamic behavior ?", "We used a computational model to simulate the general activation and i...	2008
[ "Introduction", "Discussion", "Methods" ]	[]	Dread and the Disvalue of Future Pain	journal.pcbi.1003335	null	[ [ "When faced with the choice of whether to have a painful medical or dental procedure right now or in the future , many people opt to ‘get it out of the way now’ .", "This tendency to expedite rather than delay future pain seems to challenge the generality of standard discounting models of inter-temporal c...	[ "Standard theories of decision-making involving delayed outcomes predict that people should defer a punishment , whilst advancing a reward .", "In some cases , such as pain , people seem to prefer to expedite punishment , implying that its anticipation carries a cost , often conceptualized as ‘dread’ .", "Despi...	[ "People often prefer to ‘get pain out of the way’ , treating pain in the future as more significant than pain now .", "One explanation , termed ‘dread’ , is that anticipating pain is unpleasant or disadvantageous , rather like pain itself .", "Human brain imaging studies support the existence of dread , though ...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "developmental biology", "cancer genetics", "genetics", "biology and life sciences", "cell differentiation" ]	The Tumor Suppressor BCL7B Functions in the Wnt Signaling Pathway	journal.pgen.1004921	null	[ [ "Cytogenetic abnormalities of chromosome 7 occur frequently in patients with cancer .", "Patients with certain types of malignant transformation , such as acute lymphoblastic leukemia , myelodysplastic syndrome , or juvenile myelomonocytic leukemia , frequently have deletions or abnormalities in chromosom...	[ "Human BCL7 gene family consists of BCL7A , BCL7B , and BCL7C .", "A number of clinical studies have reported that BCL7 family is involved in cancer incidence , progression , and development .", "Among them , BCL7B , located on chromosome 7q11 . 23 , is one of the deleted genes in patients with Williams-Beuren ...	[ "BCL7B , a member of the human BCL7 gene family , is deleted in patients with Williams-Beuren syndrome .", "Although several clinical studies have suggested that malignant diseases occurring in patients with Williams-Beuren syndrome are associated with aberrations in BCL7B , little is known regarding the physiolo...	2015
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "medicine and health sciences", "astrocytes", "endoplasmic reticulum", "cell processes", "electrophysiology", "neuroscience", "macroglial cells", "simulation and modeling", "ion channels", "calcium signaling", "cellular structures and organelles", "research and analysis methods", "cytosol", ...	Simulation of calcium signaling in fine astrocytic processes: Effect of spatial properties on spontaneous activity	journal.pcbi.1006795	null	[ [ "Astrocytes were first characterized as non-excitable cells of the central nervous system since , although they express voltage-gated channels [1] , they do not exhibit electrical excitability [2] .", "Astrocytes excitability instead results from variations of cytosolic calcium concentration [3] .", "...	[ "Astrocytes , a glial cell type of the central nervous system , have emerged as detectors and regulators of neuronal information processing .", "Astrocyte excitability resides in transient variations of free cytosolic calcium concentration over a range of temporal and spatial scales , from sub-microdomains to wav...	[ "Astrocytes process information in the brain via calcium signals that can modulate neuronal communication .", "Astrocytic calcium signals are associated with brain functioning , including memory and learning , and are altered in the diseased brain .", "Astrocytic calcium signals display a huge spatio-temporal d...	2019
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "microbiology", "model organisms", "dna", "chromosome biology", "biology", "molecular biology", "cell biology", "nucleic acids", "yeast and fungal models", "dna repair", "saccharomyces cerevisiae", "dna recombination", "molecular cell biology" ]	Distinct Cdk1 Requirements during Single-Strand Annealing, Noncrossover, and Crossover Recombination	journal.pgen.1002263	null	[ [ "DNA double-strand breaks ( DSBs ) occur spontaneously during DNA replication and after exposure to certain genotoxic chemicals or ionizing radiation .", "Efficient repair of DSBs can be accomplished by nonhomologous end joining ( NHEJ ) , which directly rejoins broken DNA ends , or by homologous recombin...	[ "Repair of DNA double-strand breaks ( DSBs ) by homologous recombination ( HR ) in haploid cells is generally restricted to S/G2 cell cycle phases , when DNA has been replicated and a sister chromatid is available as a repair template .", "This cell cycle specificity depends on cyclin-dependent protein kinases ( ...	[ "Homologous recombination ( HR ) provides an important mechanism to eliminate deleterious lesions , such as DNA double-strand breaks ( DSBs ) .", "DSB repair by HR uses homologous DNA sequences as a template to form recombinants that are either crossover or noncrossover with regard to flanking parental sequences ...	2011
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "connectomics", "neuroanatomy", "computational neuroscience", "biology", "neuroscience", "neuroimaging" ]	Extracting Message Inter-Departure Time Distributions from the Human Electroencephalogram	journal.pcbi.1002065	null	[ [ "Recent years have witnessed a remarkable drive to characterize the large-scale structural topology of the brain .", "The graph model of cortical connectivity – whereby space is discretized and the brain is delineated as a set of regional nodes interconnected by white matter edges – has enabled the applic...	[ "The complex connectivity of the cerebral cortex is a topic of much study , yet the link between structure and function is still unclear .", "The processing capacity and throughput of information at individual brain regions remains an open question and one that could potentially bridge these two aspects of neural...	[ "The brain may be thought of as a network of regions that communicate with each other to produce emergent phenomena such as perception and cognition .", "Many potentially interesting aspects of brain networks , such as how information is emitted at different nodes , also tend to be of interest in various types of...	2011
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "invertebrates", "dengue virus", "medicine and health sciences", "pathology and laboratory medicine", "togaviruses", "viral transmission and infection", "chikungunya infection", "atmospheric science", "pathogens", "geographical locations", "microbiology", "tropical diseases", "animals", "a...	Global expansion and redistribution of Aedes-borne virus transmission risk with climate change	journal.pntd.0007213	null	[ [ "Climate change will have a profound effect on the global distribution and burden of infectious diseases [1–3] .", "Current knowledge suggests that the range of mosquito-borne diseases could expand dramatically in response to climate change [4 , 5] .", "However , the physiological and epidemiological ...	[ "Forecasting the impacts of climate change on Aedes-borne viruses—especially dengue , chikungunya , and Zika—is a key component of public health preparedness .", "We apply an empirically parameterized model of viral transmission by the vectors Aedes aegypti and Ae .", "albopictus , as a function of temperature ...	[ "The established scientific consensus indicates that climate change will severely exacerbate the risk and burden of Aedes-transmitted viruses , including dengue , chikungunya , Zika , and other significant threats to global health security .", "Here , we show more subtle impacts of climate change on transmission ...	2019
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "medicine and health sciences", "infectious disease epidemiology", "spatial epidemiology", "vector-borne diseases", "tropical diseases", "geographical locations", "forecasting", "neglected tropical diseases", "infectious disease control", "research and analysis methods", "infectious diseases", ...	Risk of Dengue for Tourists and Teams during the World Cup 2014 in Brazil	journal.pntd.0003063	null	[ [ "Dengue is a mosquito-borne viral disease predominantly spread by female Aedes aegypti mosquitoes in ( sub ) tropical regions of the world .", "The dengue virus ( DENV ) causes an estimated 390 million infections per year worldwide resulting in 96 million clinically symptomatic cases [1] .", "The DENV...	[ "This year , Brazil will host about 600 , 000 foreign visitors during the 2014 FIFA World Cup .", "The concern of possible dengue transmission during this event has been raised given the high transmission rates reported in the past by this country .", "We used dengue incidence rates reported by each host city d...	[ "This year the 2014 FIFA World Cup will be hosted by Brazil , a country that has reported a higher number of dengue cases annually than any other country worldwide over the last decade .", "About 600 , 000 foreign tourists are expected and may be at risk for this disease .", "Games will be played in 12 differen...	2014
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "cell physiology", "cell death", "autophagic cell death", "medicine and health sciences", "fusarium", "pathology and laboratory medicine", "pathogens", "cell processes", "microbiology", "fusarium graminearum", "fungal structure", "plant science", "mycelium", "plant pathology", "molecular...	Small GTPase Rab7-mediated FgAtg9 trafficking is essential for autophagy-dependent development and pathogenicity in Fusarium graminearum	journal.pgen.1007546	null	[ [ "Pathogenic fungi are great threats to both plants and animals , hence jeopardizing food security [1] .", "Fusarium graminearum is a plant fungal pathogen which causes head blight of wheat and other cereals and has become a serious problem to agricultural production in the world [2–4] .", "During Fusa...	[ "Fusarium graminearum is a fungal pathogen that causes Fusarium head blight ( FHB ) in wheat and barley .", "Autophagy is a highly conserved vacuolar degradation pathway essential for cellular homeostasis in which Atg9 serves as a multispanning membrane protein important for generating membranes for the formation...	[ "Autophagy is an intracellular degradation pathway conserved in eukaryotes , but the mechanism of autophagy or autophagosome formation in the wheat head blight fungus Fusarium graminearum remains unclear .", "One fundamental question in the autophagy field lies on how the formation of autophagosome and recycling ...	2018
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "sequencing techniques", "medicine and health sciences", "canada", "pathology and laboratory medicine", "pathogens", "geographical locations", "microbiology", "cryptosporidium", "parasitic diseases", "parasitic protozoans", "north america", "diarrhea", "protozoans", "signs and symptoms", ...	Cryptosporidium hominis Is a Newly Recognized Pathogen in the Arctic Region of Nunavik, Canada: Molecular Characterization of an Outbreak	journal.pntd.0004534	null	[ [ "Cryptosporidium is an apicomplexan parasite that is increasingly recognised among immunocompetent hosts as a leading cause of childhood diarrhea in low-resource settings and of waterborne diarrheal outbreaks in high-income countries . [1 , 2]", "C . hominis , for which humans are the only natural host , ...	[ "Cryptosporidium is a leading cause of childhood diarrhea in low-resource settings , and has been repeatedly associated with impaired physical and cognitive development .", "In May 2013 , an outbreak of diarrhea caused by Cryptosporidium hominis was identified in the Arctic region of Nunavik , Quebec .", "Human...	[ "In mid-2013 , an outbreak of moderate-to-severe diarrhea caused by Cryptosporidium was identified in the Arctic region of Nunavik , Quebec , and it predominantly affected young children .", "Cryptosporidium is a leading cause of childhood diarrhea in low-resource settings , but was previously unknown in this reg...	2016
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "biotechnology", "neuroscience", "biomedical engineering", "motor systems", "control engineering", "biological systems engineering", "computational neuroscience", "coding mechanisms", "bioengineering", "biology", "computer science", "bionics", "control systems", "sensory systems", "neuro...	Shaping the Dynamics of a Bidirectional Neural Interface	journal.pcbi.1002578	null	[ [ "In a recent demonstration [1] , Schwartz and coworkers decoded neural activities from the motor area of a monkey's cerebral cortex to control the movement of a robotic arm .", "The monkey learned to activate the recorded neurons and to guide the arm for transporting food to the mouth .", "This is an ...	[ "Progress in decoding neural signals has enabled the development of interfaces that translate cortical brain activities into commands for operating robotic arms and other devices .", "The electrical stimulation of sensory areas provides a means to create artificial sensory information about the state of a device ...	[ "Brain-machine interfaces establish new communication channels between the brain and the external world with the goal of restoring sensory and motor functions for people with severe paralysis or sensory impairments .", "Current methodologies are based on decoding the motor intent from the recorded neural activity...	2012
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "medicine", "infectious diseases", "dengue", "viral diseases" ]	Correlation of Serotype-Specific Dengue Virus Infection with Clinical Manifestations	journal.pntd.0001638	null	[ [ "The world is experiencing a rapid increase in dengue virus ( DENV ) infections with an estimated 50 million people infected annually , and nearly two-fifths of the world's population is living in areas considered high-risk for infection [1] .", "DENVs are divided into four antigenically distinct serotype...	[ "Disease caused by the dengue virus ( DENV ) is a significant cause of morbidity throughout the world .", "Although prior research has focused on the association of specific DENV serotypes ( DENV-1 , DENV-2 , DENV-3 , and DENV-4 ) with the development of severe outcomes such as dengue hemorrhagic fever and dengue...	[ "Dengue virus ( DENV ) causes disease in millions of people annually and disproportionately affects those in the developing world .", "DENVs may be divided into four serotypes ( DENV-1 , DENV-2 , DENV-3 , and DENV-4 ) and a geographical region may be affected by one or more DENV serotypes simultaneously .", "In...	2012
[ "Introduction", "Materials and methods", "Results", "Discussion" ]	[ "animal types", "medicine and health sciences", "immunology", "tropical diseases", "vertebrates", "pets and companion animals", "dogs", "animals", "mammals", "preventive medicine", "rabies", "raccoons", "network analysis", "neglected tropical diseases", "vaccination and immunization", ...	The importance of dog population contact network structures in rabies transmission	journal.pntd.0006680	null	[ [ "The viral disease rabies , transmitted between mammals through bites , is fatal following the onset of symptoms .", "Although human rabies can be prevented by appropriate post-exposure prophylaxis ( PEP ) , approximately 60 , 000 people die annually from rabies , mainly in Africa and Asia , [1] .", "...	[ "Canine rabies transmission was interrupted in N’Djaména , Chad , following two mass vaccination campaigns .", "However , after nine months cases resurged with re-establishment of endemic rabies transmission to pre-intervention levels .", "Previous analyses investigated district level spatial heterogeneity of v...	[ "Rabies transmission between dogs and from dogs to humans can be interrupted by mass vaccination of dogs .", "Novel geo-referenced contact sensors tracked the contacts and locations of several hundred dogs in N’Djaména , the capital of Chad .", "With the data generated by the sensors we developed a contact netw...	2018
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "blood cells", "flow cytometry", "cell motility", "innate immune system", "medicine and health sciences", "immune physiology", "cytokines", "immune cells", "immunology", "tropical diseases", "cloning", "bacterial diseases", "developmental biology", "molecular development", "neglected tro...	Leprosy Reactions Show Increased Th17 Cell Activity and Reduced FOXP3+ Tregs with Concomitant Decrease in TGF-β and Increase in IL-6	journal.pntd.0004592	null	[ [ "Leprosy reactions occurring in approximately 50% of leprosy patients cause severe morbidity and need immediate clinical attention .", "Whereas the stable leprosy forms run a bland course amenable to multi drug therapy , leprosy reactions can be triggered by treatment and can also occur after the completi...	[ "50% of leprosy patients suffer from episodes of Type 1/ reversal reactions ( RR ) and Type 2/ Erythema Nodosum Leprosum ( ENL ) reactions which lead to morbidity and nerve damage .", "CD4+ subsets of Th17 cells and CD25+FOXP3+ regulatory T cells ( Tregs ) have been shown to play a major role in disease associate...	[ "Reversal reactions ( RR; Type", "1 ) and Erythema Nodosum Leprosum ( ENL; Type", "2 ) are two types of leprosy reactions which appear episodically in a proportion of leprosy patients and lead to high morbidity and peripheral nerve damage that require immediate medical attention , ENL seen in anergic lepromatou...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Non-redundant and Redundant Roles of Cytomegalovirus gH/gL Complexes in Host Organ Entry and Intra-tissue Spread	journal.ppat.1004640	null	[ [ "Herpesvirus entry is a complex process accomplished by a set of envelope glycoproteins that promote attachment of virus particles to host cells , recognition of host cell entry receptors , and fusion of the viral envelope with cellular membranes .", "All herpesviruses use a conserved core protein machine...	[ "Herpesviruses form different gH/gL virion envelope glycoprotein complexes that serve as entry complexes for mediating viral cell-type tropism in vitro; their roles in vivo , however , remained speculative and can be addressed experimentally only in animal models .", "For murine cytomegalovirus two alternative gH...	[ "The role of viral glycoprotein entry complexes in viral tropism in vivo is a question central to understanding virus pathogenesis and transmission for any virus .", "Studies were limited by the difficulty in distinguishing between viral entry into first-hit target cells and subsequent cell-to-cell spread within ...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "developmental biology/germ cells", "developmental biology/embryology", "genetics and genomics/comparative genomics", "genetics and genomics/functional genomics", "developmental biology/developmental evolution", "developmental biology/molecular development", "genetics and genomics/epigenetics" ]	The Parental Non-Equivalence of Imprinting Control Regions during Mammalian Development and Evolution	journal.pgen.1001214	null	[ [ "Mammalian development requires a subset of genes to be expressed in a parent-of-origin manner at specific stages and in specific tissues [1] .", "These so-called imprinted genes are organized around cis-acting regulatory sequences termed imprinting control regions ( ICRs ) that display allele- and parent...	[ "In mammals , imprinted gene expression results from the sex-specific methylation of imprinted control regions ( ICRs ) in the parental germlines .", "Imprinting is linked to therian reproduction , that is , the placenta and imprinting emerged at roughly the same time and potentially co-evolved .", "We assessed...	[ "In mammals , a subset of genes is expressed from only one chromosomal copy , depending on its parental origin .", "This process , known as genomic imprinting , results from DNA methylation marks deposited in gametes at regulatory sequences called imprinting control regions ( ICRs ) .", "Most of the DNA methyla...	2010
[ "Introduction", "Methods", "Results", "Discussion" ]	[]	Modeling the Geographic Spread of Rabies in China	journal.pntd.0003772	null	[ [ "Rabies , as an acute and fatal zoonotic disease , is most often transmitted through the bite or scratch of a rabid animal .", "The rabies virus infects the central nervous system , ultimately causing disease in the brain and death .", "Once the symptoms of rabies have developed , its mortality rate i...	[ "In order to investigate how the movement of dogs affects the geographically inter-provincial spread of rabies in Mainland China , we propose a multi-patch model to describe the transmission dynamics of rabies between dogs and humans , in which each province is regarded as a patch .", "In each patch the submodel ...	[ "In 1999 , human rabies cases were reported in about 120 counties in Mainland China , mainly in the southern provinces .", "Now outbreaks of human rabies have been reported in about 1000 counties and the disease has spread geographically from the south to the north .", "Phylogeographic analyses of rabies virus ...	2015
[ "Introduction", "Results", "Discussion", "Material and Methods" ]	[ "cryptococcosis", "medicine", "infectious diseases", "fungal diseases" ]	Brain Inositol Is a Novel Stimulator for Promoting Cryptococcus Penetration of the Blood-Brain Barrier	journal.ppat.1003247	null	[ [ "Cryptococcus neoformans is a basidiomycetous yeast pathogen that often causes life-threatening infections .", "It causes the most common fungal infection of the central nervous system ( CNS ) in HIV-infected persons and may present as encephalitis , meningitis , or cerebral-space-occupying lesions [1] , ...	[ "Cryptococcus neoformans is the most common cause of fungal meningitis , with high mortality and morbidity .", "The reason for the frequent occurrence of Cryptococcus infection in the central nervous system ( CNS ) is poorly understood .", "The facts that human and animal brains contain abundant inositol and th...	[ "Cryptococcus neoformans is an AIDS-associated human fungal pathogen that annually causes over 1 million cases of meningitis world-wide , and more than 600 , 000 attributable deaths .", "Cryptococcus often causes lung and brain infection and is the leading cause of fungal meningitis in immunosuppressed patients ....	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	HTLV-1 bZIP Factor Impairs Anti-viral Immunity by Inducing Co-inhibitory Molecule, T Cell Immunoglobulin and ITIM Domain (TIGIT)	journal.ppat.1005372	null	[ [ "Oncogenic viruses , including Epstein-Barr virus ( EBV ) , Kaposi’s sarcoma-associated herpesvirus ( KSHV ) , human papilloma virus ( HPV ) , hepatitis B virus ( HBV ) , hepatitis C virus ( HCV ) , Merkel cell polyomavirus and human T-cell leukemia virus type 1 ( HTLV-1 ) , cause approximately 12% of human c...	[ "Human T-cell leukemia virus type 1 ( HTLV-1 ) infects CD4+ T cells and induces proliferation of infected cells in vivo , which leads to the onset of adult T-cell leukemia ( ATL ) in some infected individuals .", "The HTLV-1 bZIP factor ( HBZ ) gene , which is encoded in the minus strand of HTLV-1 , plays critica...	[ "HTLV-1 is a T-cell-tropic , latently infectious virus that causes a T-cell malignancy , ATL , and inflammatory diseases .", "The mechanisms by which HTLV-1 evades the immune response and establishes chronic infection are not yet understood .", "Recent studies have demonstrated that TIGIT , a co-inhibitory mole...	2016
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "chemical bonding", "crystal structure", "chemical compounds", "phosphates", "condensed matter physics", "dna-binding proteins", "sequence motif analysis", "epigenetics", "crystallography", "thermodynamics", "chromatin", "hydrogen bonding", "research and analysis methods", "physical chemis...	Sequence-dependent nucleosome sliding in rotation-coupled and uncoupled modes revealed by molecular simulations	journal.pcbi.1005880	null	[ [ "Nucleosomes are the fundamental structural unit of eukaryotic chromatin , composed of approximately 147 base pairs ( bp ) of double stranded DNA wrapped around a histone octamer [1] .", "Nucleosomes enable genomic DNA to be folded into chromatin and efficiently packed inside the cell nucleus [2] .", ...	[ "While nucleosome positioning on eukaryotic genome play important roles for genetic regulation , molecular mechanisms of nucleosome positioning and sliding along DNA are not well understood .", "Here we investigated thermally-activated spontaneous nucleosome sliding mechanisms developing and applying a coarse-gra...	[ "Nucleosomes are fundamental units of chromatin folding consisting of double-stranded DNA wrapped ~1 . 7 times around a histone octamer .", "By densely populating the eukaryotic genome , nucleosomes enable efficient genome compaction inside the cellular nucleus .", "However , the portion of DNA occupied by a nu...	2017
[ "Introduction", "Materials and methods", "Results", "Discussion" ]	[ "invertebrates", "medicine and health sciences", "pathology and laboratory medicine", "togaviruses", "chikungunya infection", "atmospheric science", "pathogens", "tropical diseases", "microbiology", "animals", "alphaviruses", "viruses", "chikungunya virus", "rna viruses", "neglected trop...	Local environmental and meteorological conditions influencing the invasive mosquito Ae. albopictus and arbovirus transmission risk in New York City	journal.pntd.0005828	null	[ [ "Aedes albopictus Skuse 1984 , also known as the Asian tiger mosquito , is an invasive mosquito of growing consequence and concern especially for temperate areas [1 , 2] .", "Originating from Southeast Asia , this mosquito has expanded its range globally over the past three decades [3] .", "Its invasi...	[ "Ae .", "albopictus , an invasive mosquito vector now endemic to much of the northeastern US , is a significant public health threat both as a nuisance biter and vector of disease ( e . g . chikungunya virus ) .", "Here , we aim to quantify the relationships between local environmental and meteorological condit...	[ "This paper examines the ecological underpinnings of the invasive mosquito Ae .", "albopictus and the associated risk of arboviral transmission in New York City .", "We aim to quantify the relationships between local environmental and meteorological conditions and Ae .", "albopctus abundance .", "Further , ...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genome expression analysis", "animal genetics", "reproductive system", "functional genomics", "gene regulation", "anatomy and physiology", "neuroscience", "gene function", "developmental biology", "molecular development", "molecular genetics", "gene expression", "gene splicing", "comparat...	The Tissue-Specific RNA Binding Protein T-STAR Controls Regional Splicing Patterns of Neurexin Pre-mRNAs in the Brain	journal.pgen.1003474	null	[ [ "RNA binding proteins expand the functional complexity of the transcriptome by specifying which exons are spliced into mRNAs at key developmental steps , and make a significant contribution to animal development and complexity [1]–[7] .", "Splicing takes place in the spliceosome , which consists of 5 snRN...	[ "The RNA binding protein T-STAR was created following a gene triplication 520–610 million years ago , which also produced its two parologs Sam68 and SLM-1 .", "Here we have created a T-STAR null mouse to identify the endogenous functions of this RNA binding protein .", "Mice null for T-STAR developed normally a...	[ "Alternative splicing plays a key role in animal development and is largely controlled by the expression of RNA binding proteins .", "Most RNA binding proteins exist as families of sister proteins called paralogs , which result from gene amplification , including T-STAR , which is closely related to Sam68 and SLM...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biology and life sciences", "medicine and health sciences" ]	Cellular Oxidative Stress Response Controls the Antiviral and Apoptotic Programs in Dengue Virus-Infected Dendritic Cells	journal.ppat.1004566	null	[ [ "Dengue virus ( DENV ) is the leading arthropod-borne viral infection in the world , and represents a major global human health concern .", "DENV is endemic in more than 100 countries with up to 3 billion people in tropical regions of the world at risk of infection [1]–[3] .", "Recently , DENV has exp...	[ "Dengue virus ( DENV ) is a re-emerging arthropod borne flavivirus that infects more than 300 million people worldwide , leading to 50 , 000 deaths annually .", "Because dendritic cells ( DC ) in the skin and blood are the first target cells for DENV , we sought to investigate the early molecular events involved ...	[ "Dengue virus ( DENV ) , the leading arthropod-borne viral infection in the world , represents a major human health concern with a global at risk population of over 3 billion people .", "Currently , there are no antivirals or vaccines available to treat patients with dengue fever , nor is it possible to predict w...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "immunopathology", "animal models of infection", "virulence factors and mechanisms", "immunity", "virology", "innate immunity", "immunology", "host-pathogen interaction", "biology", "microbiology", "immune response" ]	Activation of the NLRP3 Inflammasome by IAV Virulence Protein PB1-F2 Contributes to Severe Pathophysiology and Disease	journal.ppat.1003392	null	[ [ "Influenza A virus ( IAV ) is a major cause of respiratory tract infections and may result in severe immunopathology characterised by high oxidative stress , hypercytokinemia and acute respiratory distress syndrome [1] .", "Understanding the molecular basis for disease severity for emerging influenza viru...	[ "The ability for a host to recognize infection is critical for virus clearance and often begins with induction of inflammation .", "The PB1-F2 of pathogenic influenza A viruses ( IAV ) contributes to the pathophysiology of infection , although the mechanism for this is unclear .", "The NLRP3-inflammasome has be...	[ "Influenza virus is a highly contagious respiratory pathogen that can cause pandemics , resulting in the deaths of millions worldwide .", "Previously we demonstrated that PB1-F2 protein produced by pathogenic influenza induces overwhelming inflammatory responses to infection , which enhances disease .", "The wa...	2013
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "biochemistry", "infectious diseases", "infectious diseases/neglected tropical diseases", "cell biology/extra-cellular matrix", "infectious diseases/protozoal infections" ]	Role of the gp85/Trans-Sialidases in Trypanosoma cruzi Tissue Tropism: Preferential Binding of a Conserved Peptide Motif to the Vasculature In Vivo	journal.pntd.0000864	null	[ [ "Trypanosoma cruzi , the causative agent of Chagas' disease , is an obligatory intracellular parasite that uses mammalian host cells to replicate and escape from the immune system to continue its life cycle [1] .", "The infective trypomastigote form is transmitted to humans ( and other vertebrate hosts ) ...	[ "Transmitted by blood-sucking insects , the unicellular parasite Trypanosoma cruzi is the causative agent of Chagas' disease , a malady manifested in a variety of symptoms from heart disease to digestive and urinary tract dysfunctions .", "The reasons for such organ preference have been a matter of great interest...	[ "Chagas' disease , caused by the protozoon Trypanosoma cruzi , is an ailment affecting approximately 12–14 million people in Iberoamerica and is becoming increasingly important in North America and Europe as a result of migratory currents .", "The parasite invades mainly cells of the heart or the walls of the dig...	2010
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "medicine and health sciences", "chemical compounds", "pathology and laboratory medicine", "aliphatic amino acids", "gene regulation", "pathogens", "messenger rna", "rna extraction", "organic compounds", "dna transcription", "isoleucine", "amino acids", "extraction techniques", "research a...	Controlled branched-chain amino acids auxotrophy in Listeria monocytogenes allows isoleucine to serve as a host signal and virulence effector	journal.pgen.1007283	null	[ [ "Listeria monocytogenes ( Lm ) is a facultative intracellular bacterial pathogen and the causative agent of listeriosis disease [1] .", "It invades host cells via phagocytosis , or by induction of endocytosis [2] .", "Upon invasion , it is initially found in a membrane-bound vacuole , from which it es...	[ "Listeria monocytogenes ( Lm ) is a saprophyte and intracellular pathogen .", "Transition to the pathogenic state relies on sensing of host-derived metabolites , yet it remains unclear how these are recognized and how they mediate virulence gene regulation .", "We previously found that low availability of isole...	[ "Bacterial pathogens must adapt to their host environment to carry out a successful infection .", "Sensing host-derived signals precedes adaptation , and triggers switching to the virulent state .", "Within mammalian cells L . monocytogenes responds to branched-chain amino acids ( BCAA ) deficiency by inducing ...	2018
[ "Introduction", "Results and Discussion", "Conclusions", "Methods" ]	[ "macromolecular complex analysis", "biochemistry", "protein interactions", "molecular complexes", "proteins", "evolutionary modeling", "protein structure", "biology and life sciences", "comparative genomics", "computational biology", "evolutionary biology", "biophysics", "molecular biology",...	Protein Flexibility Facilitates Quaternary Structure Assembly and Evolution	journal.pbio.1001870	The flexibility of individual proteins aids their evolutionary recruitment into complexes with increasing numbers of distinct subunits.	[ [ "The assembly of proteins into protein complexes is ubiquitous within the cell [1]–[3] .", "This provides many potential benefits , such as allosteric regulation , co-localization of distinct biological functions , and protection from aggregation or degradation [4]–[6] .", "Alternatively , protein oli...	[ "The intrinsic flexibility of proteins allows them to undergo large conformational fluctuations in solution or upon interaction with other molecules .", "Proteins also commonly assemble into complexes with diverse quaternary structure arrangements .", "Here we investigate how the flexibility of individual prote...	[ "Proteins often interact with other proteins and assemble into complexes .", "Here we show that the flexibility of individual proteins is important for their recruitment to complexes , as it facilitates the formation of asymmetric interfaces between different subunits .", "The role of flexibility becomes increa...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biomacromolecule-ligand interactions", "medicine", "biochemistry", "rna", "infectious diseases", "rna transport", "protein interactions", "nucleic acids", "proteins", "herpes simplex", "protein structure", "macromolecular assemblies", "biology", "viral diseases", "biophysics" ]	Competitive and Cooperative Interactions Mediate RNA Transfer from Herpesvirus Saimiri ORF57 to the Mammalian Export Adaptor ALYREF	journal.ppat.1003907	null	[ [ "Mammalian gene expression is coupled with mRNA maturation , where nascent transcripts undergo a continuous series of splicing and processing events finally leading to nuclear export to the cytoplasm [1] .", "This process is tightly regulated and orchestrated , ensuring that only mature and fully-processe...	[ "The essential herpesvirus adaptor protein HVS ORF57 , which has homologs in all other herpesviruses , promotes viral mRNA export by utilizing the cellular mRNA export machinery .", "ORF57 protein specifically recognizes viral mRNA transcripts , and binds to proteins of the cellular transcription-export ( TREX ) ...	[ "Herpes viruses invade cells , hijacking cellular components to sustain their lifecycle and replicate .", "A critical step of infection is the export of viral mRNA from the nucleus to the cytoplasm , where the molecular machinery to produce proteins is located .", "To provide a link between their mRNA and cellu...	2014

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