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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" ]	[ "blood cells", "medicine and health sciences", "immune cells", "pathology and laboratory medicine", "nervous system", "pathogens", "animal models of disease", "immunology", "microbiology", "animal models", "viruses", "model organisms", "rna viruses", "experimental organism systems", "inf...	CD4+T cells mediate protection against Zika associated severe disease in a mouse model of infection	journal.ppat.1007237	null	[ [ "As a member of the family Flaviviridae , Zika virus ( ZIKV ) is related to mosquito spread arboviruses including West Nile virus ( WNV ) , dengue virus ( DENV ) , Japanese encephalitis virus ( JEV ) , and yellow fever virus ( YFV ) .", "While having been identified in 1947 [1] , ZIKV first entered the di...	[ "Zika virus ( ZIKV ) has gained worldwide attention since it emerged , and a global effort is underway to understand the correlates of protection and develop diagnostics to identify rates of infection .", "As new therapeutics and vaccine approaches are evaluated in clinical trials , additional effort is focused o...	[ "Since the detection of ZIKV in the Americas in 2015 , urgent efforts have been made to develop ZIKV-specific methods of diagnosis and novel vaccines .", "However , a full understanding of the natural history of infection , interactions with other arboviruses , and the protection mediated by therapeutics or vacci...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Genome-Wide Reprogramming of Transcript Architecture by Temperature Specifies the Developmental States of the Human Pathogen Histoplasma	journal.pgen.1005395	null	[ [ "Environmental human pathogens have evolved the ability to survive in human hosts as well as diverse environmental reservoirs .", "Thus a hallmark of environmental pathogens is their capacity to adapt to varied growth conditions such as differences in temperature , alterations in nutrient sources , as wel...	[ "Eukaryotic cells integrate layers of gene regulation to coordinate complex cellular processes; however , mechanisms of post-transcriptional gene regulation remain poorly studied .", "The human fungal pathogen Histoplasma capsulatum ( Hc ) responds to environmental or host temperature by initiating unique transcr...	[ "Eukaryotic cells alter their developmental programs in response to environmental signals .", "Histoplasma capsulatum ( Hc ) , a ubiquitous fungal pathogen of humans , establishes unique transcriptional programs to specify growth in either a multicellular hyphal form or unicellular yeast form in response to tempe...	2015
[ "Introduction", "Results", "Discussion", "Methods" ]	[]	Twisting Right to Left: A…A Mismatch in a CAG Trinucleotide Repeat Overexpansion Provokes Left-Handed Z-DNA Conformation	journal.pcbi.1004162	null	[ [ "Apart from the ‘canonical’ B-DNA conformation , DNA can also adopt a variety of ‘non-canonical’ conformations such as hairpin , triplex and tetraplex depending on the sequence and environment .", "It is well known that formation of such unusual non-B-DNA structures during the overexpansion of trinucleoti...	[ "Conformational polymorphism of DNA is a major causative factor behind several incurable trinucleotide repeat expansion disorders that arise from overexpansion of trinucleotide repeats located in coding/non-coding regions of specific genes .", "Hairpin DNA structures that are formed due to overexpansion of CAG re...	[ "When a set of 3 nucleotides in a DNA sequence repeats beyond a certain number , it leads to incurable neurological or neuromuscular disorders .", "Such DNA sequences tend to form unusual DNA structures comprising of base pairing schemes different from the canonical A…T/G…C base pairs .", "Influence of such unu...	2015
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "genetics and genomics/genetics of disease", "genetics and genomics/complex traits", "genetics and genomics/gene expression" ]	Candidate Causal Regulatory Effects by Integration of Expression QTLs with Complex Trait Genetic Associations	journal.pgen.1000895	null	[ [ "The biological interpretation of genome-wide association study ( GWAS ) signals [1]–[5] is very challenging since most candidate loci fall either in gene deserts or in regions with many equally plausible causative genes .", "Following the concurrent progress in understanding the genetic basis of regulato...	[ "The recent success of genome-wide association studies ( GWAS ) is now followed by the challenge to determine how the reported susceptibility variants mediate complex traits and diseases .", "Expression quantitative trait loci ( eQTLs ) have been implicated in disease associations through overlaps between eQTLs a...	[ "Genome-wide association studies have led to the identification of susceptibility loci for a variety of human complex traits .", "What is still largely missing , however , is the understanding of the biological context in which these candidate variants act and of how they determine each trait .", "Given the loc...	2010
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "microbiology/parasitology", "infectious diseases/protozoal infections", "microbiology/cellular microbiology and pathogenesis", "microbiology/medical microbiology" ]	Longistatin, a Plasminogen Activator, Is Key to the Availability of Blood-Meals for Ixodid Ticks	journal.ppat.1001312	null	[ [ "Blood coagulation is a very complex but well-synchronized biochemical process by which blood forms a clot and the damaged blood vessel is sealed by a platelet-rich fibrin plug leading to hemostasis .", "Any damage to the vascular beds due to laceration of tissues exposes tissue factor from the endotheliu...	[ "Ixodid ticks are notorious blood-sucking ectoparasites and are completely dependent on blood-meals from hosts .", "In addition to the direct severe effects on health and productivity , ixodid ticks transmit various deadly diseases to humans and animals .", "Unlike rapidly feeding vessel-feeder hematophagous in...	[ "Ixodid ticks are serious blood-sucking ectoparasites that are essentially dependent on blood-meals from hosts for survival .", "The feeding mechanism of hard ticks , however , is very complex and is quite different from that of blood-sucking insects that suck blood rapidly and directly from blood vessels .", "...	2011
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "developmental neuroscience", "computational neuroscience", "sensory systems", "biology", "neuroscience", "coding mechanisms" ]	Sparse Coding Can Predict Primary Visual Cortex Receptive Field Changes Induced by Abnormal Visual Input	journal.pcbi.1003005	null	[ [ "Simple cells in the mammalian primary visual cortex ( V1 ) are among the cells in the brain that are best functionally characterised [1]–[3] .", "They have also been used as a key model system for studying the complex interplay of intrinsic and extrinsic factors , i . e . , nature and nurture , in contro...	[ "Receptive fields acquired through unsupervised learning of sparse representations of natural scenes have similar properties to primary visual cortex ( V1 ) simple cell receptive fields .", "However , what drives in vivo development of receptive fields remains controversial .", "The strongest evidence for the i...	[ "The responses of neurons in the primary visual cortex ( V1 ) , a region of the brain involved in encoding visual input , are modified by the visual experience of the animal during development .", "For example , most neurons in animals reared viewing stripes of a particular orientation only respond to the orienta...	2013
[ "Introduction", "Results", "Discussion", "Methods" ]	[]	Genus-Wide Comparative Genomics of Malassezia Delineates Its Phylogeny, Physiology, and Niche Adaptation on Human Skin	journal.pgen.1005614	null	[ [ "Over 100 years ago Malassezia was recognized as an inhabitant of human skin and implicated in a common skin disorder i . e . seborrheic dermatitis [1] .", "Since then , Malassezia has been found on the skin of all tested warm blooded animals [2 , 3] , including dogs , horses , pigs , goats , cats and lam...	[ "Malassezia is a unique lipophilic genus in class Malasseziomycetes in Ustilaginomycotina , ( Basidiomycota , fungi ) that otherwise consists almost exclusively of plant pathogens .", "Malassezia are typically isolated from warm-blooded animals , are dominant members of the human skin mycobiome and are associated...	[ "Malassezia are the dominant eukaryotic residents of human skin and are associated with the most common skin disorders , including dandruff , atopic dermatitis , eczema , and others .", "Despite significant effort , the role of Malassezia in skin disease and homeostasis remains unclear .", "Malassezia are also ...	2015
[ "Introduction", "Results/Discussion", "Materials and Methods", "Supporting Information" ]	[ "biochemistry", "infectious diseases", "cell biology", "microbiology", "biophysics" ]	Phosphorylation-Independent Regulation of the Diguanylate Cyclase WspR	journal.pbio.0060067	We present a model for the regulation of a conserved diguanyate cyclase fromPseudomonas that is responsible for cyclic di-GMP production and biofilm formation, providing insight into the molecular mechani7sm controlling cell signaling and virulence.	[ [ "Bacterial signal transduction pathways regulating virulence and chemotaxis are commonly composed of two-component signaling systems .", "These systems consist of a histidine protein kinase that relays environmental stimuli to phosphotransfer reactions , ultimately controlling the activity of phospho-rece...	[ "Environmental signals that trigger bacterial pathogenesis and biofilm formation are mediated by changes in the level of cyclic dimeric guanosine monophosphate ( c-di-GMP ) , a unique eubacterial second messenger .", "Tight regulation of cellular c-di-GMP concentration is governed by diguanylate cyclases and phos...	[ "Bacteria can switch from a single-cell , free-floating behavioral mode to a community life-form via colonization of surfaces and the secretion of an extracellular matrix .", "This process , called biofilm formation , has been attributed to a majority of chronic infections , including the lungs , as occurs in pat...	2008
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "medicine", "infectious diseases", "schistosomiasis", "neglected tropical diseases" ]	Inconsistent Protective Efficacy and Marked Polymorphism Limits the Value of Schistosoma japonicum Tetraspanin-2 as a Vaccine Target	journal.pntd.0001166	null	[ [ "There is now growing agreement that integrated control , which could include the use of an effective vaccine combined with chemotherapy and other measures , is the optimum direction that the future control of schistosomiasis should follow [1] , [2] .", "Vaccine development against schistosomiasis has bee...	[ "Schistosoma mansoni tetraspanin 2 ( Sm-TSP-2 ) has been shown to be strongly recognized by IgG1 and IgG3 antibodies from individuals putatively resistant to schistosome infection , but not chronically infected people , and to induce high levels of protection against challenge infection in the murine model of schis...	[ "Schistosoma mansoni tetraspanin 2 ( Sm-TSP-2 ) is considered a lead target for vaccine development against schistosomiasis mansoni because: ( 1 ) It is located in the schistosome tegument and is involved in tegument formation; ( 2 ) It is strongly recognized by IgG1 and IgG3 antibodies from individuals putatively ...	2011
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "virology/persistence and latency", "virology/viral replication and gene regulation", "virology" ]	Definition of Herpes Simplex Virus Type 1 Helper Activities for Adeno-Associated Virus Early Replication Events	journal.ppat.1000340	null	[ [ "Adeno-Associated Virus ( AAV ) type 2 is a human parvovirus that is widely used as a vector for gene transfer .", "Its 4 . 7 kb single-stranded DNA genome contains two open reading frames , rep and cap , flanked by Inverted Terminal Repeats ( ITRs ) that serve as origins of DNA replication .", "Four ...	[ "The human parvovirus Adeno-Associated Virus ( AAV ) type 2 can only replicate in cells co-infected with a helper virus , such as Adenovirus or Herpes Simplex Virus type 1 ( HSV-1 ) ; whereas , in the absence of a helper virus , it establishes a latent infection .", "Previous studies demonstrated that the ternary...	[ "The Adeno-Associated Virus ( AAV ) is a human parvovirus that is widely used as a recombinant vector for gene transfer in animal studies and clinical trials designed to treat acquired or inherited genetic diseases .", "Wild type AAV is defined as a defective virus because it requires the presence of a helper vir...	2009
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "mechanisms of signal transduction", "light microscopy", "guanine nucleotide exchange factors", "fungi", "model organisms", "microscopy", "experimental organism systems", "cellular structures and organelles", "schizosaccharomyces", "research and analysis methods", "feedback regulation", "schiz...	Exploration and stabilization of Ras1 mating zone: A mechanism with positive and negative feedbacks	journal.pcbi.1006317	null	[ [ "How cells sense a chemical concentration gradient and polarize towards regions of high or low concentrations is a fundamental biological question .", "Encoding of spatial information in chemoattractant gradients is essential for many processes , including the directional migration of leukocytes and neutr...	[ "In mating fission yeast cells , sensing and response to extracellular pheromone concentrations occurs through an exploratory Cdc42 patch that stochastically samples the cell cortex before stabilizing towards a mating partner .", "Active Ras1 ( Ras1-GTP ) , an upstream regulator of Cdc42 , and Gap1 , the GTPase-a...	[ "Unicellular fission yeasts mate by fusing with partners of the opposite mating type .", "Each pair member grows towards its selected partner that signals its presence through secreted pheromone .", "The process of partner selection occurs through an exploratory patch ( containing activated signaling protein Cd...	2018
[ "Introduction", "Materials and Methods", "Results", "Discussion", "Supporting Information" ]	[ "drosophila", "cell biology" ]	The Role of Carcinine in Signaling at the Drosophila Photoreceptor Synapse	journal.pgen.0030206	null	[ [ "An exceedingly complex regulation is involved in the synthesis , release , activity , and recycling or degradation of neurotransmitter in the nervous system of animal species .", "This regulation may involve neurotransmitter degradation within the synapse [1] , reuptake of neurotransmitter by presynaptic...	[ "The Drosophila melanogaster photoreceptor cell has long served as a model system for researchers focusing on how animal sensory neurons receive information from their surroundings and translate this information into chemical and electrical messages .", "Electroretinograph ( ERG ) analysis of Drosophila mutants h...	[ "During signaling in the nervous system , individual nerve cells transfer information to one another by a complex process called synaptic transmission .", "This communication involves the release of a specific neurotransmitter into the synaptic cleft , which then triggers signaling in the downstream neuron by bin...	2007
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genetics and genomics/epigenetics", "molecular biology/histone modification", "genetics and genomics", "molecular biology/chromatin structure" ]	Compensatory Interactions between Sir3p and the Nucleosomal LRS Surface Imply Their Direct Interaction	journal.pgen.1000301	null	[ [ "Previous work identified a nucleosome surface named the LRS domain critically important for silencing at all classically defined silent loci in Saccharomyces cerevisiae [1] , [2] .", "The relevant residues are located at Super Helical Location ( SHL ) +/−2 . 5 ( equivalent to 4 o'clock on the nucleosome ...	[ "The previously identified LRS ( Loss of rDNA Silencing ) domain of the nucleosome is critically important for silencing at both ribosomal DNA and telomeres .", "To understand the function of the LRS surface in silencing , we performed an EMS mutagenesis screen to identify suppressors of the H3 A75V LRS allele ."...	[ "The chromatin in which eukaryotic DNA is wrapped is organized in nucleosome units , consisting of eight core histone molecules .", "We study gene silencing , thought to be associated with chromatin compaction in Saccharomyces cerevisiae , which has most of its genome in the form of open chromatin , i . e . , the...	2008
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine and health sciences", "pathology and laboratory medicine", "mitochondrial dna", "autism", "social sciences", "developmental psychology", "neuroscience", "mutation", "drug design", "forms of dna", "heteroplasmy", "dna", "pharmacology", "autism spectrum disorder", "bioenergetics"...	Genetic Evidence for Elevated Pathogenicity of Mitochondrial DNA Heteroplasmy in Autism Spectrum Disorder	journal.pgen.1006391	null	[ [ "Autism Spectrum Disorder ( ASD ) refers to a broad collection of complex , neurodevelopmental disorders , characterized by impairment of communicative and social interactions [1] .", "ASD usually manifests at an early stage of development in pre-pubertal children [2] .", "The current prevalence of AS...	[ "Increasing clinical and biochemical evidence implicate mitochondrial dysfunction in the pathophysiology of Autism Spectrum Disorder ( ASD ) , but little is known about the biological basis for this connection .", "A possible cause of ASD is the genetic variation in the mitochondrial DNA ( mtDNA ) sequence , whic...	[ "Mitochondria contain their own genome , the mitochondrial DNA ( mtDNA ) , and are abundant in the brain where they produce energy and intracellular signals required for normal brain function and cognition .", "Mitochondrial dysfunction has been proposed as a cause of Autism Spectrum Disorder ( ASD ) , but the ge...	2016
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "cell biology/cell growth and division", "biophysics/theory and simulation", "computational biology/systems biology" ]	A Hybrid Model of Mammalian Cell Cycle Regulation	journal.pcbi.1001077	null	[ [ "The cell division cycle is the fundamental physiological process by which cells grow , replicate , and divide into two daughter cells that receive all the information ( genes ) and machinery ( proteins , organelles , etc . ) necessary to repeat the process under suitable conditions [1] .", "This cycle of...	[ "The timing of DNA synthesis , mitosis and cell division is regulated by a complex network of biochemical reactions that control the activities of a family of cyclin-dependent kinases .", "The temporal dynamics of this reaction network is typically modeled by nonlinear differential equations describing the rates ...	[ "The physiological behaviors of cells ( growth and division , differentiation , movement , death , etc . ) are controlled by complex networks of interacting genes and proteins , and a fundamental goal of computational cell biology is to develop dynamical models of these regulatory networks that are realistic , accu...	2011
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "neuroscience/behavioral neuroscience", "neuroscience/sensory systems", "cell biology/cell signaling", "neuroscience/neuronal signaling mechanisms", "neurological disorders/epilepsy" ]	Sensory Perception of Food and Insulin-Like Signals Influence Seizure Susceptibility	journal.pgen.1000117	null	[ [ "The feeding status of an organism can alter physiology and motor output leading to changes in health and behavior .", "For example , food deprivation can improve stress resistance , increase life-span , and alleviate muscle seizures [1]–[7] .", "In addition to promoting these phenomena under food-dep...	[ "Food deprivation is known to affect physiology and behavior .", "Changes that occur could be the result of the organism's monitoring of internal and external nutrient availability .", "In C . elegans , male mating is dependent on food availability; food-deprived males mate with lower efficiency compared to the...	[ "We demonstrate that lack of sensation of food in the environment can alleviate spontaneous muscle seizures via an insulin-like mediated pathway .", "Food restriction is known to promote many adaptive physiological responses , including the mobilization of fat-stores , increases in life span , and suppression of ...	2008
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "escherichia coli", "medicine", "bacterial diseases", "infectious diseases", "gram negative", "genetic screens", "gene identification and analysis", "genetics", "microbial pathogens", "molecular genetics", "host-pathogen interaction", "biology", "microbiology", "pathogenesis", "infectiou...	Combining Quantitative Genetic Footprinting and Trait Enrichment Analysis to Identify Fitness Determinants of a Bacterial Pathogen	journal.pgen.1003716	null	[ [ "Within the Escherichia coli lineage there are several distinct virulent subgroups that are principally classified by an ability to cause a common set of diseases .", "One specific subgroup , Extraintestinal Pathogenic E . coli ( ExPEC ) , is typically thought to be a benign inhabitant of the lower intest...	[ "Strains of Extraintestinal Pathogenic Escherichia coli ( ExPEC ) exhibit an array of virulence strategies and are a major cause of urinary tract infections , sepsis and meningitis .", "Efforts to understand ExPEC pathogenesis are challenged by the high degree of genetic and phenotypic variation that exists among...	[ "Antibiotic resistance is an increasingly serious problem , especially among pathogenic strains of Escherichia coli that cause urinary tract infections , sepsis and meningitis .", "It is important to obtain a more comprehensive genome-wide understanding of bacterial virulence because it has the potential to uncov...	2013
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "innate immune system", "medicine and health sciences", "immune physiology", "cytokines", "enzyme-linked immunoassays", "immunology", "tropical diseases", "parasitic diseases", "animal models", "preventive medicine", "developmental biology", "model organisms", "experimental organism systems"...	Trichuris muris whey acidic protein induces type 2 protective immunity against whipworm	journal.ppat.1007273	null	[ [ "It is estimated that 465 million people are living with whipworms ( Trichuris trichiura ) in their colon , predominately in the developing nations of the Americas , Asia , and Africa .", "In children , T . trichiura infections cause chronic colitis , resulting in nutritional deficiencies , growth stuntin...	[ "Human whipworm ( Trichuris trichiura ) infects approximately 1 in 15 people worldwide , representing the leading infectious cause of colitis and subsequent , inflammatory bowel disease ( IBD ) .", "Current control measures focused on mass deworming have had limited success due to low drug efficacies .", "Vacci...	[ "Human whipworm ( Trichuris trichiura ) is pervasive intestinal parasite that causes malnutrition and inflammatory bowel disease ( IBD ) , predominately among the world’s most impoverished billion people .", "Available treatment strategies have had little impact on the disease prevalence or morbidity .", "A vac...	2018
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "public health and epidemiology/epidemiology", "public health and epidemiology/infectious diseases" ]	Mass Treatment with Azithromycin for Trachoma Control: Participation Clusters in Households	journal.pntd.0000838	null	[ [ "Trachoma is the leading infectious cause of blindness [1] .", "As the most common ocular neglected tropical disease , active trachoma is estimated to affect 40 . 6 million people worldwide , and another 8 . 2 million experience visual impairment or blindness [2] .", "Trachoma is largely confined to r...	[ "Mass treatment to trachoma endemic communities is a critical part of the World Health Organization SAFE strategy .", "However , non-participation may not be at random , affecting coverage surveys and effectiveness if infection is differential .", "As part of the Partnership for Rapid Elimination of Trachoma ( ...	[ "Trachoma , an infectious disease , continues to cause blindness .", "A great deal of the trachoma burden is concentrated in developing countries .", "The World Health Organization recommends mass treatment for entire communities in trachoma-endemic regions .", "In 32 Tanzanian and 48 Gambian communities with...	2010
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "computational biology/computational neuroscience", "neuroscience/neurodevelopment", "neuroscience/theoretical neuroscience" ]	The Morphological Identity of Insect Dendrites	journal.pcbi.1000251	null	[ [ "Dendrite morphology is the most prominent feature of nerve cells , typically used by", "neuroanatomists to discriminate and classify them [1] .", "These tree-like", "ramifications represent the input region of the neurons and fulfil the role of a", "complex computational unit [2]–[5] .", ...	[ "Dendrite morphology , a neuron's anatomical fingerprint , is a", "neuroscientist's asset in unveiling organizational principles in the", "brain .", "However , the genetic program encoding the morphological identity of a", "single dendrite remains a mystery .", "In order to obtain a formal understanding o...	[ "Neural computation has been shown to be heavily dependent not only on the", "connectivity of single neurons but also on their specific dendritic", "shape—often used as a key feature for their classification .", "Still ,", "very little is known about the constraints determining a neuron's", "morphological...	2008
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "genetics and genomics/microbial evolution and genomics", "microbiology/microbial evolution and genomics", "genetics and genomics/comparative genomics" ]	Genetic Basis of Growth Adaptation of Escherichia coli after Deletion of pgi, a Major Metabolic Gene	journal.pgen.1001186	null	[ [ "Recent advances in DNA sequencing technology enable bacterial genomes to be fully sequenced with a resolution high enough to find all differences relative to a reference sequence .", "These developments make possible the study , at the whole-genome level , of the genetic basis through which bacteria adap...	[ "Bacterial survival requires adaptation to different environmental perturbations such as exposure to antibiotics , changes in temperature or oxygen levels , DNA damage , and alternative nutrient sources .", "During adaptation , bacteria often develop beneficial mutations that confer increased fitness in the new e...	[ "Bacteria must constantly adapt to many different environmental challenges , but how do they adapt when they lose a key gene product ?", "We addressed this question using Escherichia coli lacking pgi , a major metabolic gene involved in sugar utilization , by serially passing replicates lacking the pgi gene for 5...	2010
[ "Introduction", "Results/Discussion", "Material and Methods" ]	[ "genome-wide association studies", "genome expression analysis", "microbial metabolism", "spectrometric identification of proteins", "functional genomics", "host-pathogen interaction", "microbiology", "protein abundance", "fungal physiology", "gene function", "genome sequencing", "genome analy...	Deciphering the Cryptic Genome: Genome-wide Analyses of the Rice Pathogen Fusarium fujikuroi Reveal Complex Regulation of Secondary Metabolism and Novel Metabolites	journal.ppat.1003475	null	[ [ "The genus Fusarium is one of the most important groups of phytopathogenic fungi .", "They infect a broad spectrum of crops worldwide and are responsible for huge economic losses due to yield reductions and mycotoxin contamination .", "The Gibberella fujikuroi species complex ( GFC ) constitutes a mon...	[ "The fungus Fusarium fujikuroi causes “bakanae” disease of rice due to its ability to produce gibberellins ( GAs ) , but it is also known for producing harmful mycotoxins .", "However , the genetic capacity for the whole arsenal of natural compounds and their role in the fungus' interaction with rice remained unk...	[ "Fungi produce numerous “secondary metabolites” ( SMs ) that are not essential for life but can provide an advantage under natural conditions , e . g . in fungal-host interactions .", "Here , we conducted the most comprehensive analysis to date of secondary metabolism in fungi using Fusarium fujikuroi .", "This...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "microbiology/cellular microbiology and pathogenesis", "microbiology/innate immunity", "cell biology/cellular death and stress responses" ]	Rapid Pathogen-Induced Apoptosis: A Mechanism Used by Dendritic Cells to Limit Intracellular Replication of Legionella pneumophila	journal.ppat.1000478	null	[ [ "Macrophages and dendritic cells ( DCs ) are the sentinels of the innate immune system .", "They are key in sensing infection and activating downstream antimicrobial responses [1] , [2] .", "These professional phagocytes are activated following stimulation of pattern-recognition receptors , such as tr...	[ "Dendritic cells ( DCs ) are specialized phagocytes that internalize exogenous antigens and microbes at peripheral sites , and then migrate to lymphatic organs to display foreign peptides to naïve T cells .", "There are several examples where DCs have been shown to be more efficient at restricting the intracellul...	[ "The immune system is designed to identify microbes that enter the body and elicit responses that prevent the replication and dissemination of these organisms .", "Dendritic cells play an important role in regulating host immunity to pathogens .", "Their phagocytic capacity enables DCs to internalize and destro...	2009
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Comprehensive Analysis of Transcriptome Variation Uncovers Known and Novel Driver Events in T-Cell Acute Lymphoblastic Leukemia	journal.pgen.1003997	null	[ [ "T-cell acute lymphoblastic leukemia ( T-ALL ) is an aggressive malignancy that accounts for approximately 15% of pediatric and 25% of adult ALL cases .", "Despite improved outcome over the years , about 25% of children and 50% of adults still fail to respond to intensive chemotherapy protocols or relapse...	[ "RNA-seq is a promising technology to re-sequence protein coding genes for the identification of single nucleotide variants ( SNV ) , while simultaneously obtaining information on structural variations and gene expression perturbations .", "We asked whether RNA-seq is suitable for the detection of driver mutation...	[ "The quest for somatic mutations underlying oncogenic processes is a central theme in today's cancer research .", "High-throughput genomics approaches including amplicon re-sequencing , exome re-sequencing , full genome re-sequencing , and SNP arrays have contributed to cataloguing driver genes across cancer type...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "computational biology" ]	Measuring the Evolutionary Rewiring of Biological Networks	journal.pcbi.1001050	null	[ [ "With the advent of large-scale genomic and proteomic technologies in discovering interacting and regulatory relationships in cells , many types of biological networks , though incomplete , have been constructed in various eukaryotic species [1]–[19] .", "The kinds of networks currently include , but are ...	[ "We have accumulated a large amount of biological network data and expect even more to come .", "Soon , we anticipate being able to compare many different biological networks as we commonly do for molecular sequences .", "It has long been believed that many of these networks change , or “rewire” , at different ...	[ "Biological networks represent various types of molecular organizations in a cell .", "During evolution , molecules have been shown to change at varying rates .", "Therefore , it is important to investigate the evolution of biological networks in terms of network rewiring .", "Understanding how biological net...	2011
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "medicine and health sciences", "vesicles", "pathology and laboratory medicine", "gene regulation", "pathogens", "messenger rna", "rna extraction", "microbiology", "small nuclear rna", "viruses", "dna viruses", "cellular structures and organelles", "extraction techniques", "herpesviruses",...	Kaposi’s sarcoma-associated herpesvirus ORF57 protein protects viral transcripts from specific nuclear RNA decay pathways by preventing hMTR4 recruitment	journal.ppat.1007596	null	[ [ "The Kaposi’s sarcoma-associated herpesvirus ( KSHV ) is a nuclear double-stranded DNA virus that belongs to the gammaherpesvirus family .", "It infects human B lymphocytes and endothelial cells and causes Kaposi’s sarcoma ( KS ) as well as the lymphoproliferative disorders primary effusion lymphoma ( PEL...	[ "Nuclear RNAs are subject to a number of RNA decay pathways that serve quality control and regulatory functions .", "As a result , any virus that expresses its genes in the nucleus must have evolved mechanisms that avoid these pathways , but the how viruses evade nuclear RNA decay remains largely unknown .", "T...	[ "Eukaryotic cells contain numerous nuclear RNA quality control ( QC ) systems that ensure transcriptome fidelity by detecting and degrading aberrant RNAs .", "Some viral RNAs are also predicted to be degraded by these RNA QC systems , so viruses have evolved mechanisms that counter host RNA QC pathways .", "Pre...	2019
[ "Introduction", "Results and Discussion", "Materials and Methods", "Supporting Information" ]	[ "neuroscience", "evolutionary biology" ]	Mirror-Induced Behavior in the Magpie (Pica pica): Evidence of Self-Recognition	journal.pbio.0060202	The European magpie, a bird with a large brain and highly developed perspective-taking skills, shows evidence of mirror self-recognition.	[ [ "Since the pioneering work by Gallup [1] , a number of studies have investigated the occurrence of mirror-induced self-directed behavior in animals of a great range of species .", "Most animals exposed to a mirror respond with social behavior , e . g . , aggressive displays , and continue to do so during ...	[ "Comparative studies suggest that at least some bird species have evolved mental skills similar to those found in humans and apes .", "This is indicated by feats such as tool use , episodic-like memory , and the ability to use one's own experience in predicting the behavior of conspecifics .", "It is , however ...	[ "A crucial step in the emergence of self-recognition is the understanding that one's own mirror reflection does not represent another individual but oneself .", "In nonhuman species and in children , the “mark test” has been used as an indicator of self-recognition .", "In these experiments , subjects are place...	2008
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biology" ]	A Protein Thermometer Controls Temperature-Dependent Transcription of Flagellar Motility Genes in Listeria monocytogenes	journal.ppat.1002153	null	[ [ "Temperature is an important environmental condition to which organisms must adapt .", "The most universal and well-studied temperature responsive system is the heat shock response , which protects organisms from sudden stress-inducing increases in environmental temperature ( reviewed in [1] , [2] ) .", ...	[ "Facultative bacterial pathogens must adapt to multiple stimuli to persist in the environment or establish infection within a host .", "Temperature is often utilized as a signal to control expression of virulence genes necessary for infection or genes required for persistence in the environment .", "However , v...	[ "The ability to sense and respond to environmental changes is essential for the survival of all living organisms .", "Thermosensors are cellular components that can transform temperature changes into significant cellular responses necessary for adaptation and survival .", "In this study , we identify a protein ...	2011
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Molecular Framework of a Regulatory Circuit Initiating Two-Dimensional Spatial Patterning of Stomatal Lineage	journal.pgen.1005374	null	[ [ "Multicellular organisms produce complex tissues , each comprised of specialized cell types with appropriate spatial configuration for optimal function , thus contributing to the fitness of the organism .", "Seemingly uniform precursor cells self-organize into distinct , functional patterns .", "A fun...	[ "Stomata , valves on the plant epidermis , are critical for plant growth and survival , and the presence of stomata impacts the global water and carbon cycle .", "Although transcription factors and cell-cell signaling components regulating stomatal development have been identified , it remains unclear as to how t...	[ "Generation of self-organized , functional tissue patterns is critical for development and regeneration in multicellular organisms .", "Small valves on the epidermis of land plants , called stomata , mediate gas-exchange while minimizing water loss .", "Density and spacing of stomata are regulated by transcript...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "developmental biology", "cell biology", "genetics and genomics" ]	Abl Kinase Inhibits the Engulfment of Apopotic Cells in Caenorhabditis elegans	journal.pbio.1000099	We show thatC. elegans Abl (ABL-1) inhibits the engulfment of apoptotic cells via a newly defined pathway that includes theC. elegans homolog of the cytoskeletal regulator Abl-interactor.	[ [ "Regulated reorganization of the cytoskeleton is a fundamental process in tissue morphogenesis and physiologic cell migration [1] .", "Dysregulation of the cytoskeleton is a hallmark of pathologic processes , such as cancer cell invasion and metastasis [2] .", "The engulfment of apoptotic cells requir...	[ "The engulfment of apoptotic cells is required for normal metazoan development and tissue remodeling .", "In Caenorhabditis elegans , two parallel and partially redundant conserved pathways act in cell-corpse engulfment .", "One pathway includes the adaptor protein CED-2 CrkII and the small GTPase CED-10 Rac , ...	[ "Cell death or apoptosis is a normal part of animal development , as is the engulfment and removal of dead cells by other cells .", "In the nematode Caenorhabditis elegans , ten highly conserved proteins have been characterized previously for their roles in engulfment and in cell migration , both of which involve...	2009
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine and health sciences", "pathology and laboratory medicine", "ureases", "enzymes", "pathogens", "microbiology", "enzymology", "animal models", "mutation", "model organisms", "helicobacter", "stomach", "bacteria", "nickel", "bacterial pathogens", "digestive system", "research ...	Characterization in Helicobacter pylori of a Nickel Transporter Essential for Colonization That Was Acquired during Evolution by Gastric Helicobacter Species	journal.ppat.1006018	null	[ [ "Transition metals are essential elements for living organisms because they are involved in many enzymatic reactions and physiological processes .", "For bacteria , metals have been shown to be essential for survival under various conditions including those faced during infection [1] .", "Tremendous e...	[ "Metal acquisition is crucial for all cells and for the virulence of many bacterial pathogens .", "In particular , nickel is a virulence determinant for the human gastric pathogen Helicobacter pylori as it is the cofactor of two enzymes essential for in vivo colonization , urease and a [NiFe] hydrogenase .", "T...	[ "Helicobacter pylori is a bacterium that persistently colonizes the stomach of half of the human population worldwide .", "Infection by H . pylori is associated with gastritis , peptic ulcer disease and adenocarcinoma .", "To resist gastric acidity and proliferate in the stomach , H . pylori possesses an urease...	2016
[ "Introduction", "Results", "Discussion" ]	[ "biochemistry", "mutation", "evolutionary biology", "enzymes", "biology", "computational biology", "biophysics simulations", "biophysics", "evolutionary processes" ]	Enhancing Human Spermine Synthase Activity by Engineered Mutations	journal.pcbi.1002924	null	[ [ "Polyamines are widely present in many organisms including mammals , plants as well as some bacteria , and play important roles in normal cell growth , differentiation , programmed death , and tissue repair [1] , [2] .", "A particular polyamine of interest in this manuscript , the spermine ( SPM ) , was s...	[ "Spermine synthase ( SMS ) is an enzyme which function is to convert spermidine into spermine .", "It was shown that gene defects resulting in amino acid changes of the wild type SMS cause Snyder-Robinson syndrome , which is a mild-to-moderate mental disability associated with osteoporosis , facial asymmetry , th...	[ "Proteins are constantly subjected to evolutionary pressure to assure the organism's survival and reproduction .", "At the same time , the proteins' amino acid sequence undergoes mutations , some of which may cause diseases while others may be reflecting natural differences within the population ( non-synonymous ...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Whole Genome Sequencing Identifies a Deletion in Protein Phosphatase 2A That Affects Its Stability and Localization in Chlamydomonas reinhardtii	journal.pgen.1003841	null	[ [ "Forward genetics allows the identification of mutants with phenotypes of interest and the mechanistic understanding of biological processes [1] , [2] .", "While gene lesions generated by insertional mutagenesis can be identified by Southern blot analysis [3]–[6] or PCR-based approaches [7]–[9] , identifi...	[ "Whole genome sequencing is a powerful tool in the discovery of single nucleotide polymorphisms ( SNPs ) and small insertions/deletions ( indels ) among mutant strains , which simplifies forward genetics approaches .", "However , identification of the causative mutation among a large number of non-causative SNPs ...	[ "Whole genome sequencing is a powerful tool to detect changes in genomic DNA .", "However , how to identify a causative mutation from over 20 , 000 changes remains a big challenge .", "For the unicellular green alga Chlamydomonas , we built a library that consists of over 2 million changes from 16 strains .", ...	2013
[ "Introduction", "Results and Discussion", "Materials and Methods" ]	[ "evolutionary biology", "biology and life sciences", "evolutionary theory" ]	The Evolutionary Origin of Somatic Cells under the Dirty Work Hypothesis	journal.pbio.1001858	Experimental evolution of digital organisms suggests that mutagenic side effects associated with performing valuable metabolic work can produce germ-soma differentiation in multicellular organisms.	[ [ "Major transitions in evolution occur when individuals form a higher-level unit that reproduces as a single entity [1]–[3] .", "Such major transitions can occur when related lower-level units stay together , thus forming a higher-level unit .", "Examples include the transition from unicellular to mult...	[ "Reproductive division of labor is a hallmark of multicellular organisms .", "However , the evolutionary pressures that give rise to delineated germ and somatic cells remain unclear .", "Here we propose a hypothesis that the mutagenic consequences associated with performing metabolic work favor such differentia...	[ "Cells within an organism are categorized as “germ” if they are able to grow into a whole new offspring organism or as “soma” if they contribute to the body's functionality but cannot produce an offspring themselves .", "From an evolutionary perspective , it is important to ask why and how a multicellular organis...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Oxygen-Driven Tumour Growth Model: A Pathology-Relevant Mathematical Approach	journal.pcbi.1004550	null	[ [ "We hypothesise connecting tumour-stromal morphology to growth is an important step to enable a description of the differences in preclinical and clinical tumours .", "In this first step , we consider an avascular tumour analogous to a tumour nest surrounded by stroma , which is a common morphology found ...	[ "Xenografts -as simplified animal models of cancer- differ substantially in vasculature and stromal architecture when compared to clinical tumours .", "This makes mathematical model-based predictions of clinical outcome challenging .", "Our objective is to further understand differences in tumour progression an...	[ "Tumour-bearing animal models of cancer are needed to discover new drugs to treat cancer .", "We aim in this article to capture—through mathematics- some underlying phenomena of tumour growth in animals .", "We propose a set of equations that , despite being very simple , describe tumour growth , hypoxia and ne...	2015
[ "Introduction", "Materials and methods", "Results", "Discussion" ]	[ "medicine and health sciences", "chemical compounds", "variant genotypes", "tropical diseases", "immunology", "organic compounds", "genetic mapping", "bacterial diseases", "neglected tropical diseases", "molecular biology techniques", "research and analysis methods", "infectious diseases", "...	VDR polymorphism, gene expression and vitamin D levels in leprosy patients from North Indian population	journal.pntd.0006823	null	[ [ "Leprosy is a chronic , debilitating infectious disease caused by Mycobacterium leprae that involves skin , peripheral nerves and mucous membranes .", "At one pole is tuberculoid ( TT ) leprosy , characterized by strong Th1 immunity with few bacilli in skin lesions and at the opposite pole is lepromatous ...	[ "Leprosy is a chronic infectious disease caused by Mycobacterium leprae and mainly affects skin , peripheral nerves .", "Vitamin D receptor ( VDR ) gene polymorphism has been found to be associated with leprosy .", "Vitamin D has been shown to control several host immunomodulating properties through VDR gene ."...	[ "Present study was carried out to find out the association of vitamin D receptor ( VDR ) gene polymorphism , mRNA gene expression of VDR gene and level of vitamin D with leprosy reactions and leprosy patients .", "Surprisingly , level of vitamin D in leprosy patients was not found to be associated with the diseas...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine", "biology" ]	Molecular Identification of Collagen 17a1 as a Major Genetic Modifier of Laminin Gamma 2 Mutation-Induced Junctional Epidermolysis Bullosa in Mice	journal.pgen.1004068	null	[ [ "Epidermolysis bullosa ( EB ) is a group of rare heritable disorders that result in mechanical fragility of the skin and mucosal membranes .", "These disorders are caused by defects in any one of at least 18 genes whose encoded proteins control the integrity of the dermal and epidermal layers [1]–[5] .", ...	[ "Epidermolysis Bullosa ( EB ) encompasses a spectrum of mechanobullous disorders caused by rare mutations that result in structural weakening of the skin and mucous membranes .", "While gene mutated and types of mutations present are broadly predictive of the range of disease to be expected , a remarkable amount ...	[ "Epidermolysis bullosa ( EB ) is a group of rare genetic Mendelian disorders that result in mechanical fragility of the skin and mucosal membranes .", "Junctional EB is a subset caused by mutations that result in cleavage of the dermal-epidermal junction .", "All forms of EB demonstrate substantial variability ...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genomics", "genetics", "biology", "human genetics", "genetics and genomics" ]	Unraveling the Regulatory Mechanisms Underlying Tissue-Dependent Genetic Variation of Gene Expression	journal.pgen.1002431	null	[ [ "It has become clear that human genetic variants , such as single nucleotide polymorphisms ( SNPs ) , can in cis affect the expression of nearby genes [1] , [2] .", "Many loci exist that contain genetic variants that affect gene expression ( expression quantitative loci , eQTL , usually assessed by invest...	[ "It is known that genetic variants can affect gene expression , but it is not yet completely clear through what mechanisms genetic variation mediate this expression .", "We therefore compared the cis-effect of single nucleotide polymorphisms ( SNPs ) on gene expression between blood samples from 1 , 240 human sub...	[ "Gene expression can be affected by genetic variation , e . g . single nucleotide polymorphisms ( SNPs ) .", "These are called expression-affecting SNPs or eSNPs .", "Gene expression levels are known to vary across different tissues in the same individual , despite the fact that genetic variation is the same in...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine and health sciences", "pathology and laboratory medicine", "gene regulation", "pathogens", "microbiology", "notch signaling", "plasmid construction", "viruses", "dna viruses", "dna construction", "molecular biology techniques", "microbial genetics", "herpesviruses", "research and...	Fine-Tuning of the Kaposi’s Sarcoma-Associated Herpesvirus Life Cycle in Neighboring Cells through the RTA-JAG1-Notch Pathway	journal.ppat.1005900	null	[ [ "Kaposi’s sarcoma ( KS ) -associated herpesvirus ( KSHV ) is a large double-stranded DNA virus with a biphasic life cycle [1] .", "In KS lesions , KSHV latently infects most tumor cells to maintain viral DNA [2 , 3] , evade host immunosurveillance [4] , and promote cellular proliferation [5] .", "The ...	[ "Kaposi’s sarcoma ( KS ) -associated herpesvirus ( KSHV ) is an oncogenic pathogen that displays latent and lytic life cycles .", "In KS lesions , infiltrated immune cells , secreted viral and/or cellular cytokines , and hypoxia orchestrate a chronic pro-lytic microenvironment that can promote KSHV reactivation ....	[ "KSHV infected cells display significant heterogeneity in viral lytic replication within the universal pro-lytic inflammatory milieu , suggesting that the balance between latency and reactivation is carefully regulated .", "This fine-tuned regulatory mechanism is essential for KSHV to persist in the host and driv...	2016
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "public health", "medicine", "infectious diseases", "public health and epidemiology", "zoology", "pest control", "vector biology", "neglected tropical diseases", "animal management", "biology", "microbiology", "vectors and hosts", "veterinary science", "agriculture" ]	Standardizing Visual Control Devices for Tsetse Flies: West African Species Glossina tachinoides, G. palpalis gambiensis and G. morsitans submorsitans	journal.pntd.0001491	null	[ [ "Tsetse flies ( Diptera: Glossinidae ) transmit trypanosomes that cause sleeping sickness in humans ( Human African Trypanosomiasis ) and nagana in animals ( Animal African Trypanosomiasis ) in sub-Saharan Africa .", "These diseases are an intractable burden on human health and livestock production on the...	[ "Here we describe field trials designed to standardize tools for the control of Glossina tachinoides , G . palpalis gambiensis and G . morsitans submorsitans in West Africa based on existing trap/target/bait technology .", "Blue and black biconical and monoconical traps and 1 m2 targets were made in either phthal...	[ "Tsetse flies transmit trypanosomes that cause sleeping sickness in humans and ngana in animals in sub-Saharan Africa .", "These diseases remain an intractable burden on human health and livestock production on the continent .", "Visual devices made of fabrics and impregnated with insecticide have the potential...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "vertebrates", "developmental biology", "cell biology", "danio (zebrafish)", "computational biology" ]	Setting the Tempo in Development: An Investigation of the Zebrafish Somite Clock Mechanism	journal.pbio.0050150	The vertebrate somites are laid out in a regular pattern determined by the segmentation clock. Here the authors verify a mathematical model of the clock model and show that it quantitatively fits experimental details.	[ [ "How do genes set the tempo of embryonic development ?", "This basic question is still largely unanswered .", "We lack quantitative information about the dynamics of gene expression in the embryo , and in most cases , we do not even know which genes govern timing , let alone how they do so .", "In...	[ "The somites of the vertebrate embryo are clocked out sequentially from the presomitic mesoderm ( PSM ) at the tail end of the embryo .", "Formation of each somite corresponds to one cycle of oscillation of the somite segmentation clock—a system of genes whose expression switches on and off periodically in the ce...	[ "Somites—the embryonic segments of the vertebrate body—are formed sequentially , with a spacing determined by a gene expression oscillator , the segmentation clock , operating in the cells at the tail end of the embryo .", "This system provides a rare opportunity to analyse how the timing of at least one set of d...	2007
[ "Introduction", "Methods", "Results and discussion" ]	[ "machine learning algorithms", "applied mathematics", "database searching", "simulation and modeling", "algorithms", "mathematics", "artificial intelligence", "sequence motif analysis", "thermodynamics", "sequence similarity searching", "research and analysis methods", "sequence analysis", "...	Solving the RNA design problem with reinforcement learning	journal.pcbi.1006176	null	[ [ "Re-engineering and de novo design of RNA molecules to perform novel biological functions have been major focuses of modern bioengineering research [1–5] .", "The function of an RNA molecule is determined by the structure into which it folds , which is in turn determined by the sequence of nucleotides tha...	[ "We use reinforcement learning to train an agent for computational RNA design: given a target secondary structure , design a sequence that folds to that structure in silico .", "Our agent uses a novel graph convolutional architecture allowing a single model to be applied to arbitrary target structures of any leng...	[ "Designing RNA sequences that fold to desired structures is an important problem in bioengineering .", "We have applied recent advances in machine learning to address this problem .", "The computer learns without any human input , using only trial and error to figure out how to design RNA .", "It quickly disc...	2018
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "epistasis", "genome-wide association studies", "trait locus", "heredity", "genetic association studies", "genetics", "biology", "computational biology", "quantitative traits", "genetics and genomics", "complex traits", "human genetics" ]	Gene-Based Testing of Interactions in Association Studies of Quantitative Traits	journal.pgen.1003321	null	[ [ "Genome-wide association studies ( GWAS ) have identified over six thousand single-nucleotide polymorphisms ( SNPs ) associated with complex human diseases or traits [1] .", "Most of these SNPs have small effect sizes , and for most traits collectively explain only a small fraction of heritable genetic va...	[ "Various methods have been developed for identifying gene–gene interactions in genome-wide association studies ( GWAS ) .", "However , most methods focus on individual markers as the testing unit , and the large number of such tests drastically erodes statistical power .", "In this study , we propose novel inte...	[ "Epistasis is likely to play a significant role in complex diseases or traits and is one of the many possible explanations for “missing heritability . ”", "However , epistatic interactions have been difficult to detect in genome-wide association studies ( GWAS ) due to the limited power caused by the multiple-tes...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "bacteriology", "protein interactions", "enzymes", "regulatory proteins", "dna-binding proteins", "microbiology", "microbial growth and development", "enzyme kinetics", "microbial physiology", "proteins", "enzyme regulation", "biology", "recombinant proteins", "biochemistry", "transmembr...	Genetic and Biochemical Dissection of a HisKA Domain Identifies Residues Required Exclusively for Kinase and Phosphatase Activities	journal.pgen.1003084	null	[ [ "Myxococcus xanthus serves as a model for prokaryotic development .", "Upon sensing nutrient limitation , M . xanthus undergoes a complex signal transduction cascade culminating in the formation of macroscopic fruiting bodies composed of metabolically dormant myxospores .", "Entry into development is ...	[ "Two-component signal transduction systems , composed of histidine kinases ( HK ) and response regulators ( RR ) , allow bacteria to respond to diverse environmental stimuli .", "The HK can control both phosphorylation and subsequent dephosphorylation of its cognate RR .", "The majority of HKs utilize the HisKA...	[ "Bacterial histidine kinases ( HK ) serve as bifunctional enzymes capable of both phosphorylation and dephosphorylation of their cognate response regulators ( RR ) .", "The majority of HKs ( 77% ) belong to the HisKA subfamily .", "While both kinase and phosphatase functions have been assayed for HisKA proteins...	2012
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "infectious diseases/helminth infections", "infectious diseases/epidemiology and control of infectious diseases", "infectious diseases/neglected tropical diseases" ]	Helminthiasis and Hygiene Conditions of Schools in Ikenne, Ogun State, Nigeria	journal.pntd.0000146	null	[ [ "It is estimated that more than one billion of the world's population is chronically infected with soil-transmitted helminths , and 200 million are infected with schistosomiasis [1] .", "The high prevalence of these infections is closely correlated with poverty , poor environmental hygiene , and impoveris...	[ "A study of the helminth infection status of primary-school children and the hygiene condition of schools in Ikenne Local Government Area of Ogun State , Nigeria was undertaken between November 2004 and February 2005 to help guide the development of a school-based health programme .", "Three primary schools were ...	[ "We studied intestinal helminth infection status in primary-school children and the hygiene conditions of primary schools in Ikenne Local Government Area of Ogun State , Nigeria in order to help guide the development of school-based health programmes .", "Two government-owned schools ( one urban and the other rur...	2008
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "mycobacterium leprae", "medicine and health sciences", "pathology and laboratory medicine", "tropical diseases", "geographical locations", "microbiology", "bacterial diseases", "mutation", "signs and symptoms", "pharmaceutics", "neglected tropical diseases", "pharmacology", "bacteria", "i...	Leprosy Drug Resistance Surveillance in Colombia: The Experience of a Sentinel Country	journal.pntd.0005041	null	[ [ "Leprosy is a chronic infectious disease caused by M . leprae that results in disfigurement , exclusion from society and , often , in or from poverty [1] .", "Prior to the 1940s , leprosy was considered an untreatable disease .", "However , in the early 1940s , diamino-diphenyl sulfone ( DDS; also kno...	[ "An active search for Mycobacterium leprae drug resistance was carried out , 243 multibacillary patients from endemic regions of Colombia were included from 2004 to 2013 in a surveillance program .", "This program was a World Health Organization initiative for drug resistance surveillance in leprosy , where Colom...	[ "Mycobacterium leprae drug resistance is cause of surveillance due to the increase of leprosy relapsed cases .", "World Health Organization initiative for drug resistance surveillance in leprosy included Colombia , a country considered in post-elimination stage , as a sentinel country .", "During 10 years ( 200...	2016
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "medicine and health sciences", "nervous system", "paracrine signaling", "messenger rna", "geodesics", "geometry", "neuroscience", "hormones", "endocrine physiology", "dna transcription", "mathematics", "prolactin", "pituitary gland", "endocrinology", "gene expression", "peptide hormon...	Disentangling juxtacrine from paracrine signalling in dynamic tissue	journal.pcbi.1007030	null	[ [ "Gene expression at a single-cell level is highly dynamic in time , and the processes involved in gene activation and inactivation are now well-known to be highly stochastic [1–7] .", "The use of single-cell live imaging techniques , which employ luciferase or light emitting proteins such as destabilised ...	[ "Prolactin is a major hormone product of the pituitary gland , the central endocrine regulator .", "Despite its physiological importance , the cell-level mechanisms of prolactin production are not well understood .", "Having significantly improved the resolution of real-time-single-cell-GFP-imaging , the author...	[ "Prolactin is a major hormone product of the pituitary gland , the central endocrine regulator found underneath the brain .", "In mammals it is crucial for milk production and reproductive function .", "Production of such an important protein needs to be regulated tightly , and therefore one might imagine that ...	2019
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "virology/virulence factors and mechanisms", "virology/viral replication and gene regulation", "virology/diagnosis", "virology/mechanisms of resistance and susceptibility, including host genetics", "infectious diseases/viral infections", "virology/immune evasion" ]	Host Determinant Residue Lysine 627 Lies on the Surface of a Discrete, Folded Domain of Influenza Virus Polymerase PB2 Subunit	journal.ppat.1000136	null	[ [ "Influenza A viruses are orthomyxoviruses possessing an eight segment RNA genome of negative polarity .", "Each segment is packaged in a ribonucleoprotein complex ( RNP ) together with the nucleoprotein ( NP ) and the three subunits ( PA , PB1 and PB2 ) of the trimeric RNA-dependent RNA polymerase , which...	[ "Understanding how avian influenza viruses adapt to human hosts is critical for the monitoring and prevention of future pandemics .", "Host specificity is determined by multiple sites in different viral proteins , and mutation of only a limited number of these sites can lead to inter-species transmission .", "S...	[ "There is worldwide concern that currently circulating avian influenza viruses will cross the species barrier and become highly pathogenic , human transmissible strains with pandemic potential .", "This could result from residue changes in several influenza proteins , either by point mutations , or through shuffl...	2008
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "virology/viral replication and gene regulation" ]	Receptor Complementation and Mutagenesis Reveal SR-BI as an Essential HCV Entry Factor and Functionally Imply Its Intra- and Extra-Cellular Domains	journal.ppat.1000310	null	[ [ "Hepatitis C virus ( HCV ) infection is a leading cause of chronic liver disease", "world-wide .", "With 180 million persistently infected people , chronic hepatitis C", "infection , which induces end-stage liver disease such as liver cirrhosis and", "hepatocellular carcinoma ( HCC ) , represe...	[ "HCV entry into cells is a multi-step and slow process .", "It is believed that the", "initial capture of HCV particles by glycosaminoglycans and/or lipoprotein", "receptors is followed by coordinated interactions with the scavenger receptor", "class B type I ( SR-BI ) , a major receptor of high-density lip...	[ "More than 180 million people are chronically infected by hepatitis C virus ( HCV ) ,", "a leading cause of liver failure and cancer , stimulating the need to fully", "define the biology of HCV infection for developing novel and effective", "therapeutics .", "During the first steps of infection , the virus ...	2009
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "vaccines", "medicine", "vaccination", "infectious diseases", "schistosomiasis", "clinical immunology", "immunity", "neglected tropical diseases", "vaccine development", "immunology", "parasitic diseases" ]	Oral Delivery of the Sj23LHD-GST Antigen by Salmonella typhimurium Type III Secretion System Protects against Schistosoma japonicum Infection in Mice	journal.pntd.0001313	null	[ [ "Schistosomiasis , a disease cause by intravascular trematodes from the schistosome species , is one of the world's major public health problems [1] .", "It is estimated that 200 million people in seventy countries or regions from Africa , Asia and South America are infected with schistosomes [2] .", ...	[ "Schistosomiasis japonica is a zoonotic parasitic disease and oral vaccine delivery system would be benefit for prevention of this disease .", "Although attenuated salmonella has been used as an antigen expression vector for oral vaccine development , the membrane-bound vacuoles in which bacteria reside hinders t...	[ "Schistosomiasis japonica is a zoonotic parasitic disease and occurs predominantly in Southeast Asia and China .", "Using a simple , cheap , yet efficient oral method to deliver the vaccine antigen would benefit to control its transmission in that the oral vaccine could be made into a preparation and mixed with f...	2011
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "neuroscience/behavioral neuroscience", "genetics and genomics/gene function", "neuroscience/sensory systems" ]	Novel and Conserved Protein Macoilin Is Required for Diverse Neuronal Functions in Caenorhabditis elegans	journal.pgen.1001384	null	[ [ "Genome projects have determined DNA sequences of various organisms and identified locations of predicted genes in genomes .", "Surprisingly , numbers of genes are relatively similar across evolutionally divergent animal species .", "For example , estimated gene numbers are 20000–25000 in human [1] , ...	[ "Neural signals are processed in nervous systems of animals responding to variable environmental stimuli .", "This study shows that a novel and highly conserved protein , macoilin ( MACO-1 ) , plays an essential role in diverse neural functions in Caenorhabditis elegans .", "maco-1 mutants showed abnormal behav...	[ "Any animals , including humans , have to be capable of properly sensing and responding to various environmental stimuli for survival and reproduction .", "Environmental stimuli are evaluated and , based on past experiences , converted to produce appropriate adaptive behaviors .", "Even the small , free-living ...	2011
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "molecular biology/chromatin structure", "molecular biology/histone modification", "cell biology/gene expression", "cell biology/nuclear structure and function", "genetics and genomics/gene expression", "genetics and genomics/nuclear structure and function", "molecular biology/centromeres", "genetics ...	Plasmodium falciparum Heterochromatin Protein 1 Marks Genomic Loci Linked to Phenotypic Variation of Exported Virulence Factors	journal.ppat.1000569	null	[ [ "Plasmodium falciparum causes the most severe form of malaria in humans with over one million deaths annually [1] .", "Severe and fatal outcomes of infections with this protozoan parasite result from a multitude of syndromes triggered by repeated rounds of asexual reproduction within erythrocytes .", ...	[ "Epigenetic processes are the main conductors of phenotypic variation in eukaryotes .", "The malaria parasite Plasmodium falciparum employs antigenic variation of the major surface antigen PfEMP1 , encoded by 60 var genes , to evade acquired immune responses .", "Antigenic variation of PfEMP1 occurs through in ...	[ "Plasmodium falciparum causes the most severe form of malaria in humans .", "The high virulence of this unicellular parasite is in part related to the selective expression of members of falciparum-specific gene families .", "These genes encode proteins that are exported into the cytoplasm and onto the surface o...	2009
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "computational biology/population genetics", "genetics and genomics/bioinformatics", "computational biology/genomics", "genetics and genomics/population genetics" ]	Statistical Estimation of Correlated Genome Associations to a Quantitative Trait Network	journal.pgen.1000587	null	[ [ "Many complex disease syndromes , such as diabetes , asthma , and cancer , consist of a large number of highly related , rather than independent , clinical phenotypes .", "Differences between these syndromes involve a complex interplay of a large number of genomic variations that perturb the function of d...	[ "Many complex disease syndromes , such as asthma , consist of a large number of highly related , rather than independent , clinical or molecular phenotypes .", "This raises a new technical challenge in identifying genetic variations associated simultaneously with correlated traits .", "In this study , we propos...	[ "An association study examines a phenotype against genotypic variations over a large set of individuals in order to find the genetic variant that gives rise to the variation in the phenotype .", "Many complex disease syndromes consist of a large number of highly related clinical phenotypes , and the patient cohor...	2009
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "medicine and health sciences", "mycetoma", "tropical diseases", "parasitic diseases", "bacterial diseases", "ectoparasitic infections", "neglected tropical diseases", "fungal diseases", "veterinary science", "infectious diseases", "buruli ulcer", "veterinary diseases", "zoonoses", "elepha...	Association between Footwear Use and Neglected Tropical Diseases: A Systematic Review and Meta-Analysis	journal.pntd.0003285	null	[ [ "Neglected tropical diseases ( NTDs ) are caused by a variety of pathogens , such as parasites ( e . g . , ectoparasites , helminths , and protozoa ) , fungi , bacteria , and viruses , primarily found in the tropical and subtropical regions of the world [1] .", "NTDs mainly occur in rural and deprived urb...	[ "The control of neglected tropical diseases ( NTDs ) has primarily focused on preventive chemotherapy and case management .", "Less attention has been placed on the role of ensuring access to adequate water , sanitation , and hygiene and personal preventive measures in reducing exposure to infection .", "Our ai...	[ "Consistent use of footwear may help in preventing or slowing down the progression of many neglected tropical diseases ( NTDs ) .", "We conducted a systematic review and meta-analysis to assess the association between footwear use and infection or disease for those NTDs for which the route of transmission or occu...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine", "infectious diseases", "parasitic intestinal diseases", "neglected tropical diseases", "veterinary pharmacology", "biology", "molecular cell biology", "parasitic diseases", "veterinary science", "helminth infection" ]	Investigation of Acetylcholine Receptor Diversity in a Nematode Parasite Leads to Characterization of Tribendimidine- and Derquantel-Sensitive nAChRs	journal.ppat.1003870	null	[ [ "Human nematode parasite infections are of public health concern in many developing countries where over a billion people are infected [1] , [2] .", "Also very important for human nutrition are infections of livestock which cause significant production loss [3] .", "Treatment and prophylaxis for these...	[ "Nicotinic acetylcholine receptors ( nAChRs ) of parasitic nematodes are required for body movement and are targets of important “classical” anthelmintics like levamisole and pyrantel , as well as “novel” anthelmintics like tribendimidine and derquantel .", "Four biophysical subtypes of nAChR have been observed e...	[ "Parasitic nematode infections of humans and animals are world-wide .", "In humans , they cause disease and perpetuate a cycle of poverty .", "In animals , the parasites cause welfare problems and production loss .", "In developing countries , the debilitating effect of nematode parasites in school children l...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genetics", "chromatin", "epigenetics", "biology" ]	H3.3-H4 Tetramer Splitting Events Feature Cell-Type Specific Enhancers	journal.pgen.1003558	null	[ [ "H3 . 3 is a variant histone that differs from the canonical H3 histones by four amino acids [1]–[4] .", "Unlike the canonical histones that are incorporated in the replication-dependent pathway , H3 . 3 histones can also be deposited in a replication-independent manner [5] .", "Genome-wide profiling ...	[ "Previously , we reported that little canonical ( H3 . 1–H4 ) 2 tetramers split to form “hybrid” tetramers consisted of old and new H3 . 1–H4 dimers , but approximately 10% of ( H3 . 3–H4 ) 2 tetramers split during each cell cycle .", "In this report , we mapped the H3 . 3 nucleosome occupancy , the H3 . 3 nucleo...	[ "In our previous study , we unexpectedly discovered that nucleosomes containing the variant H3 . 3 histones experience substantial splitting events , resulting hybrid nucleosomes containing both “old” and “new” H3 . 3–H4 dimers .", "Here , we mapped the genomic distribution of these splitting events at the genome...	2013
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "virology/diagnosis", "infectious diseases/infectious diseases of the nervous system", "infectious diseases/viral infections", "infectious diseases/neglected tropical diseases" ]	Rabies Diagnosis for Developing Countries	journal.pntd.0000206	null	[ [ "Canine rabies is an endemic disease in most developing countries .", "Worldwide , approximately 55 , 000 ( 90% CI: 24 , 500–90 , 800 ) human deaths occur per year [1] .", "In N'Djaména , the capital of Chad , Kayali et al found a rabies incidence in the dog population of 1 . 4/1000 ( 95% CI: 1 . 2–1 ...	[ "Canine rabies is a neglected disease causing 55 , 000 human deaths worldwide per year , and 99% of all cases are transmitted by dog bites .", "In N'Djaména , the capital of Chad , rabies is endemic with an incidence of 1 . 71/1 , 000 dogs ( 95% C . I . 1 . 45–1 . 98 ) .", "The gold standard of rabies diagnosis...	[ "A new diagnostic test for rabies in animals was evaluated in N'Djaména , capital of Chad .", "The test is based on a direct immuno-histochemical detection of rabies virus in brain tissue ( dRIT ) visible by normal light microscopy .", "Rabies detection by dRIT light microscopy is 10 times less expensive than f...	2008
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "neuroscience/neuronal and glial cell biology", "cell biology/cytoskeleton" ]	Capzb2 Interacts with β-Tubulin to Regulate Growth Cone Morphology and Neurite Outgrowth	journal.pbio.1000208	An actin regulatory protein unexpectedly also controls microtubule polymerization during the formation and maintenance of cellular outgrowths in neurons.	[ [ "Growth cone morphology and neurite outgrowth are controlled by temporally and spatially coordinated interactions between two major cytoskeletal networks , F-actin and microtubules [1]–[3] .", "Recapitulation of these developmental cytoskeletal interactions is required for a successful regenerative respon...	[ "Capping protein ( CP ) is a heterodimer that regulates actin assembly by binding to the barbed end of F-actin .", "In cultured nonneuronal cells , each CP subunit plays a critical role in the organization and dynamics of lamellipodia and filopodia .", "Mutations in either α or β CP subunit result in retinal de...	[ "Neuronal growth , migration , and survival depend on the regulated formation of cellular outgrowths called neurites .", "Extension of normal neurites requires coordinated interactions between cytoskeletal networks made up of microfilaments ( composed of F-actin ) and microtubules ( formed by tubulin ) in structu...	2009
[ "Introduction", "Results", "Discussion", "Material and methods" ]	[ "invertebrates", "medicine and health sciences", "digestion", "pathology and laboratory medicine", "togaviruses", "chikungunya infection", "enzymes", "pathogens", "tropical diseases", "microbiology", "enzymology", "viral structure", "animals", "alphaviruses", "collagens", "viruses", ...	Chikungunya virus dissemination from the midgut of Aedes aegypti is associated with temporal basal lamina degradation during bloodmeal digestion	journal.pntd.0005976	null	[ [ "Aedes aegypti is the primary vector for important human pathogenic arboviruses such as dengue virus ( Flaviviridae; Flavivirus; DENV1-4 ) , chikungunya virus ( Togaviridae; Alphavirus; CHIKV ) , and Zika virus ( Flaviviridae; Flavivirus; ZIKV ) [1 , 2] .", "Following acquisition of a viremic bloodmeal fr...	[ "In the mosquito , the midgut epithelium is the initial tissue to become infected with an arthropod-borne virus ( arbovirus ) that has been acquired from a vertebrate host along with a viremic bloodmeal .", "Following its replication in midgut epithelial cells , the virus needs to exit the midgut and infect secon...	[ "The biological nature of the midgut escape barrier in insects for arthropod-borne viruses has been a mystery for decades .", "Here we show that the basal lamina ( BL ) surrounding the mosquito midgut acts as a barrier for chikungunya virus , an alphavirus , which has emerged in the New World hemisphere around th...	2017
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "genetic oscillators", "mutation", "behavioral neuroscience", "cellular neuroscience", "molecular neuroscience", "animal behavior", "phenotypes", "genetics", "biology and life sciences", "molecular genetics", "sensory perception", "zoology", "neuroscience", "molecular biology", "animals"...	Genetic Analysis of Circadian Responses to Low Frequency Electromagnetic Fields in Drosophila melanogaster	journal.pgen.1004804	null	[ [ "A wide range of animals are able to detect and exploit the Earth's magnetic field , particularly for the purposes of orientation and navigation [1]–[3] .", "The biological basis for the detection of electromagnetic fields ( EMFs ) is not understood but two main theories have been presented .", "The f...	[ "The blue-light sensitive photoreceptor cryptochrome ( CRY ) may act as a magneto-receptor through formation of radical pairs involving a triad of tryptophans .", "Previous genetic analyses of behavioral responses of Drosophila to electromagnetic fields using conditioning , circadian and geotaxis assays have lent...	[ "Low frequency electromagnetic fields ( EMFs ) are associated with electrical power lines and have been implicated in the development of childhood leukemias .", "However , the Earth also has a natural EMF that animals can detect and which they use in order to navigate and orient themselves , particularly during m...	2014
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[]	Transient Loss of Protection Afforded by a Live Attenuated Non-typhoidal Salmonella Vaccine in Mice Co-infected with Malaria	journal.pntd.0004027	null	[ [ "In immunocompetent individuals , non-typhoidal Salmonella serovars ( NTS ) cause gastroenteritis , a localized enteric infection characterized by intestinal neutrophil recruitment and diarrhea [1] .", "NTS gastroenteritis is the single most common cause of death from diarrheal disease associated with vir...	[ "In immunocompetent individuals , non-typhoidal Salmonella serovars ( NTS ) are associated with gastroenteritis , however , there is currently an epidemic of NTS bloodstream infections in sub-Saharan Africa .", "Plasmodium falciparum malaria is an important risk factor for invasive NTS bloodstream in African chil...	[ "In children , malaria is a predisposing factor for invasive bacterial infections with non-typhoidal Salmonella ( NTS ) serovars , a frequent cause of morbidity and mortality in sub-Saharan Africa .", "Since development of vaccines against NTS has been proposed as a strategy to protect African children against di...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "immunity to infections", "immunology", "immunity", "biology" ]	CYLD Enhances Severe Listeriosis by Impairing IL-6/STAT3-Dependent Fibrin Production	journal.ppat.1003455	null	[ [ "Listeria monocytogenes ( Lm ) is a facultative intracellular , gram-positive rod , which may cause life threatening infections in the elderly ( >65 years ) , immunocompromised patients and fetuses [1] .", "Clinically , listeriosis can present as septicaemia , disseminated inflammatory granuloma ( granulo...	[ "The facultative intracellular bacterium Listeria monocytogenes ( Lm ) may cause severe infection in humans and livestock .", "Control of acute listeriosis is primarily dependent on innate immune responses , which are strongly regulated by NF-κB , and tissue protective factors including fibrin .", "However , mo...	[ "Listeria monocytogenes causes high mortality in immunocompromised patients and fetuses .", "Murine studies have revealed that innate immune responses and fibrin , a major product of hepatocytes , are important to control Listeria .", "In the present study , we analysed whether the deubiquitinating enzyme CYLD ...	2013
[ "Introduction", "Results and Discussion", "Materials and Methods" ]	[]	Human Adenovirus 52 Uses Sialic Acid-containing Glycoproteins and the Coxsackie and Adenovirus Receptor for Binding to Target Cells	journal.ppat.1004657	null	[ [ "Human adenoviruses ( HAdVs ) are classified into seven species ( A-G ) , with more than 50 different types known to date [1] .", "Most HAdVs cause disease in the eyes ( members of species HAdV-B , -D , -E ) , airways ( HAdV-A , -B , -C , -E ) and gastrointestinal tract ( HAdV-F mainly ) [2] .", "HAdV...	[ "Most adenoviruses attach to host cells by means of the protruding fiber protein that binds to host cells via the coxsackievirus and adenovirus receptor ( CAR ) protein .", "Human adenovirus type 52 ( HAdV-52 ) is one of only three gastroenteritis-causing HAdVs that are equipped with two different fiber proteins ...	[ "HAdVs are common pathogens in humans , causing disease mainly in eyes , airways and gastrointestinal tract .", "Most HAdVs are equipped with twelve protruding fiber proteins that mediate attachment to host cell receptor molecules .", "Recently , a new human gastroenteritis-associated adenovirus ( HAdV-52 ) was...	2015
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "invertebrates", "medicine and health sciences", "body fluids", "tropical diseases", "parasitic diseases", "animals", "mathematics", "filariasis", "statistics (mathematics)", "forecasting", "neglected tropical diseases", "onchocerciasis", "lymphatic filariasis", "research and analysis meth...	Using Community-Level Prevalence of Loa loa Infection to Predict the Proportion of Highly-Infected Individuals: Statistical Modelling to Support Lymphatic Filariasis and Onchocerciasis Elimination Programs	journal.pntd.0005157	null	[ [ "Lymphatic Filariasis ( LF ) and Onchocerciasis are parasitic helminth diseases that constitute a serious public health issue in tropical regions [1] .", "LF causes one of the highest global burdens of all vector-borne diseases , with an estimated 120 million people infected in 83 countries [1] .", "A...	[ "Lymphatic Filariasis and Onchocerciasis ( river blindness ) constitute pressing public health issues in tropical regions .", "Global elimination programs , involving mass drug administration ( MDA ) , have been launched by the World Health Organisation .", "Although the drugs used are generally well tolerated ...	[ "Lymphatic Filariasis ( LF ) is caused by parasitic worms which live in the lymphatic system .", "Though several body parts may be affected , LF characteristically leads to the enlargement of limbs , causing pain , physical disability and social stigma .", "Onchocerciasis ( river blindness ) is caused by simila...	2016
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "invertebrates", "messenger rna", "invertebrate genomics", "animals", "dna transcription", "animal models", "developmental biology", "mutation", "drosophila melanogaster", "model organisms", "experimental organism systems", "embryos", "drosophila", "research and analysis methods", "embry...	A conserved maternal-specific repressive domain in Zelda revealed by Cas9-mediated mutagenesis in Drosophila melanogaster	journal.pgen.1007120	null	[ [ "During the first hours following fertilization , the zygotic genome is transcriptionally silent , and maternally deposited products control early development .", "These maternal products establish regulatory networks that enable the rapid and efficient transition from two specified germ cells to a popula...	[ "In nearly all metazoans , the earliest stages of development are controlled by maternally deposited mRNAs and proteins .", "The zygotic genome becomes transcriptionally active hours after fertilization .", "Transcriptional activation during this maternal-to-zygotic transition ( MZT ) is tightly coordinated wit...	[ "Following fertilization , the one-celled zygote must be rapidly reprogrammed to enable the development of a new , unique organism .", "During these initial stages of development there is little or no transcription of the zygotic genome , and maternally deposited products control this process .", "Among the ess...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "sequencing techniques", "taxonomy", "split-decomposition method", "vertebrates", "marmosets", "animals", "mammals", "animal phylogenetics", "primates", "animal models", "multiple alignment calculation", "phylogenetics", "data management", "model organisms", "phylogenetic analysis", "m...	Phylogenetic Analysis Reveals That ERVs "Die Young" but HERV-H Is Unusually Conserved	journal.pcbi.1004964	null	[ [ "By definition , endogenous retroviruses ( ERVs ) are the result of the Mendelian ( vertical germ line ) transmission of retroviruses from parent to progeny .", "Over many generations it is possible for an ERV to fix in a host population so that in humans , for example , as much as 8% of the genome is tho...	[ "About 8% of the human genome is made up of endogenous retroviruses ( ERVs ) .", "Though most human endogenous retroviruses ( HERVs ) are thought to be irrelevant to our biology notable exceptions include members of the HERV-H family that are necessary for the correct functioning of stem cells .", "ERVs are com...	[ "Animal genomes contain ancient pathogens known as endogenous retroviruses ( ERVs ) .", "Though the widespread abundance of ERVs is due to their ability to self replicate , some ERVs are known to have become important to host processes including placentation , and in the case of HERV-H , the functioning of human ...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	The Parkinson’s Disease-Associated Protein Kinase LRRK2 Modulates Notch Signaling through the Endosomal Pathway	journal.pgen.1005503	null	[ [ "Parkinson’s disease ( PD ) is thought to result from the combined effects of environmental and genetic factors .", "LRRK2 , which encodes a ROCO protein with a Ras of complex proteins ( ROC ) domain , a conserved C-terminal of ROC ( COR ) domain , a kinase domain , leucine-rich repeats ( LRRs ) , and WD4...	[ "Leucine-rich repeat kinase 2 ( LRRK2 ) is a key molecule in the pathogenesis of familial and idiopathic Parkinson’s disease ( PD ) .", "We have identified two novel LRRK2-associated proteins , a HECT-type ubiquitin ligase , HERC2 , and an adaptor-like protein with six repeated Neuralized domains , NEURL4 .", "...	[ "LRRK2 is linked to autosomal dominant late-onset Parkinson’s disease , suggesting that LRRK2 gain-of-function mutations lead to age-dependent degeneration of the midbrain dopaminergic neurons .", "In this study , we describe two novel LRRK2-associated proteins HERC2 and NEURL4 , which are a ubiquitin ligase and ...	2015
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "blood cells", "medicine and health sciences", "immune cells", "vacuoles", "immunology", "microbiology", "parasitic diseases", "parasitic protozoans", "protozoan life cycles", "immune receptor signaling", "developmental biology", "protozoans", "leishmania", "membrane receptor signaling", ...	Non-canonical NLRP3 inflammasome activation and IL-1β signaling are necessary to L. amazonensis control mediated by P2X7 receptor and leukotriene B4	journal.ppat.1007887	null	[ [ "Leishmaniases are a group of neglected human infectious diseases that affect more than 12 million people worldwide , with 1 . 5 million of new cases per year [1 , 2] .", "The protozoan parasites of Leishmania spp .", "cause several clinical manifestations , from skin lesions ( cutaneous leishmaniasis...	[ "Leishmaniasis is a neglected tropical disease affecting millions of individuals worldwide .", "P2X7 receptor has been linked to the elimination of Leishmania amazonensis .", "Biological responses evoked by P2X7 receptor activation have been well-documented , including apoptosis , phagocytosis , cytokine releas...	[ "Leishmania spp .", "is a protozoan parasite that infects human and causes several diseases .", "Leishmania amazonensis causes cutaneous leishmaniasis ( CL ) and mucocutaneous leishmaniasis ( MCL ) .", "Leishmania parasites preferentially infect macrophages .", "In macrophages , several mechanisms have been...	2019
[ "Introduction", "Materials and methods", "Results", "Discussion" ]	[ "blood cells", "medicine and health sciences", "enzyme-linked immunoassays", "immune physiology", "immune cells", "immunology", "tropical diseases", "parasitic diseases", "parasitic protozoans", "vaccines", "protozoans", "neglected tropical diseases", "infectious disease control", "antibod...	Trypanosoma cruzi 80 kDa prolyl oligopeptidase (Tc80) as a novel immunogen for Chagas disease vaccine	journal.pntd.0006384	null	[ [ "Chagas disease , also known as American Trypanosomiasis , is a chronic parasitic disease caused by the flagellated protozoan Trypanosoma cruzi .", "It is estimated that 8 million people over the world are infected by this parasite and more than 25 million are at risk of contracting the infection .", ...	[ "Chagas disease , also known as American Trypanosomiasis , is a chronic parasitic disease caused by the flagellated protozoan Trypanosoma cruzi that affects about 8 million people around the world where more than 25 million are at risk of contracting the infection .", "Despite of being endemic on 21 Latin-America...	[ "Chagas disease is a neglected tropical disease caused by the parasite Trypanosoma cruzi that affects more than 8 million people around the world .", "Unfortunately , the diagnosis is generally performed too late , when anti-parasitic drugs are no longer effective .", "About 30–40% of infected individuals progr...	2018
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[]	Elucidation of Sigma Factor-Associated Networks in Pseudomonas aeruginosa Reveals a Modular Architecture with Limited and Function-Specific Crosstalk	journal.ppat.1004744	null	[ [ "The ability to maintain homeostasis even in changing environments and under extreme conditions is one of the key traits of living organisms .", "Pseudomonas aeruginosa is a ubiquitous gram-negative bacterium that can be distinguished by its exceptional high capability to adapt and survive in various and ...	[ "Sigma factors are essential global regulators of transcription initiation in bacteria which confer promoter recognition specificity to the RNA polymerase core enzyme .", "They provide effective mechanisms for simultaneously regulating expression of large numbers of genes in response to challenging conditions , a...	[ "Pseudomonas aeruginosa is well known for its high adaptability to a large range of environmental conditions , including those encountered within the human host .", "Transcription initiation represents a major regulatory target which drives versatility , and enables bacterial adaptation to challenging conditions ...	2015
[ "Introduction", "Materials and methods", "Results", "Discussion" ]	[ "united states", "medicine and health sciences", "statistics", "influenza", "sociology", "geographical locations", "social sciences", "north america", "online encyclopedias", "mathematics", "forecasting", "internet", "regional geography", "research and analysis methods", "public and occu...	Even a good influenza forecasting model can benefit from internet-based nowcasts, but those benefits are limited	journal.pcbi.1006599	null	[ [ "Seasonal influenza causes substantial morbidity and mortality , including an estimated ten to fifty thousand deaths annually [1] .", "The ability to accurately monitor and forecast influenza outbreaks is thus of substantial public health priority .", "Traditional flu surveillance in the United States...	[ "The ability to produce timely and accurate flu forecasts in the United States can significantly impact public health .", "Augmenting forecasts with internet data has shown promise for improving forecast accuracy and timeliness in controlled settings , but results in practice are less convincing , as models augme...	[ "It has been demonstrated in retrospective settings that flu forecasting can be improved by augmenting forecasting models with internet-based nowcasts ( i . e . , one-week-ahead forecasts generated with internet data ) .", "The improvement of internet-assisted forecasting models , however , has not translated to ...	2019
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine", "genetics", "biology", "molecular cell biology", "genetics and genomics" ]	MSH3 Polymorphisms and Protein Levels Affect CAG Repeat Instability in Huntington's Disease Mice	journal.pgen.1003280	null	[ [ "At least 14 neurodegenerative and neuromuscular diseases are caused by expansions of CAG/CTG repeats including Huntington's disease ( HD ) and myotonic dystrophy type 1 .", "An inverse correlation between the length of CAG repeat tracts and age-of-onset is observed in HD families [1] , [2] .", "The e...	[ "Expansions of trinucleotide CAG/CTG repeats in somatic tissues are thought to contribute to ongoing disease progression through an affected individual's life with Huntington's disease or myotonic dystrophy .", "Broad ranges of repeat instability arise between individuals with expanded repeats , suggesting the ex...	[ "The genetic instability of repetitive DNA sequences in particular genes can lead to numerous neurodegenerative , neurological , and neuromuscular diseases .", "These diseases show progressively increasing severity of symptoms through the life of the affected individual , a phenomenon that is linked with increasi...	2013
[ "Introduction", "Models", "Results", "Discussion" ]	[ "medicine and health sciences", "chemical compounds", "pathology and laboratory medicine", "enzymes", "cell processes", "permeability", "enzymology", "organic compounds", "toxicology", "toxicity", "active transport", "materials science", "enzyme metabolism", "cellular structures and organe...	A systems-level model reveals that 1,2-Propanediol utilization microcompartments enhance pathway flux through intermediate sequestration	journal.pcbi.1005525	null	[ [ "Bacterial microcompartments ( MCPs ) are protein-bound intracellular organelles used by Salmonella enterica , Yersinia pestis , Klebsiella spp .", ", and other bacteria to spatially organize their metabolism [1–3] .", "MCP metabolons allow the growth of these pathogens on carbon and energy sources , ...	[ "The spatial organization of metabolism is common to all domains of life .", "Enteric and other bacteria use subcellular organelles known as bacterial microcompartments to spatially organize the metabolism of pathogenicity-relevant carbon sources , such as 1 , 2-propanediol .", "The organelles are thought to se...	[ "Many bacterial species , such as Salmonella enterica ( responsible for over 1 million illnesses per year in the United States ) and Yersinia pestis ( the causative agent of bubonic plague ) , have a suite of unique metabolic capabilities allowing them to proliferate in the hostile environment of the host gut .", ...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "psychology", "medicine and health sciences", "social sciences", "genetics", "biology and life sciences", "computational biology", "mental health and psychiatry", "neuroscience" ]	Integrated Pathway-Based Approach Identifies Association between Genomic Regions at CTCF and CACNB2 and Schizophrenia	journal.pgen.1004345	null	[ [ "Genome-wide association studies ( GWAS ) have identified common susceptibility variants for numerous disorders [1] , [2] .", "For complex diseases , however , many of the discovered variants have only a moderate or weak effect on disease risk .", "Due to correction for multiple testing and limited sa...	[ "In the present study , an integrated hierarchical approach was applied to: ( 1 ) identify pathways associated with susceptibility to schizophrenia; ( 2 ) detect genes that may be potentially affected in these pathways since they contain an associated polymorphism; and ( 3 ) annotate the functional consequences of ...	[ "Large-scale genetic studies of complex diseases such as schizophrenia have identified a variety of susceptibility loci .", "Since many of the respective variants have only a weak influence on disease risk , pathophysiological interpretation of the results is problematic .", "Investigation of the joint effects ...	2014
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "ecology and environmental sciences", "medicine and health sciences", "genome evolution", "population genetics", "computational biology", "geographical locations", "north america", "aquatic environments", "bodies of water", "population biology", "caribbean", "genomics", "genetic polymorphism...	Adaptive introgression from distant Caribbean islands contributed to the diversification of a microendemic adaptive radiation of trophic specialist pupfishes	journal.pgen.1006919	null	[ [ "Adaptive radiations are central to our understanding of evolution because they generate a wealth of ecological , phenotypic , and species diversity in rapid bursts .", "However , the mechanisms that trigger rapid bursts of trait divergence , niche evolution , and diversification characteristic of classic...	[ "Rapid diversification often involves complex histories of gene flow that leave variable and conflicting signatures of evolutionary relatedness across the genome .", "Identifying the extent and source of variation in these evolutionary relationships can provide insight into the evolutionary mechanisms involved in...	[ "Groups of closely related species can rapidly evolve to occupy diverse ecological roles , but the ecological and genetic conditions that trigger this diversification are still highly debated .", "We examined patterns of molecular evolution across the genomes of a recent radiation of pupfishes that includes two t...	2017
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "blood cells", "cell binding", "cell physiology", "medicine and health sciences", "immune cells", "gene regulation", "regulatory proteins", "immunology", "dna-binding proteins", "hormones", "transcription factors", "epigenetics", "estrogens", "chromatin", "genomic signal processing", "...	EBF1 binds to EBNA2 and promotes the assembly of EBNA2 chromatin complexes in B cells	journal.ppat.1006664	null	[ [ "CBF1/CSL ( C promoter binding factor , Suppressor of Hairless , and lag1 also called RBPJ or RBPJκ ) is a cellular DNA binding protein , ubiquitously expressed in all mammalian tissues .", "CBF1 serves as a DNA adaptor molecule that recruits either repressors or activators to transcriptional control elem...	[ "Epstein-Barr virus ( EBV ) infection converts resting human B cells into permanently proliferating lymphoblastoid cell lines ( LCLs ) .", "The Epstein-Barr virus nuclear antigen 2 ( EBNA2 ) plays a key role in this process .", "It preferentially binds to B cell enhancers and establishes a specific viral and ce...	[ "Epstein-Barr virus ( EBV ) infection is closely linked to cancer development .", "At particular risk are immunocompromised individuals like post-transplant patients which can develop B cell lymphomas .", "In healthy individuals EBV preferentially infects B cells and establishes a latent infection without causi...	2017
[ "Introduction", "Results", "Discussion", "Methods and materials" ]	[ "gene regulation", "regulatory proteins", "dna-binding proteins", "dna transcription", "transcription factors", "sequence motif analysis", "research and analysis methods", "sequence analysis", "selenium", "genome complexity", "genomics", "bioinformatics", "proteins", "gene expression", "...	Environmental perturbations lead to extensive directional shifts in RNA processing	journal.pgen.1006995	null	[ [ "Variation in gene expression has long been associated with cellular and organismal phenotypes .", "For example , studies have found that gene expression in blood and bronchial epithelial cells differs among individuals with asthma [1 , 2 , 3 , 4] .", "Such differences in gene expression occur in spec...	[ "Environmental perturbations have large effects on both organismal and cellular traits , including gene expression , but the extent to which the environment affects RNA processing remains largely uncharacterized .", "Recent studies have identified a large number of genetic variants associated with variation in RN...	[ "Changes in a cell’s environment and genetic variation have been shown to impact gene expression .", "Here , we demonstrate that environmental perturbations also lead to extensive changes in alternative RNA processing across a large number of cellular environments that we investigated .", "These changes often o...	2017
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "medicine and health sciences", "pathology and laboratory medicine", "pathogens", "geographical locations", "microbiology", "hepatitis b virus", "retroviruses", "viruses", "immunodeficiency viruses", "vaccines", "mutation", "rna viruses", "pharmaceutics", "pharmacology", "mutation databa...	A systematic review of hepatitis B virus (HBV) drug and vaccine escape mutations in Africa: A call for urgent action	journal.pntd.0006629	null	[ [ "In 2015 , the World Health Organisation ( WHO ) estimated that 3 . 5% of the world’s population ( 257 million people ) were living with Hepatitis B virus ( HBV ) infection , resulting in 887 , 000 deaths each year , mostly from complications including cirrhosis and hepatocellular carcinoma ( HCC ) [1] .", ...	[ "International sustainable development goals for the elimination of viral hepatitis as a public health problem by 2030 highlight the pressing need to optimize strategies for prevention , diagnosis and treatment .", "Selected or transmitted resistance associated mutations ( RAMs ) and vaccine escape mutations ( VE...	[ "The Global Hepatitis Health Sector Strategy is aiming for the elimination of viral hepatitis as a public health threat by 2030 .", "However , mutations associated with drug resistance and vaccine escape may reduce the success of existing treatment and prevention strategies .", "In the current literature , the ...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "pharmacology/drug resistance", "pharmacology/drug development", "pharmacology", "computational biology", "pharmacology/adverse reactions", "biochemistry/drug discovery" ]	A Multidimensional Strategy to Detect Polypharmacological Targets in the Absence of Structural and Sequence Homology	journal.pcbi.1000648	null	[ [ "Researchers have traditionally focused in silico efforts on designing inhibitors of specific protein targets , giving less attention to the computational identification of unpredicted secondary targets .", "This tendency is surprising given the frequency with which secondary receptors are responsible for...	[ "Conventional drug design embraces the “one gene , one drug , one disease” philosophy .", "Polypharmacology , which focuses on multi-target drugs , has emerged as a new paradigm in drug discovery .", "The rational design of drugs that act via polypharmacological mechanisms can produce compounds that exhibit inc...	[ "Proteins play a critical role in human disease; bacteria , viruses , and parasites have unique proteins that can interfere with human health , and dysfunctional human proteins can likewise lead to illness .", "In order to find cures , scientists often try to identify small molecules ( drugs ) that can inhibit di...	2010
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "cell biology/neuronal and glial cell biology", "neuroscience/motor systems", "cell biology/cell growth and division", "neuroscience/neural homeostasis", "neuroscience/neurodevelopment", "neuroscience/neuronal signaling mechanisms", "neurological disorders/neuropsychiatric disorders", "neurological di...	A PI3-Kinase–Mediated Negative Feedback Regulates Neuronal Excitability	journal.pgen.1000277	null	[ [ "Negative feedback processes , which can enable maintenance of neuronal homeostasis , are widely observed in neuronal systems [1]–[3] .", "For example , neuronal silencing via tetrodotoxin application both in vivo and in vitro increases excitability [4]–[6] .", "This effect occurs in vitro via both in...	[ "Use-dependent downregulation of neuronal activity ( negative feedback ) can act as a homeostatic mechanism to maintain neuronal activity at a particular specified value .", "Disruption of this negative feedback might lead to neurological pathologies , such as epilepsy , but the precise mechanisms by which this f...	[ "Use-dependent downregulation of neuronal excitability ( negative feedback ) can act to maintain neuronal activity within specified levels .", "Disruption of this homeostasis can lead to neurological disorders , such as epilepsy .", "Here , we report a novel mechanism for negative feedback control of excitabili...	2008
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "neuroscience/cognitive neuroscience" ]	Influence of Low-Level Stimulus Features, Task Dependent Factors, and Spatial Biases on Overt Visual Attention	journal.pcbi.1000791	null	[ [ "In daily life , eye movements center parts of a scene on the human fovea several times a second [1] .", "The part of the visual field falling onto the fovea is represented with the highest spatial acuity and , compared to the periphery , receives disproportionately more cortical processing resources [2] ...	[ "Visual attention is thought to be driven by the interplay between low-level visual features and task dependent information content of local image regions , as well as by spatial viewing biases .", "Though dependent on experimental paradigms and model assumptions , this idea has given rise to varying claims that ...	[ "In our lifetime we make about 5 billion eye movements .", "Yet our knowledge about what determines where we look at is surprisingly sketchy .", "Some traditional approaches assume that gaze is guided by simple image properties like local contrast ( low-level features ) .", "Recent arguments emphasize the inf...	2010
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine", "biochemistry", "infectious diseases", "immunology", "biology", "microbiology", "biophysics" ]	Structural and Functional Basis for Inhibition of Erythrocyte Invasion by Antibodies that Target Plasmodium falciparum EBA-175	journal.ppat.1003390	null	[ [ "PfEBA-175 is a P . falciparum parasite ligand that binds to its receptor GpA on erythrocytes in a sialic acid-dependent manner [1]–[5] .", "This binding event is necessary for erythrocyte invasion and consequently PfEBA-175 is a leading vaccine candidate [6]–[9] .", "PfEBA-175 has also paved the way ...	[ "Disrupting erythrocyte invasion by Plasmodium falciparum is an attractive approach to combat malaria .", "P . falciparum EBA-175 ( PfEBA-175 ) engages the host receptor Glycophorin A ( GpA ) during invasion and is a leading vaccine candidate .", "Antibodies that recognize PfEBA-175 can prevent parasite growth ...	[ "Malaria is a devastating parasitic disease that kills one million people annually .", "The parasites invade and multiply within red blood cells , leading to the clinical symptoms of malaria .", "Therefore , preventing red blood cell , entry through vaccines is an attractive approach to controlling the disease ...	2013
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "taxonomy", "organismal evolution", "medicine and health sciences", "pathology and laboratory medicine", "viral transmission and infection", "microbiology", "animal phylogenetics", "viruses", "phylogenetics", "data management", "rna viruses", "phylogenetic analysis", "dna viruses", "microb...	Comparative analysis estimates the relative frequencies of co-divergence and cross-species transmission within viral families	journal.ppat.1006215	null	[ [ "Emerging pathogens that cross the species barrier to infect new hosts can profoundly affect human and animal health , as well as wildlife and the agricultural industries .", "Although most emerging diseases seemingly result from such a process of cross-species transmission , it is also the case that some...	[ "The cross-species transmission of viruses from one host species to another is responsible for the majority of emerging infections .", "However , it is unclear whether some virus families have a greater propensity to jump host species than others .", "If related viruses have an evolutionary history of co-diverg...	[ "Emerging infectious diseases are often characterized by host switching events , in which a pathogen jumps from its original host to infect a novel species .", "However , given the ecological and genetic barriers a virus must overcome to jump species and adapt to new hosts , it might be reasonable to assume that ...	2017
[ "Introduction", "Materials and methods", "Results", "Discussion" ]	[ "antimicrobials", "medicine and health sciences", "drugs", "tropical diseases", "microbiology", "animal models", "bacterial diseases", "streptomycin", "model organisms", "pharmaceutics", "antibiotics", "experimental organism systems", "neglected tropical diseases", "pharmacology", "bacte...	Triple oral beta-lactam containing therapy for Buruli ulcer treatment shortening	journal.pntd.0007126	null	[ [ "Buruli ulcer ( BU ) is a chronic debilitating mycobacterial disease of the skin and soft tissue .", "Although mortality is low , permanent disfigurement and disability are high , mainly affecting children and young adults .", "BU is found primarily in tropical regions of Africa , South America and th...	[ "The potential use of clinically approved beta-lactams for Buruli ulcer ( BU ) treatment was investigated with representative classes analyzed in vitro for activity against Mycobacterium ulcerans .", "Beta-lactams tested were effective alone and displayed a strong synergistic profile in combination with antibioti...	[ "Buruli ulcer ( BU ) is a chronic debilitating disease of the skin and soft tissue , mainly affecting children and young adults in tropical regions .", "Before 2004 , the only treatment option was surgery; a major breakthrough was the discovery that BU could be cured in most cases with a standard treatment that i...	2019
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "computational biology/systems biology", "computational biology/genomics" ]	Mapping Dynamic Histone Acetylation Patterns to Gene Expression in Nanog-Depleted Murine Embryonic Stem Cells	journal.pcbi.1001034	null	[ [ "The number of data sets in ESC linking epigenetic mechanisms to other molecular regulatory mechanisms and following that relationship over time is very limited .", "Recently , however , Lu and coworkers [25] presented a dynamic systems-level study to assess how different molecular regulatory mechanisms i...	[ "Embryonic stem cells ( ESC ) have the potential to self-renew indefinitely and to differentiate into any of the three germ layers .", "The molecular mechanisms for self-renewal , maintenance of pluripotency and lineage specification are poorly understood , but recent results point to a key role for epigenetic me...	[ "Stem cell differentiation and the maintenance of self-renewal are intrinsically complex processes that require coordinated regulation on many different cellular levels .", "Here we focus on the relationship between two important layers and follow it over the first five days of differentiation .", "The first la...	2010
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "virology/viral replication and gene regulation", "virology" ]	Protein Expression Redirects Vesicular Stomatitis Virus RNA Synthesis to Cytoplasmic Inclusions	journal.ppat.1000958	null	[ [ "RNA viruses that replicate within the cytoplasm often form specialized structures that are the sites of RNA replication [1] .", "For positive-strand RNA viruses , replication occurs on cellular membranes , including those of the endoplasmic reticulum , secretory pathway , mitochondria and other organelle...	[ "Positive-strand and double-strand RNA viruses typically compartmentalize their replication machinery in infected cells .", "This is thought to shield viral RNA from detection by innate immune sensors and favor RNA synthesis .", "The picture for the non-segmented negative-strand ( NNS ) RNA viruses , however , ...	[ "Positive-strand and double-strand RNA viruses compartmentalize their replication machinery in infected cells .", "This compartmentalization is thought to favor the catalysis of RNA synthesis , and sequester viral RNA molecules from detection by innate immune sensors .", "For the negative-strand RNA viruses tha...	2010
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "vero cells", "medicine and health sciences", "pathology and laboratory medicine", "viral transmission and infection", "biological cultures", "tropical diseases", "microbiology", "parasitic diseases", "protozoan life cycles", "parasitic protozoans", "toxicology", "developmental biology", "to...	Identification of Trypanocidal Activity for Known Clinical Compounds Using a New Trypanosoma cruzi Hit-Discovery Screening Cascade	journal.pntd.0004584	null	[ [ "Chagas disease affects approximately 7 to 8 million people in Latin America [1] and a recent study estimates the mortality rate at 2 . 78 deaths per 100 , 000 inhabitants in Brazil [2] resulting in more than 5000 deaths annually in this country alone .", "Currently the only drugs approved for treatment o...	[ "Chagas disease is a significant health problem in Latin America and the available treatments have significant issues in terms of toxicity and efficacy .", "There is thus an urgent need to develop new treatments either via a repurposing strategy or through the development of new chemical entities .", "A key fir...	[ "Chagas disease is an important health problem in Latin America .", "The disease is caused by the parasite Trypanosoma cruzi , which is transmitted to people via insects of the Triatomine family .", "There are currently only two treatments available , Nifurtimox and Benznidazole .", "These have serious proble...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biochemistry", "molecular cell biology", "evolutionary biology", "proteins", "gene expression", "genetics", "molecular genetics", "biology", "biophysics", "molecular biology", "genetics and genomics" ]	Probing the Informational and Regulatory Plasticity of a Transcription Factor DNA–Binding Domain	journal.pgen.1002614	null	[ [ "The precise regulation of gene expression depends upon the specific binding of transcription factors to their cognate binding sites .", "For this process to be accurate , the sites for each factor need to be separable from all other sequences in the genome [1] , [2] .", "Many groups have studied spec...	[ "Transcription factors have two functional constraints on their evolution: ( 1 ) their binding sites must have enough information to be distinguishable from all other sequences in the genome , and ( 2 ) they must bind these sites with an affinity that appropriately modulates the rate of transcription .", "Since b...	[ "The main role of transcription factors is to modulate the expression levels of functionally related genes in response to environmental and cellular cues .", "For this process to be precise , the transcription factor needs to locate and bind specific DNA sequences in the genome and needs to bind these sites with ...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "gene regulation", "anatomy and physiology", "hormones", "endocrine physiology", "gene function", "animal models", "developmental biology", "drosophila melanogaster", "model organisms", "organism development", "molecular development", "molecular genetics", "gene expression", "nuclear recep...	Translational Control by the DEAD Box RNA Helicase belle Regulates Ecdysone-Triggered Transcriptional Cascades	journal.pgen.1003085	null	[ [ "Steroid hormones regulate a wide variety of biological responses during development and physiological homeostasis .", "These small lipophilic compounds act , through their respective nuclear receptors , to directly regulate target gene transcription .", "This initial transcriptional response occurs w...	[ "Steroid hormones act , through their respective nuclear receptors , to regulate target gene expression .", "Despite their critical role in development , physiology , and disease , however , it is still unclear how these systemic cues are refined into tissue-specific responses .", "We identified a mutation in t...	[ "Pulses of steroid hormones regulate a variety of biological processes , but how these simple global cues are converted into specific local responses remains unclear .", "While steroid responses have traditionally been thought to be regulated at the transcriptional level , here we demonstrate that translational c...	2012
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "invertebrates", "medicine and health sciences", "rna interference", "nuclear staining", "social sciences", "neuroscience", "animals", "animal models", "c-jun n-terminal kinase signaling cascade", "developmental biology", "drosophila melanogaster", "model organisms", "experimental organism s...	dMyc is required in retinal progenitors to prevent JNK-mediated retinal glial activation	journal.pgen.1006647	null	[ [ "The nervous system is formed by neurons , which transmit information from cell to cell , and by glia , which supports and maintains a healthy and functional neuronal network ( reviewed in [1] ) .", "A key function of glial cells is to provide insulation , trophic and survival support to neurons [2] .", ...	[ "In the nervous system , glial cells provide crucial insulation and trophic support to neurons and are important for neuronal survival .", "In reaction to a wide variety of insults , glial cells respond with changes in cell morphology and metabolism to allow repair .", "Additionally , these cells can acquire mi...	[ "For a functional nervous system , neurons transmit information from cell to cell while glial cells provide crucial insulation and trophic support to neurons , which is important for neuronal survival .", "Glial cells are one of the most plastic cell types being able to adapt and respond to changing environmental...	2017
[ "Introduction", "Materials and Methods", "Results and Discussion" ]	[]	Combining Evolutionary Information and an Iterative Sampling Strategy for Accurate Protein Structure Prediction	journal.pcbi.1004661	null	[ [ "The computational prediction of protein structures from their amino acid sequence is an ongoing challenge that has occupied scientists for more than four decades .", "While Anfinsen’s dogma [1] suggests that for most proteins the information contained in their amino acid sequence is sufficient to define ...	[ "Recent work has shown that the accuracy of ab initio structure prediction can be significantly improved by integrating evolutionary information in form of intra-protein residue-residue contacts .", "Following this seminal result , much effort is put into the improvement of contact predictions .", "However , th...	[ "Recently , a breakthrough has been achieved in modeling the atomic 3D structures of proteins from their sequence alone without requiring any experimental work on the protein itself .", "To achieve this goal , a database of evolutionary related sequences is analyzed to find co-evolving residues , giving insight i...	2015
[ "Introduction", "Methods", "Results", "Discussion" ]	[]	Input-Dependent Frequency Modulation of Cortical Gamma Oscillations Shapes Spatial Synchronization and Enables Phase Coding	journal.pcbi.1004072	null	[ [ "How the millions of neurons in the brain are coordinated to permit meaningful computations is one of the fundamental questions of neuroscience .", "Spike synchrony and relative spike timing play important roles in dynamically coordinating neural activity [1–7] with substantial impact on neuronal function...	[ "Fine-scale temporal organization of cortical activity in the gamma range ( ∼25–80Hz ) may play a significant role in information processing , for example by neural grouping ( ‘binding’ ) and phase coding .", "Recent experimental studies have shown that the precise frequency of gamma oscillations varies with inpu...	[ "Almost 350 years ago the physicist and polymath Christiaan Huygens first observed the synchronization between two pendulum clocks attached to a common support .", "Since then synchronization has been recognized as a universal phenomenon from astronomy to biology .", "The phase-locking ( synchrony ) and the pha...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "viral attachment", "coreceptors", "viral entry", "host cells", "viral transmission and infection", "virology", "biology", "microbiology" ]	Temporal Analysis of Hepatitis C Virus Cell Entry with Occludin Directed Blocking Antibodies	journal.ppat.1003244	null	[ [ "Hepatitis C virus ( HCV ) , a member of the Hepacivirus genus within the family Flaviviridae , is the causative agent of over half of all liver cancers and responsible for the majority of liver transplants worldwide [1]–[3] .", "Even with the recent approval of HCV protease inhibitors , HCV directed ther...	[ "Hepatitis C virus ( HCV ) is a major cause of liver disease worldwide .", "A better understanding of its life cycle , including the process of host cell entry , is important for the development of HCV therapies and model systems .", "Based on the requirement for numerous host factors , including the two tight ...	[ "HCV is a serious public health problem .", "Although new treatments have recently become available , it is clear that effective therapies will require combinations of inhibitors targeting diverse stages of the viral life cycle .", "While the HCV cell entry process is considered a suitable antiviral target , a ...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine and health sciences", "vesicular stomatitis virus", "pathology and laboratory medicine", "molecular probe techniques", "293t cells", "pathogens", "biological cultures", "immunology", "immunoblotting", "microbiology", "viruses", "rna viruses", "immunoprecipitation", "molecular bio...	Deubiquitinase USP2a Sustains Interferons Antiviral Activity by Restricting Ubiquitination of Activated STAT1 in the Nucleus	journal.ppat.1005764	null	[ [ "The interferons ( IFNs ) family of cytokines plays a critical role in the defense against viral infection and regulating innate immunity .", "Three classes of IFNs ( type I , II , and III ) have been identified , all of which exert their activity by activating a signaling cascade comprised of Janus kinas...	[ "STAT1 is a critical transcription factor for regulating host antiviral defenses .", "STAT1 activation is largely dependent on phosphorylation at tyrosine 701 site of STAT1 ( pY701-STAT1 ) .", "Understanding how pY701-STAT1 is regulated by intracellular signaling remains a major challenge .", "Here we find th...	[ "Phosphorylated STAT1 at tyrosine 701 site ( pY701-STAT1 ) is critical for regulating many cellular functions including antiviral immunity .", "Maintaining sufficient pY701-STAT1 levels in the nucleus is essential to sustain efficient interferons ( IFNs ) signaling and antiviral functions .", "Therefore , it is...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "animal models", "morphogens", "biochemistry", "developmental biology", "drosophila melanogaster", "model organisms", "proteins", "signaling", "molecular development", "lipoproteins", "biology" ]	Secretion and Signaling Activities of Lipoprotein-Associated Hedgehog and Non-Sterol-Modified Hedgehog in Flies and Mammals	journal.pbio.1001505	We identify two distinct Hh secretion forms with complementary signaling activities produced in both mammals and flies: one sterol-modified and lipoprotein-associated, and another lacking sterol modification.	[ [ "Hedgehog ( Hh ) family proteins are secreted signaling molecules that control animal development and tissue homeostasis [1] , [2] .", "They are produced as precursors that are processed through autocatalytic cleavage and sterol modification to generate the active N-terminal signaling domain [3] , [4] , w...	[ "Hedgehog ( Hh ) proteins control animal development and tissue homeostasis .", "They activate gene expression by regulating processing , stability , and activation of Gli/Cubitus interruptus ( Ci ) transcription factors .", "Hh proteins are secreted and spread through tissue , despite becoming covalently linke...	[ "Hedgehog ( Hh ) proteins are conserved secreted signaling molecules that regulate embryonic development and adult tissue homeostasis .", "Ectopic Hh signaling promotes tumorigenesis , and secretion of mammalian Sonic Hedgehog ( Shh ) by many tumors supports their growth and survival .", "As Hh proteins are cov...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "organismal evolution", "segmentation", "gene function", "developmental biology", "organism development", "body plan organization", "zoology", "morphogenesis", "pattern formation", "biology", "entomology", "animal evolution", "genetics", "evolutionary biology", "genetics and genomics", ...	Novel Function of Distal-less as a Gap Gene during Spider Segmentation	journal.pgen.1002342	null	[ [ "The genetic regulation of head segmentation in Drosophila melanogaster is one of the best-studied examples of how tissues become specified and patterned during early embryonic development [1] , [2] .", "Moreover , some features of the Drosophila segmentation gene cascade are evolutionarily conserved amon...	[ "Despite many aspects of the regulation of segmentation being conserved among arthropods , the evolution of novel gene functions has played an important role in the evolution of developmental regulation and the emergence of new segmental structures .", "Moreover the study of such novel gene functions can be infor...	[ "The development and segmentation of the head of the fly Drosophila is one of the best-studied examples of how tissues become genetically specified during embryonic development .", "However , the mechanisms for head segmentation vary considerably among the arthropods .", "This is on the one hand surprising beca...	2011
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "kinesins", "crystal structure", "split-decomposition method", "condensed matter physics", "simulation and modeling", "multiple alignment calculation", "dyneins", "molecular motors", "crystallography", "motor proteins", "research and analysis methods", "sequence analysis", "solid state physi...	Allosteric conformational change cascade in cytoplasmic dynein revealed by structure-based molecular simulations	journal.pcbi.1005748	null	[ [ "Dynein is an ATP-hydrolysis driven molecular motor that linearly proceeds along the microtubule ( MT ) towards its minus end [1–3] .", "Cytoplasmic dynein is involved in the transport of many different types of cargo such as mRNAs , proteins , and vesicles [4 , 5] and is also involved in mitosis [6 , 7] ...	[ "Cytoplasmic dynein is a giant ATP-driven molecular motor that proceeds to the minus end of the microtubule ( MT ) .", "Dynein hydrolyzes ATP in a ring-like structure , containing 6 AAA+ ( ATPases associated with diverse cellular activities ) modules , which is ~15 nm away from the MT binding domain ( MTBD ) .", ...	[ "The linear molecular motor dynein is an intriguing allosteric model protein .", "ATP hydrolysis , catalyzed by modules in the AAA+ ring , regulates the binding to the rail molecule , microtubule , which is ~15 nm away from the AAA+ ring .", "The molecular mechanisms underpinning this long-distance communicatio...	2017
[ "Introduction", "Materials and methods", "Results", "Discussion" ]	[ "cell physiology", "medicine and health sciences", "pathology and laboratory medicine", "viral transmission and infection", "cell activation", "antiviral therapy", "pathogens", "immunology", "microbiology", "biomarkers", "retroviruses", "viruses", "immunodeficiency viruses", "preventive me...	Predictions of time to HIV viral rebound following ART suspension that incorporate personal biomarkers	journal.pcbi.1007229	null	[ [ "Antiretroviral therapy ( ART ) for HIV infection can very effectively control the infection and hold the amount of circulating virus below the level detectable by clinical assays , improving both the quality and length of life .", "ART suspension generally is followed by HIV rebound to high viral loads [...	[ "Antiretroviral therapy ( ART ) effectively controls HIV infection , suppressing HIV viral loads .", "Suspension of therapy is followed by rebound of viral loads to high , pre-therapy levels .", "However , there is significant heterogeneity in speed of rebound , with some rebounds occurring within days , weeks ...	[ "Antiretroviral therapy ( ART ) effectively controls HIV infection , holding HIV viral loads to levels undetectable by commercial assays .", "Therapy interruption is followed by rebound of viral loads to high , pre-therapy levels , but there is significant heterogeneity in the timing of the rebound to those high ...	2019
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "blood cells", "t helper cells", "hiv infections", "medicine and health sciences", "immune cells", "pathology and laboratory medicine", "biopsy", "pathogens", "immunology", "microbiology", "staphylococcus aureus", "surgical and invasive medical procedures", "methicillin-resistant staphylococ...	MRSA Infections in HIV-Infected People Are Associated with Decreased MRSA-Specific Th1 Immunity	journal.ppat.1005580	null	[ [ "Community-acquired methicillin-resistant Staphylococcus aureus ( CA-MRSA ) emerged as a major cause of skin and soft tissue infections ( SSTIs ) in the 1990s .", "SSTIs manifest as cellulitis , abscesses , folliculitis , furuncles and carbuncles [1] .", "MRSA colonizes 8 . 8% of HIV-infected persons ...	[ "People with HIV infection are at increased risk for community-acquired methicillin-resistant Staphylococcus aureus ( CA-MRSA ) skin and soft tissue infections ( SSTIs ) .", "Lower CD4 T-cell counts , higher peak HIV RNA levels and epidemiological factors may be associated with increased risk but no specific immu...	[ "Methicillin-resistant Staphylococcus aureus ( MRSA ) causes infections of the skin and associated tissue .", "HIV-infected people are at increased risks of these infections for unclear reasons .", "We recruited participants with or without HIV infection who had a MRSA skin or soft tissue infection , MRSA colon...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "infectious diseases", "microbiology" ]	The Pseudomonas Quinolone Signal (PQS) Balances Life and Death in Pseudomonas aeruginosa Populations	journal.ppat.1000166	null	[ [ "Infectious diseases are the result of a dynamic interplay between the pathogen and the host .", "The host responds to an infection by activating diverse innate and adaptive immune defence mechanisms , whereas the disease causing pathogen produces an arsenal of virulence factors and evades the activated i...	[ "When environmental conditions deteriorate and become inhospitable , generic survival strategies for populations of bacteria may be to enter a dormant state that slows down metabolism , to develop a general tolerance to hostile parameters that characterize the habitat , and to impose a regime to eliminate damaged m...	[ "A little poison may be generically beneficial to bacterial populations .", "By eliminating damaged members and by promoting survival of the fittest , selective poisoning may significantly contribute to multi-cellular bacterial behavior .", "Here , we report that the pseudomonas quinolone signal ( PQS ) exhibit...	2008

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