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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" ]	[ "cancer genetics", "gene expression", "genetics", "epigenetics", "biology", "genomics", "histone modification" ]	Ras-Induced Changes in H3K27me3 Occur after Those in Transcriptional Activity	journal.pgen.1003698	null	[ [ "Epigenetic modification of chromatin is a key mechanism for regulation of gene expression [1] , [2] .", "Trimethylation of histone H3 at lysine-27 ( H3K27 ) is associated with transcriptional repression and is regulated by Polycomb repressive complex 2 ( PRC2 ) , a histone methyltransferase specific for ...	[ "Oncogenic signaling pathways regulate gene expression in part through epigenetic modification of chromatin including DNA methylation and histone modification .", "Trimethylation of histone H3 at lysine-27 ( H3K27 ) , which correlates with transcriptional repression , is regulated by an oncogenic form of the smal...	[ "Trimethylation of histone H3 at lysine-27 ( H3K27 ) has been associated with silencing of gene expression .", "Abnormalities of this modification are thought to contribute to the epigenetic silencing of tumor suppressor genes and are regarded as a hallmark of cancer .", "It has remained unclear , however , whe...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "immunology", "computational biology" ]	A Systematic Assessment of MHC Class II Peptide Binding Predictions and Evaluation of a Consensus Approach	journal.pcbi.1000048	null	[ [ "The activation of CD4+ helper T cells is essential for the development of adaptive immunity against pathogens [1]–[4] .", "A critical step in CD4+ T cell activation is the recognition of epitopes presented by MHC class II molecules [5] .", "MHC class II molecules are heterodimers expressed on the sur...	[ "The identification of MHC class II restricted peptide epitopes is an important goal in immunological research .", "A number of computational tools have been developed for this purpose , but there is a lack of large-scale systematic evaluation of their performance .", "Herein , we used a comprehensive dataset c...	[ "A critical step in developing immune response against pathogens is the recognition of antigenic peptides presented by MHC class II molecules .", "Since experiments for MHC class II binding peptide identification are expensive and time consuming , computational tools have been developed as fast alternatives but w...	2008
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "medicine and health sciences", "immune physiology", "pathology and laboratory medicine", "pathogens", "immunology", "microbiology", "retroviruses", "viruses", "immunodeficiency viruses", "preventive medicine", "vaccines", "rna viruses", "vaccination and immunization", "antibodies", "ant...	CD4/CD8 Ratio and KT Ratio Predict Yellow Fever Vaccine Immunogenicity in HIV-Infected Patients	journal.pntd.0005219	null	[ [ "Effective antiretroviral treatment ( ART ) drastically improved clinical outcomes for people living with HIV .", "However , these patients still present increased risk of death , higher prevalence of comorbidities , and impaired responses to vaccines [1–6] .", "Prior studies have shown impaired Yello...	[ "HIV-infected individuals have deficient responses to Yellow Fever vaccine ( YFV ) and may be at higher risk for adverse events ( AE ) .", "Chronic immune activation–characterized by low CD4/CD8 ratio or high indoleamine 2 , 3-dioxygenase-1 ( IDO ) activity—may influence vaccine response in this population .", ...	[ "Yellow Fever ( YF ) vaccine is considered one of the most effective vaccines ever produced .", "However , previous studies suggest that HIV impairs YF vaccine response .", "In this study , we assessed if HIV infection impacts the risk of adverse events and could reduce antibody response to YF vaccine .", "We...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "immunology/cellular microbiology and pathogenesis", "infectious diseases/bacterial infections", "immunology/immune response", "immunology/innate immunity" ]	Secreted Bacterial Effectors That Inhibit Host Protein Synthesis Are Critical for Induction of the Innate Immune Response to Virulent Legionella pneumophila	journal.ppat.1001289	null	[ [ "In metazoans , the innate immune system senses infection through the use of germline-encoded pattern recognition receptors ( PRRs ) that detect pathogen-associated molecular patterns ( PAMPs ) , such as lipopolysaccharide or flagellin [1] .", "PAMPs are conserved molecules that are found on non-pathogeni...	[ "The intracellular bacterial pathogen Legionella pneumophila causes an inflammatory pneumonia called Legionnaires' Disease .", "For virulence , L . pneumophila requires a Dot/Icm type IV secretion system that translocates bacterial effectors to the host cytosol .", "L . pneumophila lacking the Dot/Icm system is...	[ "In animals , the innate immune system senses infection primarily through detection of conserved microbial molecules .", "It has been suggested , but not clearly established , that the immune system may also respond to pathogen-associated activities—i . e . , the manipulations of host cell processes that a pathog...	2011
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "chemical biology/small molecule chemistry", "microbiology/environmental microbiology", "microbiology/plant-biotic interactions", "plant biology/plant-biotic interactions", "plant biology/plant biochemistry and physiology", "plant biology/agricultural biotechnology" ]	Imbalanced Lignin Biosynthesis Promotes the Sexual Reproduction of Homothallic Oomycete Pathogens	journal.ppat.1000264	null	[ [ "Lignin accounts for about 30% of the organic carbon in the biosphere and is the second most abundant terrestrial biopolymer after cellulose [1] .", "Lignin fortifies plant cell walls , is the essential composite of wood , and allows terrestrial plants to gain size and volume .", "This polymer renders...	[ "Lignin is incorporated into plant cell walls to maintain plant architecture and to ensure long-distance water transport .", "Lignin composition affects the industrial value of plant material for forage , wood and paper production , and biofuel technologies .", "Industrial demands have resulted in an increase i...	[ "Lignin is an essential component of wood and the second most abundant terrestrial biopolymer .", "Plants synthesize lignin to strengthen cell walls and to resist pathogen attack .", "Because the technological value of plants is determined by the amount and composition of lignin , genetic engineering approaches...	2009
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "flow cytometry", "cell physiology", "enzyme-linked immunoassays", "microbiology", "viral structure", "membrane fusion", "coevolution", "immunologic techniques", "cellular structures and organelles", "research and analysis methods", "sequence analysis", "sequence alignment", "bioinformatics"...	A protein coevolution method uncovers critical features of the Hepatitis C Virus fusion mechanism	journal.ppat.1006908	null	[ [ "Flaviviridae such as Hepatitis C Virus ( HCV ) , Dengue Virus ( DENV ) , Zika Virus ( ZIKV ) or West Nile Virus ( WNV ) are cause of several acute and chronic diseases worldwide .", "The continuous investigation of the molecular processes by which these RNA viruses infect and replicate into their host is...	[ "Amino-acid coevolution can be referred to mutational compensatory patterns preserving the function of a protein .", "Viral envelope glycoproteins , which mediate entry of enveloped viruses into their host cells , are shaped by coevolution signals that confer to viruses the plasticity to evade neutralizing antibo...	[ "Several virus-mediated molecular processes remain poorly described , which dampen the development of potent anti-viral therapies .", "Hence , new experimental strategies need to be undertaken to improve and accelerate our understanding of these processes .", "Here , as a proof of concept , we employ amino-acid...	2018
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "medicine and health sciences", "action potentials", "neurochemistry", "vesicles", "nervous system", "membrane potential", "electrophysiology", "neuroscience", "synaptic plasticity", "neurotransmitters", "cellular structures and organelles", "neuronal dendrites", "excitatory postsynaptic pot...	A kinetic model for Brain-Derived Neurotrophic Factor mediated spike timing-dependent LTP	journal.pcbi.1006975	null	[ [ "Brain-Derived Neurotrophic Factor ( BDNF ) is a member of the protein family of mammalian neurotrophins , further comprising nerve growth factor , neurotrophin 3 and neurotrophin 4/5 .", "Neurotrophins are well known across the animal kingdom to support survival , ontogenetic development , differentiatio...	[ "Across the mammalian nervous system , neurotrophins control synaptic plasticity , neuromodulation , and neuronal growth .", "The neurotrophin Brain-Derived Neurotrophic Factor ( BDNF ) is known to promote structural and functional synaptic plasticity in the hippocampus , the cerebral cortex , and many other brai...	[ "Storing memory traces in the brain is essential for learning and memory formation , and it occurs through synaptic plasticity processes .", "Timing-dependent Long-Term Potentiation ( t-LTP ) is a physiologically relevant type of synaptic plasticity that results from the repeated sequential firing of action poten...	2019
[ "Introduction", "Results and Discussion", "Materials and Methods" ]	[ "genome-wide association studies", "deletion mutation", "demography", "population genetics", "twins", "simulation and modeling", "developmental biology", "mutation", "genome analysis", "population biology", "research and analysis methods", "genetic loci", "people and places", "genetics", ...	A Model of Compound Heterozygous, Loss-of-Function Alleles Is Broadly Consistent with Observations from Complex-Disease GWAS Datasets	journal.pgen.1006573	null	[ [ "Risk for complex diseases in humans , such as diabetes and hypertension , is highly heritable yet the causal DNA sequence variants responsible for that risk remain largely unknown .", "Genome-wide association studies ( GWAS ) have found many genetic markers associated with disease risk [1] .", "Howev...	[ "The genetic component of complex disease risk in humans remains largely unexplained .", "A corollary is that the allelic spectrum of genetic variants contributing to complex disease risk is unknown .", "Theoretical models that relate population genetic processes to the maintenance of genetic variation for quan...	[ "Gene action determines how mutations affect phenotype .", "When placed in an evolutionary context , the details of the genotype-to-phenotype model can impact the maintenance of genetic variation for complex traits .", "Likewise , non-equilibrium demographic history may affect patterns of genetic variation .", ...	2017
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "metabolic networks", "enzymology", "genomic databases", "prosthetic groups", "network analysis", "genome analysis", "enzyme chemistry", "research and analysis methods", "computer and information sciences", "biochemical cofactors", "prokaryotic cells", "metabolic pathways", "biological datab...	Metabolic models and gene essentiality data reveal essential and conserved metabolism in prokaryotes	journal.pcbi.1006556	null	[ [ "Prokaryotes are the simplest contemporary life forms known , and nevertheless are characterized by an immense complexity .", "The debate on the features of such complexity and its breadth in the primordial life forms has been around for years [1–3] , and was furthermore expanded and detailed since the ad...	[ "Essential metabolic reactions are shaping constituents of metabolic networks , enabling viable and distinct phenotypes across diverse life forms .", "Here we analyse and compare modelling predictions of essential metabolic functions with experimental data and thereby identify core metabolic pathways in prokaryot...	[ "If we tried to list every known chemical reaction within an organism–human , plant or even bacteria–we would get quite a long and confusing read .", "But when this information is represented in so-called genome-scale metabolic networks , we have the means to access computationally each of those reactions and the...	2018
[ "Introduction", "Results/Discussion", "Materials and Methods" ]	[ "microarrays", "sequence analysis", "organismal evolution", "genomics", "evolutionary biology", "human evolution", "biology", "computational biology" ]	MicroRNA Expression and Regulation in Human, Chimpanzee, and Macaque Brains	journal.pgen.1002327	null	[ [ "Phenotypic differences between species , including human-specific features such as language and tool-making , are thought to have arisen , to a large extent , through changes in gene expression [1] .", "Indeed , humans and the closest living primate relatives , chimpanzees , display substantial gene expr...	[ "Among other factors , changes in gene expression on the human evolutionary lineage have been suggested to play an important role in the establishment of human-specific phenotypes .", "However , the molecular mechanisms underlying these expression changes are largely unknown .", "Here , we have explored the rol...	[ "Humans are remarkably similar to apes and monkeys on the genome sequence level but remain remarkably distinct with respect to cognitive abilities .", "How could human cognition evolve within such a short evolutionary time ?", "Among many hypotheses , evolution in expression of a few key regulators affecting hu...	2011
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "death rates", "reverse transcriptase-polymerase chain reaction", "medicine and health sciences", "clinical laboratory sciences", "leptospira", "pathology and laboratory medicine", "demography", "pathogens", "tropical diseases", "geographical locations", "microbiology", "north america", "sig...	Enhanced Surveillance for Fatal Dengue-Like Acute Febrile Illness in Puerto Rico, 2010-2012	journal.pntd.0005025	null	[ [ "Dengue is a major public health problem worldwide .", "While most dengue virus ( DENV ) infections are asymptomatic or result in a mild acute febrile illness ( AFI ) , some are life-threatening due to plasma leakage [1 , 2] .", "With no antivirals to treat dengue or prevent its severe manifestations ...	[ "Dengue is a leading cause of morbidity throughout the tropics; however , accurate population-based estimates of mortality rates are not available .", "We established the Enhanced Fatal Acute Febrile Illness Surveillance System ( EFASS ) to estimate dengue mortality rates in Puerto Rico .", "Healthcare professi...	[ "Dengue is a major public health problem in the tropics .", "Despite its global importance , population-based mortality rates attributable to dengue are largely unknown .", "Dengue vaccines are now in late stage clinical trials and one vaccine has been licensed in several countries .", "Evidence-based decisio...	2016
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "infectious diseases/protozoal infections", "infectious diseases/neglected tropical diseases" ]	Helminth Infection and Eosinophilia and the Risk of Plasmodium falciparum Malaria in 1- to 6-Year-Old Children in a Malaria Endemic Area	journal.pntd.0000164	null	[ [ "Helminth and malaria endemic areas frequently coincide , and an interaction between the two would be of considerable public health importance [1] , [2] .", "Animal models suggest that helminth infections may alter susceptibility to malaria , although the results are conflicting [3] , [4] .", "In stud...	[ "Helminth infection is common in malaria endemic areas , and an interaction between the two would be of considerable public health importance .", "Animal models suggest that helminth infections may increase susceptibility to malaria , but epidemiological data has been limited and contradictory .", "In a vaccine...	[ "Malaria infection and other parasitic infections are widespread in developing countries .", "There is evidence from some studies that intestinal worm infections may increase the risk of developing febrile malaria .", "However , the evidence is mixed , and some studies have found no effect or even protective ef...	2008
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[]	Proteomic Analysis of Urine Exosomes Reveals Renal Tubule Response to Leptospiral Colonization in Experimentally Infected Rats	journal.pntd.0003640	null	[ [ "Leptospirosis is among the world’s most important zoonotic infectious diseases [1 , 2] , characterized by variable manifestations ranging from asymptomatic or self-resolving acute febrile illness to severe disease with a combination of fever , acute kidney injury , jaundice , severe pulmonary hemorrhage synd...	[ "Infectious Leptospira colonize the kidneys of reservoir ( e . g . rats ) and accidental hosts such as humans .", "The renal response to persistent leptospiral colonization , as measured by urinary protein biosignatures , has not been systematically studied .", "Urinary exosomes--bioactive membrane-bound nanove...	[ "Leptospirosis is a bacterial disease commonly transmitted from animals to humans .", "Though this disease affects more than three quarters of a million people every year and takes a disproportionate toll on the poor in in tropical regions , few virulence factors have been identified and very little is known rega...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biotechnology", "biochemistry", "cell biology", "immunology", "biophysics" ]	Surface-Anchored Monomeric Agonist pMHCs Alone Trigger TCR with High Sensitivity	journal.pbio.0060043	Why is it that T cells are blind to antigens in solution but highly sensitive to antigens anchored on a surface? The authors show that this is not due to antigen clustering, but could involve mechanical forces associated with cell locomotion.	[ [ "Using T cell receptors ( TCRs ) as sensors , T cells probe the surface of antigen-presenting cells ( APCs ) for the presence of antigenic ( agonist ) peptides presented by major histocompatibility complex ( pMHC ) molecules .", "Engagement of TCRs by agonist pMHCs initiates a signal , which is transmitte...	[ "At the interface between T cell and antigen-presenting cell ( APC ) , peptide antigen presented by MHC ( pMHC ) binds to the T cell receptor ( TCR ) and initiates signaling .", "The mechanism of TCR signal initiation , or triggering , remains unclear .", "An interesting aspect of this puzzle is that although s...	[ "Using the T cell receptor ( TCR ) as a sensor , T cells of the immune system constantly migrate in lymphoid organs and probe the surface of antigen-presenting cells ( APCs ) for foreign antigens , a sign of pathogen infection .", "Antigen binding by TCRs leads to T cell activation and subsequent immune response ...	2008
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "biotechnology", "invertebrates", "medicine and health sciences", "caenorhabditis", "oxygen", "neuroscience", "animals", "animal models", "organisms", "oxygen metabolism", "caenorhabditis elegans", "model organisms", "experimental organism systems", "molecular biology techniques", "genot...	Oxygen-sensing neurons reciprocally regulate peripheral lipid metabolism via neuropeptide signaling in Caenorhabditis elegans	journal.pgen.1007305	null	[ [ "The central nervous system plays a critical role in regulating whole body energy balance .", "In mammals , in addition to the role of the hypothalamus , there is good evidence showing that the sensory nervous system also regulates whole body metabolism [1–4] .", "However , the identification of discr...	[ "The mechanisms by which the sensory environment influences metabolic homeostasis remains poorly understood .", "In this report , we show that oxygen , a potent environmental signal , is an important regulator of whole body lipid metabolism .", "C . elegans oxygen-sensing neurons reciprocally regulate periphera...	[ "We now appreciate that the sensory nervous systems of complex multicellular animals play a profound role in influencing energy balance , and body fat stores .", "Understanding the precise molecular mechanisms and neuroendocrine pathways by which the nervous system controls metabolic tissues has remained a tremen...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "neuroscience" ]	Timing Precision in Population Coding of Natural Scenes in the Early Visual System	journal.pbio.0060324	Early neural representation of visual scenes occurs with a temporal precision on the order of 10 ms, which is precise enough to strongly drive downstream neurons in the visual pathway. Unlike individual neurons, the neural population code is largely insensitive to pronounced changes in visual contrast.	[ [ "The precision of neuronal spike trains is at the center of a fundamental debate in neuroscience as to what aspects of neuronal signaling are important in representing information in the brain .", "Individual neurons can have extremely precise and repeatable responses to the visual stimuli that strongly d...	[ "The timing of spiking activity across neurons is a fundamental aspect of the neural population code .", "Individual neurons in the retina , thalamus , and cortex can have very precise and repeatable responses but exhibit degraded temporal precision in response to suboptimal stimuli .", "To investigate the func...	[ "Neurons convey information about the world in the form of trains of action potentials ( spikes ) .", "These trains are highly repeatable when the same stimulus is presented multiple times , and this temporal precision across repetitions can be as fine as a few milliseconds .", "It is usually assumed that this ...	2008
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "invertebrates", "deletion mutation", "rna interference", "caenorhabditis", "gene regulation", "animals", "animal models", "germ cells", "mutation", "caenorhabditis elegans", "model organisms", "immunoprecipitation", "experimental organism systems", "silent mutation", "epigenetics", "c...	Distinct regions of the intrinsically disordered protein MUT-16 mediate assembly of a small RNA amplification complex and promote phase separation of Mutator foci	journal.pgen.1007542	null	[ [ "RNA silencing is an anciently conserved pathway that regulates gene expression in most eukaryotes .", "Key to this pathway are members of the Argonaute protein family , which bind a diverse set of small regulatory RNAs , ranging from ~18–30 nucleotides in length .", "This small RNA-Argonaute complex ...	[ "In C . elegans , efficient RNA silencing requires small RNA amplification mediated by RNA-dependent RNA polymerases ( RdRPs ) .", "RRF-1 , an RdRP , and other Mutator complex proteins localize to Mutator foci , which are perinuclear germline foci that associate with nuclear pores and P granules to facilitate sma...	[ "Small RNAs are a driving force behind the regulation of both essential genes and deleterious transcripts .", "The Mutator complex is critical to the amplification of high levels of small RNAs and it requires the protein MUT-16 for its assembly .", "Here we investigate the function of MUT-16 by generating small...	2018
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "medicine and health sciences", "disorders of imprinting", "animal models", "developmental biology", "model organisms", "methylation", "tongue", "experimental organism systems", "beckwith-wiedemann syndrome", "epigenetics", "dna", "embryos", "kidneys", "dna methylation", "chromatin", "...	Tissue-specific and mosaic imprinting defects underlie opposite congenital growth disorders in mice	journal.pgen.1007243	null	[ [ "Imprinted genes show monoallelic and parent-of-origin-dependent expression and play key roles in the control of growth and development .", "In humans , altered expression of imprinted genes is associated with Imprinting Disorders ( IDs ) that are characterized by growth , metabolic and behavioural distur...	[ "Differential DNA methylation defects of H19/IGF2 are associated with congenital growth disorders characterized by opposite clinical pictures .", "Due to structural differences between human and mouse , the mechanisms by which mutations of the H19/IGF2 Imprinting Control region ( IC1 ) result in these diseases ar...	[ "A humanized mouse line carrying a mutation of the H19/IGF2 imprinting control region demonstrates how tissue-specific and mosaic imprinting alterations result in growth disorders with opposite clinical pictures and asymmetric growth of bilateral organs ." ]	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	TopBP1 Governs Hematopoietic Stem/Progenitor Cells Survival in Zebrafish Definitive Hematopoiesis	journal.pgen.1005346	null	[ [ "Hematopoietic stem/progenitor cells ( HSPCs ) possess the capabilities of self-renewal and differentiation into all lineages of mature blood cells [1] .", "Dysregulated self-renewal of HSPCs is tightly associated with the human blood diseases including leukemia and bone marrow failure ( BMF ) syndrome [2...	[ "In vertebrate definitive hematopoiesis , nascent hematopoietic stem/progenitor cells ( HSPCs ) migrate to and reside in proliferative hematopoietic microenvironment for transitory expansion .", "In this process , well-established DNA damage response pathways are vital to resolve the replication stress , which is...	[ "The rapidly proliferating hematopoietic stem/progenitor cells ( HSPCs ) require well-established DNA damage response/repair pathways to resolve the DNA replication stress-induced DNA damage , which is deleterious for the genome stability and cell survival .", "Impairment of these pathways could lead to the progr...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genetics and genomics/disease models", "genetics and genomics/cancer genetics", "oncology/breast cancer" ]	Genetic Mechanisms in Apc-Mediated Mammary Tumorigenesis	journal.pgen.1000367	null	[ [ "Breast cancer is one of the most common malignancies in women in Western countries and it is the cause of death in approximately 20% of all females who die from cancer .", "Breast epithelium is a dynamic organ capable of rapid proliferation and functional differentiation upon pregnancy and lactation , fo...	[ "Many components of Wnt/β-catenin signaling pathway also play critical roles in mammary tumor development , yet the role of the tumor suppressor gene APC ( adenomatous polyposis coli ) in breast oncongenesis is unclear .", "To better understand the role of Apc in mammary tumorigenesis , we introduced conditional ...	[ "Breast cancer is one of the most common malignanices in women in Western countries .", "Many components of Wnt/β-catenin signaling pathway are known to play critical roles in mammary tumor development , yet the role of the tumor suppressor gene APC ( adenomatous polyposis coli ) in breast oncongenesis is unclear...	2009
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "sequencing techniques", "plant anatomy", "trichomes", "molecular probe techniques", "gene regulation", "plant science", "micrornas", "molecular biology techniques", "seedlings", "rna sequencing", "plants", "research and analysis methods", "probe hybridization", "gene expression", "leave...	Threshold-dependent repression of SPL gene expression by miR156/miR157 controls vegetative phase change in Arabidopsis thaliana	journal.pgen.1007337	null	[ [ "Leaves produced at different times in shoot development are often morphologically distinct .", "In Arabidopsis , for example , successive rosette leaves differ in size , length:width ratio , the angle of the leaf base , hydathode number , the complexity of the vascular system , cell size , sensitivity to...	[ "Vegetative phase change is regulated by a decrease in the abundance of the miRNAs , miR156 and miR157 , and the resulting increase in the expression of their targets , SQUAMOSA PROMOTER BINDING PROTEIN-LIKE ( SPL ) transcription factors .", "To determine how miR156/miR157 specify the quantitative and qualitative...	[ "Leaves produced at different stages in the development of an Arabidopsis shoot vary predictably in shape and size .", "Previous studies have shown that this phenomenon is regulated by variation in the abundance of the miRNAs , miR156 and miR157 , but how miR156/miR157 produce the changes in leaf morphology that ...	2018
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "genome-wide association studies", "medicine and health sciences", "maternal health", "obstetrics and gynecology", "population genetics", "alleles", "ethnicities", "women's health", "pregnancy", "genome analysis", "population biology", "tibetan people", "genetic loci", "people and places",...	Detecting past and ongoing natural selection among ethnically Tibetan women at high altitude in Nepal	journal.pgen.1007650	null	[ [ "Understanding the impact of natural selection on phenotypic variation has been a central focus of evolutionary biology since its beginning as a modern scientific discipline .", "Decades of research have accumulated evidence for widespread adaptive phenotypic evolution in nature , including correlations b...	[ "Adaptive evolution in humans has rarely been characterized for its whole set of components , i . e . selective pressure , adaptive phenotype , beneficial alleles and realized fitness differential .", "We combined approaches for detecting polygenic adaptations and for mapping the genetic bases of physiological an...	[ "The adaptations to high altitude environments in Tibetan populations have long been highlighted as an important case study of adaptive evolution in our species .", "Recent genetic studies found two genes , EGLN1 and EPAS1 , the genetic variants in which were swept to high frequency in Tibetans due to strong posi...	2018
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "blood cells", "colorimetric assays", "medicine and health sciences", "luciferase", "immune cells", "pathology and laboratory medicine", "natural antisense transcripts", "gene regulation", "enzymes", "immunology", "pathogens", "microbiology", "enzymology", "biochemical analysis", "viruse...	Epstein-Barr virus microRNAs regulate B cell receptor signal transduction and lytic reactivation	journal.ppat.1007535	null	[ [ "Epstein Barr virus ( EBV ) is a human gamma-herpesvirus that infects >90% of adults worldwide .", "Primary infection is often asymptomatic or presents as infectious mononucleosis .", "In immunocompromised individuals , the virus is linked to post-transplant lymphoproliferative disease ( PTLD ) and he...	[ "MicroRNAs ( miRNAs ) are post-transcriptional regulatory RNAs that can modulate cell signaling and play key roles in cell state transitions .", "Epstein-Barr virus ( EBV ) expresses >40 viral miRNAs that manipulate both viral and cellular gene expression patterns and contribute to reprogramming of the host envir...	[ "Understanding the molecular mechanisms regulating EBV latency and entry into the lytic replication cycle is important in developing therapies for viral disease .", "We demonstrate here that a subset of EBV miRNAs target host factors within the BCR signaling pathway and consequently , negatively regulate cellular...	2019
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "plant science", "viroids", "plant pathogens", "plant pathology", "biology and life sciences" ]	Discovery of Replicating Circular RNAs by RNA-Seq and Computational Algorithms	journal.ppat.1004553	null	[ [ "Viroids and a group of satellite RNAs ( satRNAs ) have single-stranded circular RNA genomes that range in size from 220 to 457 nucleotides ( nt ) [1]–[4] .", "These subviral pathogenic RNAs lack protein-coding capabilities and thus depend on either host-encoded DNA-dependent RNA polymerase ( viroids ) or...	[ "Replicating circular RNAs are independent plant pathogens known as viroids , or act to modulate the pathogenesis of plant and animal viruses as their satellite RNAs .", "The rate of discovery of these subviral pathogens was low over the past 40 years because the classical approaches are technical demanding and t...	[ "Viroids are a unique class of subviral pathogens found in plants , and they are difficult to identify since they are free circular non-coding RNAs and often replicate to low levels in host cells .", "We previously described the computational algorithm PFOR that discovers viroids by analyzing total small RNAs of ...	2014
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "medicine", "infectious diseases", "environmental health", "zoonoses", "hantavirus", "environmental epidemiology", "epidemiology", "infectious disease modeling", "public health" ]	Atmospheric Moisture Variability and Transmission of Hemorrhagic Fever with Renal Syndrome in Changsha City, Mainland China, 1991–2010	journal.pntd.0002260	null	[ [ "Hemorrhagic fever with renal syndrome ( HFRS ) is a rodent-borne disease caused by hantavirus , and is characterized by fever , hemorrhage , kidney damage , and hypotension .", "HFRS has been recognized as an important public health problem in Hunan Province , which is one of the most seriously affected ...	[ "The transmission of hemorrhagic fever with renal syndrome ( HFRS ) is influenced by environmental determinants .", "This study aimed to explore the association between atmospheric moisture variability and the transmission of hemorrhagic fever with renal syndrome ( HFRS ) for the period of 1991–2010 in Changsha ,...	[ "Hemorrhagic fever with renal syndrome ( HFRS ) , a rodentborne disease caused by Hantaviruses , is characterized by fever , haemorrhage , headache , back pain , abdominal pain , and acute kidney injury .", "At present , it is endemic in all 31 provinces , autonomous regions , and metropolitan areas in mainland C...	2013
[ "Introduction", "Methods", "Results & discussion" ]	[ "tissue mechanics", "medicine and health sciences", "classical mechanics", "fluid mechanics", "biomechanics", "pulmonology", "pleurae", "simulation and modeling", "respiratory system", "trachea", "research and analysis methods", "respiratory physiology", "fluid dynamics", "pulmonary functi...	A multi-scale model of gas transport in the lung to study heterogeneous lung ventilation during the multiple-breath washout test	journal.pcbi.1007079	null	[ [ "The multiple-breath washout ( MBW ) is a lung function test that measures the degree of ventilation inhomogeneity [1] and is increasingly used for both research and clinical purposes in patients with obstructive lung disease , such as cystic fibrosis , primary ciliary dyskinesia , etc .", "[2–4] .", ...	[ "The multiple-breath washout ( MBW ) is a lung function test that measures the degree of ventilation inhomogeneity ( VI ) .", "The test is used to identify small airway impairment in patients with lung diseases like cystic fibrosis .", "However , the physical and physiological factors that influence the test ou...	[ "Obstructive lung diseases , like cystic fibrosis or primary ciliary dyskinesia , lead to inhomogeneous ventilation .", "The degree of observed inhomogeneity represents a clinical measure for the progression of the disease .", "The multiple-breath washout ( MBW ) is a lung function test that measures this inhom...	2019
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "organismal evolution", "chemical bonding", "medicine and health sciences", "crystal structure", "pathology and laboratory medicine", "condensed matter physics", "microbiology", "microbial evolution", "crystallography", "hydrogen bonding", "physical chemistry", "infectious diseases", "solid ...	Structural basis of glycan specificity of P[19] VP8*: Implications for rotavirus zoonosis and evolution	journal.ppat.1006707	null	[ [ "Rotaviruses ( RVs ) are a major cause of severe gastroenteritis in children under the age of 5 , causing 200 , 000 deaths[1–3]and account for 2 million childhood hospital admissions with an estimated cost of over 1 billion US dollars per year[4 , 5] .", "It has been shown that RV attachment to cell surfa...	[ "Recognition of specific cell surface glycans , mediated by the VP8* domain of the spike protein VP4 , is the essential first step in rotavirus ( RV ) infection .", "Due to lack of direct structural information of virus-ligand interactions , the molecular basis of ligand-controlled host ranges of the major human ...	[ "Rotaviruses ( RVs ) are diverse , infecting humans and/or animals .", "Significant advances in understanding ligand-associated RV host ranges have been made but how such host ligands drive RV evolution leading to the diverse genotypes/genogroups already identified remains unclear .", "In this study , through s...	2017
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "h7n9", "chemical characterization", "medicine and health sciences", "microbial mutation", "pathology and laboratory medicine", "pathogens", "microbiology", "vertebrates", "orthomyxoviruses", "animals", "viruses", "respiratory system", "h5n1", "rna viruses", "h1n1", "trachea", "resea...	Three mutations switch H7N9 influenza to human-type receptor specificity	journal.ppat.1006390	null	[ [ "The 2013 avian H7N9 virus outbreak in China was tied to human exposure to infected poultry in live bird markets [1] .", "Closure of the markets halted new human infections , but upon reopening , several additional outbreaks occurred; 779 human infections have been documented to date according to the WHO ...	[ "The avian H7N9 influenza outbreak in 2013 resulted from an unprecedented incidence of influenza transmission to humans from infected poultry .", "The majority of human H7N9 isolates contained a hemagglutinin ( HA ) mutation ( Q226L ) that has previously been associated with a switch in receptor specificity from ...	[ "Influenza A virus of the H7N9 subtype continues to cross the species barrier from poultry to humans .", "This zoonotic ability is remarkable as the virus retains specificity to avian-type receptors .", "To effectively transmit between humans , the virus needs to acquire human-type receptor specificity .", "I...	2017
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "sequence analysis", "bio-ontologies", "biology", "computational biology", "signaling networks" ]	Gene Network Homology in Prokaryotes Using a Similarity Search Approach: Queries of Quorum Sensing Signal Transduction	journal.pcbi.1002637	null	[ [ "Comparing prokaryotic whole genome sequences to identify operons is a mature area of research [1] , [2] , [3] , [4] .", "Orthologous operon identification can imply a secondary degree of relation between components , reaffirming Clusters of Orthologous Groups ( COG ) and other assignments of function as ...	[ "Bacterial cell-cell communication is mediated by small signaling molecules known as autoinducers .", "Importantly , autoinducer-2 ( AI-2 ) is synthesized via the enzyme LuxS in over 80 species , some of which mediate their pathogenicity by recognizing and transducing this signal in a cell density dependent manne...	[ "Bacteria communicate with each other through a network of small molecules that are secreted and perceived by nearest neighbors .", "In a process known as quorum sensing , bacteria communicate their cell density and certain behaviors emerge wherein the population of cells acts as a coordinated community .", "On...	2012
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "medicine and health sciences", "animal diseases", "enzymes", "enzymology", "vertebrates", "neuroscience", "animals", "mammals", "organisms", "animal prion diseases", "gel electrophoresis", "zoology", "neuronal dendrites", "research and analysis methods", "specimen preparation and treatm...	A Neuronal Culture System to Detect Prion Synaptotoxicity	journal.ppat.1005623	null	[ [ "Prion diseases are fatal neurodegenerative conditions of humans and animals that have significantly impacted public health and the safety of the food and blood supplies .", "These disorders are caused by infectious proteins called prions , which propagate themselves by a self-templating mechanism in whic...	[ "Synaptic pathology is an early feature of prion as well as other neurodegenerative diseases .", "Although the self-templating process by which prions propagate is well established , the mechanisms by which prions cause synaptotoxicity are poorly understood , due largely to the absence of experimentally tractable...	[ "Prion diseases are fatal neurodegenerative disorders that cause memory loss , impaired coordination , and abnormal movements .", "The molecular culprit in prion diseases is PrPSc , an infectious isoform of a host-encoded glycoprotein ( PrPC ) that can propagate itself by a self-templating mechanism .", "Whethe...	2016
[ "Introduction", "Material and methods", "Results", "Discussion" ]	[ "medicine and health sciences", "education", "sociology", "tropical diseases", "geographical locations", "social sciences", "indirect costs", "health care", "pediatrics", "neglected tropical diseases", "patients", "public and occupational health", "infectious diseases", "health economics",...	Household costs of hospitalized dengue illness in semi-rural Thailand	journal.pntd.0005961	null	[ [ "Dengue , an arbovirus infection with an explosive epidemic potential , is a major public health problem in many tropical and subtropical countries today [1] .", "The incidence of dengue has dramatically increased over the past decades , with the number of symptomatic dengue infections reported to be doub...	[ "Dengue-related illness is a leading cause of hospitalization and death in Thailand and other Southeast Asian countries , imposing a major economic burden on households , health systems , and governments .", "This study aims to assess the economic impact of hospitalized dengue cases on households in Chachoengsao ...	[ "Dengue , an arbovirus infection with an explosive epidemic potential , is a major public health problem in Thailand and other developing countries in subtropical and tropical regions .", "Dengue illness often leads to school and work absenteeism , medical and non-medical expenditures , and foregone income .", ...	2017
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "genome sequencing", "genomics", "metagenomics", "mathematics", "statistics", "biology", "computational biology", "biostatistics" ]	A Platform-Independent Method for Detecting Errors in Metagenomic Sequencing Data: DRISEE	journal.pcbi.1002541	null	[ [ "Accurate quantification of sequencing error is the single most essential consideration of sequence-dependent biological investigations .", "While true of all investigations that utilize sequencing data , this is particularly true with respect to metagenomics .", "Metagenomic studies produce biologica...	[ "We provide a novel method , DRISEE ( duplicate read inferred sequencing error estimation ) , to assess sequencing quality ( alternatively referred to as “noise” or “error” ) within and/or between sequencing samples .", "DRISEE provides positional error estimates that can be used to inform read trimming within a ...	[ "Sequence quality ( referred to alternatively as the level of sequencing error or noise ) is a primary concern to all sequence-dependent investigations .", "This is particularly true in the field of metagenomics where automated tools ( e . g . annotation pipelines like MG-RAST ) rely on high fidelity sequence dat...	2012
[ "Introduction", "Materials and methods", "Results", "Discussion" ]	[ "medicine and health sciences", "body fluids", "pathology and laboratory medicine", "respiratory infections", "pulmonology", "signs and symptoms", "fungal evolution", "bacteria", "clinical microbiology", "sputum", "mycology", "mucus", "clinical pathology", "lesions", "actinobacteria", ...	Predictive factors for a one-year improvement in nontuberculous mycobacterial pulmonary disease: An 11-year retrospective and multicenter study	journal.pntd.0005841	null	[ [ "Infection with nontuberculous mycobacteria ( NTM ) preferentially affects the lungs and occurs by inhalation of aerosols containing mycobacteria [1 , 2] .", "NTM are ubiquitous environmental bacteria found in soil , but also in other sources such as contaminated water taps .", "The frequency of NTM s...	[ "Nontuberculous mycobacterial pulmonary disease ( NTM-PD ) has become an emerging infectious disease and is responsible for more deaths than tuberculosis in industrialized countries .", "NTM-PD mortality remains high in some series reportedly ranging from 25% to 40% at five years and often due to unfavorable evol...	[ "Early predictive factors for a favorable development of nontuberculous mycobacterial pulmonary disease ( NTM-PD ) are important to improve management due to the high mortality of this infection at 5 years .", "The purpose of this study was to search for early factors that could predict at the first year , the fa...	2017
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "biotechnology", "plant anatomy", "rna interference", "protein interactions", "brassica", "plant physiology", "protein expression", "plant science", "model organisms", "genetically modified plants", "experimental organism systems", "molecular biology techniques", "epigenetics", "plants", ...	COP1, a negative regulator of photomorphogenesis, positively regulates plant disease resistance via double-stranded RNA binding proteins	journal.ppat.1006894	null	[ [ "Resistance ( R ) protein-mediated immunity is induced when a strain-specific avirulence ( avr ) protein from the pathogen associates with a cognate plant R protein [1] .", "Induction of R-mediated responses is often accompanied by the formation of a hypersensitive response ( HR ) , a form of programmed c...	[ "The E3 ubiquitin ligase COP1 ( Constitutive Photomorphogenesis 1 ) is a well known component of the light-mediated plant development that acts as a repressor of photomorphogenesis .", "Here we show that COP1 positively regulates defense against turnip crinkle virus ( TCV ) and avrRPM1 bacteria by contributing to...	[ "Plants must constantly regulate the allocation of resources between photomorphogenesis and defense signaling .", "Although light is known to influence plant defense , the underlying mechanisms remain largely unknown .", "Here we show that light plays specific and direct signaling roles in plant defense .", "...	2018
[ "Introduction", "Materials and methods", "Results", "Discussion" ]	[ "cell walls", "control theory", "engineering and technology", "plant cell biology", "cell processes", "plant cell walls", "control engineering", "viscosity", "plant science", "developmental biology", "systems science", "mathematics", "model organisms", "fungi", "materials science", "ex...	Mechanical feedback coordinates cell wall expansion and assembly in yeast mating morphogenesis	journal.pcbi.1005940	null	[ [ "From cell division to polarization and growth , cells constantly change their shapes to perform specific tasks [1–3] .", "These morphological changes are achieved through remodeling of the structures that mechanically sustain the cell , such as the cytoskeleton in animal cells and the cell wall in walled...	[ "The shaping of individual cells requires a tight coordination of cell mechanics and growth .", "However , it is unclear how information about the mechanical state of the wall is relayed to the molecular processes building it , thereby enabling the coordination of cell wall expansion and assembly during morphogen...	[ "All morphogenesis processes , whether at the cell scale or tissue level , require the coordination of growth and mechanics to properly shape functional structures .", "However , the mechanisms that coordinate these two processes in the sculpting of individual cells , and especially in walled cells , remain unkno...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	In Silico Molecular Comparisons of C. elegans and Mammalian Pharmacology Identify Distinct Targets That Regulate Feeding	journal.pbio.1001712	This paper takes advantage of similarities between the C. elegans and human pharmacopeia to identify and validate pharmacological targets that regulate C. elegans feeding rates.	[ [ "Before the molecular biology era , pharmacological targets were typically classified by the effects of organic molecules on whole tissues [1] .", "Many pathways were first recognized based on phenotypic responsiveness to compounds without knowledge of underlying molecular mechanisms .", "Examples inc...	[ "Phenotypic screens can identify molecules that are at once penetrant and active on the integrated circuitry of a whole cell or organism .", "These advantages are offset by the need to identify the targets underlying the phenotypes .", "Additionally , logistical considerations limit screening for certain physio...	[ "Many beneficial pharmacological interventions were first discovered by observing the effects of perturbation of intact biological systems by small organic molecules without a priori knowledge of their targets .", "This forward pharmacological approach has the advantage of directly identifying new pharmacological...	2013
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "organismal evolution", "medicine and health sciences", "microbial mutation", "immune physiology", "pathology and laboratory medicine", "influenza", "pathogens", "immunology", "microbiology", "orthomyxoviruses", "viruses", "mutation", "rna viruses", "microbial evolution", "antibodies", ...	Complete mapping of viral escape from neutralizing antibodies	journal.ppat.1006271	null	[ [ "Host immunity drives the evolution of many viruses .", "For instance , potent immunity against influenza virus is provided by antibodies against hemagglutinin ( HA ) , the virus’s most abundant surface protein [1] .", "Unfortunately , these antibodies also select amino-acid substitutions in the HA of...	[ "Identifying viral mutations that confer escape from antibodies is crucial for understanding the interplay between immunity and viral evolution .", "We describe a high-throughput approach to quantify the selection that monoclonal antibodies exert on all single amino-acid mutations to a viral protein .", "This a...	[ "Many viruses evolve rapidly , and this evolution sometimes enables them to escape antibodies that would otherwise neutralize their infectivity .", "An important aspect of studying this evolution is determining which viral mutations can mediate antibody escape .", "The classic way of identifying such mutations ...	2017
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "medicine", "public health and epidemiology", "neurocysticercosis", "parasitic diseases", "neglected tropical diseases", "veterinary science", "infectious diseases", "infectious diseases of the nervous system", "epilepsy", "zoonoses", "veterinary diseases", "zoonotic diseases", "epidemiology...	Prevalence and Risk Factors Associated with Human Taenia Solium Infections in Mbozi District, Mbeya Region, Tanzania	journal.pntd.0002102	null	[ [ "Taeniosis and cysticercosis are different stages of Taenia solium infection involving swine as intermediate hosts and humans as definitive and/or intermediate hosts .", "Taeniosis is the intestinal infection with the adult cestode in humans and is caused by consumption of raw or undercooked pork containi...	[ "Taenia solium cysticercosis/taeniosis is emerging as a serious public health and economic problem in many developing countries .", "This study was conducted to determine prevalence and risk factors of human T . solium infections in Mbeya Region , Tanzania .", "A cross-sectional survey was conducted in 13 villa...	[ "Cysticercosis caused by the zoonotic pork tapeworm , Taenia solium , is emerging as a serious public health and agricultural problem in sub-Saharan Africa .", "Surveys have shown cysticercosis in pigs to be highly prevalent in multiple foci in Tanzania , and a hospital-based study in the northern highlands indic...	2013
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "carbohydrate metabolism", "ecology and environmental sciences", "chemical compounds", "atmospheric science", "carbohydrates", "glucose metabolism", "organic compounds", "glucose", "monomers (chemistry)", "metabolites", "thermodynamics", "polymer chemistry", "proteins", "carboxylation", ...	OptMDFpathway: Identification of metabolic pathways with maximal thermodynamic driving force and its application for analyzing the endogenous CO2 fixation potential of Escherichia coli	journal.pcbi.1006492	null	[ [ "The reconstruction of organism-specific genome-scale metabolic models and their in silico analysis by techniques of constraint-based modeling has become a key to understand structure , function , and capabilities of metabolic networks [1–3] .", "Applications include the calculation of optimal flux distri...	[ "Constraint-based modeling techniques have become a standard tool for the in silico analysis of metabolic networks .", "To further improve their accuracy , recent methodological developments focused on integration of thermodynamic information in metabolic models to assess the feasibility of flux distributions by ...	[ "When analyzing metabolic networks , one often searches for metabolic pathways with certain ( desired ) properties , for example , conversion routes that maximize the yield of a product from a given substrate .", "While those problems can be solved with established methods of constraint-based modeling , no algori...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genetics and genomics/animal genetics", "cell biology/membranes and sorting", "genetics and genomics/disease models", "ophthalmology/inherited eye disorders", "ophthalmology/glaucoma" ]	Elevated Oxidative Membrane Damage Associated with Genetic Modifiers of Lyst-Mutant Phenotypes	journal.pgen.1001008	null	[ [ "LYST is a large cytoplasmic protein that influences several traits relevant to human health and disease [1] .", "Mutations in the encoding gene , LYST , can cause Chediak-Higashi syndrome , a rare , autosomal recessive disorder characterized by variable degrees of oculocutaneous albinism , immunodeficien...	[ "LYST is a large cytosolic protein that influences the biogenesis of lysosome-related organelles , and mutation of the encoding gene , LYST , can cause Chediak-Higashi syndrome .", "Recently , Lyst-mutant mice were recognized to also exhibit an iris disease resembling exfoliation syndrome , a common cause of glau...	[ "LYST is a poorly understood protein involved in hereditary disease .", "Mutations in the encoding gene cause Chediak-Higashi syndrome , a rare lethal disease affecting multiple tissues of the body .", "Mutations in Lyst also recapitulate features of exfoliation syndrome , a common disease affecting the anterio...	2010
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine", "control theory", "functional genomics", "applied mathematics", "population genetics", "genome sequencing", "mutation", "systems ecology", "mathematics", "theoretical ecology", "infectious diseases", "biology", "evolutionary theory", "nonlinear dynamics", "infectious disease ...	When the Most Potent Combination of Antibiotics Selects for the Greatest Bacterial Load: The Smile-Frown Transition	journal.pbio.1001540	Finding the most potent combinations of antibiotics in the lab can be a challenge if antibiotic interactions are not robust to evolutionary adaptation.	[ [ "Our arsenal of antimicrobials boasts a wide diversity of drugs and we continue to invest in the search for new ones [1] .", "Yet bacteria adapt so readily to their ambient environment that all antibiotics in clinical use have bacteria that resist them [2] , [3] .", "A Staphylococcus aureus infection ...	[ "Conventional wisdom holds that the best way to treat infection with antibiotics is to ‘hit early and hit hard’ .", "A favoured strategy is to deploy two antibiotics that produce a stronger effect in combination than if either drug were used alone .", "But are such synergistic combinations necessarily optimal ?...	[ "We take an evolutionary approach to a problem from the medical sciences in seeking to understand how our knowledge of rapid bacterial evolution should shape the way we treat pathogens with antibiotic drugs .", "We pay particular attention to combinations of different drugs that are purposefully used to produce p...	2013
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "medicine and health sciences", "science policy", "biology and life sciences", "social sciences", "veterinary science" ]	Eliminating Rabies in Tanzania? Local Understandings and Responses to Mass Dog Vaccination in Kilombero and Ulanga Districts	journal.pntd.0002935	null	[ [ "Rabies has been known since antiquity as one of the most feared human diseases [1]–[3] .", "Today , it remains a significant albeit neglected disease , causing some 55 , 000 deaths each year , predominately among children and the rural poor in Asia and Africa [4]–[6] .", "Transmitted by saliva from t...	[ "With increased global attention to neglected diseases , there has been a resurgence of interest in eliminating rabies from developing countries through mass dog vaccination .", "Tanzania recently embarked on an ambitious programme to repeatedly vaccinate dogs in 28 districts .", "To understand community percep...	[ "Mass vaccination of dogs is the most effective strategy to eliminate dog-mediated human rabies from developing countries .", "In 2009 , a large-scale elimination demonstration project was funded and coordinated by the Bill and Melinda Gates Foundation ( BMGF ) and the World Health Organisation ( WHO ) in three s...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "microbiology/parasitology", "microbiology/medical microbiology", "microbiology" ]	Alternative Sigma Factor σH Modulates Prophage Integration and Excision in Staphylococcus aureus	journal.ppat.1000888	null	[ [ "Prophages are viral cellular parasites that integrate into bacterial genomes and co-replicate with host chromosomes .", "A subset of bacteriophage genomes encodes additional virulence factors , and the production of these virulence factors can enhance bacterial toxicity as well as survival ability in var...	[ "The prophage is one of the most important components of variable regions in bacterial genomes .", "Some prophages carry additional genes that may enhance the toxicity and survival ability of their host bacteria .", "This phenomenon is predominant in Staphylococcus aureus , a very common human pathogen .", "B...	[ "Staphylococcus aureus is a widely distributed opportunistic pathogen causing numerous foreign-body-associated infections .", "A large group of virulence factors are encoded by genes of prophages integrated in the bacterial genome .", "Here we show a heretofore unrecognized mechanism whereby an alternative sigm...	2010
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine", "nutrition", "endocrinology", "vitamins", "diabetes and endocrinology", "endocrine physiology" ]	The Abnormal Phenotypes of Cartilage and Bone in Calcium-Sensing Receptor Deficient Mice Are Dependent on the Actions of Calcium, Phosphorus, and PTH	journal.pgen.1002294	null	[ [ "The extracellular calcium-sensing receptor ( CaR ) is a G protein-coupled receptor that plays an essential role in the regulation of extracellular calcium homeostasis .", "This receptor is expressed in nearly all tissues [1] .", "Cloning of the CaR was immediately followed by the association of human...	[ "Patients with neonatal severe hyperparathyroidism ( NSHPT ) are homozygous for the calcium-sensing receptor ( CaR ) mutation and have very high circulating PTH , abundant parathyroid hyperplasia , and severe life-threatening hypercalcemia .", "Mice with homozygous deletion of CaR mimic the syndrome of NSHPT .", ...	[ "Mice with homozygous deletion of the calcium-sensing receptor ( CaR ) mimic the syndrome of neonatal severe hyperparathyroidism ( NSHPT ) in humans with very high circulating parathyroid hormone ( PTH ) and severe life-threatening hypercalcemia .", "To determine effects of CaR deficiency on skeletal development ...	2011
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "model organisms", "genetics", "biology", "molecular cell biology", "genetics and genomics" ]	Coordination of Chromatid Separation and Spindle Elongation by Antagonistic Activities of Mitotic and S-Phase CDKs	journal.pgen.1003319	null	[ [ "In eukaryotic cells , spindle elongation and sister-chromatid separation are two critical mitotic events , and the coordination of these two events is essential for the fidelity of chromosome segregation .", "During mitosis , the cleavage of sister chromatid cohesion allows the sister chromatids to move ...	[ "Because cohesion prevents sister-chromatid separation and spindle elongation , cohesion dissolution may trigger these two events simultaneously .", "However , the relatively normal spindle elongation kinetics in yeast cohesin mutants indicates an additional mechanism for the temporal control of spindle elongatio...	[ "Before anaphase onset , the presence of securin Pds1 prevents the cleavage of cohesin , a protein complex that holds sister chromatids together , but the degradation of Pds1 leads to robust cohesion dissolution , resulting in synchronous separation of all chromosomes .", "Since sister chromatids are attached to ...	2013
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "chemical compounds", "oxides", "electron donors", "cell cycle and cell division", "cell processes", "dna transcription", "fungi", "model organisms", "dna replication", "experimental organism systems", "dna", "synthesis phase", "schizosaccharomyces", "research and analysis methods", "gen...	Lack of a peroxiredoxin suppresses the lethality of cells devoid of electron donors by channelling electrons to oxidized ribonucleotide reductase	journal.pgen.1006858	null	[ [ "Cysteine residues are not very abundant in proteins , but they are over-represented in functional regions of proteins , such as surfaces and catalytic centers [1] .", "The thiol group of cysteines is subject of post-translational modifications altering its redox state; several of these oxidation states a...	[ "The thioredoxin and glutaredoxin pathways are responsible of recycling several enzymes which undergo intramolecular disulfide bond formation as part of their catalytic cycles such as the peroxide scavengers peroxiredoxins or the enzyme ribonucleotide reductase ( RNR ) .", "RNR , the rate-limiting enzyme of deoxy...	[ "The essential enzyme ribonucleotide reductase ( RNR ) , the rate-limiting enzyme of deoxyribonucleotide synthesis , relies on the thioredoxin and glutaredoxin electron flow cascades for recycling .", "RNR is tightly regulated in a cell cycle-dependent manner at different levels .", "Here , we show that cytosol...	2017
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "physics", "mathematics", "theoretical biology", "computational neuroscience", "interdisciplinary physics", "signal processing", "applied mathematics", "biology", "computational biology", "sensory systems", "biophysics", "neuroscience", "neuroimaging", "engineering" ]	Hemodynamic Traveling Waves in Human Visual Cortex	journal.pcbi.1002435	null	[ [ "Functional magnetic resonance imaging ( fMRI ) experiments have substantially advanced our understanding of the structure and function of the human brain [1] .", "Hemodynamic responses to neuronal activity are observed experimentally in fMRI data via the blood oxygenation dependent ( BOLD ) signal , whic...	[ "Functional MRI ( fMRI ) experiments rely on precise characterization of the blood oxygen level dependent ( BOLD ) signal .", "As the spatial resolution of fMRI reaches the sub-millimeter range , the need for quantitative modelling of spatiotemporal properties of this hemodynamic signal has become pressing .", ...	[ "Functional magnetic resonance imaging ( fMRI ) experiments have advanced our understanding of the structure and function of the human brain .", "Dynamic changes in the flow and concentration of oxygen in blood are observed experimentally in fMRI data via the blood oxygen level dependent ( BOLD ) signal .", "Si...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "blood cells", "innate immune system", "medicine and health sciences", "immune cells", "immune physiology", "cytokines", "antiviral therapy", "immune activation", "immunology", "microbiology", "preventive medicine", "developmental biology", "antiretroviral therapy", "molecular development"...	Multi-dose Romidepsin Reactivates Replication Competent SIV in Post-antiretroviral Rhesus Macaque Controllers	journal.ppat.1005879	null	[ [ "Viral reservoirs are infected cells that persist even in the face of seemingly effective suppressive antiretroviral therapy ( ART ) and can give rise to recrudescent infection when ART is stopped .", "Reservoir cells include latently infected resting , memory CD4+ T cells , as well as other cells , such ...	[ "Viruses that persist despite seemingly effective antiretroviral treatment ( ART ) and can reinitiate infection if treatment is stopped preclude definitive treatment of HIV-1 infected individuals , requiring lifelong ART .", "Among strategies proposed for targeting these viral reservoirs , the premise of the “sho...	[ "Antiretroviral therapy ( ART ) does not eradicate HIV-1 in infected individuals due to virus persistence in latently infected reservoir cells , despite apparently effective ART .", "The persistent virus and can rekindle infection when ART is interrupted .", "The goal of the “shock and kill” viral clearance str...	2016
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "veterinary immunology", "veterinary diseases", "zoonoses", "medicine and health sciences", "epidemiology", "african trypanosomiasis", "vector biology", "immunoassays", "biology and life sciences", "immunologic techniques", "trypanosomiasis", "disease vectors", "veterinary science", "veter...	Serological Responses and Biomarker Evaluation in Mice and Pigs Exposed to Tsetse Fly Bites	journal.pntd.0002911	null	[ [ "Tsetse flies ( Glossina spp . ) are notorious transmitters of trypanosome parasites responsible for Human and Animal African Trypanosomiasis ( HAT and AAT ) .", "Since 2009 , the annual number of reported cases of HAT has dropped below 10000 ( www . who . int; [1] ) with the prospect and challenge of ent...	[ "Tsetse flies are obligate blood-feeding insects that transmit African trypanosomes responsible for human sleeping sickness and nagana in livestock .", "The tsetse salivary proteome contains a highly immunogenic family of the endonuclease-like Tsal proteins .", "In this study , a recombinant version of Tsal1 ( ...	[ "Salivary proteins of hematophagous disease vectors represent potential biomarkers of exposure and could be used in serological assays that are complementary to entomological surveys .", "We illustrate that a recombinant version of the highly immunogenic Tsal1 protein of the savannah tsetse fly ( Glossina morsita...	2014
[ "Introduction", "Materials and Methods", "Results/Discussion" ]	[ "molecular biology/bioinformatics", "infectious diseases/helminth infections", "molecular biology/molecular evolution", "infectious diseases/neglected tropical diseases" ]	Tissue Specific Profiling of Females of Schistosoma japonicum by Integrated Laser Microdissection Microscopy and Microarray Analysis	journal.pntd.0000469	null	[ [ "Members of the genus Schistosoma are parasitic blood flukes responsible for the serious but neglected human disease of schistosomiasis [1] , [2] .", "In common with other platyhelminths , schistosomes exhibit acoelomy , the body plan characteristic of basal bilaterians whereby tissues are bound together ...	[ "The functions of many schistosome gene products remain to be characterized .", "A major step towards elucidating function of these genes would be in defining their sites of expression .", "This goal is rendered difficult to achieve by the generally small size of the parasites and the lack of a body cavity , wh...	[ "Schistosomes are parasitic worms responsible for important human diseases in tropical and developing nations .", "There is urgent need to develop new drugs and vaccines to augment current treatments for this disease .", "In recent years , concerted efforts by many laboratories have led to extensive genetic seq...	2009
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Intracellular Survival of Leishmania major Depends on Uptake and Degradation of Extracellular Matrix Glycosaminoglycans by Macrophages	journal.ppat.1005136	null	[ [ "Protozoan parasites , belonging to the genus Leishmania , cause a number of important diseases in humans , that affect over 12 million people worldwide with more than 2 million new infections each year [1] .", "Clinical disease ranges from self-healing cutaneous lesions to visceral leishmaniasis , which ...	[ "Leishmania parasites replicate within the phagolysosome compartment of mammalian macrophages .", "Although Leishmania depend on sugars as a major carbon source during infections , the nutrient composition of the phagolysosome remains poorly described .", "To determine the origin of the sugar carbon source in m...	[ "Macrophages are the primary host cells for a number of important microbial pathogens , including protozoan parasites belonging to the genus Leishmania .", "With few exceptions , little is known about the nutrient composition of the vacuolar compartments occupied by these pathogens .", "Leishmania proliferate w...	2015
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "zoology", "biochemistry", "immunology", "biology" ]	Venom of the Brazilian Spider Sicarius ornatus (Araneae, Sicariidae) Contains Active Sphingomyelinase D: Potential for Toxicity after Envenomation	journal.pntd.0002394	null	[ [ "The spider family Sicariidae includes two genera , Sicarius and Loxosceles .", "Sicarius species ( six-eyed crab spiders , six-eyed sand spiders ) live in dry forests and deserts throughout Southern Africa , South America and Central America .", "The genus Sicarius is composed of robust flattened spi...	[ "The spider family Sicariidae includes two genera , Sicarius and Loxosceles .", "Bites by Sicarius are uncommon in humans and , in Brazil , a single report is known of a 17-year old man bitten by a Sicarius species that developed a necrotic lesion similar to that caused by Loxosceles .", "Envenomation by Loxosc...	[ "The spider family Sicariidae includes two genera , Sicarius and Loxosceles .", "These spiders' venoms share a common characteristic , i . e . , the presence of Sphingomyelinases D ( SMase D ) .", "This toxin is the main component responsible for the local and systemic effects observed in loxoscelism .", "In ...	2013
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "invertebrates", "medicine and health sciences", "plagues", "ecology and environmental sciences", "pathology and laboratory medicine", "pathogens", "geographical locations", "microbiology", "vertebrates", "animals", "bacterial diseases", "yersinia", "habitats", "fleas", "bacteria", "ba...	The Fleas (Siphonaptera) in Iran: Diversity, Host Range, and Medical Importance	journal.pntd.0005260	null	[ [ "Vector-borne diseases ( VBDs ) are globally responsible for more than 17% of all infectious diseases [1] .", "There are a large number of viral , rickettsial , bacterial and parasitic diseases that are transmitted by insect vectors [2] .", "In the last two decades , many zoonotic VBDs have emerged in...	[ "Flea-borne diseases have a wide distribution in the world .", "Studies on the identity , abundance , distribution and seasonality of the potential vectors of pathogenic agents ( e . g . Yersinia pestis , Francisella tularensis , and Rickettsia felis ) are necessary tools for controlling and preventing such disea...	[ "The data about flea-borne emerging or re-emerging infections throughout Iran are limited .", "This paper showed that the flea fauna of Iran were dominated by seven families .", "Moreover flea-host association analysis indicates that rodents are common hosts of flea families and most vertebrates hosted fleas be...	2017
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "genetic networks", "chemical compounds", "gene regulation", "enzymes", "enzymology", "neuroscience", "organic compounds", "learning and memory", "cognition", "network analysis", "memory", "alcohols", "computer and information sciences", "proteins", "gene expression", "chemistry", "e...	A systems level approach to temporal expression dynamics in Drosophila reveals clusters of long term memory genes	journal.pgen.1007054	null	[ [ "The ability to form a memory is one of the hallmarks of the advanced nervous system .", "This capacity to learn from , and remember , past experiences is a critical attribute to many eukaryotes .", "It is this function that allows organisms to meet the various demands and challenges of a changing and...	[ "The ability to integrate experiential information and recall it in the form of memory is observed in a wide range of taxa , and is a hallmark of highly derived nervous systems .", "Storage of past experiences is critical for adaptive behaviors that anticipate both adverse and positive environmental factors .", ...	[ "Long term memory formation is a complex process , and at different stages , requires regulation of transcription and protein synthesis .", "In a novel learning and memory paradigm , we examined transcriptional changes in the fly brain during and after memory formation .", "With RNA sequencing , we captured tra...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "immunopathology", "virology", "immunology", "biology", "microbiology", "host-pathogen interaction", "immune response", "pathogenesis" ]	Increased CD8+ T Cell Response to Epstein-Barr Virus Lytic Antigens in the Active Phase of Multiple Sclerosis	journal.ppat.1003220	null	[ [ "Multiple sclerosis ( MS ) is the most common chronic inflammatory disease of the central nervous system ( CNS ) causing demyelination , neurodegeneration and disability .", "In most cases , MS is characterized by a relapsing-remitting course at onset which eventually develops into a progressive form; mor...	[ "It has long been known that multiple sclerosis ( MS ) is associated with an increased Epstein-Barr virus ( EBV ) seroprevalence and high immune reactivity to EBV and that infectious mononucleosis increases MS risk .", "This evidence led to postulate that EBV infection plays a role in MS etiopathogenesis , althou...	[ "There is general consensus that multiple sclerosis ( MS ) is associated with Epstein-Barr virus ( EBV ) infection but the mechanistic links are still debated .", "EBV is a B-lymphotropic herpesvirus widespread in the human population and normally contained as a persistent , asymptomatic infection by immune surve...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine and health sciences", "neurogenesis", "microcephaly", "neuroscience", "animal models", "developmental biology", "model organisms", "genome analysis", "morphogenesis", "cellular structures and organelles", "research and analysis methods", "developmental neuroscience", "genomics", ...	Haploinsufficiency for Core Exon Junction Complex Components Disrupts Embryonic Neurogenesis and Causes p53-Mediated Microcephaly	journal.pgen.1006282	null	[ [ "Proper function of the cerebral cortex , our brain structure responsible for higher cognitive functions , relies upon embryonic neurogenesis .", "During neurogenesis , neural stem cells ( NSCs ) generate excitatory neurons [1 , 2] .", "In mice the onset of neurogenesis is embryonic day ( E ) 10 . 5 ,...	[ "The exon junction complex ( EJC ) is an RNA binding complex comprised of the core components Magoh , Rbm8a , and Eif4a3 .", "Human mutations in EJC components cause neurodevelopmental pathologies .", "Further , mice heterozygous for either Magoh or Rbm8a exhibit aberrant neurogenesis and microcephaly .", "Ye...	[ "The mammalian neocortex is the brain structure responsible for higher cognition , abstract thought , and language .", "One process critical for brain development is neurogenesis , in which neural stem cell populations generate neurons .", "Alterations in neurogenesis can lead to neurodevelopmental disorders af...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine and health sciences", "bipolar disorder", "social sciences", "autism", "developmental psychology", "neuroscience", "diabetes mellitus", "endocrine disorders", "autism spectrum disorder", "mood disorders", "alcoholism", "public and occupational health", "developmental neuroscience",...	Constraints on Biological Mechanism from Disease Comorbidity Using Electronic Medical Records and Database of Genetic Variants	journal.pcbi.1004885	null	[ [ "When two diseases occur together in the same individuals more or less often than would be expected by chance , this may signal the operation of important biological processes .", "Pairs of diseases occurring more than expected are called synergistic; such interactions are familiar from clinical practice ...	[ "Patterns of disease co-occurrence that deviate from statistical independence may represent important constraints on biological mechanism , which sometimes can be explained by shared genetics .", "In this work we study the relationship between disease co-occurrence and commonly shared genetic architecture of dise...	[ "Diseases do not always occur together at random , and patterns of disease association may reflect important biological constraints on disease mechanism .", "When a disease pair occurs more ( or less ) often than would be expected by chance given the frequencies of each disease separately , that may signal the pr...	2016
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "mycobacterium leprae", "medicine and health sciences", "pathology and laboratory medicine", "nervous system", "tropical diseases", "geographical locations", "bacterial diseases", "signs and symptoms", "neglected tropical diseases", "molecular biology techniques", "bacteria", "extraction techn...	Evaluation of Polymerase Chain Reaction (PCR) with Slit Skin Smear Examination (SSS) to Confirm Clinical Diagnosis of Leprosy in Eastern Nepal	journal.pntd.0005220	null	[ [ "Leprosy is a chronic infectious disease which mainly affects the skin , nasal mucosa , and peripheral nerve .", "It is caused by Mycobacterium leprae , an acid-fast bacillus which is transmitted via droplets from the nose and mouth during close contacts with untreated cases [1] .", "It eventually lea...	[ "Detection of Mycobacterium leprae in slit skin smear ( SSS ) is a gold standard technique for the leprosy diagnosis .", "Over recent years , molecular diagnosis by using PCR has been increasingly used as an alternative for its diagnosis due to its higher sensitivity .", "This study was carried out for comparat...	[ "Although leprosy has been eliminated at the national level , but region wise eastern Nepal has still the higher number of leprosy cases .", "Early diagnosis and then timely treatment is very crucial to prevent disabilities due to leprosy .", "Slit-skin smear ( SSS ) , the routine diagnostic method was compared...	2016
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "medicine and health sciences", "engineering and technology", "nervous system", "information processing", "electrical circuits", "population dynamics", "membrane potential", "electrophysiology", "neuroscience", "learning and memory", "cognition", "memory", "population biology", "informatio...	Leveraging heterogeneity for neural computation with fading memory in layer 2/3 cortical microcircuits	journal.pcbi.1006781	null	[ [ "On a macroscopic level , hierarchical modularity is easily identifiable as a parsimonious design principle underlying various structural and functional aspects of cortical organization [19–23] .", "Different anatomophysiological [24 , 25] , genetic / biochemical [26–30] or functional [31–33] criteria giv...	[ "Complexity and heterogeneity are intrinsic to neurobiological systems , manifest in every process , at every scale , and are inextricably linked to the systems’ emergent collective behaviours and function .", "However , the majority of studies addressing the dynamics and computational properties of biologically ...	[ "Cortical microcircuits are highly inhomogeneous dynamical systems whose information processing capacity is determined by the characteristics of its heterogeneous components and their complex interactions .", "The high degree of variability that characterizes macroscopic population dynamics , both during ongoing ...	2019
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "cell biology/plant genetics and gene expression", "cell biology/cell growth and division", "marine and aquatic sciences/genetics, genomics, and barcoding", "cell biology/cell signaling" ]	Integration of Light Signals by the Retinoblastoma Pathway in the Control of S Phase Entry in the Picophytoplanktonic Cell Ostreococcus	journal.pgen.1000957	null	[ [ "The cell division cycle ( CDC ) is a highly conserved and regulated process , which controls the proliferation of unicellular organisms and development and tissue renewal in multicellular organisms .", "In eukaryotes the main steps of CDC progression are controlled by Cyclin Dependent Kinases ( CDKs ) ."...	[ "Although the decision to proceed through cell division depends largely on the metabolic status or the size of the cell , the timing of cell division is often set by internal clocks such as the circadian clock .", "Light is a major cue for circadian clock entrainment , and for photosynthetic organisms it is also ...	[ "Microalgae from phytoplankton play an essential role in the biogeochemical cycles through carbon dioxide assimilation in the oceans where they account for more than half of organic carbon production .", "Photosynthetic cells use light energy for cell growth , but light can also reset the circadian clock , which ...	2010
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "physics", "neural networks", "computational neuroscience", "biology", "computational biology", "neuroscience" ]	The Correlation Structure of Local Neuronal Networks Intrinsically Results from Recurrent Dynamics	journal.pcbi.1003428	null	[ [ "The spatio-temporal structure and magnitude of correlations in cortical neural activity have been subject of research for a variety of reasons: the experimentally observed task-dependent modulation of correlations points at a potential functional role .", "In the motor cortex of behaving monkeys , for ex...	[ "Correlated neuronal activity is a natural consequence of network connectivity and shared inputs to pairs of neurons , but the task-dependent modulation of correlations in relation to behavior also hints at a functional role .", "Correlations influence the gain of postsynaptic neurons , the amount of information ...	[ "The co-occurrence of action potentials of pairs of neurons within short time intervals has been known for a long time .", "Such synchronous events can appear time-locked to the behavior of an animal , and also theoretical considerations argue for a functional role of synchrony .", "Early theoretical work tried...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "bacteriology", "medicine and health sciences", "pathology and laboratory medicine", "host-pathogen interactions", "medical microbiology", "microbial pathogens", "biology and life sciences", "microbiology", "pathogenesis", "bacterial pathogens" ]	A Screen of Coxiella burnetii Mutants Reveals Important Roles for Dot/Icm Effectors and Host Autophagy in Vacuole Biogenesis	journal.ppat.1004286	null	[ [ "Coxiella burnetii is a highly infectious human pathogen responsible for a global zoonotic disease called Q fever .", "Inhalation of contaminated aerosols by humans can lead to an acute systemic illness or a more serious chronic infection that commonly presents as endocarditis [1] , [2] .", "The anima...	[ "Coxiella burnetii is an intracellular pathogen that replicates in a lysosome-derived vacuole .", "The molecular mechanisms used by this bacterium to create a pathogen-occupied vacuole remain largely unknown .", "Here , we conducted a visual screen on an arrayed library of C . burnetii NMII transposon insertion...	[ "Coxiella burnetii is the causative agent of the human disease Q fever .", "This bacterium uses the Dot/Icm type IV secretion system to deliver effectors into the cytosol of host cells .", "The Dot/Icm system is required for intracellular replication of C . burnetii .", "To determine the contribution of indiv...	2014
[ "Introduction", "Discussion" ]	[]	An Integrated Framework Advancing Membrane Protein Modeling and Design	journal.pcbi.1004398	null	[ [ "Membrane proteins are critical participants in a wide variety of biological processes including cell adhesion , signaling , transport , and enzymatic activity [1] .", "They comprise more than 30% of open reading frames [2] and are targeted by over half of currently available pharmaceutical drugs [3 , 4] ...	[ "Membrane proteins are critical functional molecules in the human body , constituting more than 30% of open reading frames in the human genome .", "Unfortunately , a myriad of difficulties in overexpression and reconstitution into membrane mimetics severely limit our ability to determine their structures .", "C...	[ "Over 30% of the human proteome consists of proteins embedded in biological membranes .", "These proteins are critical in many processes such as transport of materials in and out of the cell and transmitting signals to other cells in the body .", "They are implicated in a large number of diseases; in fact , the...	2015
[ "Introduction", "Model", "Results", "Discussion" ]	[ "oncology", "medicine", "cancer detection and diagnosis", "stochastic processes", "mathematics", "cancer prevention", "cancers and neoplasms", "probability theory" ]	Number and Size Distribution of Colorectal Adenomas under the Multistage Clonal Expansion Model of Cancer	journal.pcbi.1002213	null	[ [ "Adenomatous polyps ( or adenomas ) in the large intestine are considered benign precursors of colorectal cancer ( CRC ) and both clinical and molecular evidence suggest that they may sojourn for many years before turning into cancer [1] , [2] .", "For this reason , adenomas are considered a primary inter...	[ "Colorectal cancer ( CRC ) is believed to arise from mutant stem cells in colonic crypts that undergo a well-characterized progression involving benign adenoma , the precursor to invasive carcinoma .", "Although a number of ( epi ) genetic events have been identified as drivers of this process , little is known a...	[ "The adenomatous polyp ( or adenoma ) is considered the common precursor lesion for colorectal cancer ( CRC ) .", "Although the natural history of adenomas is well-characterized in terms of their histopathology and ( epi ) genomic changes , little is known about their dynamics in the stage-wise progression from t...	2011
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine", "biology" ]	Relative Contribution of Th1 and Th17 Cells in Adaptive Immunity to Bordetella pertussis: Towards the Rational Design of an Improved Acellular Pertussis Vaccine	journal.ppat.1003264	null	[ [ "Bordetella pertussis is a Gram-negative bacterium that causes whooping cough ( pertussis ) , a severe respiratory tract infection that kills almost 200 , 000 children annually worldwide .", "Whole cell vaccines ( Pw ) introduced in the 1950s significantly reduced the incidence of pertussis but were assoc...	[ "Whooping cough caused by Bordetella pertussis is a re-emerging infectious disease despite the introduction of safer acellular pertussis vaccines ( Pa ) .", "One explanation for this is that Pa are less protective than the more reactogenic whole cell pertussis vaccines ( Pw ) that they replaced .", "Although Pa...	[ "The bacterium Bordetella pertussis causes whooping cough , a severe and often lethal respiratory infection in humans .", "The disease was largely controlled through vaccination with whole cell pertussis vaccines ( Pw ) .", "However , Pw had side effects and were replaced in developed countries in the 1990s wit...	2013
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "linguistics", "psychology", "biology and life sciences", "social sciences", "speech" ]	No, There Is No 150 ms Lead of Visual Speech on Auditory Speech, but a Range of Audiovisual Asynchronies Varying from Small Audio Lead to Large Audio Lag	journal.pcbi.1003743	null	[ [ "Sensory processing has long been conceived as modular and hierarchic , beginning by monosensory cue extraction in the primary sensory cortices before higher level multisensory interactions took place in associative areas , preparing the route for final decision and adequate behavioral answer .", "However...	[ "An increasing number of neuroscience papers capitalize on the assumption published in this journal that visual speech would be typically 150 ms ahead of auditory speech .", "It happens that the estimation of audiovisual asynchrony in the reference paper is valid only in very specific cases , for isolated consona...	[ "Since a paper was published in this journal , an increasing number of neuroscience papers capitalize on the assumption that visual speech would be typically 150 ms ahead of auditory speech .", "It happens that the estimation of audiovisual asynchrony in the mentioned paper is valid only in very specific cases , ...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine", "urology", "developmental biology", "model organisms", "biology" ]	An Essential Role for Katanin p80 and Microtubule Severing in Male Gamete Production	journal.pgen.1002698	null	[ [ "The regulation of microtubule dynamics is an essential requirement for all cells and in many aspects of their daily function .", "The ability to precisely regulate microtubule number , the assembly of networks , and the rate of microtubule assembly and disassembly underpins cellular processes including d...	[ "Katanin is an evolutionarily conserved microtubule-severing complex implicated in multiple aspects of microtubule dynamics .", "Katanin consists of a p60 severing enzyme and a p80 regulatory subunit .", "The p80 subunit is thought to regulate complex targeting and severing activity , but its precise role remai...	[ "Microtubules are critical components of cells , acting as a “scaffold” for the movement of organelles and proteins within the cytoplasm .", "The control of microtubule length , number , and movement is essential for many cellular processes , including division , architecture , and migration .", "We have define...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "developmental biology", "medicine and health sciences", "genomics", "hematopoiesis", "gene regulatory networks", "molecular development", "gene expression", "genetics", "biology and life sciences", "computational biology", "anemia", "hematology", "cell differentiation" ]	Altered Chromatin Occupancy of Master Regulators Underlies Evolutionary Divergence in the Transcriptional Landscape of Erythroid Differentiation	journal.pgen.1004890	null	[ [ "Red blood cell ( RBC ) production ( erythropoiesis ) is one of the best understood examples of lineage commitment and cellular differentiation [1]–[4] .", "This process begins as multipotent hematopoietic stem cells ( HSCs ) differentiate into lineage committed erythroid progenitors , losing multipotency...	[ "Erythropoiesis is one of the best understood examples of cellular differentiation .", "Morphologically , erythroid differentiation proceeds in a nearly identical fashion between humans and mice , but recent evidence has shown that networks of gene expression governing this process are divergent between species ....	[ "The process whereby blood progenitor cells differentiate into red blood cells , known as erythropoiesis , is very similar between mice and humans .", "Yet , while studies of this process in mouse have substantially improved our knowledge of human erythropoiesis , recent work has shown a significant divergence in...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods", "Supporting Information" ]	[ "neuroscience", "computational biology" ]	Omnidirectional Sensory and Motor Volumes in Electric Fish	journal.pbio.0050301	Most animals have sensory and motor capabilities that are biased in the forward direction. The black ghost, a nocturnal weakly electric fish, is an exception to this general rule. We demonstrate that these fish have omnidirectional sensing and motor capabilities.	[ [ "The motor volume is the swept volume of positions a body occupies for a given trajectory or set of trajectories .", "It is a function of the way the body moves , as well as the geometric extent of the body .", "To define it more clearly , we first present a definition of the time-limited reachable se...	[ "Active sensing organisms , such as bats , dolphins , and weakly electric fish , generate a 3-D space for active sensation by emitting self-generated energy into the environment .", "For a weakly electric fish , we demonstrate that the electrosensory space for prey detection has an unusual , omnidirectional shape...	[ "Most animals , including humans , have sensory and motor capabilities that are biased in the forward direction .", "The black ghost knifefish , a nocturnal , weakly electric fish from the Amazon , is an interesting exception to this general rule .", "We demonstrate that these fish have sensing and motor capabi...	2007
[ "Introduction" ]	[ "biophysics/macromolecular assemblies and machines", "biophysics/theory and simulation" ]	Global Motions of the Nuclear Pore Complex: Insights from Elastic Network Models	journal.pcbi.1000496	null	[ [ "Any macromolecule entering or exiting the nucleus must pass through a nuclear pore complex ( NPC ) .", "NPCs are formed by hundreds of proteins organized into cylindrically symmetric pores that act as gateways to the cell nucleus .", "The NPC has a mass of ∼50 MDa in yeast and up to 125 MDa in verteb...	[ "The nuclear pore complex ( NPC ) is the gate to the nucleus .", "Recent determination of the configuration of proteins in the yeast NPC at ∼5 nm resolution permits us to study the NPC global dynamics using coarse-grained structural models .", "We investigate these large-scale motions by using an extended elast...	[ "The nuclear pore complex ( NPC ) serves as the sole gateway to the cell nucleus , and its proper functioning is therefore crucial for gene expression and many vital signaling pathways .", "Although it is typically circular , the overall structure of the NPC has been observed to change in response to the presence...	2009
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "evolutionary biology", "centromeres", "microbiology", "mitosis", "model organisms", "cell division", "dna", "chromatin", "chromosome biology", "biology", "molecular biology", "cell biology", "nucleic acids", "genetics", "yeast and fungal models", "molecular cell biology", "genetics ...	A Coordinated Interdependent Protein Circuitry Stabilizes the Kinetochore Ensemble to Protect CENP-A in the Human Pathogenic Yeast Candida albicans	journal.pgen.1002661	null	[ [ "The centromeric histone CENP-A acts as the epigenetic mark of a functional centromere from yeast to humans [1] .", "As a histone H3 variant , CENP-A replaces canonical histone H3 to mark specialized centromeric chromatin by a mechanism that remains largely unknown .", "While CENP-A deposition occurs ...	[ "Unlike most eukaryotes , a kinetochore is fully assembled early in the cell cycle in budding yeasts Saccharomyces cerevisiae and Candida albicans .", "These kinetochores are clustered together throughout the cell cycle .", "Kinetochore assembly on point centromeres of S . cerevisiae is considered to be a step-...	[ "The kinetochore , a macromolecular protein complex that assembles on centromere DNA , interacts with spindle microtubules to mediate faithful chromosome segregation .", "The sequence of centromere DNA , which varies from 125 bp long point centromere in Saccharomyces cerevisiae to a few Mb long regional centromer...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "molecular biology/histone modification", "molecular biology/rna splicing" ]	Acetylation by the Transcriptional Coactivator Gcn5 Plays a Novel Role in Co-Transcriptional Spliceosome Assembly	journal.pgen.1000682	null	[ [ "Eukaryotic genes are interrupted by stretches of noncoding sequence ( introns ) , which are removed from the newly-synthesized RNA by the spliceosome , a dynamic ribonucleoprotein complex made up of 5 highly structured snRNAs and over a hundred snRNA-associated proteins .", "Although RNA synthesis and RN...	[ "In the last several years , a number of studies have shown that spliceosome assembly and splicing catalysis can occur co-transcriptionally .", "However , it has been unclear which specific transcription factors play key roles in coupling splicing to transcription and the mechanisms through which they act .", "...	[ "Pre-messenger RNA splicing , the removal of non-coding RNA sequences ( introns ) that interrupt the protein-coding sequence of genes , is required for proper gene expression .", "While recent studies have revealed that intron recognition begins while the RNA is actively being synthesized by RNA polymerase II , l...	2009
[ "Introduction", "Results and Discussion", "Methods" ]	[ "body weight", "medicine and health sciences", "microbiome", "pathology and laboratory medicine", "pathogens", "microbiology", "neuroscience", "liver diseases", "group f streptococci", "organisms", "metagenomics", "physiological parameters", "forecasting", "mathematics", "statistics (mat...	Machine Learning Meta-analysis of Large Metagenomic Datasets: Tools and Biological Insights	journal.pcbi.1004977	null	[ [ "The human microbiome constitutes the whole set of microbial organisms associated with the human host .", "It has been shown to be crucial for human health and for the development and maintenance of the immune system and for several metabolic activities [1–3] .", "Significant effort has been devoted t...	[ "Shotgun metagenomic analysis of the human associated microbiome provides a rich set of microbial features for prediction and biomarker discovery in the context of human diseases and health conditions .", "However , the use of such high-resolution microbial features presents new challenges , and validated computa...	[ "The human microbiome–the entire set of microbial organisms associated with the human host–interacts closely with host immune and metabolic functions and is crucial for human health .", "Significant advances in the characterization of the microbiome associated with healthy and diseased individuals have been obtai...	2016
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "plant anatomy", "homologous chromosomes", "chromosome structure and function", "centromeres", "metaphase", "cell cycle and cell division", "cell processes", "brassica", "pollen", "plant science", "model organisms", "experimental organism systems", "dna", "plants", "homologous recombinat...	Arabidopsis RAD51, RAD51C and XRCC3 proteins form a complex and facilitate RAD51 localization on chromosomes for meiotic recombination	journal.pgen.1006827	null	[ [ "Homologous recombination ( HR ) is important for repairing DNA damage and maintaining genomic stability .", "Meiotic HR and sister chromatid cohesion are required for maintaining physical associations between homologous chromosomes ( homologs ) and ensuring their accurate segregation .", "Meiotic HR ...	[ "Meiotic recombination is required for proper homologous chromosome segregation in plants and other eukaryotes .", "The eukaryotic RAD51 gene family has seven ancient paralogs with important roles in mitotic and meiotic recombination .", "Mutations in mammalian RAD51 homologs RAD51C and XRCC3 lead to embryonic ...	[ "Meiotic recombination and sister chromatid cohesion are important for maintaining the association between homologous chromosomes and ensuring their accurate segregation .", "Meiotic recombination starts with a set of programmed DNA double-strand breaks ( DSBs ) , catalyzed by the SPO11 endonuclease .", "Proces...	2017
[ "Introduction", "Results/Discussion", "Materials and Methods" ]	[]	Human Genome Replication Proceeds through Four Chromatin States	journal.pcbi.1003233	null	[ [ "Understanding the role of chromatin structure and dynamics in the regulation of the nuclear functions including transcription and replication , is a major challenge of current research in genomics and epigenomics [1]–[7] .", "Since the initial sequencing of complete genomes and more than a decade ago of ...	[ "Advances in genomic studies have led to significant progress in understanding the epigenetically controlled interplay between chromatin structure and nuclear functions .", "Epigenetic modifications were shown to play a key role in transcription regulation and genome activity during development and differentiatio...	[ "Previous studies revealed spatially coherent and biological-meaningful chromatin mark combinations in human cells .", "Here , we analyze thirteen epigenetic mark maps in the human cell line K562 at 100 kb resolution of MRT data .", "The complexity of epigenetic data is reduced to four chromatin states that dis...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "growth control", "cellular stress responses", "cancer genetics", "developmental biology", "morphogenesis", "gene expression", "biology", "molecular biology", "signal transduction", "cell biology", "cell migration", "genetics", "molecular cell biology", "genetics and genomics" ]	The Archipelago Ubiquitin Ligase Subunit Acts in Target Tissue to Restrict Tracheal Terminal Cell Branching and Hypoxic-Induced Gene Expression	journal.pgen.1003314	null	[ [ "Metabolically active tissues require an adequate supply of dioxygen ( O2 ) for metabolic production of ATP by aerobic glycolysis and as a necessary substrate in a variety of enzymatic reactions ( reviewed in [1] ) .", "Consequently , cells in metazoan organisms have evolved a conserved hypoxia-response m...	[ "The Drosophila melanogaster gene archipelago ( ago ) encodes the F-box/WD-repeat protein substrate specificity factor for an SCF ( Skp/Cullin/F-box ) -type polyubiquitin ligase that inhibits tumor-like growth by targeting proteins for degradation by the proteasome .", "The Ago protein is expressed widely in the ...	[ "Cells in multicellular animals must adapt to changing environmental conditions in order to ensure survival of the larger organism .", "One key challenge they face is fluctuation in the availability of dissolved oxygen .", "As cells get low on oxygen , they respond by turning on a program of gene expression tha...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "blood cells", "t helper cells", "innate immune system", "medicine and health sciences", "immune cells", "immune physiology", "cytokines", "immunology", "animal models", "developmental biology", "model organisms", "stem cells", "molecular development", "tcr signaling cascade", "research ...	A Natural Variant of the T Cell Receptor-Signaling Molecule Vav1 Reduces Both Effector T Cell Functions and Susceptibility to Neuroinflammation	journal.pgen.1006185	null	[ [ "The guanine nucleotide exchange factor ( GEF ) Vav1 is essential for transducing T cell antigen receptor ( TCR ) signals and therefore plays a critical role in the development and activation of T cells [1–5] .", "Following TCR engagement , Vav1 becomes rapidly tyrosine phosphorylated by kinases of the Sr...	[ "The guanine nucleotide exchange factor Vav1 is essential for transducing T cell antigen receptor signals and therefore plays an important role in T cell development and activation .", "Our previous genetic studies identified a locus on rat chromosome 9 that controls the susceptibility to neuroinflammation and co...	[ "The understanding of the physiological role of Vav1 , a key regulator of T cell receptor signaling , was primarily inferred from studies using Vav1-deficient mice .", "Such models , however , provide little insight on how polymorphisms leading to quantitative changes in Vav1 activity could affect immune system f...	2016
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "infectious diseases", "medicine and health sciences", "dengue fever", "neglected tropical diseases", "tropical diseases", "viral diseases" ]	Field Evaluation of Picaridin Repellents Reveals Differences in Repellent Sensitivity between Southeast Asian Vectors of Malaria and Arboviruses	journal.pntd.0003326	null	[ [ "Vector-borne diseases remain major contributors to the burden of diseases in the tropics [1] , [2] .", "The most important vectors for transmission of diseases are bloodsucking arthropods , and especially mosquitoes .", "Worldwide , about 3500 mosquito species have been described , but only a few of ...	[ "Scaling up of insecticide treated nets has contributed to a substantial malaria decline .", "However , some malaria vectors , and most arbovirus vectors , bite outdoors and in the early evening .", "Therefore , topically applied insect repellents may provide crucial additional protection against mosquito-borne...	[ "Malaria and arboviruses are transmitted by several mosquitoes .", "Targeting these mosquitoes instead of the pathogens can contribute to prevention of these diseases .", "For mosquitoes biting throughout the night , mosquito nets ( preferably impregnated with insecticides ) are very effective for mosquito cont...	2014
[ "Introduction", "Materials and Methods" ]	[ "infectious diseases/protozoal infections", "infectious diseases/tropical and travel-associated diseases", "genetics and genomics" ]	Shotgun Sequencing Analysis of Trypanosoma cruzi I Sylvio X10/1 and Comparison with T. cruzi VI CL Brener	journal.pntd.0000984	null	[ [ "The protozoan parasite Trypanosoma cruzi , causative agent of Chagas disease , infects 7 . 7 million people in Latin America and causes 12 , 500 deaths annually [1] .", "Transmission of the parasite most commonly occurs if infected faeces of the haematophagous triatomine insect vector makes contact with ...	[ "Trypanosoma cruzi is the causative agent of Chagas disease , which affects more than 9 million people in Latin America .", "We have generated a draft genome sequence of the TcI strain Sylvio X10/1 and compared it to the TcVI reference strain CL Brener to identify lineage-specific features .", "We found virtual...	[ "Chagas disease is a major health problem in Latin America and it is caused by the protozoan parasite Trypanosoma cruzi .", "The genome sequence of the T . cruzi strain CL Brener ( TcVI ) has revealed a genome with large repertoires of genes for surface antigens , among other features .", "In the present study ...	2011
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Developmental Dynamics of X-Chromosome Dosage Compensation by the DCC and H4K20me1 in C. elegans	journal.pgen.1005698	null	[ [ "Dosage compensation equalizes X chromosome gene expression between sexes .", "Different animals use different strategies of dosage compensation by co-opting diverse mechanisms of gene regulation to the X chromosome [1] .", "In mammals , dosage compensation transcriptionally inactivates one of the two...	[ "In Caenorhabditis elegans , the dosage compensation complex ( DCC ) specifically binds to and represses transcription from both X chromosomes in hermaphrodites .", "The DCC is composed of an X-specific condensin complex that interacts with several proteins .", "During embryogenesis , DCC starts localizing to t...	[ "In many animals , males have a single X and females have two X chromosomes , creating an X chromosomal gene dosage imbalance between sexes .", "This imbalance is corrected by dosage compensation mechanisms , which are essential for development in mammals , flies and worms .", "The timing and the molecular mech...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genetics and genomics/gene expression", "evolutionary biology/evolutionary and comparative genetics", "molecular biology/molecular evolution", "evolutionary biology/genomics", "genetics and genomics/gene function", "genetics and genomics/epigenetics", "molecular biology/chromatin structure" ]	Co-Evolution of Transcriptional Silencing Proteins and the DNA Elements Specifying Their Assembly	journal.pbio.1000550	As shown by genetic assays in Saccharomyces interspecies hybrids, the co-evolution of heterochromatin assembly proteins with silencer elements allows transcriptional silencing functions to be maintained in rapidly evolving regions of the genome.	[ [ "Among all specialized chromatin structures , the difference between heterochromatin and euchromatin is perhaps the most fundamental , motivating intense study of the differences between these two structures .", "DNA sequences within heterochromatic regions evolve rapidly in animals [1] , [2] , plants [3]...	[ "Co-evolution of transcriptional regulatory proteins and their sites of action has been often hypothesized but rarely demonstrated .", "Here we provide experimental evidence of such co-evolution in yeast silent chromatin , a finding that emerged from studies of hybrids formed between two closely related Saccharom...	[ "As eukaryotic species evolve , transcriptionally silent portions of their genomes—termed “heterochromatin”—mutate rapidly .", "To maintain the “off” state of certain genes in silenced regions , regulatory DNA sequences called silencers , which reside within a rapidly mutating region , must co-evolve with the reg...	2010
[ "Introduction", "Results", "Discussion", "Methods" ]	[]	Bacterial Temporal Dynamics Enable Optimal Design of Antibiotic Treatment	journal.pcbi.1004201	null	[ [ "Bacteria eventually develop resistance to all antibiotics they encounter [1–3] .", "Unfortunately , the evolution of antibiotic resistant bacteria is accelerating due to the widespread use of antibiotics [4 , 5] .", "As the antibiotic pipeline is drying up and the threat of antibiotic resistance is b...	[ "There is a critical need to better use existing antibiotics due to the urgent threat of antibiotic resistant bacteria coupled with the reduced effort in developing new antibiotics .", "β-lactam antibiotics represent one of the most commonly used classes of antibiotics to treat a broad spectrum of Gram-positive a...	[ "Antibiotic resistance is a growing problem that the World Health Organization describes as “one of the top three threats to global health . ”", "To date , bacteria have developed resistance to all antibiotics used in clinical settings .", "Unfortunately , the evolution of antibiotic resistant bacteria is accel...	2015
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "b vitamins", "chemical compounds", "endoplasmic reticulum", "cell processes", "organic compounds", "cholines", "membrane proteins", "fungi", "cellular structures and organelles", "lipids", "chemistry", "vitamins", "sterols", "cell membranes", "yeast", "biochemistry", "eukaryota", ...	Endoplasmic reticulum-plasma membrane contact sites integrate sterol and phospholipid regulation	journal.pbio.2003864	null	[ [ "Most lipids are synthesized in the endoplasmic reticulum ( ER ) and distributed to other membranes by non-vesicular mechanisms .", "These mechanisms act in conjunction with lipid metabolic networks to maintain the unique lipid profile of the plasma membrane ( PM ) and subcellular organelles , and enable ...	[ "Tether proteins attach the endoplasmic reticulum ( ER ) to other cellular membranes , thereby creating contact sites that are proposed to form platforms for regulating lipid homeostasis and facilitating non-vesicular lipid exchange .", "Sterols are synthesized in the ER and transported by non-vesicular mechanism...	[ "Almost half of the inner surface area of the yeast plasma membrane ( PM ) is covered with closely associated cortical endoplasmic reticulum ( ER ) .", "In yeast and human cells , it has been proposed that ER-anchored tether proteins staple the ER to the PM , creating membrane contact sites at which lipid transpo...	2018
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "cell physiology", "medicine and health sciences", "protein interactions", "cancer treatment", "protein interaction networks", "cancers and neoplasms", "oncology", "ewing sarcoma", "network analysis", "molecular biology techniques", "research and analysis methods", "computer and information sc...	FusionPathway: Prediction of pathways and therapeutic targets associated with gene fusions in cancer	journal.pcbi.1006266	null	[ [ "Gene fusions resulting from chromosome rearrangements and chimeric RNAs generated by trans-splicing or read-through events play important roles in cancer .", "Recently , the advent of massively parallel sequencing has accelerated the rate of the discovery of fusions across multiple cancer types [1] .", ...	[ "Numerous gene fusions have been uncovered across multiple cancer types .", "Although the ability to target several of these fusions has led to the development of some successful anti-cancer drugs , most of them are not druggable .", "Understanding the molecular pathways of a fusion is important in determining ...	[ "We present a computational framework , FusionPathway , to infer the oncogenesis pathways of a fusion and help develop therapeutic strategies in these pathways for patients harboring the fusion .", "In this work , we successfully validated the capabilities of this approach through its application to the well-stud...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods", "Supporting Information" ]	[ "biochemistry", "none", "cell biology", "neuroscience", "drosophila", "genetics and genomics" ]	Integration of Light and Temperature in the Regulation of Circadian Gene Expression in Drosophila	journal.pgen.0030054	null	[ [ "Organisms on Earth have evolved an internal timekeeping system , or circadian clock ( circa = about , diem = day ) , that allows them to both respond to and predict changes in the 24-h environmental day .", "Much has been learned about the genes involved in this precise , 24-h molecular timekeeping mecha...	[ "Circadian clocks are aligned to the environment via synchronizing signals , or Zeitgebers , such as daily light and temperature cycles , food availability , and social behavior .", "In this study , we found that genome-wide expression profiles from temperature-entrained flies show a dramatic difference in the pr...	[ "A key adaptation to life on Earth is provided by internal daily time-keeping mechanisms that allow anticipation of the alternations between night and day .", "To act as reliable time-keeping mechanisms , circadian clocks have to be able to synchronize to environmental time cues , maintain ∼24-h rhythms under con...	2007
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biochemistry", "immunology", "biology" ]	Unique Interplay between Sugar and Lipid in Determining the Antigenic Potency of Bacterial Antigens for NKT Cells	journal.pbio.1001189	Structural and biophysical studies reveal the induced-fit mechanism underlying the stringent specificity of invariant natural killer T cells for unique glycolipid antigens from the pathogen Streptococcus pneumoniae.	[ [ "Invariant NKT cells ( iNKT ) are an evolutionarily conserved population of T lymphocytes able to respond to lipid antigens when presented by CD1d , a non-classical MHC class I–like molecule [1] .", "Antigen recognition by iNKT cells is mediated by a semi-invariant αβ T cell receptor ( TCR ) formed by a c...	[ "Invariant natural killer T ( iNKT ) cells are an evolutionary conserved T cell population characterized by features of both the innate and adaptive immune response .", "Studies have shown that iNKT cells are required for protective responses to Gram-positive pathogens such as Streptococcus pneumoniae , and that ...	[ "Invariant natural killer T ( iNKT ) cells are an evolutionarily conserved population of immune cells that recognize lipid antigens .", "A protein called a T cell receptor for antigen ( TCR ) on the surface of these iNKT cells recognizes lipids bound to a protein called CD1d on the surface of antigen-presenting c...	2011
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine and health sciences", "liver", "vertebrates", "animals", "mammals", "dna transcription", "animal models", "model organisms", "pharmaceutics", "genome analysis", "bioassays and physiological analysis", "research and analysis methods", "genomics", "animal cells", "gene expression...	Assessing Concordance of Drug-Induced Transcriptional Response in Rodent Liver and Cultured Hepatocytes	journal.pcbi.1004847	null	[ [ "Transcriptional changes in model systems are often used to elucidate mechanism-based effects of drug treatment and the relevance for humans [1 , 2] .", "While the use of model systems is viewed with skepticism by some , it is common practice to use nonclinical species to inform our understanding of human...	[ "The effect of drugs , disease and other perturbations on mRNA levels are studied using gene expression microarrays or RNA-seq , with the goal of understanding molecular effects arising from the perturbation .", "Previous comparisons of reproducibility across laboratories have been limited in scale and focused on...	[ "Gene expression studies in model systems are widely used for understanding the mechanism of drugs and other perturbations in biological systems .", "Other researchers have examined the reproducibility of microarray studies between laboratories , or comparing microarrays and/or RNA sequencing .", "However , no ...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genome-wide association studies", "chemical compounds", "social sciences", "biomarkers", "anthropology", "organic compounds", "carbohydrates", "glucose", "simulation and modeling", "genome analysis", "research and analysis methods", "anthropometry", "chemistry", "creatinine", "biochemis...	Pedigree- and SNP-Associated Genetics and Recent Environment are the Major Contributors to Anthropometric and Cardiometabolic Trait Variation	journal.pgen.1005804	null	[ [ "Phenotypic variation for a quantitative trait is attributable to the summed effects of genetic and environmental influences together with any covariances and interactions .", "The proportion of phenotypic variance contributed by genetic variation is termed the heritability ( h2 ) [1] .", "The heritab...	[ "Genome-wide association studies have successfully identified thousands of loci for a range of human complex traits and diseases .", "The proportion of phenotypic variance explained by significant associations is , however , limited .", "Given the same dense SNP panels , mixed model analyses capture a greater p...	[ "Unravelling overall trait architecture of complex traits and diseases is important for phenotype prediction and disease prevention and correct modelling of the trait will further aid discovery of causative loci .", "Here we take advantage of genome-wide data and a large family-based study to examine the role of ...	2016
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "medicine and health sciences", "applied mathematics", "cancer treatment", "enzymology", "simulation and modeling", "oncology", "algorithms", "genomic databases", "tyrosine kinase inhibitors", "mathematics", "forecasting", "statistics (mathematics)", "genome analysis", "pharmacology", "e...	Large-Scale Off-Target Identification Using Fast and Accurate Dual Regularized One-Class Collaborative Filtering and Its Application to Drug Repurposing	journal.pcbi.1005135	null	[ [ "Conventional one-drug-one-gene drug discovery and drug development is a time-consuming and expensive process .", "It suffers from high attrition rate and possible unexpected post-market withdrawal [1] .", "It has been recognized that a drug rarely only binds to its intended target , and off-target in...	[ "Target-based screening is one of the major approaches in drug discovery .", "Besides the intended target , unexpected drug off-target interactions often occur , and many of them have not been recognized and characterized .", "The off-target interactions can be responsible for either therapeutic or side effects...	[ "High-throughput techniques have generated vast amounts of diverse omics and phenotypic data .", "However , these sets of data have not yet been fully explored to improve the effectiveness and efficiency of drug discovery , a process which has traditionally adopted a one-drug-one-gene paradigm .", "Consequently...	2016
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "decision making", "engineering and technology", "signal processing", "social sciences", "light", "neuroscience", "learning and memory", "electromagnetic radiation", "perception", "cognitive psychology", "luminance", "cognition", "memory", "visible light", "vision", "computer and infor...	Noise, multisensory integration, and previous response in perceptual disambiguation	journal.pcbi.1005546	null	[ [ "Perception is well described as an inference process based on noisy and often ambiguous sensory signals .", "As such , a single sensory modality most often cannot provide enough information to univocally specify the actual state of the world .", "Throughout the history of vision science , numerous am...	[ "Sensory information about the state of the world is generally ambiguous .", "Understanding how the nervous system resolves such ambiguities to infer the actual state of the world is a central quest for sensory neuroscience .", "However , the computational principles of perceptual disambiguation are still poorl...	[ "Sensory information is generally ambiguous , and a single sensory modality most often cannot provide enough information to univocally specify the actual state of the world .", "A primary task for the brain is therefore to resolve perceptual ambiguity .", "Here we use a dynamic audiovisual ambiguous display emb...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "dna viruses", "viral classification", "virology", "biology", "microbiology" ]	Mutualistic Polydnaviruses Share Essential Replication Gene Functions with Pathogenic Ancestors	journal.ppat.1003348	null	[ [ "Microorganisms form associations with metazoan hosts that range from beneficial symbiosis ( mutualists ) to parasitic ( pathogens ) .", "Mutualists serve as important sources of evolutionary innovation for hosts , while pathogens often acquire genes from hosts or other organisms that facilitate their own...	[ "Viruses are usually thought to form parasitic associations with hosts , but all members of the family Polydnaviridae are obligate mutualists of insects called parasitoid wasps .", "Phylogenetic data founded on sequence comparisons of viral genes indicate that polydnaviruses in the genus Bracovirus ( BV ) are clo...	[ "Microorganisms form symbiotic associations with animals and plants that range from parasitic ( pathogens ) to beneficial ( mutualists ) .", "Although numerous examples of obligate , mutualistic bacteria , fungi , and protozoans exist , viruses are almost always considered to be pathogens .", "An exception is t...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biology" ]	An Essential Function for the ATR-Activation-Domain (AAD) of TopBP1 in Mouse Development and Cellular Senescence	journal.pgen.1003702	null	[ [ "In response to endogenous and exogenous stress , cells have evolved a range DNA damage response ( DDR ) pathways to maintain genomic stability [1] , [2] , [3] , [4] .", "In all eukaryotes , two evolutionarily conserved PI3-kinase-like protein kinases , ATM ( Ataxia telangiectasia mutated ) and ATR ( ATM-...	[ "ATR activation is dependent on temporal and spatial interactions with partner proteins .", "In the budding yeast model , three proteins – Dpb11TopBP1 , Ddc1Rad9 and Dna2 - all interact with and activate Mec1ATR .", "Each contains an ATR activation domain ( ADD ) that interacts directly with the Mec1ATR:Ddc2ATR...	[ "DNA damage checkpoint signalling is an essential component of the DNA damage response .", "Many of the key proteins initiating the checkpoint signal have been identified and characterised in yeast .", "Here we explore the role of the ATR activating domain ( AAD ) of TopBP1 in embryonic development , cell growt...	2013
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "medicine and health sciences", "toxins", "crystal structure", "pathology and laboratory medicine", "chemical compounds", "aliphatic amino acids", "condensed matter physics", "organic compounds", "toxicology", "toxic agents", "collagens", "mutation", "integrins", "amino acids", "sequence...	Dramatic and concerted conformational changes enable rhodocetin to block α2β1 integrin selectively	journal.pbio.2001492	null	[ [ "Most cellular processes depend on the formation of interactions between cells and the extracellular matrix ( ECM ) .", "Key facilitators of these interactions are the integrins .", "They consist of 2 subunits , α and β , each of which has multiple isoforms [1 , 2] .", "The different subunit compo...	[ "The collagen binding integrin α2β1 plays a crucial role in hemostasis , fibrosis , and cancer progression amongst others .", "It is specifically inhibited by rhodocetin ( RC ) , a C-type lectin-related protein ( CLRP ) found in Malayan pit viper ( Calloselasma rhodostoma ) venom .", "The structure of RC alone ...	[ "In animals , collagen-mediated platelet aggregation is an essential component of the blood’s clotting response following vascular injury .", "A small group of snake venom toxins belonging to the C-type lectin protein family exert their harmful effects by directly targeting this pathway .", "Rhodocetin ( RC ) i...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "molecular probe techniques", "dna replication", "molecular biology techniques", "translocations", "dna", "duplications", "research and analysis methods", "genome complexity", "probe hybridization", "chromosome biology", "chromosomal aberrations", "molecular biology", "biochemistry", "fluo...	Mechanisms for Complex Chromosomal Insertions	journal.pgen.1006446	null	[ [ "Chromosomal insertion occurs when a segment of one chromosome is translocated and inserted into an interstitial region of another non-homologous chromosome ( interchromosomal insertion ) , or into a different region of the same chromosome ( intrachromosomal insertion ) .", "Insertions are considered as c...	[ "Chromosomal insertions are genomic rearrangements with a chromosome segment inserted into a non-homologous chromosome or a non-adjacent locus on the same chromosome or the other homologue , constituting ~2% of nonrecurrent copy-number gains .", "Little is known about the molecular mechanisms of their formation ....	[ "By traditional cytogenetic techniques , the incidence of microscopically visible chromosomal insertions was estimated to be 1 in 80 , 000 live births .", "More recently , by aCGH in conjunction with FISH confirmation of the aCGH findings , insertion events were demonstrated to occur much more frequently ( 1 in ~...	2016
[ "Introduction", "Model", "Results", "Discussion" ]	[ "bacteriology", "signaling networks", "evolutionary selection", "microbiology", "cell differentiation", "developmental biology", "microbial evolution", "molecular development", "microbial growth and development", "theoretical biology", "evolutionary modeling", "biology", "adaptation", "sig...	The Evolution of Cell-to-Cell Communication in a Sporulating Bacterium	journal.pcbi.1002818	null	[ [ "Complex systems in biology often come about through the communication of their parts , such as pheromone communication in insect societies and language in humans .", "Communication has been found to be ubiquitous in microorganisms as well [1]–[4] .", "Due to self-produced molecular signals that are s...	[ "Traditionally microorganisms were considered to be autonomous organisms that could be studied in isolation .", "However , over the last decades cell-to-cell communication has been found to be ubiquitous .", "By secreting molecular signals in the extracellular environment microorganisms can indirectly assess th...	[ "Biological systems are characterized by communication; humans talk , insects produce pheromones and birds sing .", "Over the last decades it has been shown that even the simplest organisms on earth , the bacteria , communicate .", "Despite the prevalence of communication , it is often hard to explain how commu...	2012
[ "Introduction", "Results", "Discussion", "Methods" ]	[]	Segment-Specific Adhesion as a Driver of Convergent Extension	journal.pcbi.1004092	null	[ [ "Convergent extension refers to the simultaneous narrowing and extension of tissues due to extensive cell rearrangements , and is a key morphogenetic event during formation of the bilaterian body plan .", "In bilaterian animals , convergent extension first occurs when the main body axis forms and extends ...	[ "Convergent extension , the simultaneous extension and narrowing of tissues , is a crucial event in the formation of the main body axis during embryonic development .", "It involves processes on multiple scales: the sub-cellular , cellular and tissue level , which interact via explicit or intrinsic feedback mecha...	[ "The process of convergent extension is a major contributor to the formation of the anterior-posterior body axis in the early embryo .", "Convergent extension refers to the directed movement of cells that leads to the extension of tissue in one direction and narrowing of the tissue in the perpendicular direction ...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "invertebrates", "ecology and environmental sciences", "honey bees", "population genetics", "invertebrate genomics", "animals", "population biology", "bees", "genomic signal processing", "hymenoptera", "parasitism", "genetic loci", "animal genomics", "insects", "arthropoda", "community...	Identification of Multiple Loci Associated with Social Parasitism in Honeybees	journal.pgen.1006097	null	[ [ "In most colonies of the honeybee Apis mellifera , the queen is the only reproductively active female and it produces pheromones that inhibit ovary activation in the workers [1 , 2] , keeping them sterile .", "Under some circumstances , particularly when the colony lacks a queen , workers may activate the...	[ "In colonies of the honeybee Apis mellifera , the queen is usually the only reproductive female , which produces new females ( queens and workers ) by laying fertilized eggs .", "However , in one subspecies of A . mellifera , known as the Cape bee ( A . m . capensis ) , worker bees reproduce asexually by thelytok...	[ "Honeybee colonies are mainly composed of female worker bees that are unable to lay eggs and reproduce; a task that is performed by a single queen bee .", "However , in a subspecies of the Western honeybee ( Apis mellifera ) known as the Cape bee ( A . m . capensis ) , worker bees can lay eggs produced by an abno...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "virology/host antiviral responses", "virology/emerging viral diseases", "pathology/pathophysiology", "immunology/innate immunity" ]	Endothelial Galectin-1 Binds to Specific Glycans on Nipah Virus Fusion Protein and Inhibits Maturation, Mobility, and Function to Block Syncytia Formation	journal.ppat.1000993	null	[ [ "Nipah virus ( NiV ) is a lethal emerging virus that infects agricultural livestock and humans .", "In 1999–2000 , NiV infection of agricultural workers in Malaysia and Singapore resulted in a 40% mortality rate , and subsequent outbreaks in Bangladesh resulted in an average case-fatality ratio greater th...	[ "Nipah virus targets human endothelial cells via NiV-F and NiV-G envelope glycoproteins , resulting in endothelial syncytia formation and vascular compromise .", "Endothelial cells respond to viral infection by releasing innate immune effectors , including galectins , which are secreted proteins that bind to spec...	[ "Nipah virus ( NiV ) is classified as a “priority pathogen” by the NIH .", "NiV infection of humans results in multi-organ hemorrhage due to endothelial syncytia formation , and also causes fatal encephalitis in up to 70% of patients .", "As there are no effective vaccines or therapeutics for NiV , understandin...	2010
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "medicine and health sciences", "chemical characterization", "pathology and laboratory medicine", "pathogens", "microbiology", "vertebrates", "viral structure", "orthomyxoviruses", "animals", "viruses", "rna viruses", "research and analysis methods", "receptor binding assays", "influenza a...	The 2nd sialic acid-binding site of influenza A virus neuraminidase is an important determinant of the hemagglutinin-neuraminidase-receptor balance	journal.ppat.1007860	null	[ [ "Influenza A virus ( IAV ) particles contain hemagglutinin ( HA ) and neuraminidase ( NA ) glycoproteins .", "HA functions as a sialic acid ( SIA ) -binding and fusion protein .", "NA has receptor-destroying activity by cleaving SIAs from sialoglycans .", "The HA and NA protein functionalities are...	[ "Influenza A virus ( IAV ) neuraminidase ( NA ) receptor-destroying activity and hemagglutinin ( HA ) receptor-binding affinity need to be balanced with the host receptor repertoire for optimal viral fitness .", "NAs of avian , but not human viruses , contain a functional 2nd sialic acid ( SIA ) -binding site ( 2...	[ "Influenza A viruses infect birds and mammals .", "They contain receptor-binding ( HA ) and receptor-destroying ( NA ) proteins , which are crucial determinants of host tropism and pathogenesis .", "It is generally accepted that the functional properties of HA and NA need to be well balanced to enable virion pe...	2019
[ "Introduction", "Results/Discussion", "Materials and Methods" ]	[ "evolutionary biology/human evolution", "genetics and genomics/complex traits", "genetics and genomics/medical genetics", "genetics and genomics/population genetics" ]	The CFTR Met 470 Allele Is Associated with Lower Birth Rates in Fertile Men from a Population Isolate	journal.pgen.1000974	null	[ [ "The cystic fibrosis transmembrane conductance regulator ( CFTR; OMIM 602421 ) gene functions as a chloride channel that regulates salt and water transport across epithelial cell membranes .", "More than 1 , 600 mutations ( Cystic Fibrosis Mutation Database; http://www . genet . sickkids . on . ca/cftr/ )...	[ "Although little is known about the role of the cystic fibrosis transmembrane regulator ( CFTR ) gene in reproductive physiology , numerous variants in this gene have been implicated in etiology of male infertility due to congenital bilateral absence of the vas deferens ( CBAVD ) .", "Here , we studied the fertil...	[ "Cystic fibrosis ( CF ) is the most common lethal recessive disorder in European-derived populations and is characterized by clinical heterogeneity that involves multiple organ systems .", "Over 1 , 600 disease-causing mutations have been identified in the cystic fibrosis transmembrane regulator ( CFTR ) gene , b...	2010

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