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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" ]	[ "virology/virulence factors and mechanisms", "cell biology/cellular death and stress responses", "cell biology/cell signaling", "virology/immunodeficiency viruses", "biochemistry/replication and repair" ]	Formation of Mobile Chromatin-Associated Nuclear Foci Containing HIV-1 Vpr and VPRBP Is Critical for the Induction of G2 Cell Cycle Arrest	journal.ppat.1001080	null	[ [ "HIV-1 encodes several proteins termed accessory that have been implicated in the modulation of host cell environment to promote efficient viral replication and evasion from innate and acquired immunity [1] .", "One of these accessory proteins , viral protein R ( Vpr ) , is a small amphipathic protein of ...	[ "HIV-1 Viral protein R ( Vpr ) induces a cell cycle arrest at the G2/M phase by activating the ATR DNA damage/stress checkpoint .", "Recently , we and several other groups showed that Vpr performs this activity by recruiting the DDB1-CUL4A ( VPRBP ) E3 ubiquitin ligase .", "While recruitment of this E3 ubiquiti...	[ "HIV-1 , the causative agent of AIDS , encodes several proteins termed accessory , which play a critical role in viral pathogenesis .", "One of these accessory proteins , viral protein R ( Vpr ) , has been found to block normal cell division .", "This impairment of cell division by Vpr is thought to increase vi...	2010
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "biology", "neuroscience" ]	Minimal Size of Cell Assemblies Coordinated by Gamma Oscillations	journal.pcbi.1002362	null	[ [ "Mechanisms underlying the formation of gamma-frequency ( 25–100 Hz ) rhythms in networks of excitatory and inhibitory neurons ( E- and I-cells ) have been investigated extensively [1]–[11] .", "However , mechanisms underlying the loss of rhythmicity , as parameters change , have been given less attention...	[ "In networks of excitatory and inhibitory neurons with mutual synaptic coupling , specific drive to sub-ensembles of cells often leads to gamma-frequency ( 25–100 Hz ) oscillations .", "When the number of driven cells is too small , however , the synaptic interactions may not be strong or homogeneous enough to su...	[ "Gamma-frequency ( 25–100 Hz ) oscillations in the brain often arise as a result of an interaction between excitatory and inhibitory cell populations .", "For this mechanism to work , the interaction must be sufficiently strong , and connectivity and external drives to participating neurons must be sufficiently h...	2012
[ "Introduction", "Results", "Discussion", "Material and methods" ]	[ "fish", "medicine and health sciences", "body fluids", "kinesins", "nervous system", "vertebrates", "animals", "animal models", "osteichthyes", "mutation", "model organisms", "molecular motors", "experimental organism systems", "molecular biology techniques", "frameshift mutation", "ce...	Mutations in Kinesin family member 6 reveal specific role in ependymal cell ciliogenesis and human neurological development	journal.pgen.1007817	null	[ [ "The delicate balance of cerebrospinal fluid ( CSF ) production and flow is important for the morphogenesis and function of the brain during development and homeostasis .", "CSF circulation in human is largely due to gradients established by the secretion of CSF from the choroid plexuses , and its resorpt...	[ "Cerebrospinal fluid flow is crucial for neurodevelopment and homeostasis of the ventricular system of the brain , with localized flow being established by the polarized beating of the ependymal cell ( EC ) cilia .", "Here , we report a homozygous one base-pair deletion , c . 1193delT ( p . Leu398Glnfs*2 ) , in t...	[ "Cerebrospinal fluid flow is crucial for neurodevelopment and homeostasis of the ventricular system of the brain .", "Localized flows of cerebrospinal fluid throughout the ventricular system of the brain are established from the polarized beating of the ependymal cell ( EC ) cilia .", "Here , we identified a ho...	2018
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "genetic mutation", "cell differentiation", "histone modification", "animal models", "developmental biology", "model organisms", "epigenetics", "embryology", "genomic imprinting", "gene expression", "biology", "mouse", "molecular biology", "genetics", "molecular cell biology", "genetic...	UTX and UTY Demonstrate Histone Demethylase-Independent Function in Mouse Embryonic Development	journal.pgen.1002964	null	[ [ "Post-translational modifications of histones establish and maintain active or repressive chromatin states throughout cell lineages .", "Thus , the enzymes that catalyze these modifications often have crucial roles in establishing genomic transcriptional states in developmental decision-making .", "Hi...	[ "UTX ( KDM6A ) and UTY are homologous X and Y chromosome members of the Histone H3 Lysine 27 ( H3K27 ) demethylase gene family .", "UTX can demethylate H3K27; however , in vitro assays suggest that human UTY has lost enzymatic activity due to sequence divergence .", "We produced mouse mutations in both Utx and ...	[ "Trimethylation at Lysine 27 of histone H3 ( H3K27me3 ) establishes a repressive chromatin state in silencing an array of crucial developmental genes .", "Polycomb repressive complex 2 ( PRC2 ) catalyzes this precise posttranslational modification and is required in several critical aspects of development includi...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "neuroscience", "motor systems", "biology", "computational neuroscience" ]	Interference and Shaping in Sensorimotor Adaptations with Rewards	journal.pcbi.1003377	null	[ [ "Transformations that map sensory inputs to motor commands are referred to as sensorimotor mappings [1] .", "While sensorimotor mappings are already formed at early stages of development [2] , they are subject to modifications , since the brain , the body and/or the environment are constantly changing .",...	[ "When a perturbation is applied in a sensorimotor transformation task , subjects can adapt and maintain performance by either relying on sensory feedback , or , in the absence of such feedback , on information provided by rewards .", "For example , in a classical rotation task where movement endpoints must be rot...	[ "The brain has a robust ability to adapt to external perturbations imposed on acquired sensorimotor transformations .", "Here , we used a mathematical model to investigate the reward-based component in sensorimotor adaptations .", "We show that the shape of the delivered reward signal , which in experiments is ...	2014
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "medicine and health sciences" ]	Rapid Identification of Black Grain Eumycetoma Causative Agents Using Rolling Circle Amplification	journal.pntd.0003368	null	[ [ "Black grain eumycetoma represents the most common fungal mycetoma worldwide .", "This chronic , erosive infection of subcutaneous tissues particularly affects the lower extremities and leads to severe disability [1] .", "The disease is considered a major health problem in tropical areas and is preval...	[ "Accurate identification of mycetoma causative agent is a priority for treatment .", "However , current identification tools are far from being satisfactory for both reliable diagnosis and epidemiological investigations .", "A rapid , simple , and highly efficient molecular based method for identification of ag...	[ "Treatment of eumycetoma largely depends on the causative pathogen .", "Identification of mycetoma agent with phenotypic features is too limited , and physiological and biochemical techniques are laborious , time-consuming and nonspecific , whereas the currently available molecular methods based on DNA sequencing...	2014
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "medicine and health sciences", "genetic networks", "pathology and laboratory medicine", "gene regulation", "pathogens", "regulatory proteins", "bacillus", "microbiology", "dna-binding proteins", "fungi", "prokaryotic models", "model organisms", "regulator genes", "network analysis", "ex...	Multi-study inference of regulatory networks for more accurate models of gene regulation	journal.pcbi.1006591	null	[ [ "Gene regulatory network inference aims at computationally deriving and ranking regulatory hypotheses on transcription factor-target gene interactions [1–3] .", "Often , these regulatory models are learned from gene expression measurements across a large number of samples .", "Strategies to obtain suc...	[ "Gene regulatory networks are composed of sub-networks that are often shared across biological processes , cell-types , and organisms .", "Leveraging multiple sources of information , such as publicly available gene expression datasets , could therefore be helpful when learning a network of interest .", "Integr...	[ "Due to increasing availability of biological data , methods to properly integrate data generated across the globe become essential for extracting reproducible insights into relevant research questions .", "In this work , we developed a framework to reconstruct gene regulatory networks from expression datasets ge...	2019
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "carbohydrate metabolism", "invertebrates", "glucose metabolism", "animals", "animal models", "metabolomics", "drosophila melanogaster", "model organisms", "experimental organism systems", "mitochondria", "bioenergetics", "peroxisomes", "cellular structures and organelles", "drosophila", ...	Peroxisomal biogenesis is genetically and biochemically linked to carbohydrate metabolism in Drosophila and mouse	journal.pgen.1006825	null	[ [ "Peroxisomes are ubiquitous organelles present in all eukaryotic cells [1–3] .", "Peroxisomes perform specific biochemical functions in the cell including fatty acid β-oxidation of very-long-chain fatty acids ( VLCFA ) [4] , α-oxidation of branched chain fatty acids [5 , 6] , plasmalogen biosynthesis [7 ,...	[ "Peroxisome biogenesis disorders ( PBD ) are a group of multi-system human diseases due to mutations in the PEX genes that are responsible for peroxisome assembly and function .", "These disorders lead to global defects in peroxisomal function and result in severe brain , liver , bone and kidney disease .", "In...	[ "Peroxisomes are organelles or component of cells that are involved in body chemistry for a number of specialized fats .", "Peroxisome biogenesis disorders ( PBD ) are a group of rare diseases in which patients have genetic defects in the synthesis of peroxisomes .", "These disorders affect multiple organs incl...	2017
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "transcriptional regulation", "computational biology", "evolutionary biology", "evolution", "yeast" ]	Evolution and Selection in Yeast Promoters: Analyzing the Combined Effect of Diverse Transcription Factor Binding Sites	journal.pcbi.0040007	null	[ [ "Genomic regulatory regions harbor complex control schemes that collectively allow the genome to operate in a flexible and dynamic fashion .", "Such control schemes are encoded into the DNA sequence in a way that is not yet fully understood .", "Important elements of such regulatory code are short DNA...	[ "In comparative genomics one analyzes jointly evolutionarily related species in order to identify conserved and diverged sequences and to infer their function .", "While such studies enabled the detection of conserved sequences in large genomes , the evolutionary dynamics of regulatory regions as a whole remain p...	[ "Cells use sophisticated regulation to transform static genomic information into flexible function .", "We are still far from understanding how such regulation evolves .", "Short DNA sequences that physically bind transcription factors in promoter areas near target genes play an important role in gene regulatio...	2008
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "immunopathology", "medicine", "infectious diseases", "schistosomiasis", "public health and epidemiology", "epidemiology", "infectious disease epidemiology", "neglected tropical diseases", "immunology", "biology", "parasitic diseases", "immune response", "helminth infection" ]	Chitinase 3-Like 1 Protein Levels Are Elevated in Schistosoma haematobium Infected Children	journal.pntd.0001898	null	[ [ "Urogenital schistosomiasis , caused by the blood fluke Schistosoma haematobium , is one of the world's most prevalent human parasitic diseases .", "Morbidity includes anaemia , malnutrition , impaired memory cognition and physical growth [1] , and immune-mediated pathology in the urogenital tract , the k...	[ "Currently there are few studies characterising the nature and aetiology of human schistosome-related inflammatory processes .", "The aim of this study was to determine the relationship between Chitinase 3-like 1 ( CHI3L1 ) , also known as YKL-40 , a molecule associated with inflammatory processes , and schistoso...	[ "Over 100 million people , mainly living in sub-Saharan Africa , are infected with the blood fluke Schistosoma haematobium .", "Morbidity includes anaemia , malnutrition , impaired cognition and physical growth as well as pathology of the urogenital tract .", "Urogenital morbidity is initiated by eggs laid at t...	2012
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "protein interaction networks", "signaling networks", "protein expression", "network analysis", "molecular biology techniques", "research and analysis methods", "computer and information sciences", "oncogenic signaling", "proteins", "metabolic pathways", "ras signaling", "proteomics", "metab...	Connecting signaling and metabolic pathways in EGF receptor-mediated oncogenesis of glioblastoma	journal.pcbi.1007090	null	[ [ "Diseases like cancer involve a large range of components that interact via complex and highly dynamic networks [1–3] , and are interconnected with biochemical pathways [4–7] .", "These multipath interconnections may allow cancer and other diseases to take alternate routes and bypass the effects of therap...	[ "As malignant transformation requires synchronization of growth-driving signaling ( S ) and metabolic ( M ) pathways , defining cancer-specific S-M interconnected networks ( SMINs ) could lead to better understanding of oncogenic processes .", "In a systems-biology approach , we developed a mathematical model for...	[ "Complex and highly dynamic interconnected networks allow cancer to take different routes and circumvent chemotherapy .", "Therefore , understanding these context-specific networks and their dynamics of molecular interactions driven by different oncogenic signaling and metabolic pathways is very much needed to pr...	2019
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "infectious disease immunology", "medicine and health sciences", "clinical immunology", "biology and life sciences", "immunology" ]	RNF26 Temporally Regulates Virus-Triggered Type I Interferon Induction by Two Distinct Mechanisms	journal.ppat.1004358	null	[ [ "Host pattern-recognition receptors ( PRRs ) detect nucleic acid from invading viruses or necrotic cells and trigger a series of signaling events that lead to the induction of type I interferons ( IFNs ) , which plays a central role in autoimmune diseases as well as protective immune responses against viruses...	[ "Viral infection triggers induction of type I interferons ( IFNs ) , which are critical mediators of innate antiviral immune response .", "Mediator of IRF3 activation ( MITA , also called STING ) is an adapter essential for virus-triggered IFN induction pathways .", "How post-translational modifications regulat...	[ "Virus infection induces the host cells to produce type I interferons , which are secreted proteins important for the host to clear viruses .", "Previously , we identified a cellular protein called MITA , which is essential for virus-triggered induction of interferons .", "In this study , we found an enzyme cal...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Huntingtin Is Required for Epithelial Polarity through RAB11A-Mediated Apical Trafficking of PAR3-aPKC	journal.pbio.1002142	Huntingtin—the protein that is aberrant in Huntington Disease—regulates apical vesicular trafficking to help establish apical-basolateral polarity during the development of mammary epithelia.	[ [ "Epithelial cells in glandular and tubular epithelial systems are organized as one layer surrounding a lumen .", "The establishment of apical-basolateral polarity in these systems is characterized by the formation of cell–cell adherens and tight junctions and accompanies lumen formation ( reviewed in [1–3...	[ "The establishment of apical-basolateral polarity is important for both normal development and disease , for example , during tumorigenesis and metastasis .", "During this process , polarity complexes are targeted to the apical surface by a RAB11A-dependent mechanism .", "Huntingtin ( HTT ) , the protein that i...	[ "In the adult mammary gland , tissue architecture is maintained through the regulation of the polarity of epithelial cells , which organize around a central cavity called the lumen .", "The mammary epithelium comprises a basal layer , which contains myoepithelial contractile cells and so-called mammary stem cells...	2015
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "livestock", "medicine and health sciences", "rift valley fever virus", "pathology and laboratory medicine", "ruminants", "infectious disease epidemiology", "pathogens", "tropical diseases", "microbiology", "vertebrates", "animals", "mammals", "viruses", "rift valley fever", "farms", "...	The Epidemiology of Rift Valley Fever in Mayotte: Insights and Perspectives from 11 Years of Data	journal.pntd.0004783	null	[ [ "Rift Valley fever ( RVF ) is a zoonotic arboviral disease ( Phlebovirus , Family Bunyaviridae ) primarily affecting domestic livestock ( cattle , sheep and goats ) .", "Epidemics of RVF in livestock mainly cause abortions and neonatal deaths .", "In humans , symptoms are usually non-specific causing ...	[ "Rift Valley fever ( RVF ) is a zoonotic arboviral disease that is a threat to human health , animal health and production , mainly in Sub-Saharan Africa .", "RVF virus dynamics have been poorly studied due to data scarcity .", "On the island of Mayotte in the Indian Ocean , off the Southeastern African coast ,...	[ "Rift Valley fever ( RVF ) is a viral zoonotic disease mainly present in Sub-Saharan Africa , transmitted by mosquitoes and primarily affecting livestock ( cattle , sheep and goats ) .", "The epidemiology of the disease is not fully known , mainly because of data scarcity .", "In Mayotte , an island close to Ma...	2016
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "death rates", "invertebrates", "dengue virus", "medicine and health sciences", "pathology and laboratory medicine", "infectious disease epidemiology", "demography", "pathogens", "vector-borne diseases", "microbiology", "animals", "viruses", "rna viruses", "population biology", "insect v...	Comparative Analysis of Dengue and Zika Outbreaks Reveals Differences by Setting and Virus	journal.pntd.0005173	null	[ [ "Many infections of humans are transmitted by mosquitoes .", "Dengue virus is one of the major pathogens infecting humans worldwide , causing an estimated 50–100 million cases resulting in about 10 , 000 deaths annually [1] .", "Confined mainly to tropical regions because of its reliance on transmissi...	[ "The pacific islands of Micronesia have experienced several outbreaks of mosquito-borne diseases over the past decade .", "In outbreaks on small islands , the susceptible population is usually well defined , and there is no co-circulation of pathogens .", "Because of this , analysing such outbreaks can be usefu...	[ "Dengue and Zika are related viruses that are transmitted by the same species of mosquitoes .", "While dengue is well described and has affected people around the world for a long time , Zika has only recently caused outbreaks in human populations .", "To investigate whether the expected behaviour of Zika is si...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "infographics", "medicine and health sciences", "neural networks", "nervous system", "vertebrates", "mice", "neuroscience", "animals", "mammals", "primates", "network analysis", "old world monkeys", "computer and information sciences", "monkeys", "network motifs", "animal cells", "ma...	Spatial Embedding and Wiring Cost Constrain the Functional Layout of the Cortical Network of Rodents and Primates	journal.pbio.1002512	The cortical network obeys common architectural principals in mouse and macaque. Differences include a relative decrease in long-range connections in the large brain of the macaque compared to the mouse.	[ [ "Understanding brain networks is arguably one of the major challenges of the 21st century [1] .", "The mammalian cortex is an extraordinary computational device , and analysis of its network properties with 107–1010 neurons and 1011–1015 synaptic connections is still largely unresolved .", "In the bra...	[ "Mammals show a wide range of brain sizes , reflecting adaptation to diverse habitats .", "Comparing interareal cortical networks across brains of different sizes and mammalian orders provides robust information on evolutionarily preserved features and species-specific processing modalities .", "However , these...	[ "It was recently shown that the network of connections between different areas of the macaque cortex has strong structural specificity in terms of the strength of connections as a function of the distance between areas .", "This has led to a model of cortex connectivity that predicts many observed architectural f...	2016
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "evolutionary biology/microbial evolution and genomics", "virology/virus evolution and symbiosis", "computational biology/comparative sequence analysis", "molecular biology/molecular evolution", "computational biology/evolutionary modeling", "infectious diseases/viral infections" ]	Identifying Changes in Selective Constraints: Host Shifts in Influenza	journal.pcbi.1000564	null	[ [ "Influenza A has the distinction of being an old disease , a recurring disease , and an ‘emerging’ disease .", "Influenza A viruses are found in humans as well as in other animals including swine , horses , sea mammals , and birds , of which waterfowl are considered the natural reservoir [1] .", "Subt...	[ "The natural reservoir of Influenza A is waterfowl .", "Normally , waterfowl viruses are not adapted to infect and spread in the human population .", "Sometimes , through reassortment or through whole host shift events , genetic material from waterfowl viruses is introduced into the human population causing wor...	[ "Influenza A's natural reservoir is waterfowl .", "Sometimes avian virus genomic segments are able to shift to a human host , either in toto or by combining with those that underwent a previous host shift event .", "Such host shift events can cause worldwide pandemics in their immunologically naive hosts .", ...	2009
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Mucosal B Cells Are Associated with Delayed SIV Acquisition in Vaccinated Female but Not Male Rhesus Macaques Following SIVmac251 Rectal Challenge	journal.ppat.1005101	null	[ [ "Sex differences in the pathogenesis of numerous viral diseases , including HIV , are well-known [1] .", "HIV-infected women exhibit lower viral loads and higher CD4 counts than men , but progress faster to AIDS [2] .", "Women with similar viral loads as men exhibit a 1 . 6-fold higher risk of AIDS [3...	[ "Many viral infections , including HIV , exhibit sex-based pathogenic differences .", "However , few studies have examined vaccine-related sex differences .", "We compared immunogenicity and protective efficacy of monomeric SIV gp120 with oligomeric SIV gp140 in a pre-clinical rhesus macaque study and explored ...	[ "Viral infections can have different disease courses in men and women .", "Following HIV infection , women generally exhibit lower viral loads and higher CD4 counts than men , but paradoxically progress faster to AIDS .", "Sex differences result from effects of X-linked genes and hormonal influences , and are b...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine", "infectious diseases", "virology", "biology", "microbiology", "viral diseases", "viral replication" ]	EphrinA2 Regulates Clathrin Mediated KSHV Endocytosis in Fibroblast Cells by Coordinating Integrin-Associated Signaling and c-Cbl Directed Polyubiquitination	journal.ppat.1003510	null	[ [ "During the initiation of infection of target cells , viruses bind to the cellular receptors and utilize a plethora of cellular signal molecules .", "The utilization of receptors , adaptors and signal molecules largely depends on the nature of the target cells [1] .", "Animal viruses can utilize diffe...	[ "Kaposi's sarcoma-associated herpesvirus ( KSHV ) interacts with human dermal endothelial cell surface tyrosine kinase EphrinA2 ( EphA2 ) and integrins ( α3β1 and αVβ3 ) in the lipid raft ( LR ) region , and EphA2 regulates macropinocytic virus entry by coordinating integrin-c-Cbl associated signaling .", "In con...	[ "KSHV is etiologically associated with Kaposi's sarcoma and primary effusion B-cell lymphoma .", "To initiate its in vitro infection of endothelial cells , KSHV interacts with cell surface heparan sulfate , integrins , and EphrinA2 ( EphA2 ) molecules in the lipid raft ( LR ) regions , which induces the integrin-...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "viral enzymes", "microbiology", "host-pathogen interaction", "viral structure", "protein folding", "virulence factors and mechanisms", "proteins", "biology", "pathogenesis", "biophysics", "biochemistry", "protein chemistry", "viral envelope", "virology" ]	Structure of the Ulster Strain Newcastle Disease Virus Hemagglutinin-Neuraminidase Reveals Auto-Inhibitory Interactions Associated with Low Virulence	journal.ppat.1002855	null	[ [ "Newcastle disease virus ( NDV ) belongs to the large and diverse family of paramyxoviruses , which is responsible for many human and animal diseases [1] .", "The paramyxoviruses include other viruses such as mumps virus , measles virus , Sendai virus , respiratory syncytial virus ( RSV ) , metapneumoviru...	[ "Paramyxovirus hemagglutinin-neuraminidase ( HN ) plays roles in viral entry and maturation , including binding to sialic acid receptors , activation of the F protein to drive membrane fusion , and enabling virion release during virus budding .", "HN can thereby directly influence virulence and in a subset of avi...	[ "Newcastle disease virus ( NDV ) can cause severe disease in birds , with the most virulent strains causing sudden death , even in vaccinated populations in the poultry industry .", "Highly virulent exotic NDV ( END ) strains have caused largescale outbreaks in the US in 1971 and 2003 , requiring the culling of 1...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genome analysis tools", "genomics", "genetics", "population genetics", "biology", "evolutionary biology", "evolutionary processes", "genetics and genomics" ]	Genome-Wide Analysis of the World's Sheep Breeds Reveals High Levels of Historic Mixture and Strong Recent Selection	journal.pbio.1001258	Genomic structure in a global collection of domesticated sheep reveals a history of artificial selection for horn loss and traits relating to pigmentation, reproduction, and body size.	[ [ "Man's earliest agricultural systems were based on the captive management of sheep and goats .", "The transition from hunting to animal husbandry involved human control over the reproduction , diet , and protection of animals .", "The process of domestication was initiated approximately 11 , 000 years...	[ "Through their domestication and subsequent selection , sheep have been adapted to thrive in a diverse range of environments .", "To characterise the genetic consequence of both domestication and selection , we genotyped 49 , 034 SNP in 2 , 819 animals from a diverse collection of 74 sheep breeds .", "We find t...	[ "During the process of domestication , mankind recruited animals from the wild into a captive environment , changing their morphology , behaviour , and genetics .", "In the case of sheep , domestication and subsequent selection by their animal handlers over thousands of years has produced a spectrum of breeds spe...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Antibiotic and Antiinflammatory Therapy Transiently Reduces Inflammation and Hypercoagulation in Acutely SIV-Infected Pigtailed Macaques	journal.ppat.1005384	null	[ [ "The current paradigm of HIV/SIV pathogenesis is that chronic systemic immune activation is a major determinant of progression to AIDS , independent of the levels of chronic viral replication or CD4+ T cell depletion [1] .", "Several lines of evidence support this paradigm .", "In both HIV-infected pa...	[ "Increased chronic immune activation and inflammation are hallmarks of HIV/SIV infection and are highly correlated with progression to AIDS and development of non-AIDS comorbidities , such as hypercoagulability and cardiovascular disease .", "Intestinal dysfunction resulting in microbial translocation has been pr...	[ "We report that administration of the intraluminal antibiotic Rifaximin and the gut-focused anti-inflammatory drug Sulfasalazine to acutely SIV-infected pigtailed macaques is associated with a transient disruption of the vicious circle of inflammation-microbial translocation-immune activation which is pathognomonic...	2016
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "fluorescence imaging", "plant anatomy", "plastids", "gene regulation", "plant cell biology", "regulatory proteins", "brassica", "dna-binding proteins", "pollen", "plant science", "model organisms", "experimental organism systems", "transcription factors", "plants", "arabidopsis thaliana...	Regulation of pollen lipid body biogenesis by MAP kinases and downstream WRKY transcription factors in Arabidopsis	journal.pgen.1007880	null	[ [ "Plastids including those that are non-photosynthetic are important sites of metabolism in plants .", "How the metabolic pathways in plastids and those outsides are coordinated is not well understood .", "Pollen , the male gametophyte , is critical to reproductive success of all flowering plants [1 , ...	[ "Signaling pathways that control the activities in non-photosynthetic plastids , important sites of plant metabolism , are largely unknown .", "Previously , we demonstrated that WRKY2 and WRKY34 transcription factors play an essential role in pollen development downstream of mitogen-activated protein kinase 3 ( M...	[ "Plastids are important sites of plant metabolism including fatty acid and starch biosynthesis .", "At present , how the activities in the plastids are coordinated with those in the cytoplasm and the signaling pathway ( s ) involved are largely unknown .", "Previously , we demonstrated that WRKY2 and WRKY34 tra...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Visualization of HIV-1 Interactions with Penile and Foreskin Epithelia: Clues for Female-to-Male HIV Transmission	journal.ppat.1004729	null	[ [ "The World Health Organization estimates that over 35 million people world-wide are currently infected with the human immunodeficiency virus ( HIV ) [1] .", "The majority of these infections are acquired through heterosexual transmission events , with female-to-male HIV transmission rates approaching that...	[ "To gain insight into female-to-male HIV sexual transmission and how male circumcision protects against this mode of transmission , we visualized HIV-1 interactions with foreskin and penile tissues in ex vivo tissue culture and in vivo rhesus macaque models utilizing epifluorescent microscopy .", "12 foreskin and...	[ "Although several clinical trials have demonstrated that male circumcision can protect men from becoming infected with HIV , we know very little about how men get infected through sex and how circumcision changes this .", "In this study , we explored possible sites of virus transmission across the penis by lookin...	2015
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "developmental biology", "computational biology/transcriptional regulation" ]	Quantitative Analysis of the Drosophila Segmentation Regulatory Network Using Pattern Generating Potentials	journal.pbio.1000456	A new computational method uses gene expression databases and transcription factor binding specificities to describe regulatory elements in the Drosophila A/P patterning network in unprecedented detail.	[ [ "A central challenge in understanding metazoan genome sequences is to identify and annotate genomic regions that regulate the complex spatial and temporal patterns of gene transcription .", "Analysis of the regulatory regions for many individual genes has typically identified discrete enhancers or “cis-re...	[ "Cis-regulatory modules that drive precise spatial-temporal patterns of gene expression are central to the process of metazoan development .", "We describe a new computational strategy to annotate genomic sequences based on their “pattern generating potential” and to produce quantitative descriptions of transcrip...	[ "The developmental program specifying segmentation along the anterior-posterior axis of the Drosophila embryo is one of the best studied examples of transcriptional regulatory networks .", "Previous work has identified the location and function of dozens of DNA segments called cis-regulatory “modules” that regula...	2010
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "infectious diseases/bacterial infections" ]	A Dominant Clone of Leptospira interrogans Associated with an Outbreak of Human Leptospirosis in Thailand	journal.pntd.0000056	null	[ [ "Leptospirosis is a zoonotic infection caused by pathogenic members of the genus Leptospira .", "Human disease is usually acquired following environmental exposure to Leptospira shed in the urine of an infected animal [1] , [2] .", "Infection is acquired during occupational or recreational exposure to...	[ "A sustained outbreak of leptospirosis occurred in northeast Thailand between 1999 and 2003 , the basis for which was unknown .", "A prospective study was conducted between 2000 and 2005 to identify patients with leptospirosis presenting to Udon Thani Hospital in northeast Thailand , and to isolate the causative ...	[ "A sustained outbreak of human leptospirosis occurred in northeast Thailand between 1999 and 2003 , the basis for which was unknown .", "Leptospirosis is a potentially serious infection cause by bacteria known as Leptospira; infection usually occurs following environmental exposure to pathogenic Leptospira shed i...	2007
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "flow cytometry", "genome engineering", "cell death", "autophagic cell death", "methods and resources", "vesicles", "engineering and technology", "synthetic biology", "cell processes", "green fluorescent protein", "synthetic bioengineering", "crispr", "membrane proteins", "luminescent prot...	CRISPR screening using an expanded toolkit of autophagy reporters identifies TMEM41B as a novel autophagy factor	journal.pbio.2007044	null	[ [ "Autophagy is an umbrella term for a broad family of trafficking pathways that transport cytoplasmic material to the lysosome for destruction .", "Its most studied form , macroautophagy ( hereafter “autophagy” ) , involves the formation of a double-membrane vesicle ( the autophagosome ) that sequesters cy...	[ "The power of forward genetics in yeast is the foundation on which the field of autophagy research firmly stands .", "Complementary work on autophagy in higher eukaryotes has revealed both the deep conservation of this process , as well as novel mechanisms by which autophagy is regulated in the context of develop...	[ "Eukaryotic cells use autophagy to eliminate unwanted structures—such as protein aggregates , intracellular pathogens , and damaged organelles—that are too large to be handled by the proteasome .", "This unusual vesicle transport pathway begins with packaging of cytoplasmic targets into a double-membrane vesicle ...	2019
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "taxonomy", "medicine and health sciences", "biopsy", "cloning", "surgical and invasive medical procedures", "phylogenetics", "data management", "phylogenetic analysis", "gastroenterology and hepatology", "molecular biology techniques", "genotyping", "digestive system", "research and analysi...	Bulk Genotyping of Biopsies Can Create Spurious Evidence for Hetereogeneity in Mutation Content	journal.pcbi.1004413	null	[ [ "The somatic genotypes of cancerous and pre-cancerous tissues are frequently assayed by taking biopsies containing a substantial number of cells and genotyping each biopsy as a whole ( via SNP chip , exome or genome sequencing , or other techniques ) .", "For example , in a study of Barrett’s esophagus ge...	[ "When multiple samples are taken from the neoplastic tissues of a single patient , it is natural to compare their mutation content .", "This is often done by bulk genotyping of whole biopsies , but the chance that a mutation will be detected in bulk genotyping depends on its local frequency in the sample .", "W...	[ "Researchers who take multiple samples from a cancer or pre-cancer tissue and find that some samples show far more mutations than others are likely to conclude that the high-mutation samples reflect cells with an abnormal mutation or growth rate .", "We considered the common practice of testing a bulk sample for ...	2016
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "quantum chemistry", "chemical compounds", "density functional theory", "enzymes", "enzymology", "organic compounds", "carboxylic acids", "quantum mechanics", "thermodynamics", "oxidation-reduction reactions", "proteins", "acids", "oxidoreductases", "chemistry", "oxidation", "physics",...	Quantum chemistry reveals thermodynamic principles of redox biochemistry	journal.pcbi.1006471	null	[ [ "In order to understand life we need to understand the forces that support and constrain it .", "Thermodynamics provides the fundamental constraints that shape metabolism [1–5] .", "Redox reactions constitute the primary metabolic pillars that support life .", "Life itself can be viewed as an elec...	[ "Thermodynamics dictates the structure and function of metabolism .", "Redox reactions drive cellular energy and material flow .", "Hence , accurately quantifying the thermodynamics of redox reactions should reveal design principles that shape cellular metabolism .", "However , only few redox potentials have ...	[ "Redox reactions define the energetic constraints within which life can exist .", "However , measurements of reduction potentials are scarce and unstandardized , and current prediction methods fall short of desired accuracy and coverage .", "Here , we harness quantum chemistry tools to enable the high-throughpu...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Geometric Constraints Dominate the Antigenic Evolution of Influenza H3N2 Hemagglutinin	journal.ppat.1004940	null	[ [ "The influenza virus causes one of the most common infections in the human population .", "The success of influenza is largely driven by the virus’s ability to rapidly adapt to its host and escape host immunity .", "The antibody response to the influenza virus is determined by the surface proteins hem...	[ "We have carried out a comprehensive analysis of the determinants of human influenza A H3 hemagglutinin evolution .", "We consider three distinct predictors of evolutionary variation at individual sites: solvent accessibility ( as a proxy for protein fold stability and/or conservation ) , Immune Epitope Database ...	[ "The influenza virus is one of the most rapidly evolving human viruses .", "Every year , it accumulates mutations that allow it to evade the host immune response of previously infected individuals .", "Which sites in the virus’ genome allow this immune escape and the manner of escape is not entirely understood ...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods", "Supporting Information" ]	[ "biochemistry", "plant biology", "arabidopsis", "computational biology", "plants", "genetics and genomics" ]	Linking Metabolic QTLs with Network and cis-eQTLs Controlling Biosynthetic Pathways	journal.pgen.0030162	null	[ [ "A longstanding goal in genetics is to unravel the molecular and genetic bases of complex traits such as disease resistance , growth , and development .", "While phenotypic variation in natural populations is largely quantitative and polygenic , understanding this variation is complicated by the interacti...	[ "Phenotypic variation between individuals of a species is often under quantitative genetic control .", "Genomic analysis of gene expression polymorphisms between individuals is rapidly gaining popularity as a way to query the underlying mechanistic causes of variation between individuals .", "However , there is...	[ "Natural genetic variation and the resulting phenotypic variation between individuals within a species have been of longstanding interest in wide-ranging fields .", "However , the molecular underpinnings of this phenotypic variation are relatively uncharted .", "Recently , genomics methodologies have been appli...	2007
[ "Introduction", "Materials and methods", "Accession numbers", "Results", "Discussion" ]	[ "taxonomy", "medicine and health sciences", "parasitic diseases", "parasitic protozoans", "phylogenetics", "data management", "protozoans", "mitochondria", "molecular biology techniques", "bioenergetics", "cellular structures and organelles", "genetic epidemiology", "research and analysis me...	Elucidating diversity in the class composition of the minicircle hypervariable region of Trypanosoma cruzi: New perspectives on typing and kDNA inheritance	journal.pntd.0007536	null	[ [ "The protozoan parasite Trypanosoma cruzi ( Kinetoplastea: Trypanosomatidae ) is the causative agent of Chagas disease .", "This parasite infects millions of people throughout its distribution in Latin America .", "Chagas disease can display a broad pathological spectrum , including potentially fatal ...	[ "Trypanosoma cruzi , the protozoan causative of Chagas disease , is classified into six main Discrete Typing Units ( DTUs ) : TcI-TcVI .", "This parasite has around 105 copies of the minicircle hypervariable region ( mHVR ) in their kinetoplastic DNA ( kDNA ) .", "The genetic diversity of the mHVR is virtually ...	[ "Chagas disease is an important public health problem in Latin America showing a wide diversity of clinical manifestations and epidemiological patterns .", "It is caused by the parasite Trypanosoma cruzi .", "This parasite is genetically diverse and classified into six main lineages .", "However , the relatio...	2019
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "fungal biochemistry", "signal transduction", "mycology", "mitogenic signaling", "fungi", "cell biology", "neurospora crassa", "fungal genetics", "genetics", "biology and life sciences", "molecular genetics", "molecular cell biology", "cell signaling", "molecular biology", "neurospora", ...	HAM-5 Functions As a MAP Kinase Scaffold during Cell Fusion in Neurospora crassa	journal.pgen.1004783	null	[ [ "Fusion between genetically identical cells occurs in many different organisms and plays pivotal roles in different developmental processes , such as myoblast fusion during muscle formation , macrophage fusion involved in tissue remodeling and fusion of trophoblasts during placental development [1] , [2] .", ...	[ "Cell fusion in genetically identical Neurospora crassa germlings and in hyphae is a highly regulated process involving the activation of a conserved MAP kinase cascade that includes NRC-1 , MEK-2 and MAK-2 .", "During chemotrophic growth in germlings , the MAP kinase cascade members localize to conidial anastomo...	[ "Cell fusion between genetically identical cells of the fungus Neurospora crassa occurs when germinating asexual cells ( conidia ) sense each other's proximity and redirect their growth .", "Chemotropic growth is dependent upon the assembly of a MAPK cascade ( NRC-1/MEK-2/MAK-2 ) at the cell cortex ( conidial ana...	2014
[ "Introduction", "Methods", "Results and Discussion" ]	[ "biology and life sciences", "parasitology", "microbiology" ]	Identification of Giardia lamblia DHHC Proteins and the Role of Protein S-palmitoylation in the Encystation Process	journal.pntd.0002997	null	[ [ "The flagellated protozoan parasite Giardia lamblia is a major cause of non-viral/non-bacterial diarrheal disease worldwide .", "This parasite can cause asymptomatic colonization or acute or chronic diarrheal illness and malabsorption [1] .", "Infection begins with the ingestion of Giardia in its cyst...	[ "Protein S-palmitoylation , a hydrophobic post-translational modification , is performed by protein acyltransferases that have a common DHHC Cys-rich domain ( DHHC proteins ) , and provides a regulatory switch for protein membrane association .", "In this work , we analyzed the presence of DHHC proteins in the pr...	[ "Giardiasis is a major cause of non-viral/non-bacterial diarrheal disease worldwide and has been included within the WHO Neglected Disease Initiative since 2004 .", "Infection begins with the ingestion of Giardia lamblia in cyst form , which , after exposure to gastric acid in the host stomach and proteases in th...	2014
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "invertebrates", "medicine and health sciences", "body fluids", "pathology and laboratory medicine", "togaviruses", "chikungunya infection", "pathogens", "geographical locations", "microbiology", "tropical diseases", "saliva", "animals", "alphaviruses", "viruses", "chikungunya virus", ...	Zika Virus, a New Threat for Europe?	journal.pntd.0004901	null	[ [ "Zika virus ( ZIKV ) ( genus Flavivirus , family Flaviviridae ) is an emerging arthropod-borne virus transmitted to humans by Aedes mosquitoes .", "ZIKV infection in humans was first observed in Africa in 1952 [1] , and can cause a broad range of clinical symptoms presenting as a “dengue-like” syndrome: h...	[ "Since its emergence in 2007 in Micronesia and Polynesia , the arthropod-borne flavivirus Zika virus ( ZIKV ) has spread in the Americas and the Caribbean , following first detection in Brazil in May 2015 .", "The risk of ZIKV emergence in Europe increases as imported cases are repeatedly reported .", "Together...	[ "In May 2015 , local transmission of Zika virus ( ZIKV ) was reported in Brazil and since then , more than 1 . 5 million human cases have been reported in Latin America and the Caribbean .", "This arbovirus , primarily found in Africa and Asia , is mainly transmitted by Aedes mosquitoes , Aedes aegypti and Aedes ...	2016
[ "Introduction", "Results", "Discussion", "Material and methods" ]	[ "population genetics", "geographical locations", "social sciences", "neuroscience", "ancient dna", "ethnicities", "cognitive psychology", "paleontology", "dna", "population biology", "paleogenetics", "persian people", "arabic people", "language", "iran", "people and places", "biochem...	Distinct genetic variation and heterogeneity of the Iranian population	journal.pgen.1008385	null	[ [ "The highlands of Iran have been at the crossroads of human migrations [1–6] since the dispersal of modern humans out of Africa due to their geostrategic position .", "While exercising a strong cultural influence on neighboring regions , Iran has also repeatedly received migratory influx in the past mille...	[ "Iran , despite its size , geographic location and past cultural influence , has largely been a blind spot for human population genetic studies .", "With only sparse genetic information on the Iranian population available , we pursued its genome-wide and geographic characterization based on 1021 samples from elev...	[ "Based on genome-wide genotype data on over 1000 samples from eleven ethnic groups present in Iran and by comparison to reference data sets of both extant populations and ancient DNA samples , we show that the Iranian population comprises distinct genetic variation with respect to populations in close geographic pr...	2019
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "invertebrates", "children", "medicine and health sciences", "helminths", "tropical diseases", "hookworms", "parasitic diseases", "anemia", "animals", "health care", "age groups", "neglected tropical diseases", "strongyloides stercoralis", "families", "morbidity", "public and occupatio...	Albendazole and ivermectin for the control of soil-transmitted helminths in an area with high prevalence of Strongyloides stercoralis and hookworm in northwestern Argentina: A community-based pragmatic study	journal.pntd.0006003	null	[ [ "Soil-transmitted helminth ( STH ) infections are the most prevalent Neglected Tropical Diseases ( NTD ) worldwide affecting over 2 billion people .", "Four nematode species ( Ascaris lumbricoides , Trichuris trichiura , Necator americanus and Ancylostoma duodenale ) are the most common STH infections of ...	[ "Recommendations for soil-transmitted helminth ( STH ) control give a key role to deworming of school and pre-school age children with albendazole or mebendazole; which might be insufficient to achieve adequate control , particularly against Strongyloides stercoralis .", "The impact of preventive chemotherapy ( P...	[ "Soil-transmitted helminth ( STH ) infections are a relevant public health problem in resource restricted settings due to their potential to perpetuate poverty , since chronic infections are associated with learning and grow impairment in children and reduced productivity in adults .", "The current strategy for S...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	B Cells Enhance Antigen-Specific CD4 T Cell Priming and Prevent Bacteria Dissemination following Chlamydia muridarum Genital Tract Infection	journal.ppat.1003707	null	[ [ "Chlamydia trachomatis is an obligate intracellular pathogen that causes the most prevalent bacterial sexual transmitted infection worldwide [1] .", "In the US , Chlamydia is now the most common notifiable disease reported to the US Centers for Disease Control ( CDC ) .", "The 1 . 4 million cases of C...	[ "B cells can contribute to acquired immunity against intracellular bacteria , but do not usually participate in primary clearance .", "Here , we examined the endogenous CD4 T cell response to genital infection with Chlamydia muridarum using MHC class-II tetramers .", "Chlamydia-specific CD4 T cells expanded rap...	[ "Sexually transmitted infections caused by Chlamydia are increasing every year in the US and an effective vaccine is urgently required .", "Unfortunately , we currently only have a rudimentary understanding of the natural host immune response to Chlamydia infection , especially in the context of the female genita...	2013
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "physiology", "neuroscience", "homo (human)", "primates" ]	The Peri-Saccadic Perception of Objects and Space	journal.pcbi.0040031	null	[ [ "Our visual experience is derived from a multitude of rapid scanning gaze shifts called saccades .", "However , perception is even more tightly coupled to saccades than by the mere selection of gaze position .", "This can be observed in at least three dynamic phenomena that occur time-locked to an upc...	[ "Eye movements affect object localization and object recognition .", "Around saccade onset , briefly flashed stimuli appear compressed towards the saccade target , receptive fields dynamically change position , and the recognition of objects near the saccade target is improved .", "These effects have been attri...	[ "Early in the vertebrate lineage fast movements of the eye , called saccades , developed .", "This improvement in spatial direction selectivity has been achieved at a cost to handle a sequence of different views .", "Recent experiments showed that the brain uses its knowledge about the upcoming eye movement to ...	2008
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "cell binding", "glycolipids", "cell physiology", "medicine and health sciences", "methods and resources", "toxins", "cell viability testing", "pathology and laboratory medicine", "sphingolipids", "toxic agents", "toxicology", "ricin", "bioassays and physiological analysis", "glycosylation...	Genome-wide CRISPR screens for Shiga toxins and ricin reveal Golgi proteins critical for glycosylation	journal.pbio.2006951	null	[ [ "The plant toxin ricin is derived from castor oil plant seeds .", "It has been utilized as a poison in criminal cases and is classified as a potential bioterrorism agent [1] .", "Shiga and Shiga-like toxins ( Stxs ) are a family of bacterial toxins including the prototype Stx , produced by the bacteri...	[ "Glycosylation is a fundamental modification of proteins and membrane lipids .", "Toxins that utilize glycans as their receptors have served as powerful tools to identify key players in glycosylation processes .", "Here , we carried out Clustered Regularly Interspaced Short Palindromic Repeats ( CRISPR ) -Cas9–...	[ "Shiga and Shiga-like toxins ( Stxs ) are a family of bacterial toxins and key virulence factors for the bacteria Shigella dysenteriae and enterohemorrhagic Escherichia coli ( EHEC ) , which cause food poisoning throughout the world .", "Ricin is a plant toxin and a potential bioterrorism agent .", "Stxs recogn...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Nutritional Control of DNA Replication Initiation through the Proteolysis and Regulated Translation of DnaA	journal.pgen.1005342	null	[ [ "The ability of cells to arrest their growth and proliferation in response to nutrient depletion or stressful conditions is typically critical for their survival .", "Growth arrest requires global changes in protein synthesis leading to a decline in the production of cellular mass .", "Importantly , g...	[ "Bacteria can arrest their own growth and proliferation upon nutrient depletion and under various stressful conditions to ensure their survival .", "However , the molecular mechanisms responsible for suppressing growth and arresting the cell cycle under such conditions remain incompletely understood .", "Here ,...	[ "The duplication of genetic material is a prerequisite for cellular growth and proliferation .", "Under optimal growth conditions , when cells strive to grow and divide , DNA replication must be initiated with high frequency .", "However , under nutrient limiting conditions cells stop initiating DNA replication...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biology" ]	Dynamic Association of NUP98 with the Human Genome	journal.pgen.1003308	null	[ [ "In eukaryotes , the nuclear envelope ( NE ) forms a membrane barrier around the nuclear genome .", "All molecular trafficking in and out of the nucleus is mediated by nuclear pore complexes , large multiprotein channels composed of ∼30 different nuclear pore proteins ( Nups ) that span the NE [1]–[3] .",...	[ "Faithful execution of developmental gene expression programs occurs at multiple levels and involves many different components such as transcription factors , histone-modification enzymes , and mRNA processing proteins .", "Recent evidence suggests that nucleoporins , well known components that control nucleo-cyt...	[ "Development of multicellular organisms such as humans requires appropriate activation of gene expression programs according to stages of differentiation .", "Many proteins that directly regulate this process have been identified , including histone-modifying enzymes and transcription factors .", "It is not cle...	2013
[ "Introduction", "Model", "Results", "Discussion" ]	[ "infectious diseases/epidemiology and control of infectious diseases" ]	Game Theory of Social Distancing in Response to an Epidemic	journal.pcbi.1000793	null	[ [ "Epidemics of infectious diseases are a continuing threat to the health of human communities , and one brought to prominence in the public mind by the 2009 pandemic of H1N1 influenza [1] .", "One of the key questions of public health epidemiology is how individual and community actions can help mitigate a...	[ "Social distancing practices are changes in behavior that prevent disease transmission by reducing contact rates between susceptible individuals and infected individuals who may transmit the disease .", "Social distancing practices can reduce the severity of an epidemic , but the benefits of social distancing dep...	[ "One of the easiest ways for people to lower their risk of infection during an epidemic is for them to reduce their rate of contact with infectious individuals .", "However , the value of such actions depends on how the epidemic progresses .", "Few analyses of behavior change to date have accounted for how chan...	2010
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biochemistry", "nucleic acids", "proteins", "gene expression", "genetics", "dna", "biology", "molecular genetics", "microbiology", "genetics and genomics", "bacterial pathogens" ]	A Fundamental Regulatory Mechanism Operating through OmpR and DNA Topology Controls Expression of Salmonella Pathogenicity Islands SPI-1 and SPI-2	journal.pgen.1002615	null	[ [ "Salmonella enterica is a facultative intracellular pathogen of the mammalian gut .", "After passing through the diverse environments of the stomach and digestive tract , S . enterica can invade host epithelial cells to gain access to internal tissues where it can persist inside macrophage [1] .", "Th...	[ "DNA topology has fundamental control over the ability of transcription factors to access their target DNA sites at gene promoters .", "However , the influence of DNA topology on protein–DNA and protein–protein interactions is poorly understood .", "For example , relaxation of DNA supercoiling strongly induces ...	[ "DNA is often considered to be a passive carrier of genetic information , but in fact DNA is an active participant in coordinating the expression of the genes it carries .", "This is because DNA is a dynamic molecule that can assume a wide range of topologies , and this has a direct impact on the formation of the...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Keeping up with the Joneses: Interpersonal Prediction Errors and the Correlation of Behavior in a Tandem Sequential Choice Task	journal.pcbi.1003275	null	[ [ "Humans learn a range of information from one another [1] and show a particular sensitivity to the influence of group behavior [2] .", "The ultimate evolutionary origins of these behaviors and their dependence on other relevant variables raise broad-ranging questions [3]–[6] however , they also invite imp...	[ "In many settings , copying , learning from or assigning value to group behavior is rational because such behavior can often act as a proxy for valuable returns .", "However , such herd behavior can also be pathologically misleading by coaxing individuals into behaviors that are otherwise irrational and it may be...	[ "In this study we examine the neural substrates of inter-personal error signals on behavior in an investment task using real historical markets .", "We show that behaviorally , subjects correlate their investments , despite the fact that another trader has no extra information about how the market may move .", ...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genetics and genomics/chromosome biology", "computational biology/transcriptional regulation" ]	The Insulator Binding Protein CTCF Positions 20 Nucleosomes around Its Binding Sites across the Human Genome	journal.pgen.1000138	null	[ [ "The positioning of nucleosomes along eukaryotic chromatin affects accessibility of the genomic DNA in vivo .", "Nucleosomes may bind to some genomic regions tightly and prevent transcription factors from approaching their sites .", "Alternatively , strategically positioned nucleosomes can promote lon...	[ "Chromatin structure plays an important role in modulating the accessibility of genomic DNA to regulatory proteins in eukaryotic cells .", "We performed an integrative analysis on dozens of recent datasets generated by deep-sequencing and high-density tiling arrays , and we discovered an array of well-positioned ...	[ "The accessibility of genomic DNA to regulatory proteins and to the transcriptional machinery plays an important role in eukaryotic transcription regulation .", "Some regulatory proteins alter chromatin structures by evicting histones in selected loci .", "Nonetheless , no regulatory proteins have been reported...	2008
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "microbial mutation", "interaction networks", "medicine and health sciences", "pathology and laboratory medicine", "viruses and cancer", "pathogens", "cancer risk factors", "microbiology", "retroviruses", "viruses", "immunodeficiency viruses", "oncology", "rna viruses", "medical risk facto...	Convergent perturbation of the human domain-resolved interactome by viruses and mutations inducing similar disease phenotypes	journal.pcbi.1006762	null	[ [ "Cellular function and behaviour are driven by highly coordinated biomolecular interaction networks .", "A prime example is the protein-protein interaction ( PPI ) network , also known as the protein “interactome” or interactome for short .", "A central focus of disease systems biology is to use inter...	[ "An important goal of systems medicine is to study disease in the context of genetic and environmental perturbations to the human interactome network .", "For diseases with both genetic and infectious contributors , a key postulate is that similar perturbations of the human interactome by either disease mutations...	[ "Cellular function and behaviour are driven by highly coordinated biomolecular interaction networks .", "A prime example is the protein-protein interaction network , often simply referred to as the “interactome” .", "Recent advances in systems biology have spawned the view of human disease as a manifestation of...	2019
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "infectious diseases/bacterial infections", "infectious diseases/neglected tropical diseases", "infectious diseases/tropical and travel-associated diseases", "microbiology/immunity to infections" ]	A Novel Animal Model of Borrelia recurrentis Louse-Borne Relapsing Fever Borreliosis Using Immunodeficient Mice	journal.pntd.0000522	null	[ [ "Bacteria of the genus Borrelia are spirochetes that cause either Lyme disease or relapsing fever ( RF ) .", "Borrelia species are transferred from animals to humans by tick bites , with the single exception of B . recurrentis , which is transmitted between humans by the body louse Pediculus humanus human...	[ "Louse-borne relapsing fever ( LBRF ) borreliosis is caused by Borrelia recurrentis , and it is a deadly although treatable disease that is endemic in the Horn of Africa but has epidemic potential .", "Research on LBRF has been severely hampered because successful infection with B . recurrentis has been achieved ...	[ "Research on Borrelia recurrentis , the agent of louse-borne relapsing fever ( LBRF ) , has been hampered by the lack of a feasible non-primate animal model .", "By using immunocompromised SCID mice deficient in B- and T-cells , we were able to establish a stable , persistent B . recurrentis infection with low sp...	2009
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Angiogenic Activity of Breast Cancer Patients’ Monocytes Reverted by Combined Use of Systems Modeling and Experimental Approaches	journal.pcbi.1004050	null	[ [ "Elucidating the various cell signaling cascades , pathway crosstalk , and how they influence final cell fate and behavior is crucial for defining therapeutic intervention points aimed at driving a cell towards a desired state .", "To this end , modeling approaches can be used to perturb a biological syst...	[ "Angiogenesis plays a key role in tumor growth and cancer progression .", "TIE-2-expressing monocytes ( TEM ) have been reported to critically account for tumor vascularization and growth in mouse tumor experimental models , but the molecular basis of their pro-angiogenic activity are largely unknown .", "Moreo...	[ "Tumor vascularization is essential for tumor growth and cancer progression .", "In breast cancer , monocytes are angiogenic , i . e . able to induce tumor vascularization .", "In patients , blood circulating monocytes drastically increase their angiogenic activity when reaching the tumor , suggesting that the ...	2015
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "medicine and health sciences", "legs", "gene regulation", "regulatory proteins", "dna-binding proteins", "limbs (anatomy)", "cloning", "transcription factors", "sequence motif analysis", "molecular biology techniques", "research and analysis methods", "sequence analysis", "specimen preparat...	Tissue-specific enhancer repression through molecular integration of cell signaling inputs	journal.pgen.1006718	null	[ [ "In developing arthropod and vertebrate appendages , morphogen gradients play critical roles in instructing the spatially-restricted expression of patterning genes that mostly encode transcription factors ( TFs ) [1 , 2] .", "However , how their expression domains are set up precisely and how their cross-...	[ "Drosophila leg morphogenesis occurs under the control of a relatively well-known genetic cascade , which mobilizes both cell signaling pathways and tissue-specific transcription factors .", "However , their cross-regulatory interactions , deployed to refine leg patterning , remain poorly characterized at the gen...	[ "Limb morphogenesis is controlled by a well-known genetic cascade , mobilizing both cell signaling and tissue-specific transcription factors ( TFs ) .", "However , how their concerted action refines gene expression remains to be deciphered .", "It is thus crucial to understand how cell signaling inputs are inte...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "model organisms", "genetics", "biology", "microbiology", "molecular cell biology", "biophysics", "genetics and genomics" ]	Regulation of Budding Yeast Mating-Type Switching Donor Preference by the FHA Domain of Fkh1	journal.pgen.1002630	null	[ [ "Saccharomyces mating-type switching occurs through a DSB-initiated intrachromosomal gene conversion event at MAT , using one of two donors on chromosome III , HML and HMR ( Figure 1A ) [1]–[3] .", "Switching is initiated by expression of the site-specific HO endonuclease that cleaves only one site in the...	[ "During Saccharomyces cerevisiae mating-type switching , an HO endonuclease-induced double-strand break ( DSB ) at MAT is repaired by recombining with one of two donors , HMLα or HMRa , located at opposite ends of chromosome III .", "MATa cells preferentially recombine with HMLα; this decision depends on the Reco...	[ "Mating-type gene switching occurs by a DSB–initiated gene conversion event using one of two donors , HML or HMR .", "MATa cells preferentially recombine with HML whereas MATα cells choose HMR .", "Donor preference is governed by the Recombination Enhancer ( RE ) , located about 17 kb from HML .", "RE is repr...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "neuroscience/behavioral neuroscience", "neuroscience/sensory systems", "cell biology/neuronal signaling mechanisms", "genetics and genomics/gene function", "pharmacology" ]	Plant Insecticide L-Canavanine Repels Drosophila via the Insect Orphan GPCR DmX	journal.pbio.1000147	An orphan G-protein-coupled gustatory receptor mediates detection of the plant poison L-canavanine in fruit flies.	[ [ "Taste is essential to distinguish between nutritious and toxic substances .", "To avoid eating toxins , animals are able to detect them by using a repertoire of taste receptors [1] .", "Although it is recognized that a bitter taste sensation is critical to avoid toxic substances [2] , [3] , the cellu...	[ "For all animals , the taste sense is crucial to detect and avoid ingesting toxic molecules .", "Many toxins are synthesized by plants as a defense mechanism against insect predation .", "One example of such a natural toxic molecule is l-canavanine , a nonprotein amino acid found in the seeds of many legumes ."...	[ "Plants evolve to fend off the insects that attack them , often by synthesizing compounds toxic to insects .", "In turn , insects develop strategies to avoid these plants or resist their toxins .", "Some plant toxins are nonprotein amino acids .", "For example , seeds from numerous legumes contain high amount...	2009
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "neuropsychiatric disorders", "medicine and health sciences", "neurochemistry", "chemical compounds", "dopaminergics", "brain", "vertebrates", "neuroscience", "organic compounds", "animals", "mammals", "hormones", "primates", "amines", "neurotransmitters", "cerebellum", "catecholamin...	Dysfunctions of the basal ganglia-cerebellar-thalamo-cortical system produce motor tics in Tourette syndrome	journal.pcbi.1005395	null	[ [ "Tourette syndrome ( TS ) is a neuropsychiatric disorder characterized by the presence of sudden and repetitive involuntary movements or vocalizations , generally termed as “tics” , having differing degrees of intensity and frequency , and unpredictable duration [1 , 2] .", "Tics can be simple , for examp...	[ "Motor tics are a cardinal feature of Tourette syndrome and are traditionally associated with an excess of striatal dopamine in the basal ganglia .", "Recent evidence increasingly supports a more articulated view where cerebellum and cortex , working closely in concert with basal ganglia , are also involved in ti...	[ "Tourette syndrome is a neuropsychiatric disorder characterized by vocal and motor tics .", "Tics represent a cardinal symptom traditionally associated with a dysfunction of the basal ganglia leading to an excess of the dopamine neurotransmitter .", "This view gives a restricted clinical picture and limits ther...	2017
[ "Introduction", "Materials and methods", "Results", "Discussion", "Conclusions" ]	[ "invertebrates", "medicine and health sciences", "pathology and laboratory medicine", "population genetics", "geographical locations", "tropical diseases", "australia", "animals", "gene pool", "bacterial diseases", "signs and symptoms", "ulcers", "neglected tropical diseases", "molecular b...	A survey on Mycobacterium ulcerans in Mosquitoes and March flies captured from endemic areas of Northern Queensland, Australia	journal.pntd.0006745	null	[ [ "Buruli ulcer ( BU ) , also known regionally as Daintree ulcer in north Queensland , Australia or Bairnsdale ulcer in Victoria , Australia , is an emerging disease of skin and underlying tissue , with a potential to lead to permanent disability , particularly if treatment is inadequate or delayed .", "The...	[ "Mycobacterium ulcerans is the causative agent of Buruli ulcer ( BU ) .", "This nontuberculous mycobacterial infection has been reported in 34 countries worldwide .", "In Australia , the majority of cases of BU have been recorded in coastal Victoria and the Mossman-Daintree areas of north Queensland .", "Mosq...	[ "The causative agent of Buruli ulcer is Mycobacterium ulcerans .", "This destructive skin disease is characterized by extensive and painless necrosis of skin and underlying tissues usually on extremities of body due to production of toxin named mycolactone .", "The disease is prevalent in Africa and coastal Aus...	2019
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biochemistry", "protein chemistry", "proteins", "protein folding", "macromolecular assemblies", "biology", "biophysics", "neuroscience" ]	Small Heat Shock Proteins Potentiate Amyloid Dissolution by Protein Disaggregases from Yeast and Humans	journal.pbio.1001346	The authors define how small heat-shock proteins synergize to regulate the assembly and disassembly of a beneficial prion, and then they exploit this knowledge to identify the human amyloid depolymerase.	[ [ "Amyloid fibers are thread-like protein polymers with cross-β structure .", "These unusually stable , self-templating structures were first identified in various systemic amyloidoses and neurodegenerative disorders such as Alzheimer's disease [1] .", "In isolation , many proteins can form amyloid fibe...	[ "How small heat shock proteins ( sHsps ) might empower proteostasis networks to control beneficial prions or disassemble pathological amyloid is unknown .", "Here , we establish that yeast sHsps , Hsp26 and Hsp42 , inhibit prionogenesis by the [PSI+] prion protein , Sup35 , via distinct and synergistic mechanisms...	[ "Amyloid fibers are protein aggregates that are associated with numerous neurodegenerative diseases , including Parkinson's disease , for which there are no effective treatments .", "They can also play beneficial roles; in yeast , for example , they are associated with increased survival and the evolution of new ...	2012
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "invertebrates", "medicine and health sciences", "plagues", "pathology and laboratory medicine", "respiratory infections", "pathogens", "geographical locations", "microbiology", "uganda", "vertebrates", "animals", "pulmonology", "mammals", "bacterial diseases", "yersinia", "fleas", "...	Two Distinct Yersinia pestis Populations Causing Plague among Humans in the West Nile Region of Uganda	journal.pntd.0004360	null	[ [ "Yersinia pestis is the etiological agent of plague , a severe and often fatal disease in humans [1] .", "Transmission of Y . pestis to humans most often occurs through the bite of an infectious flea or by direct exposure to an infected mammalian host .", "Less frequently , human infection is the resu...	[ "Plague is a life-threatening disease caused by the bacterium , Yersinia pestis .", "Since the 1990s , Africa has accounted for the majority of reported human cases .", "In Uganda , plague cases occur in the West Nile region , near the border with Democratic Republic of Congo .", "Despite the ongoing risk of ...	[ "Plague , a severe and often fatal zoonotic disease , is caused by the bacterium Yersinia pestis .", "Currently , the majority of human cases have been reported from resource limited areas of Africa , where the proximity to commensal rats and other small mammals increases the likelihood for human contact with inf...	2016
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "blood cells", "medicine and health sciences", "parasite groups", "liver", "plasmodium", "gene regulation", "parasitic diseases", "parasitic protozoans", "parasitology", "developmental biology", "apicomplexa", "protozoans", "red blood cells", "monomers (chemistry)", "small interfering rn...	Plasmodium parasite exploits host aquaporin-3 during liver stage malaria infection	journal.ppat.1007057	null	[ [ "Malaria remains one of the greatest burdens to global health with an estimated 440 , 000 deaths in 2015 [1] .", "While fatalities attributed to malaria have significantly declined over the past decade as a result of increased interventions , the spread of resistance to current antimalarial treatments and...	[ "Within the liver a single Plasmodium parasite transforms into thousands of blood-infective forms to cause malaria .", "Here , we use RNA-sequencing to identify host genes that are upregulated upon Plasmodium berghei infection of hepatocytes with the hypothesis that host pathways are hijacked to benefit parasite ...	[ "Plasmodium parasites undergo an obligatory morphogenesis and replication within the liver before they invade red blood cells and cause malaria .", "The liver stage is clinically silent but essential for the Plasmodium parasite to complete its life cycle .", "During this time , the parasite relies on the host c...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Experimental Evidence for Phonemic Contrasts in a Nonhuman Vocal System	journal.pbio.1002171	The chestnut-crowned babbler, a social species of bird from the Australian outback, possesses the basic capacity to generate words, shedding new light on the origins of word generation in our own species.	[ [ "The vast lexicons that characterise human languages are the product of physical and cognitive processes that guide the combination of a limited number of meaningless sounds ( phonemes ) in a variety of ways to generate new meaning [1 , 2] .", "In a simple example , the phonemes /k/ , /æ/ and /t/ can be r...	[ "The ability to generate new meaning by rearranging combinations of meaningless sounds is a fundamental component of language .", "Although animal vocalizations often comprise combinations of meaningless acoustic elements , evidence that rearranging such combinations generates functionally distinct meaning is lac...	[ "A major question in language evolution is how its generative power emerged .", "This power , which allows the communication of limitless thoughts and ideas , is a result of the combinatorial nature of human language: meaningless phonemes can be combined to form meaningful words ( phonology ) , and words can be c...	2015
[ "Introduction", "Results", "Discussion", "Methods" ]	[]	Transcript Expression Data from Human Islets Links Regulatory Signals from Genome-Wide Association Studies for Type 2 Diabetes and Glycemic Traits to Their Downstream Effectors	journal.pgen.1005694	null	[ [ "Genome-wide association studies ( GWAS ) have identified approximately 80 loci robustly associated with predisposition to type 2 diabetes ( T2D ) [1–3] and a further 70 influencing a range of continuous glycemic traits [4–10] in non-diabetic subjects .", "There is substantial , though far from complete ,...	[ "The intersection of genome-wide association analyses with physiological and functional data indicates that variants regulating islet gene transcription influence type 2 diabetes ( T2D ) predisposition and glucose homeostasis .", "However , the specific genes through which these regulatory variants act remain poo...	[ "Genetic studies have uncovered many different parts of the genome playing a role in the risk of developing diabetes , or affecting blood sugar levels in the normal population .", "However , it has so far been difficult to tie these parts of the genome to genes that are responsible for the observed changes in ris...	2015
[ "Introduction", "Materials and methods", "Results", "Discussion" ]	[ "medicine and health sciences", "body fluids", "diagnostic radiology", "pathology and laboratory medicine", "tropical diseases", "bile", "parasitic diseases", "surgical and invasive medical procedures", "magnetic resonance imaging", "signs and symptoms", "neglected tropical diseases", "researc...	Standardized endocystectomy technique for surgical treatment of uncomplicated hepatic cystic echinococcosis	journal.pntd.0007516	null	[ [ "Cystic echinococcosis ( CE ) is a parasitic disease caused by ingestion of the larval stage of Echinococcus granulosus .", "The liver is the most commonly infected organ ( about 75% of cases ) , followed by the lungs and other organs .", "In most high-income countries , the incidence of CE is very lo...	[ "Two surgical options are available for cystic echinococcosis ( CE ) .", "The two principal approaches are radical ( resection of the cyst ) and conservative ( evacuation of the cyst content and partial removal of the cyst capsule ) .", "Here , we describe a standardized endocystectomy technique for hepatic ech...	[ "Cystic echinococcosis ( CE ) is a parasitic disease caused by ingestion of the larval stage of Echinococcus granulosus .", "The liver is the most commonly infected organ .", "There are currently four treatments for CE: surgery , percutaneous treatment , medical treatment ( benzimidazoles ) , and watch-and-wait...	2019
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "genetics", "biology", "computational biology", "evolutionary biology", "population biology", "genetics and genomics" ]	The Probability of a Gene Tree Topology within a Phylogenetic Network with Applications to Hybridization Detection	journal.pgen.1002660	null	[ [ "A molecular systematics paradigm that views molecular sequences as the characters of gene trees , and gene trees as characters of the species tree [1] is being increasingly adopted in the post-genomic era [2] , [3] .", "Several models of evolution for the former type of characters have been devised [4] ,...	[ "Gene tree topologies have proven a powerful data source for various tasks , including species tree inference and species delimitation .", "Consequently , methods for computing probabilities of gene trees within species trees have been developed and widely used in probabilistic inference frameworks .", "All the...	[ "Species trees depict how species split and diverge .", "Within the branches of a species tree , gene trees , which depict the evolutionary histories of different genomic regions in the species , grow .", "Evolutionary analyses of the genomes of closely related organisms have highlighted the phenomenon that gen...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "cellular stress responses", "model organisms", "rna processing", "dna replication", "nucleic acids", "gene expression", "genetics", "gene regulation", "molecular genetics", "yeast and fungal models", "biology", "saccharomyces cerevisiae", "molecular cell biology", "dna", "dna recombinat...	Cleavage Factor I Links Transcription Termination to DNA Damage Response and Genome Integrity Maintenance in Saccharomyces cerevisiae	journal.pgen.1004203	null	[ [ "All cells are continuously exposed to DNA damaging agents , which can arise from exogenous sources or from endogenous metabolic processes .", "The DNA damage response ( DDR ) includes the activation of checkpoints and induction of DNA repair pathways .", "DNA lesions can generate structural distortio...	[ "During transcription , the nascent pre-mRNA undergoes a series of processing steps before being exported to the cytoplasm .", "The 3′-end processing machinery involves different proteins , this function being crucial to cell growth and viability in eukaryotes .", "Here , we found that the rna14-1 , rna15-1 , a...	[ "DNA damage occurs constantly in living cells and needs to be recognized and repaired to avoid mutations .", "DNA repair is particularly relevant for lesions occurring in actively transcribed DNA strands because the RNA polymerase cannot proceed through a damaged site .", "Stalled RNA polymerases and persisting...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "invertebrates", "animal genetics", "protein interactions", "enzymology", "dna-binding proteins", "animals", "cell differentiation", "dna transcription", "animal models", "developmental biology", "drosophila melanogaster", "model organisms", "organism development", "morphogenesis", "patt...	Drosophila melanogaster Hox Transcription Factors Access the RNA Polymerase II Machinery through Direct Homeodomain Binding to a Conserved Motif of Mediator Subunit Med19	journal.pgen.1004303	null	[ [ "The finely regulated gene transcription permitting development of pluricellular organisms involves the action of transcription factors ( TFs ) that bind DNA targets and convey this information to RNA polymerase II ( PolII ) .", "Hox TFs , discovered through iconic mutations of the Drosophila melanogaster...	[ "Hox genes in species across the metazoa encode transcription factors ( TFs ) containing highly-conserved homeodomains that bind target DNA sequences to regulate batteries of developmental target genes .", "DNA-bound Hox proteins , together with other TF partners , induce an appropriate transcriptional response b...	[ "Mutations of Hox developmental genes in the fruit fly Drosophila melanogaster may provoke spectacular changes in form: transformations of one body part into another , or loss of organs .", "This attribute identifies them as important developmental genes .", "Insect and vertebrate Hox proteins contain highly re...	2014
[ "Introduction", "Methods", "Results and discussion" ]	[ "medicine and health sciences", "chemical compounds", "electricity", "electrophysiology", "neuroscience", "organic compounds", "simulation and modeling", "ion channels", "electrostatics", "basic amino acids", "amino acids", "thermodynamics", "research and analysis methods", "sodium channel...	Selective ion permeation involves complexation with carboxylates and lysine in a model human sodium channel	journal.pcbi.1006398	null	[ [ "Voltage-gated sodium ( Nav ) channels are widely distributed in the central and peripheral nervous systems where they participate in essential functions , including heartbeat , muscle contraction and brain activity [1 , 2] .", "Dysfunctional Navs are associated with several physiological disorders , incl...	[ "Bacterial and human voltage-gated sodium channels ( Navs ) exhibit similar cation selectivity , despite their distinct EEEE and DEKA selectivity filter signature sequences .", "Recent high-resolution structures for bacterial Navs have allowed us to learn about ion conduction mechanisms in these simpler homo-tetr...	[ "Ion channels can rapidly and selectively conduct an ionic species , essential for the firing of neurons , where sodium and potassium channels respond to changes in membrane potential to release stores of sodium and potassium ions in succession .", "The ability of a protein pore to discriminate between these two ...	2018
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "genetics", "biology", "evolutionary biology", "genomic evolution", "genetics and genomics" ]	Mechanisms Involved in the Functional Divergence of Duplicated GroEL Chaperonins in Myxococcus xanthus DK1622	journal.pgen.1003306	null	[ [ "Chaperonins are essential cellular components that are responsible for protein folding , assembly and transport [1]–[6] .", "Chaperonins are also a major group of heat shock proteins that are over-expressed at high temperatures and have fundamental roles in growth and survival at non-permissive temperatu...	[ "The gene encoding the GroEL chaperonin is duplicated in nearly 30% of bacterial genomes; and although duplicated groEL genes have been comprehensively determined to have distinct physiological functions in different species , the mechanisms involved have not been characterized to date .", "Myxococcus xanthus DK1...	[ "GroEL is a type I chaperonin , involved in protein folding , assembly , and transport .", "It is a major group of heat-shock proteins that are over-expressed at high temperatures and has fundamental roles in growth and survival at non-permissive temperatures .", "Because of its importance in many cellular proc...	2013
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "medicine and health sciences", "molecular probe techniques", "immunoblotting", "dyneins", "molecular motors", "respiratory system", "immunoprecipitation", "co-immunoprecipitation", "molecular biology techniques", "trachea", "immunologic techniques", "cellular structures and organelles", "mo...	ZMYND10 stabilizes intermediate chain proteins in the cytoplasmic pre-assembly of dynein arms	journal.pgen.1007316	null	[ [ "Primary ciliary dyskinesia ( PCD ) is an autosomal-recessive disorder caused by defective motile cilia or flagella that is characterized by respiratory distress , impaired mucociliary clearance , chronic cough , sinusitis , bronchiectasis , male infertility , laterality defects , and cardiac anomalies in ter...	[ "Zinc finger MYND-type-containing 10 ( ZMYND10 ) , a cytoplasmic protein expressed in ciliated cells , causes primary ciliary dyskinesia ( PCD ) when mutated; however , its function is poorly understood .", "Therefore , in this study , we examined the roles of ZMYND10 using Zmynd10–/–mice exhibiting typical PCD p...	[ "Dynein arm defects are linked to primary ciliary dyskinesia ( PCD ) .", "ZMYND10 increased the stability of its interacting proteins and specifically regulated intermediate chain protein assembly , revealing tightly regulated mechanisms underlying dynein arm assembly and PCD-related pathogenesis .", "Increasin...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "germ cells", "meiosis", "molecular cell biology", "cell biology", "chromosome biology", "cellular types", "biology", "genomics", "genetics and genomics" ]	CRL2LRR-1 E3-Ligase Regulates Proliferation and Progression through Meiosis in the Caenorhabditis elegans Germline	journal.pgen.1003375	null	[ [ "The ubiquitin-proteolytic system has emerged as a central mechanism to regulate protein turnover spatially and temporally [1] , [2] .", "In this system , ubiquitin , a small polypeptide of 76 amino acids , is covalently linked to a target protein through an enzymatic cascade , and the assembly of a poly-...	[ "The ubiquitin-proteolytic system controls the stability of proteins in space and time .", "In this study , using a temperature-sensitive mutant allele of the cul-2 gene , we show that CRL2LRR-1 ( CUL-2 RING E3 ubiquitin-ligase and the Leucine Rich Repeat 1 substrate recognition subunit ) acts at multiple levels ...	[ "Maintenance of the germline depends on the presence of a germline stem cell pool with self-renewal potential that produces gametes upon meiotic differentiation .", "Factors regulating the balance between germline stem cell self-renewal and meiotic differentiation ensure germline homeostasis , whereas disruption ...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "dimers (chemical physics)", "medicine and health sciences", "toxins", "pathology and laboratory medicine", "engineering and technology", "gene regulation", "signal processing", "messenger rna", "signal filtering", "toxic agents", "toxicology", "dna transcription", "physiological processes",...	Hierarchical Post-transcriptional Regulation of Colicin E2 Expression in Escherichia coli	journal.pcbi.1005243	null	[ [ "Regulation of gene expression occurs at transcriptional and post-transcriptional levels , and has been studied intensively both experimentally and theoretically [1–10] .", "Bacterial stress responses , such as the well-studied production and release of the toxin colicin E2 in Escherichia coli , represent...	[ "Post-transcriptional regulation of gene expression plays a crucial role in many bacterial pathways .", "In particular , the translation of mRNA can be regulated by trans-acting , small , non-coding RNAs ( sRNAs ) or mRNA-binding proteins , each of which has been successfully treated theoretically using two-compo...	[ "Gene expression is a fundamental biological process , in which living cells use genetic information to synthesize functional products like proteins .", "To control this process , cells make use of many different mechanisms .", "A well-studied example is the binding of expression intermediates by a cellular com...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "public health and epidemiology" ]	Meta-Analysis of the INSIG2 Association with Obesity Including 74,345 Individuals: Does Heterogeneity of Estimates Relate to Study Design?	journal.pgen.1000694	null	[ [ "One of the first genome-wide association ( GWA ) studies ever and the first on obesity identified the INSIG2 gene represented by the rs7566605 polymorphism as a novel gene for common obesity [1] .", "Functional evidence depicted the INSIG2 gene from the very start as an interesting candidate for obesity ...	[ "The INSIG2 rs7566605 polymorphism was identified for obesity ( BMI≥30 kg/m2 ) in one of the first genome-wide association studies , but replications were inconsistent .", "We collected statistics from 34 studies ( n = 74 , 345 ) , including general population ( GP ) studies , population-based studies with subjec...	[ "A polymorphism of the INSIG2 gene was identified as being associated with obesity in one of the first genome-wide association studies .", "However , this association has since then been highly debated upon inconsistent subsequent reports .", "We collected association information from 34 studies including a tot...	2009
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "taste buds", "organoids", "medicine and health sciences", "chemical compounds", "biological cultures", "social sciences", "vertebrates", "mice", "neuroscience", "animals", "mammals", "tongue", "organ cultures", "digestive system", "research and analysis methods", "specimen preparation...	Gli3 is a negative regulator of Tas1r3-expressing taste cells	journal.pgen.1007058	null	[ [ "In mouse tongue taste buds are found in three types of papillae: anterior fungiform ( FF ) , lateral foliate ( FO ) , and posterior circumvallate ( CV ) .", "The numerous FF papillae each contain a single taste bud , while the two FO and single CV papillae each contain hundreds of taste buds [1 , 2] .", ...	[ "Mouse taste receptor cells survive from 3–24 days , necessitating their regeneration throughout adulthood .", "In anterior tongue , sonic hedgehog ( SHH ) , released by a subpopulation of basal taste cells , regulates transcription factors Gli2 and Gli3 in stem cells to control taste cell regeneration .", "Usi...	[ "Adult taste cell regeneration is essential for maintaining peripheral taste cells throughout life .", "The Shh pathway is an important regulator of taste bud development and regeneration in both embryonic and adult stages .", "We show that the transcription factor Gli3 , an important effector of the Shh pathwa...	2018
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "sequencing techniques", "urology", "medicine and health sciences", "cancer treatment", "immunology", "clinical oncology", "cancers and neoplasms", "vertebrates", "genitourinary tract tumors", "cancer immunotherapy", "dogs", "animals", "mammals", "oncology", "clinical medicine", "bladd...	Naturally-occurring canine invasive urothelial carcinoma harbors luminal and basal transcriptional subtypes found in human muscle invasive bladder cancer	journal.pgen.1007571	null	[ [ "Muscle invasive bladder cancer or more specifically , invasive urothelial carcinoma ( iUC ) , is lethal in approximately 50% of patients , with most deaths being due to drug-resistant metastatic disease [1] .", "Clearly better therapies for iUC are needed .", "One of the key advances that could impro...	[ "There is growing evidence that molecular subtypes ( e . g . luminal and basal subtypes ) affect the prognosis and treatment response in patients with muscle invasive urinary bladder cancer ( invasive urothelial carcinoma , iUC ) .", "Modeling these subtypes in pre-clinical animal studies is essential , but it is...	[ "Approximately 50% of patients with invasive urinary bladder cancer ( invasive urothelial carcinoma , “iUC” ) die from their cancer .", "Better therapeutic strategies are essential .", "A relatively recent important finding in iUC is the presence of molecular subtypes ( luminal and basal subtypes ) .", "These...	2018
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "genome expression analysis", "animal genetics", "functional genomics", "quantitative trait loci", "population genetics", "quantitative traits", "diet", "mutation", "nutrition", "genome analysis", "trait locus analysis", "missense mutation", "mutant strains", "genetic polymorphism", "gen...	An Evolutionarily Conserved Role for the Aryl Hydrocarbon Receptor in the Regulation of Movement	journal.pgen.1004673	null	[ [ "Recent studies have highlighted the utility of the BXD murine genetic reference population in the study of metabolism [1] .", "The BXD population consists of ∼100 related strains descended from C57BL/6J ( B6 ) and DBA/2J ( D2 ) [2] , and has wide phenotypic variance in key traits such as blood pressure [...	[ "The BXD genetic reference population is a recombinant inbred panel descended from crosses between the C57BL/6 ( B6 ) and DBA/2 ( D2 ) strains of mice , which segregate for about 5 million sequence variants .", "Recently , some of these variants have been established with effects on general metabolic phenotypes s...	[ "Using 43 strains from the BXD mouse reference population , we observed a 5-fold difference in spontaneous activity .", "QTL analysis indicated that ∼40% of this variance is due to the aryl hydrocarbon receptor ( Ahr ) .", "Ahr is a conserved transcription factor found in nearly all multicellular organisms and ...	2014
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[]	Coevolution of the Ile1,016 and Cys1,534 Mutations in the Voltage Gated Sodium Channel Gene of Aedes aegypti in Mexico	journal.pntd.0004263	null	[ [ "Worldwide Aedes aegypti ( L . ) mosquitoes are the principal urban vectors of dengue , chikungunya , and yellow fever viruses .", "Approximately 2 . 5 billion people ( 40% of the human population ) currently live with the risk of dengue transmission .", "In Mexico , Ae .", "aegypti is the primary...	[ "Worldwide the mosquito Aedes aegypti ( L . ) is the principal urban vector of dengue viruses .", "Currently 2 . 5 billion people are at risk for infection and reduction of Ae .", "aegypti populations is the most effective means to reduce the risk of transmission .", "Pyrethroids are used extensively for adul...	[ "Constant use of pyrethroid insecticides has driven mosquito populations to develop resistance .", "In Aedes aegypti , the primary mosquito vector of dengue , yellow Fever , and chikungunya viruses , pyrethroid resistance is primarily associated with mutations in the voltage-gated sodium channel protein .", "On...	2015
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "evolutionary biology/evolutionary ecology", "immunology/innate immunity", "immunology", "infectious diseases/protozoal infections", "evolutionary biology", "immunology/immunity to infections" ]	Sex and Death: The Effects of Innate Immune Factors on the Sexual Reproduction of Malaria Parasites	journal.ppat.1001309	null	[ [ "Malaria parasites are obliged to undertake a single round of sexual reproduction in the mosquito vector before they can transmit to new hosts , making this stage of their life-cycle a potential target for medical interventions [1] , [2] .", "The success of interventions aiming to disrupt mating success w...	[ "Malaria parasites must undergo a round of sexual reproduction in the blood meal of a mosquito vector to be transmitted between hosts .", "Developing a transmission-blocking intervention to prevent parasites from mating is a major goal of biomedicine , but its effectiveness could be compromised if parasites can c...	[ "Malaria and related parasites cause some of the most serious infectious diseases of humans , domestic animals and wildlife .", "To be transmitted , these parasites produce male and female sexual stages that differentiate into gametes and mate when taken up in a mosquito blood meal .", "Despite the need to deve...	2011
[ "Introduction", "Results and discussion", "Materials and methods" ]	[ "medicine and health sciences", "pathology and laboratory medicine", "pathogens", "dna-binding proteins", "microbiology", "campylobacter jejuni", "genetic elements", "molecular biology techniques", "bacteria", "campylobacter", "bacterial pathogens", "digestive system", "research and analysis...	Metabolic and fitness determinants for in vitro growth and intestinal colonization of the bacterial pathogen Campylobacter jejuni	journal.pbio.2001390	null	[ [ "Campylobacter jejuni subsp .", "jejuni ( C . jejuni ) is one of the most common causes of infectious food-borne illness in industrialized countries [1 , 2] .", "The high incidence of this pathogen is due to its ability to persistently colonize the intestinal tract of food-producing animals .", "C...	[ "Campylobacter jejuni is one of the leading infectious causes of food-borne illness around the world .", "Its ability to persistently colonize the intestinal tract of a broad range of hosts , including food-producing animals , is central to its epidemiology since most infections are due to the consumption of cont...	[ "There is accumulating evidence that in addition to canonical virulence factors such as toxins , adhesins , or invasins , bacterial pathogens utilize specific metabolic traits to colonize and proliferate within their hosts , a concept that is increasingly referred to as “nutritional virulence” .", "We have used t...	2017
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "schistosoma", "invertebrates", "innate immune system", "medicine and health sciences", "immune cells", "immune physiology", "cytokines", "helminths", "granulomas", "immunology", "animals", "vaccines", "preventive medicine", "developmental biology", "immunologic adjuvants", "molecular ...	Combined IL-12 Plasmid and Recombinant SjGST Enhance the Protective and Anti-pathology Effect of SjGST DNA Vaccine Against Schistosoma japonicum	journal.pntd.0004459	null	[ [ "Schistosomiasis is an important helminth parasitic disease , and it remains a major health problem worldwide , especially in tropical and subtropical countries [1] .", "Schistosoma japonicum causes the most severe pathological symptoms , and it is estimated that several million people in China are infect...	[ "Schistosomiasis is listed as one of most important tropical diseases and more than 200 million people are estimated to be infected .", "Development of a vaccine is thought to be the most effective way to control this disease .", "Recombinant 26-kDa glutathione S-transferase ( rSjGST ) has previously been repor...	[ "Schistosomiasis continues to be a serious global public health problem that considered by World Health Organization ( WHO ) .", "More than 200 million people are infected and cause 280 thousand deaths every year .", "Among , Schistosoma japonicum causes the most severe pathological damages and the slowest immu...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "developmental biology", "evolutionary biology", "biology", "pattern formation", "evolutionary developmental biology" ]	Reciprocal Signaling between the Ectoderm and a Mesendodermal Left-Right Organizer Directs Left-Right Determination in the Sea Urchin Embryo	journal.pgen.1003121	null	[ [ "Left-right ( L/R ) asymmetry is an essential feature of development in most bilaterian animals .", "In vertebrates , the morphology and positioning of many internal organs as well as development of the nervous system is left-right asymmetric and failure to establish these asymmetries can result in pathol...	[ "During echinoderm development , expression of nodal on the right side plays a crucial role in positioning of the rudiment on the left side , but the mechanisms that restrict nodal expression to the right side are not known .", "Here we show that establishment of left-right asymmetry in the sea urchin embryo reli...	[ "Asymmetries between the left and the right sides of the body are an essential feature of most bilaterian animals , and failure to establish these asymmetries can result in pathological disorders in humans .", "Left-right asymmetries are established during early development by the asymmetric activity of a signali...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genetics and genomics/gene expression", "developmental biology/developmental evolution", "genetics and genomics/epigenetics", "developmental biology/developmental molecular mechanisms", "evolutionary biology/developmental evolution" ]	Postnatal Survival of Mice with Maternal Duplication of Distal Chromosome 7 Induced by a Igf2/H19 Imprinting Control Region Lacking Insulator Function	journal.pgen.1000803	null	[ [ "Parthenogenetic mouse embryos usually die before 6½ days post coitum ( dpc ) .", "Occasionally they develop to the 25 somite forelimb bud stage or approximately 9½ dpc [1]–[5] .", "Parthenogenones possess two maternally-derived genomes and would be expected to possess abnormal levels of transcript of...	[ "The misexpressed imprinted genes causing developmental failure of mouse parthenogenones are poorly defined .", "To obtain further insight , we investigated misexpressions that could cause the pronounced growth deficiency and death of fetuses with maternal duplication of distal chromosome ( Chr ) 7 ( MatDup . dis...	[ "Parthenogenetic mouse embryos with two maternal genomes die early in development due to the misexpression of imprinted genes .", "To gain further insight into which misexpressions might be involved , we examined some of the misexpressions that could determine the small size and fetal death of a “partial partheno...	2010
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "population genetics", "vertebrates", "animals", "mammals", "alleles", "genetic mapping", "mutation", "population biology", "frameshift mutation", "swine", "genetic loci", "genetic drift", "haplotypes", "heterosis", "eukaryota", "heredity", "genetics", "biology and life sciences", ...	Loss of function mutations in essential genes cause embryonic lethality in pigs	journal.pgen.1008055	null	[ [ "Lethal recessive alleles cause pre- or postnatal death in homozygous affected individuals , reducing fertility in various populations [1] .", "Although recessive lethals are generally widespread throughout populations , their effect is generally masked by the extremely low frequency of individual mutatio...	[ "Lethal recessive alleles cause pre- or postnatal death in homozygous affected individuals , reducing fertility .", "Especially in small size domestic and wild populations , those alleles might be exposed by inbreeding , caused by matings between related parents that inherited the same recessive lethal allele fro...	[ "Lethal recessives are mutations that cause early lethality in homozygous state that usually occur at very low frequency in wild and domestic populations .", "In livestock , however , those mutations might become more prevalent as a result of inbreeding .", "In this study , we report five such recessive lethal ...	2019
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine and health sciences", "homologous chromosomes", "reproductive system", "rna interference", "chromosome structure and function", "centromeres", "cell cycle and cell division", "cell processes", "germ cells", "oocytes", "epigenetics", "chromatin", "prophase", "genetic interference"...	Kdm5/Lid Regulates Chromosome Architecture in Meiotic Prophase I Independently of Its Histone Demethylase Activity	journal.pgen.1006241	null	[ [ "Meiosis I differs from the second meiotic and mitotic divisions in that homologous chromosomes are segregated , not sister chromatids .", "Accurate chromosome segregation in meiosis I is preceded by dramatic changes in prophase chromatin organisation .", "Eventually , homologous chromosomes are mecha...	[ "During prophase of the first meiotic division ( prophase I ) , chromatin dynamically reorganises to recombine and prepare for chromosome segregation .", "Histone modifying enzymes are major regulators of chromatin structure , but our knowledge of their roles in prophase I is still limited .", "Here we report o...	[ "Accurate transmission of chromosomes carrying genetic materials from generation to generation is essential for life .", "Cell divisions that generate gametes , such as eggs and sperm , are critical , as chromosomes inherited from both parents recombine and are accurately sorted into gametes .", "Errors in thes...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "cell biology/gene expression", "genetics and genomics/gene expression" ]	Roles for H2A.Z and Its Acetylation in GAL1 Transcription and Gene Induction, but Not GAL1-Transcriptional Memory	journal.pbio.1000401	H2A.Z does not appear to have a role in GAL1 transcriptional memory, but it does have both acetylation-dependent and acetylation-independent roles in GAL1 induction and expression.	[ [ "In addition to their role in genome packaging , histones also play a role in the functional organization of eukaryotic genomes .", "Clear causal relationships have been established between some specific modifications of histones at specific loci and the subsequent events that occur at these loci .", ...	[ "H2A . Z is a histone H2A variant conserved from yeast to humans , and is found at 63% of promoters in Saccharomyces cerevisiae .", "This pattern of localization suggests that H2A . Z is somehow important for gene expression or regulation .", "H2A . Z can be acetylated at up to four lysine residues on its amino...	[ "Transcriptional memory is the well-documented phenomenon by which cells can “remember” prior transcriptional states .", "A paradigmatic example of transcriptional memory is found in the yeast Saccharomyces .", "S . cerevisiae remembers prior transcription of the galactose metabolism gene GAL1 .", "When a gen...	2010
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "medicine and health sciences", "clinical laboratory sciences", "pathology and laboratory medicine", "respiratory infections", "tropical diseases", "geographical locations", "australia", "biomarkers", "pulmonology", "bacterial diseases", "signs and symptoms", "neglected tropical diseases", "...	A simple score to predict severe leptospirosis	journal.pntd.0007205	null	[ [ "Leptospirosis is a zoonotic infection with a global distribution [1 , 2] .", "Although most infections are mild and self-limiting , the disease is believed to kill almost 60 , 000 people every year [1] .", "Severe disease–manifesting as pulmonary haemorrhage , acute kidney injury ( AKI ) or multiorga...	[ "The case-fatality rate of severe leptospirosis can exceed 50% .", "While prompt supportive care can improve survival , predicting those at risk of developing severe disease is challenging , particularly in settings with limited diagnostic support .", "We retrospectively identified all adults with laboratory-co...	[ "Leptospirosis , a neglected tropical disease with a global distribution , is estimated to kill 60 , 000 people every year .", "Predicting those at risk of developing severe disease is challenging , and a simple scoring system to quantify the risk of severe disease has proven elusive .", "Identifying the high-r...	2019
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "biophysics/protein folding", "biophysics/theory and simulation", "biophysics/biomacromolecule-ligand interactions", "computational biology", "chemical biology/protein chemistry and proteomics" ]	Disordered Flanks Prevent Peptide Aggregation	journal.pcbi.1000241	null	[ [ "The biological function of many proteins is determined by their native , three-dimensional structure and unfolded ( or incorrectly folded ) copies of such proteins tend to be inactive , if not outright dangerous .", "However , many proteins contain large regions ( >30 amino acids ) that are disordered in...	[ "Natively unstructured or disordered regions appear to be abundant in eukaryotic proteins .", "Many such regions have been found alongside small linear binding motifs .", "We report a Monte Carlo study that aims to elucidate the role of disordered regions adjacent to such binding motifs .", "The coarse-graine...	[ "In their natural cellular environment proteins are dissolved in a concentrated aqueous solution of biomolecules .", "Even under such crowded conditions , proteins must not clump together or aggregate; otherwise their biological functions may be compromised , and the cell could die .", "Diseases such as Parkins...	2008
[ "Introduction", "Results", "Discussion", "Materials and Methods", "Supporting Information" ]	[ "viruses", "infectious diseases", "cell biology", "virology", "microbiology" ]	Higher-Order Oligomerization Targets Plasma Membrane Proteins and HIV Gag to Exosomes	journal.pbio.0050158	Experiments in Jurkat T cells suggest that HIV and other retroviruses may co-opt the normal nonviral pathway of exosome biogenesis.	[ [ "Exosomes are secreted organelles that have the same topology as the cell and a diameter of approximately 50–150 nm , though larger exosomes have also been reported [1–3] .", "Exosome content varies considerably , but commonly includes tetraspanins , integrins , major histocompatibility complex proteins ,...	[ "Exosomes are secreted organelles that have the same topology as the cell and bud outward ( outward is defined as away from the cytoplasm ) from endosome membranes or endosome-like domains of plasma membrane .", "Here we describe an exosomal protein-sorting pathway in Jurkat T cells that selects cargo proteins on...	[ "Exosomes are small , secreted organelles with the same topology as the cell and a similar size and composition as retrovirus particles .", "Based on these similarities , we proposed that retroviruses are , at their most fundamental level , exosomes .", "Little is known about the mechanisms of exosome biogenesi...	2007
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	A Change in the Ion Selectivity of Ligand-Gated Ion Channels Provides a Mechanism to Switch Behavior	journal.pbio.1002238	A study in Caenorhabditis elegans shows that switching the sign of a synapse within a neural circuit can reverse the behavioral output, providing an evolutionary and synthetic mechanism for changing behavior.	[ [ "Mapping the neural connections of nervous systems is often considered to be a fundamental step in understanding behavior [1 , 2] .", "However , a neural connectivity map carries no information about the activity of neurons and the nature of the connections that each neuron makes .", "Neurons are embe...	[ "Behavioral output of neural networks depends on a delicate balance between excitatory and inhibitory synaptic connections .", "However , it is not known whether network formation and stability is constrained by the sign of synaptic connections between neurons within the network .", "Here we show that switching...	[ "Fast neurotransmission in the nervous system is mediated by ligand-gated ion channels .", "Within the nervous system , the sign of synaptic connections , i . e . , whether they are excitatory or inhibitory , is determined by the charge of the ions that flow through these channels .", "In general , channels tha...	2015
[ "Introduction", "Results", "Discussion", "Methods" ]	[]	Cell-Specific Cardiac Electrophysiology Models	journal.pcbi.1004242	null	[ [ "Mathematical models of cardiac electrophysiology trace their roots to Hodgkin and Huxley’s seminal work from 1952 [1] .", "Since then many models have been developed describing cardiac electrophysiology in a number of species and cell types helping to make modeling an integral part of cardiac research [2...	[ "The traditional cardiac model-building paradigm involves constructing a composite model using data collected from many cells .", "Equations are derived for each relevant cellular component ( e . g . , ion channel , exchanger ) independently .", "After the equations for all components are combined to form the c...	[ "Mathematical models of cardiac cell electrophysiology are widely used as predictive and illuminatory tools , but have been developed for decades using a suboptimal process .", "The models are typically constructed by manual adjustment of parameters to fit simple data and therefore often underperform when used to...	2015
[ "Introduction", "Results/Discussion", "Materials and Methods" ]	[ "genetics and genomics/gene expression", "evolutionary biology/evolutionary and comparative genetics", "infectious diseases/fungal infections", "genetics and genomics/gene function", "evolutionary biology/morphogenesis and cell biology" ]	A Phenotypic Profile of the Candida albicans Regulatory Network	journal.pgen.1000783	null	[ [ "The transcriptional networks that orchestrate gene expression are complex .", "Even in single-celled organisms , these networks must specify different cell types , must coordinate responses to different external cues , and must maintain homeostasis in a constantly changing environment .", "The evolut...	[ "Candida albicans is a normal resident of the gastrointestinal tract and also the most prevalent fungal pathogen of humans .", "It last shared a common ancestor with the model yeast Saccharomyces cerevisiae over 300 million years ago .", "We describe a collection of 143 genetically matched strains of C . albica...	[ "A key goal in the understanding of the biology of an organism is the description of the regulatory networks that control the expression of its genes .", "Changes in gene expression result in new cellular phenotypes that can be acted upon by evolutionary forces to influence the configuration of these networks .",...	2009
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "gene regulation", "regulatory proteins", "dna-binding proteins", "random variables", "covariance", "regression analysis", "regulator genes", "mathematics", "statistics (mathematics)", "transcription factors", "gene types", "epigenetics", "chromatin", "research and analysis methods", "ch...	Genome-Wide Association between Transcription Factor Expression and Chromatin Accessibility Reveals Regulators of Chromatin Accessibility	journal.pcbi.1005311	null	[ [ "In higher eukaryotes , certain sequence-specific transcription factors ( TFs ) , which we will call chromatin accessibility regulators ( CARs ) , are responsible for establishing and maintaining open chromatin configurations [1 , 2] .", "CARs therefore play a fundamental role in transcriptional regulatio...	[ "To better understand genome regulation , it is important to uncover the role of transcription factors in the process of chromatin structure establishment and maintenance .", "Here we present a data-driven approach to systematically characterise transcription factors that are relevant for this process .", "Our ...	[ "Transcription factor binding occurs mainly in regions of open chromatin .", "For many transcription factors , it is unclear whether binding is the cause or the consequence of open chromatin .", "Here , we used datasets on open chromatin and gene expression provided by the ENCODE project to predict which transc...	2017
[ "Introduction", "Results", "Discussion", "Methods" ]	[]	PHABULOSA Controls the Quiescent Center-Independent Root Meristem Activities in Arabidopsis thaliana	journal.pgen.1004973	null	[ [ "Plants , unlike animals , grow continuously and dynamically adjust their architecture .", "Meristems at the apices of shoots and roots harbor stem cells and serve as the center of cell division and growth .", "In the root apical meristem ( RAM ) , the quiescent center ( QC ) maintains a stem cell pop...	[ "Plant growth depends on stem cell niches in meristems .", "In the root apical meristem , the quiescent center ( QC ) cells form a niche together with the surrounding stem cells .", "Stem cells produce daughter cells that are displaced into a transit-amplifying ( TA ) domain of the root meristem .", "TA cells...	[ "Plant roots are programmed to grow continuously into the soil , searching for nutrients and water .", "The iterative process of cell division , elongation , and differentiation contributes to root growth .", "The quiescent center ( QC ) is known to maintain the root meristem , and thus ensure root growth .", ...	2015
[ "Introduction", "Materials and methods", "Results", "Discussion" ]	[ "blood cells", "medicine and health sciences", "immune cells", "immune physiology", "pathology and laboratory medicine", "immunology", "tropical diseases", "bacterial diseases", "b cell receptors", "neglected tropical diseases", "memory b cells", "antibodies", "immune system proteins", "in...	Increased activated memory B-cells in the peripheral blood of patients with erythema nodosum leprosum reactions	journal.pntd.0006121	null	[ [ "B-cells enable the antigen-specific humoral immunity by forming highly specific antibodies during primary immune response .", "B-cells within the lymphoid tissue of the body such as bone marrow , spleen and lymph nodes , are stimulated by antigenic substances to proliferate and transform into plasma cell...	[ "B-cells , in addition to antibody secretion , have emerged increasingly as effector and immunoregulatory cells in several chronic inflammatory diseases .", "Although Erythema Nodosum Leprosum ( ENL ) is an inflammatory complication of leprosy , the role of B- cell subsets has never been studied in this patient g...	[ "Some leprosy patients develop reactions which cause a significant morbidity and mortality in leprosy patients .", "There are two types of leprosy reactions , type 1 and type 2 reactions .", "Type 2 or Erythema nodosum leprosum ( ENL ) is an immune-mediated inflammatory complication of leprosy which occurs in l...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "cell biology", "cell biology/gene expression", "microbiology" ]	Control of Transcription by Cell Size	journal.pbio.1000523	The demonstration of a causal, regulatory relationship between cell size and gene expression in yeast suggests that cells maintain size in order to maintain transcriptional homeostasis.	[ [ "The size of cells can vary significantly within an organism , and cells of the same type display pronounced increase in size with increasing ploidy [1] , [2] .", "During development , specific cell types in many diploid organisms perform endoreplication and differentiate into polyploid cells that are fun...	[ "Cell size increases significantly with increasing ploidy .", "Differences in cell size and ploidy are associated with alterations in gene expression , although no direct connection has been made between cell size and transcription .", "Here we show that ploidy-associated changes in gene expression reflect tran...	[ "Cells of the same type , whether microbial , plant , or metazoan in origin , exhibit remarkable uniformity in size .", "This uniformity arises from control mechanisms that respond to internal cellular changes as well as external environmental factors .", "Although precise control of cell size is a universal ph...	2010
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "biotechnology", "deletion mutation", "engineering and technology", "population genetics", "brassica", "simulation and modeling", "mutation", "plant science", "model organisms", "experimental organism systems", "plant genomics", "population biology", "plants", "research and analysis method...	Deleterious variation shapes the genomic landscape of introgression	journal.pgen.1007741	null	[ [ "There is tremendous interest in quantifying the effects that demographic history has had on the patterns and dynamics of deleterious variation and genetic load [1–8] .", "Several studies have suggested that recent human demography has had little impact on load [9 , 10] while others have suggested weak , ...	[ "While it is appreciated that population size changes can impact patterns of deleterious variation in natural populations , less attention has been paid to how gene flow affects and is affected by the dynamics of deleterious variation .", "Here we use population genetic simulations to examine how gene flow impact...	[ "Individuals from distinct populations sometimes will produce fertile offspring and will exchange genetic material in a process called hybridization .", "Genomes of hybrid individuals often show non-random patterns of hybrid ancestry across the genome , where some regions have a high frequency of ancestry from th...	2018
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "cell death", "medicine and health sciences", "cell cycle and cell division", "cancer treatment", "cell processes", "departures from diploidy", "oncology", "pharmacodynamics", "pharmacology", "synthesis phase", "aneuploidy", "signal transduction", "apoptotic signaling cascade", "cell biolo...	Modelling of the cancer cell cycle as a tool for rational drug development: A systems pharmacology approach to cyclotherapy	journal.pcbi.1005529	null	[ [ "Pharmacokinetic and pharmacodynamic ( PK/PD ) models of anticancer drug action have many potential applications [1–3] .", "Among the most promising are the ability to match tumours with particular gene expression profiles to selective treatments [4] , the ability to search for potential synthetic lethali...	[ "The dynamic of cancer is intimately linked to a dysregulation of the cell cycle and signalling pathways .", "It has been argued that selectivity of treatments could exploit loss of checkpoint function in cancer cells , a concept termed “cyclotherapy” .", "Quantitative approaches that describe these dysregulati...	[ "Neoplastic transformation results from mutations , chromosomal abnormalities , or expression changes affecting components of the cell cycle , the signalling pathways leading into it , and the apoptosis pathways resulting from cell cycle arrest .", "Cytotoxic agents , but also newer drugs that target the cell cyc...	2017
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "biotechnology", "genome-wide association studies", "carbohydrate metabolism", "medicine and health sciences", "toxins", "pathology and laboratory medicine", "glucose metabolism", "alleles", "toxic agents", "toxicology", "glucose tolerance", "fungi", "model organisms", "genome analysis", ...	Genome-wide association across Saccharomyces cerevisiae strains reveals substantial variation in underlying gene requirements for toxin tolerance	journal.pgen.1007217	null	[ [ "The increased interest in renewable energy has focused attention on non-food plant biomass for the production of biofuels and biochemicals [1] .", "Lignocellulosic plant material contains significant amounts of sugars that can be extracted through a variety of chemical pretreatments and used for microbia...	[ "Cellulosic plant biomass is a promising sustainable resource for generating alternative biofuels and biochemicals with microbial factories .", "But a remaining bottleneck is engineering microbes that are tolerant of toxins generated during biomass processing , because mechanisms of toxin defense are only beginni...	[ "Understanding the genetic architecture of complex traits is important for elucidating the genotype-phenotype relationship .", "Many studies have sought genetic variants that underlie phenotypic variation across individuals , both to implicate causal variants and to inform on architecture .", "Here we used geno...	2018
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "meiosis", "medicine and health sciences", "reproductive system", "spermatocytes", "cell cycle and cell division", "cell processes", "germ cells", "molecular biology techniques", "dna", "sperm", "homologous recombination", "research and analysis methods", "artificial gene amplification and e...	Dual functions for the ssDNA-binding protein RPA in meiotic recombination	journal.pgen.1007952	null	[ [ "During sexual reproduction , meiotic recombination permits reciprocal exchange of genetic materials between homologous chromosomes and ensures faithful chromosome segregation [1 , 2] .", "Abnormalities in meiotic recombination are a leading cause of aneuploidy , infertility , and pregnancy loss in humans...	[ "Meiotic recombination permits exchange of genetic material between homologous chromosomes .", "The replication protein A ( RPA ) complex , the predominant ssDNA-binding complex , is required for nearly all aspects of DNA metabolism , but its role in mammalian meiotic recombination remains unknown due to the embr...	[ "Meiosis , a process unique to germ cells , results in production of haploid gametes .", "Meiotic recombination , a hallmark of meiosis , together with random segregation of homologous chromosomes , generates genetic diversity in haploid gametes at every generation so that each gamete has a unique genetic composi...	2019
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "neuroscience/motor systems", "neuroscience/neurodevelopment", "developmental biology/neurodevelopment" ]	Dendritic Targeting in the Leg Neuropil of Drosophila: The Role of Midline Signalling Molecules in Generating a Myotopic Map	journal.pbio.1000199	During development of the Drosophila motor system, global guidance cues control and coordinate the targeting of both input and output elements of the neural system.	[ [ "The fidelity with which connections are made between neurons is a striking feature of nervous system design and essential for proper function [1] .", "How appropriate presynaptic and postsynaptic elements are brought together during development to generate such ordered connectivity is still a major unans...	[ "Neural maps are emergent , highly ordered structures that are essential for organizing and presenting synaptic information .", "Within the embryonic nervous system of Drosophila motoneuron dendrites are organized topographically as a myotopic map that reflects their pattern of innervation in the muscle field .",...	[ "During development the axons of sensory neurons generate highly ordered ”sensory maps„ within the nervous system that represent specific qualities of the environment .", "Much less is known about the anatomical organization and development of motor systems .", "Here , we show that the leg motoneurons of Drosop...	2009
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "animal models of infection", "inflammation", "immunity", "virology", "immune activation", "innate immunity", "immune defense", "biology", "microbiology", "immunoregulation" ]	Transcriptomic Analysis of Host Immune and Cell Death Responses Associated with the Influenza A Virus PB1-F2 Protein	journal.ppat.1002202	null	[ [ "Influenza A virus ( IAV ) commonly causes acute respiratory infection and is one of the most important human pathogens , causing between 250 , 000 and 500 , 000 deaths every year around the world [1] .", "IAV are enveloped viruses belonging to the Orthomyxoviridae family .", "Their negative strand RN...	[ "Airway inflammation plays a major role in the pathogenesis of influenza viruses and can lead to a fatal outcome .", "One of the challenging objectives in the field of influenza research is the identification of the molecular bases associated to the immunopathological disorders developed during infection .", "W...	[ "Influenza A viruses may cause severe respiratory disease .", "PB1-F2 , a viral protein identified in 2001 is suspected to play a role in influenza-related pneumonia .", "In order to understand the impact of PB1-F2 in the pathogenesis underlying Influenza A virus infection , we engineered a mutant virus unable ...	2011
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Role of Hypoxia Inducible Factor-1α (HIF-1α) in Innate Defense against Uropathogenic Escherichia coli Infection	journal.ppat.1004818	null	[ [ "Urinary tract infection ( UTI ) is a very common and frequently recurrent bacterial disease accounting for approximately 8 million doctor visits per year , with an estimated total cost of $450 million annually in the United States [1 , 2] .", "More than 50% of women will experience at least one UTI durin...	[ "Uropathogenic E . coli ( UPEC ) is the primary cause of urinary tract infections ( UTI ) affecting approximately 150 million people worldwide .", "Here , we revealed the importance of transcriptional regulator hypoxia-inducible factor-1 α subunit ( HIF-1α ) in innate defense against UPEC-mediated UTI .", "The ...	[ "Urinary tract infection ( UTI ) , commonly caused by uropathogenic E . coli ( UPEC ) , affects more than 150 million people worldwide , resulting in 14 million hospital visits per year and an estimated total cost of 6 billion dollars in direct health care .", "Due to the high prevalence of UTI and rapid emergenc...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "computational biology/literature analysis", "computational biology/bio-ontology" ]	Benchmarking Ontologies: Bigger or Better?	journal.pcbi.1001055	null	[ [ "The word ontology historically represented the product of one person's philosophical inquiry into the structure of the real world: What entities exist ?", "What are their properties ?", "How are they grouped and hierarchically related ?", "While this original definition still holds in philosophy ...	[ "A scientific ontology is a formal representation of knowledge within a domain , typically including central concepts , their properties , and relations .", "With the rise of computers and high-throughput data collection , ontologies have become essential to data mining and sharing across communities in the biome...	[ "An ontology represents the concepts and their interrelation within a knowledge domain .", "Several ontologies have been developed in biomedicine , which provide standardized vocabularies to describe diseases , genes and gene products , physiological phenotypes , anatomical structures , and many other phenomena ....	2011
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "invertebrates", "livestock", "medicine and health sciences", "rift valley fever virus", "pathology and laboratory medicine", "ruminants", "pathogens", "geographical locations", "microbiology", "uganda", "vertebrates", "diet", "tropical diseases", "animals", "mammals", "animal products...	Prevalence and risk factors of Rift Valley fever in humans and animals from Kabale district in Southwestern Uganda, 2016	journal.pntd.0006412	null	[ [ "Rift Valley fever virus ( RVFV ) is a single-stranded RNA virus in the order Bunyavirales , and recently classified in the Phenuiviridae family [1] and the Phlebovirus genus .", "RVFV causes disease in humans and animals [2] , and is transmitted by mosquitoes to livestock such as sheep , goats , and catt...	[ "Rift Valley fever ( RVF ) is a zoonotic disease caused by Rift Valley fever virus ( RVFV ) found in Africa and the Middle East .", "Outbreaks can cause extensive morbidity and mortality in humans and livestock .", "Following the diagnosis of two acute human RVF cases in Kabale district , Uganda , we conducted ...	[ "Viral hemorrhagic fevers are known to cause high morbidity and mortality and pose a serious threat to human and animal populations in endemic countries .", "An outbreak of Rift Valley fever was detected in Kabale district in March , 2016 and identified the first human cases in Uganda since 1968 .", "There was ...	2018

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