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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", "Methods", "Results/Discussion" ]	[]	Network-Based Integration of Disparate Omic Data To Identify "Silent Players" in Cancer	journal.pcbi.1004595	null	[ [ "In recent years , there have been substantial efforts in integrating multiple omic data types that provide information on cancer pathogenesis and progression , with a view to predicting patient outcome , identifying drug targets , and understanding the functional relationships among key players in cancer .",...	[ "Development of high-throughput monitoring technologies enables interrogation of cancer samples at various levels of cellular activity .", "Capitalizing on these developments , various public efforts such as The Cancer Genome Atlas ( TCGA ) generate disparate omic data for large patient cohorts .", "As demonstr...	[ "Identification of cancer-related genes is an important task , made more difficult by heterogeneity between samples and even within individual patients .", "Methods for identifying disease-related genes typically focus on individual data sets such as mutational and differential expression data , and therefore are...	2015
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "infectious diseases", "public health and epidemiology/health policy", "infectious diseases/neglected tropical diseases", "infectious diseases/helminth infections", "public health and epidemiology/preventive medicine", "infectious diseases/skin infections", "infectious diseases/tropical and travel-assoc...	Feasibility and Effectiveness of Basic Lymphedema Management in Leogane, Haiti, an Area Endemic for Bancroftian Filariasis	journal.pntd.0000668	null	[ [ "Lymphedema of the leg and its advanced form , known as elephantiasis , are major causes of disability and morbidity in filariasis-endemic areas , with an estimated 14 million cases worldwide [1] .", "When the World Health Organization's Global Program to Eliminate Lymphatic Filariasis ( GPELF ) was launc...	[ "Approximately 14 million persons living in areas endemic for lymphatic filariasis have lymphedema of the leg .", "Clinical studies indicate that repeated episodes of bacterial acute dermatolymphangioadenitis ( ADLA ) lead to progression of lymphedema and that basic lymphedema management , which emphasizes hygien...	[ "Lymphatic filariasis is a parasitic disease that is spread by mosquitoes .", "In tropical countries where lymphatic filariasis occurs , approximately 14 million people suffer from chronic swelling of the leg , known as lymphedema .", "Repeated episodes of bacterial skin infection ( acute attacks ) cause lymphe...	2010
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[]	Analysis of Cross-Reactive Antibodies Recognizing the Fusion Loop of Envelope Protein and Correlation with Neutralizing Antibody Titers in Nicaraguan Dengue Cases	journal.pntd.0002451	null	[ [ "The four serotypes of dengue virus ( DENV1–4 ) are the leading cause of arboviral diseases in humans in tropical and subtropical regions [1] , [2] .", "It has been estimated that more than 3 billion people in over 100 countries are at risk of infection and 50–100 million DENV infections occur annually wo...	[ "Dengue virus ( DENV ) is the leading cause of arboviral diseases in humans worldwide .", "The envelope ( E ) protein of DENV is the major target of neutralizing antibodies ( Abs ) .", "Previous studies have shown that a significant proportion of anti-E Abs in human serum after DENV infection recognize the high...	[ "The four serotypes of dengue virus ( DENV ) are the leading cause of mosquito-borne viral diseases in humans .", "Whereas infection with one DENV serotype is thought to confer protection against re-infection with that serotype , it can be either protective or enhance disease severity upon subsequent ( “secondary...	2013
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "medicine", "public health and epidemiology", "ecology", "epidemiology", "biology" ]	Biodiversity Can Help Prevent Malaria Outbreaks in Tropical Forests	journal.pntd.0002139	null	[ [ "The dynamics of malaria transmission involve a tritrophic interaction among vector mosquitoes ( Anopheles species ) , protozoan parasites ( Plasmodium species ) , and vertebrate hosts .", "Malaria is endemic in tropical and subtropical regions [1]–[3] .", "The Global Malaria Eradication Program adopt...	[ "Plasmodium vivax is a widely distributed , neglected parasite that can cause malaria and death in tropical areas .", "It is associated with an estimated 80–300 million cases of malaria worldwide .", "Brazilian tropical rain forests encompass host- and vector-rich communities , in which two hypothetical mechani...	[ "Plasmodium vivax malaria is a neglected infectious disease that can cause severe symptoms and death in tropical regions .", "It is associated with an estimated 80–300 million cases of malaria worldwide .", "Brazilian tropical rain forests are home to a rich community of animals that can participate in the dyna...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "invertebrates", "acoustics", "waggle-dancing", "classical mechanics", "honey bees", "vibration", "animals", "animal signaling and communication", "signal inhibition", "animal behavior", "zoology", "bees", "hymenoptera", "behavior", "alarm pheromones", "insects", "arthropoda", "phy...	Honey Bee Inhibitory Signaling Is Tuned to Threat Severity and Can Act as a Colony Alarm Signal	journal.pbio.1002423	Honey bees possess a vibrational alarm signal that encodes information about the level of danger at food and at the nest entrance.	[ [ "Animals have evolved sophisticated abilities to communicate predator threats .", "These warning signals are found in a wide range of organisms , such as insects , birds , and primates [1–3] .", "In some vertebrates , these signals can be referential , encoding information about objects or events exte...	[ "Alarm communication is a key adaptation that helps social groups resist predation and rally defenses .", "In Asia , the world’s largest hornet , Vespa mandarinia , and the smaller hornet , Vespa velutina , prey upon foragers and nests of the Asian honey bee , Apis cerana .", "We attacked foragers and colony ne...	[ "Asian honey bees are attacked by formidable predators , giant hornets , at food sources and at their nests .", "We show that one species of honey bee , Apis cerana , has evolved an alarm signal , the stop signal , which warns nestmates of this danger .", "The stop signal consists of a brief vibrational pulse t...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "neuroscience/cognitive neuroscience", "radiology and medical imaging/magnetic resonance imaging", "neuroscience/motor systems", "neurological disorders/neuroimaging", "neuroscience/neuronal signaling mechanisms", "radiology and medical imaging", "computational biology/systems biology" ]	Broca's Region: Novel Organizational Principles and Multiple Receptor Mapping	journal.pbio.1000489	A novel map of Broca's language region is proposed based on transmitter receptor distributions as functionally relevant molecular markers. It sheds new light on the relation between anatomy and functional segregation.	[ [ "For more than a century , Broca's region in the posterior part of the inferior frontal gyrus has been considered essential for speech production [1] .", "Effortful , telegraphic speech , impairment in articulation and melodic line , semantic and phonemic paraphasias are some of the symptoms associated wi...	[ "There is a considerable contrast between the various functions assigned to Broca's region and its relatively simple subdivision into two cytoarchitectonic areas ( 44 and 45 ) .", "Since the regional distribution of transmitter receptors in the cerebral cortex has been proven a powerful indicator of functional di...	[ "Broca's region is involved in many aspects of language processing in the brain .", "Such detailed functional diversity , however , is in contrast to its classical anatomical subdivision into only two cortical areas .", "Since the regional distribution of neurotransmitter receptors has been proven to be a power...	2010
[ "Introduction", "Results", "Discussion", "Material and methods" ]	[ "cell motility", "innate immune system", "medicine and health sciences", "body fluids", "immune physiology", "pathology and laboratory medicine", "cytokines", "nervous system", "pathogens", "immunology", "microbiology", "neuroscience", "retroviruses", "viruses", "developmental biology", ...	Spinal cord hypometabolism associated with infection by human T-cell lymphotropic virus type 1(HTLV-1)	journal.pntd.0006720	null	[ [ "The Human T-cell lymphotropic virus ( HTLV-1 ) was associated with tropical spastic paraparesis ( TSP ) and HTLV-1 associated myelopathy ( HAM ) in the eighties [1–2] .", "Both diseases were recognized as the same neurological disorder in 1988 and called HAM/TSP [3] .", "Since then , a wide range of ...	[ "HTLV-1 infection is endemic in Brazil .", "About 1 to 2% of the Brazilian population is estimated to be infected , but most infected HTLV-1 individuals do not know about their own infection , which favors the continuity of sexual and vertical virus transmission .", "In addition , HTLV-1 associated central nerv...	[ "For the past 30 years , human T-cell lymphotropic virus type-1 ( HTLV-1 ) has been isolated and associated with neoplastic , inflammatory , and infectious diseases .", "It is known that the neurological disorder associated with HTLV-1 comprises HTLV-1-associated myelopathy ( HAM/TSP ) or any other isolated signa...	2018
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "sequence analysis", "medicine", "infectious diseases", "hiv", "evolutionary modeling", "population genetics", "biology", "computational biology", "viral diseases" ]	Reconstructing the Dynamics of HIV Evolution within Hosts from Serial Deep Sequence Data	journal.pcbi.1002753	null	[ [ "Human immunodeficiency virus type 1 ( HIV-1 ) enters into a host cell by binding the CD4 receptor and one of two HIV coreceptors , CCR5 or CXCR4 .", "Most HIV-1 variants manifest preferential binding to one or the other coreceptor , a phenotype that is referred to as HIV coreceptor usage or tropism .", ...	[ "At the early stage of infection , human immunodeficiency virus ( HIV ) -1 predominantly uses the CCR5 coreceptor for host cell entry .", "The subsequent emergence of HIV variants that use the CXCR4 coreceptor in roughly half of all infections is associated with an accelerated decline of CD4+ T-cells and rate of ...	[ "At the start of infection , human immunodeficiency virus ( HIV ) generally requires a specific protein receptor ( CCR5 ) on the cell surface to bind and enter the cell .", "In roughly half of all HIV infections , the virus population eventually switches to using a different receptor ( CXCR4 ) .", "This ‘HIV co...	2012
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[]	Regulation of Mycolactone, the Mycobacterium ulcerans Toxin, Depends on Nutrient Source	journal.pntd.0002502	null	[ [ "Mycobacterium ulcerans , a slow-growing environmental bacterium , is the causative agent of Buruli ulcer , a severe infectious skin disease .", "This disease mainly occurs in humid tropical zones , especially in West African countries .", "Its incidence is increasing and this disease became the third...	[ "Mycobacterium ulcerans , a slow-growing environmental bacterium , is the etiologic agent of Buruli ulcer , a necrotic skin disease .", "Skin lesions are caused by mycolactone , the main virulence factor of M . ulcerans , with dermonecrotic ( destruction of the skin and soft tissues ) and immunosuppressive activi...	[ "Mycolactone , a polyketide cytotoxic toxin , is the key virulence factor responsible for large skin ulcers in Buruli ulcer .", "This disease , mainly occurring in humid tropical zones , especially in West African countries , is due to infection by Mycobacterium ulcerans , a slow-growing environmental mycobacteri...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "bacterial diseases", "infectious diseases", "medicine and health sciences", "pathology and laboratory medicine", "host-pathogen interactions", "medical microbiology", "gastroenterology and hepatology", "microbial pathogens", "biology and life sciences", "microbiology", "salmonella", "gastroin...	Salmonella enterica Serovar Typhi Conceals the Invasion-Associated Type Three Secretion System from the Innate Immune System by Gene Regulation	journal.ppat.1004207	null	[ [ "One function of the innate immune system in the intestinal tract is to generate temporary inflammatory responses against invasive enteric pathogens while avoiding detrimental overreaction against harmless commensal bacteria under homeostatic conditions .", "In contrast to commensal microbes , pathogenic ...	[ "Delivery of microbial products into the mammalian cell cytosol by bacterial secretion systems is a strong stimulus for triggering pro-inflammatory host responses .", "Here we show that Salmonella enterica serovar Typhi ( S . Typhi ) , the causative agent of typhoid fever , tightly regulates expression of the inv...	[ "Bacterial pathogens translocate effector proteins into the cytoplasm of host cells to manipulate the mammalian host .", "These processes , e . g . the stimulation of small regulatory GTPases , activate the innate immune system and induce pro-inflammatory responses aimed at clearing invading microbes from the inf...	2014
[ "Introduction", "Results", "Discussion", "Methods" ]	[]	Intracellular Information Processing through Encoding and Decoding of Dynamic Signaling Features	journal.pcbi.1004563	null	[ [ "Cells continuously sense a variety of physical and chemical signals and respond suitably to changes in their environment [1–3] .", "Depending on the nature of the environmental change , a subset of membrane receptors gets stimulated , eliciting specific signaling pathways and enabling cells to make infor...	[ "Cell signaling dynamics and transcriptional regulatory activities are variable within specific cell types responding to an identical stimulus .", "In addition to studying the network interactions , there is much interest in utilizing single cell scale data to elucidate the non-random aspects of the variability i...	[ "Single cell studies have shown that differential patterns in the dynamics of signaling proteins , transcription factor activity , gene expression , etc . produce distinct downstream outcomes .", "The opposite also holds true where particular cellular outcomes have been found to be associated with the dynamical p...	2015
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "genomics", "genome evolution", "genetics", "biology and life sciences", "comparative genomics", "computational biology", "evolutionary biology" ]	Odorant and Gustatory Receptors in the Tsetse Fly Glossina morsitans morsitans	journal.pntd.0002663	null	[ [ "Trypanosomiasis management has been a longstanding development preoccupation in sub-Saharan Africa , with tsetse fly control constituting the cornerstone in this effort [1] .", "Since all tsetse species are able to transmit trypanosomes , the critical determinant of transmission is their obligate blood f...	[ "Tsetse flies use olfactory and gustatory responses , through odorant and gustatory receptors ( ORs and GRs ) , to interact with their environment .", "Glossina morsitans morsitans genome ORs and GRs were annotated using homologs of these genes in Drosophila melanogaster and an ab initio approach based on OR and ...	[ "Tsetse flies navigate their environments using chemosensory receptors , which permit them to locate hosts , mating partners , and resting and larviposition sites .", "The genome of G . m .", "morsitans was interrogated for coding genes of odorant receptors ( ORs ) and gustatory receptors ( GRs ) that express i...	2014
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "medicine and health sciences", "parasite groups", "body fluids", "plasmodium", "tropical diseases", "geographical locations", "parasitic diseases", "parasitic protozoans", "parasitology", "apicomplexa", "plasmodium vivax", "protozoans", "infectious disease control", "infectious diseases",...	Reactive Case Detection for Plasmodium vivax Malaria Elimination in Rural Amazonia	journal.pntd.0005221	null	[ [ "Over one-third of the world's population is currently at risk of infection with Plasmodium vivax , the human malaria parasite with the widest global distribution [1] .", "Where both species coexist , P . vivax typically causes less severe cases and deaths than P . falciparum , but its distinctive biologi...	[ "Malaria burden in Brazil has reached its lowest levels in 35 years and Plasmodium vivax now accounts for 84% of cases countrywide .", "Targeting residual malaria transmission entrenched in the Amazon is the next major challenge for ongoing elimination efforts .", "Better strategies are urgently needed to addre...	[ "Addressing the vast reservoir of asymptomatic Plasmodium vivax carriers clustered in hard-to-reach rural communities is a major challenge faced by countries approaching malaria elimination across Latin America and Asia .", "Routine surveillance targets subjects presenting with fever or reporting recent fever , b...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "computational biology/evolutionary modeling", "ecology/community ecology and biodiversity", "evolutionary biology", "ecology/theoretical ecology" ]	Frequency-Dependent Selection Predicts Patterns of Radiations and Biodiversity	journal.pcbi.1000892	null	[ [ "Speciation is one of the most complex phenomena in nature , yet the effects of its tempo and mode for biodiversity patterns are still controversial [1] , [2] .", "Pre-existing niches is considered the dominant mechanism explaining the initial explosion of diversity observed in radiations [3]–[7] .", ...	[ "Most empirical studies support a decline in speciation rates through time , although evidence for constant speciation rates also exists .", "Declining rates have been explained by invoking pre-existing niches , whereas constant rates have been attributed to non-adaptive processes such as sexual selection and mut...	[ "Ecological opportunity , or filling a pre-existing unoccupied adaptive zone , is considered the dominant mechanism explaining the initial explosion of diversity .", "Although this type of niche filling can explain rates of diversification in some lineages , it is not sufficient for a radiation to occur .", "In...	2010
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "medicine and health sciences", "reproductive system", "body fluids", "chemical compounds", "organic compounds", "hormones", "developmental biology", "testosterone", "steroids", "androgens", "embryology", "placenta", "chemistry", "blood plasma", "fetuses", "biochemistry", "testes", ...	Alternative (backdoor) androgen production and masculinization in the human fetus	journal.pbio.3000002	Fetal human masculinisation depends on testosterone production by the testes and an alternative “backdoor” androgen. This study shows that this androgen is likely to be androsterone, which is sexually dimorphic in the fetus but does not come from the testes; instead, synthesis probably depends on placental substrates.	[ [ "The male external genitalia are the most common site of congenital abnormalities in the human , with up to 0 . 8% of male births affected [1 , 2] .", "The most frequent of these abnormalities is hypospadias , which is characterized by abnormal opening of the urethra on the ventral side of the penis .", ...	[ "Masculinization of the external genitalia in humans is dependent on formation of 5α-dihydrotestosterone ( DHT ) through both the canonical androgenic pathway and an alternative ( backdoor ) pathway .", "The fetal testes are essential for canonical androgen production , but little is known about the synthesis of ...	[ "The human penis starts to develop before birth from a structure called the genital tubercle .", "This process is dependent on the secretion of testosterone from the fetal testes and subsequent conversion of testosterone into dihydrotestosterone ( DHT ) by enzymes in the genital tubercle .", "Recently , an alte...	2019
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "invertebrates", "medicine and health sciences", "chemical compounds", "mitochondrial dna", "caenorhabditis", "parasitic diseases", "animals", "organic compounds", "nematode infections", "animal models", "caenorhabditis elegans", "model organisms", "forms of dna", "mitochondria", "molecu...	Using C. elegans Forward and Reverse Genetics to Identify New Compounds with Anthelmintic Activity	journal.pntd.0005058	null	[ [ "Over 60 species of nematodes parasitize humans .", "According to a 2005 report by the World Health Organization ( WHO ) , approximately two billion humans have helminth infections worldwide [1] , and the problem has worsened in the intervening decade [2] .", "Parasitic nematodes are the most common i...	[ "The lack of new anthelmintic agents is of growing concern because it affects human health and our food supply , as both livestock and plants are affected .", "Two principal factors contribute to this problem .", "First , nematode resistance to anthelmintic drugs is increasing worldwide and second , many effect...	[ "With over two billion people infected and many billions of dollars of lost crops annually , nematode infections are a serious problem for human health and for agricultural production .", "While there are drugs to treat infections , many pockets of parasites have been identified worldwide that are developing immu...	2016
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "computer science", "computational neuroscience", "synthetic vision systems", "biology", "sensory systems", "neuroscience" ]	Cortical Surround Interactions and Perceptual Salience via Natural Scene Statistics	journal.pcbi.1002405	null	[ [ "Contextual influences collectively denote a variety of phenomena associated with the way information is integrated and segmented across the visual field .", "Spatial context strongly modulates the perceptual salience of even simple visual stimuli , as well as influencing cortical responses , as early as ...	[ "Spatial context in images induces perceptual phenomena associated with salience and modulates the responses of neurons in primary visual cortex ( V1 ) .", "However , the computational and ecological principles underlying contextual effects are incompletely understood .", "We introduce a model of natural images...	[ "One of the most important and enduring hypotheses about the way that mammalian brains process sensory information is that they are exquisitely attuned to the statistical structure of the natural world .", "This allows them to come , over the course of development , to represent inputs in a way that reflects the ...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "arthropoda", "animal models", "invertebrates", "behavioral neuroscience", "drosophila melanogaster", "model organisms", "research and analysis methods", "gene expression", "genetics", "biology and life sciences", "molecular genetics", "mouse models", "drosophila", "neuroscience", "anima...	Obesity-Linked Homologues TfAP-2 and Twz Establish Meal Frequency in Drosophila melanogaster	journal.pgen.1004499	null	[ [ "The human genes TFAP2B ( encoding AP-2β ) and KCTD15 were strongly linked to obesity in multiple genome-wide association studies ( GWAS ) [1]–[4] , though it is still not understood how they regulate obesity .", "In the fruit fly Drosophila melanogaster , TFAP2B and KCTD15 are both highly conserved , enc...	[ "In all animals managing the size of individual meals and frequency of feeding is crucial for metabolic homeostasis .", "In the current study we demonstrate that the noradrenalin analogue octopamine and the cholecystokinin ( CCK ) homologue Drosulfakinin ( Dsk ) function downstream of TfAP-2 and Tiwaz ( Twz ) to ...	[ "The size of individual meals and feeding frequency are important for homeostatic control .", "Due to the complex neuroendocrine system regulating human food intake it is difficult to uncover the mechanisms underlying eating disorders .", "The genetically tractable model system Drosophila melanogaster has a com...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biochemistry", "enzyme structure", "enzymes", "enzyme regulation", "macromolecular assemblies", "biology", "enzyme kinetics", "biophysics" ]	Mechanistic Insights Revealed by the Crystal Structure of a Histidine Kinase with Signal Transducer and Sensor Domains	journal.pbio.1001493	A crystal structure reveals an elegant mechanistic switch whereby helical bending and catalytic domain rotation allow self-activation of a histidine kinase during a bacterial stress response.	[ [ "Protein phosphorylation is an essential signal carrier .", "Bacteria respond to transient living environments through transmembrane-integrated sensor histidine kinases ( SKs ) , which act in concert with their intracellular cognate response regulators ( RRs ) to elicit necessary adaptive responses that a...	[ "Two-component systems ( TCSs ) are important for the adaptation and survival of bacteria and fungi under stress conditions .", "A TCS is often composed of a membrane-bound sensor histidine kinase ( SK ) and a response regulator ( RR ) , which are relayed through sequential phosphorylation steps .", "However , ...	[ "Two-component signal transduction systems ( TCSs ) are promising targets for new antimicrobial research because they help bacteria and fungi adapt and survive .", "One of the main components of TCSs is a sensor histidine kinase ( SK ) , which relays extracellular signals to intracellular pathways .", "Despite ...	2013
[ "Introduction", "Results/Discussion", "Materials and Methods" ]	[ "molecular biology/chromatin structure", "molecular biology/histone modification", "molecular biology/transcription initiation and activation", "cell biology/nuclear structure and function", "genetics and genomics/gene expression", "molecular biology/nucleolus and nuclear bodies", "biochemistry/chemical...	Poised Transcription Factories Prime Silent uPA Gene Prior to Activation	journal.pbio.1000270	The association of poised genes with transcription factories may contribute to rapid transcriptional activation in response to stimuli and to silencing when genes are located at the interior of their chromosome territories.	[ [ "The spatial folding of chromatin within the mammalian cell nucleus , from the level of whole chromosomes down to single genomic regions , is thought to contribute to the expression status of genes [1]–[3] .", "Mammalian chromosomes occupy discrete domains called chromosome territories ( CTs ) and have pr...	[ "The position of genes in the interphase nucleus and their association with functional landmarks correlate with active and/or silent states of expression .", "Gene activation can induce chromatin looping from chromosome territories ( CTs ) and is thought to require de novo association with transcription factories...	[ "The spatial organization of the genome inside the cell nucleus is important in regulating gene expression and in the response to external stimuli .", "Examples of changing spatial organization are the repositioning of genes outside chromosome territories during the induction of gene expression , and the gatherin...	2010
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "developmental neuroscience", "animal genetics", "model organisms", "genetics", "biology", "neuroscience", "genetics and genomics" ]	A Genome-Wide RNAi Screen for Factors Involved in Neuronal Specification in Caenorhabditis elegans	journal.pgen.1002109	null	[ [ "When establishing the nematode C . elegans as a genetic model system , Sydney Brenner's stated goal was the identification of genes required to build a nervous system [1] , [2] .", "Several decades of investigation , mainly using the classic forward screening methods established by Brenner [1] , have ind...	[ "One of the central goals of developmental neurobiology is to describe and understand the multi-tiered molecular events that control the progression of a fertilized egg to a terminally differentiated neuron .", "In the nematode Caenorhabditis elegans , the progression from egg to terminally differentiated neuron ...	[ "The generation of a neuron from a fertilized egg requires a multi-step cascade of molecules acting from within and outside that cell to direct it towards a neuronal fate , rather than , say , a muscle cell .", "These cascades are not fully understood .", "In this study we systematically eliminate the function ...	2011
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "developmental biology/molecular development", "developmental biology/developmental molecular mechanisms", "cell biology/cell signaling" ]	Caenorhabditis elegans SMA-10/LRIG Is a Conserved Transmembrane Protein that Enhances Bone Morphogenetic Protein Signaling	journal.pgen.1000963	null	[ [ "Bone morphogenetic protein ( BMP ) receptor serine/threonine kinases ( BMPRs ) are pivotal signal transducers for the small , secreted BMP morphogens , members of the transforming growth factor β ( TGF- β ) superfamily ( comprising subfamilies of TGF- βs , BMPs , activins , and others ) [1] , [2] .", "BM...	[ "Bone morphogenetic protein ( BMP ) pathways control an array of developmental and homeostatic events , and must themselves be exquisitely controlled .", "Here , we identify Caenorhabditis elegans SMA-10 as a positive extracellular regulator of BMP–like receptor signaling .", "SMA-10 acts genetically in a BMP–l...	[ "Bone morphogenetic protein ( BMP ) family members , small secreted signaling molecules , play diverse roles in development and homeostasis .", "Uncontrolled BMP signaling results in a variety of disorders and diseases .", "BMPs signal to receiving cells through two receptor types , which act together to propag...	2010
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine", "genome expression analysis", "functional genomics", "gene regulation", "dna transcription", "gene function", "cardiovascular", "genome sequencing", "developmental biology", "organism development", "molecular development", "molecular genetics", "epigenetics", "chromatin", "se...	Target Gene Analysis by Microarrays and Chromatin Immunoprecipitation Identifies HEY Proteins as Highly Redundant bHLH Repressors	journal.pgen.1002728	null	[ [ "NOTCH signaling is a key regulatory pathway for cardiovascular development and homeostasis [1] .", "Its receptors mainly act through transcriptional activation of target genes by a complex of the NOTCH intracellular domain , released by gamma-secretase , the transcription factor CBF1 ( RBP-Jk ) and the M...	[ "HEY bHLH transcription factors have been shown to regulate multiple key steps in cardiovascular development .", "They can be induced by activated NOTCH receptors , but other upstream stimuli mediated by TGFß and BMP receptors may elicit a similar response .", "While the basic and helix-loop-helix domains exhib...	[ "NOTCH signaling is a central developmental pathway that influences a multitude of cell fate decisions and differentiation steps as well as later tissue homeostasis and regeneration .", "The three HEY genes encode basic helix-loop-helix transcription factors that are critical effectors to convey signaling by NOTC...	2012
[ "", "Introduction", "Methods", "Results", "Discussion" ]	[ "medicine and health sciences", "epidemiology" ]	Explaining the Host-Finding Behavior of Blood-Sucking Insects: Computerized Simulation of the Effects of Habitat Geometry on Tsetse Fly Movement	journal.pntd.0002901	null	[ [ "An Excel spreadsheet was provided with a series of square “maps” , composed of 200×200 cells representing a total 2×2 km .", "If flies had to be allowed to move off the maps , each map was assumed to adjoin mirror-image maps on all four sides , so that the number of flies leaving the map at any point was...	[ "Male and female tsetse flies feed exclusively on vertebrate blood .", "While doing so they can transmit the diseases of sleeping sickness in humans and nagana in domestic stock .", "Knowledge of the host-orientated behavior of tsetse is important in designing bait methods of sampling and controlling the flies ...	[ "Tsetse flies and other blood-sucking insects spread devastating diseases of humans and livestock .", "We must understand the host-finding behavior of these vectors to assess their epidemiological importance and to design optimal bait methods for controlling or sampling them .", "Unfortunately , mysteries aboun...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "fluorescence imaging", "medicine and health sciences", "cellular stress responses", "pathology and laboratory medicine", "engineering and technology", "pathogens", "signal processing", "cell processes", "bacillus", "microbiology", "light microscopy", "noise reduction", "prokaryotic models",...	Noise Expands the Response Range of the Bacillus subtilis Competence Circuit	journal.pcbi.1004793	null	[ [ "Snapshots of bacterial populations often reveal large phenotypic heterogeneity in the gene expression states of its composite individuals .", "Such phenotypic heterogeneity in a clonal population of bacterial cells in a single environment has significant consequences for how well the organisms can adapt ...	[ "Gene regulatory circuits must contend with intrinsic noise that arises due to finite numbers of proteins .", "While some circuits act to reduce this noise , others appear to exploit it .", "A striking example is the competence circuit in Bacillus subtilis , which exhibits much larger noise in the duration of i...	[ "Fluctuations , or “noise” , in the response of a system is usually thought to be harmful .", "However , it is becoming increasingly clear that in single-celled organisms , noise can sometimes help cells survive .", "This is because noise can enhance the diversity of responses within a cell population .", "In...	2016
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "infectious diseases", "medicine and health sciences", "veterinary diseases", "zoonoses", "biology and life sciences", "parasitic diseases", "veterinary science" ]	Disease Progression in Plasmodium knowlesi Malaria Is Linked to Variation in Invasion Gene Family Members	journal.pntd.0003086	null	[ [ "Plasmodium knowlesi malaria is widespread in Southeast Asia ( SEA ) .", "Descriptions of the aetiology of knowlesi malaria support a zoonotic origin of infection [1] and highlight variability in disease severity between those at risk across the region [2] .", "For example , very young children living...	[ "Emerging pathogens undermine initiatives to control the global health impact of infectious diseases .", "Zoonotic malaria is no exception .", "Plasmodium knowlesi , a malaria parasite of Southeast Asian macaques , has entered the human population .", "P . knowlesi , like Plasmodium falciparum , can reach hig...	[ "Plasmodium knowlesi , a parasite of Southeast Asian macaques , has entered the human population .", "Approximately 10% of P . knowlesi infections are severe , 1–2% are fatal , in Sarawak , Malaysian Borneo .", "Increase in parasitaemia is associated with disease severity , but little is known about parasite vi...	2014
[ "Introduction", "Results/Discussion", "Materials and Methods" ]	[ "physiology/immune response", "physiology/cardiovascular physiology and circulation", "nutrition", "immunology/innate immunity", "cell biology/cell adhesion", "immunology/leukocyte activation" ]	Omega-3 Fatty Acids and Inflammation: Novel Interactions Reveal a New Step in Neutrophil Recruitment	journal.pbio.1000177	While investigating new mechanisms by which the dietary omega-3 fatty acids regulate inflammation, the authors have identified a new step in the regulation of neutrophil migration across vascular endothelial cells.	[ [ "In vertebrates , tissue trauma or infection causes the rapid initiation of an inflammatory reaction .", "The early phase of this phylactic response results in the localised recruitment of cells of the innate immune system from the blood , a tissue infiltrate that is dominated by neutrophils .", "The ...	[ "Inflammation is a physiological response to tissue trauma or infection , but leukocytes , which are the effector cells of the inflammatory process , have powerful tissue remodelling capabilities .", "Thus , to ensure their precise localisation , passage of leukocytes from the blood into inflamed tissue is tightl...	[ "Inflammation is a physiological response to tissue trauma or infection .", "Neutrophils , which circulate in the blood stream , are the first inflammatory cells to be recruited to a site of tissue inflammation .", "In response to recruitment signals provided by chemotactic peptides called chemokines , neutroph...	2009
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biochemistry/chemical biology of the cell", "infectious diseases/hiv infection and aids", "biochemistry/cell signaling and trafficking structures", "microbiology/parasitology", "infectious diseases/protozoal infections", "microbiology/microbial physiology and metabolism", "cell biology/chemical biology...	Host Cell Egress and Invasion Induce Marked Relocations of Glycolytic Enzymes in Toxoplasma gondii Tachyzoites	journal.ppat.1000188	null	[ [ "Toxoplasma gondii is an obligate intracellular protozoan parasite of humans and other warm-blooded animals , and is closely related to Plasmodium sp .", ", the causative agent of malaria .", "Although the majority of Toxoplasma infections in humans are asymptomatic , severe disease and death can occu...	[ "Apicomplexan parasites are dependent on an F-actin and myosin-based motility system for their invasion into and escape from animal host cells , as well as for their general motility .", "In Toxoplasma gondii and Plasmodium species , the actin filaments and myosin motor required for this process are located in a ...	[ "Protozoan parasites of humans are important causes of disease throughout the world .", "Amongst these , the apicomplexan parasites are an especially important group of pathogens , as they include Plasmodium species , the causative agents of malaria , and Toxoplasma gondii , an important cause of disease in peopl...	2008
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "organismal evolution", "innate immune system", "viral immune evasion", "viral genes", "microbial evolution", "virology", "biology and life sciences", "immunology", "microbiology", "evolutionary biology", "viral evolution", "immune system" ]	Natural Polymorphisms in Human APOBEC3H and HIV-1 Vif Combine in Primary T Lymphocytes to Affect Viral G-to-A Mutation Levels and Infectivity	journal.pgen.1004761	null	[ [ "The human APOBEC3 ( A3 ) family of DNA cytosine deaminases is encoded by seven genes arranged in tandem on chromosome 22 ( reviewed by [1] , [2] ) .", "These proteins inhibit the replication of a broad number of parasitic elements , including many retroviruses , some DNA viruses , and several endogenous ...	[ "The Vif protein of HIV-1 allows virus replication by degrading several members of the host-encoded APOBEC3 family of DNA cytosine deaminases .", "Polymorphisms in both host APOBEC3 genes and the viral vif gene have the potential to impact the extent of virus replication among individuals .", "The most genetica...	[ "The APOBEC3 enzymes protect cells by inhibiting the spread of retroelements , including HIV-1 , by blocking reverse transcription and mutating cytosines in single-stranded DNA replication intermediates .", "HIV-1 Vif counteracts restriction by marking APOBEC3 proteins for proteasomal degradation .", "APOBEC3H ...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Existence and Control of Go/No-Go Decision Transition Threshold in the Striatum	journal.pcbi.1004233	null	[ [ "The basal ganglia ( BG ) are a set of nuclei , located at the base of the forebrain , which play a crucial role in a variety of motor and cognitive functions .", "The striatum is the main input stage of the basal ganglia , receiving inputs from widely distributed areas in the cortex [1] , and projecting ...	[ "A typical Go/No-Go decision is suggested to be implemented in the brain via the activation of the direct or indirect pathway in the basal ganglia .", "Medium spiny neurons ( MSNs ) in the striatum , receiving input from cortex and projecting to the direct and indirect pathways express D1 and D2 type dopamine rec...	[ "The basal ganglia ( BG ) play a crucial role in a variety of cognitive and motor functions .", "BG dysfunction leads to brain disorders such as Parkinson’s disease .", "At the main input stage of the BG , the striatum , two competing pathways originate .", "Neurons projecting on these pathways either express...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	The Chromatin Remodeler CHD8 Is Required for Activation of Progesterone Receptor-Dependent Enhancers	journal.pgen.1005174	null	[ [ "During the last decade it has become clear that regulation of gene transcription is accompanied by extensive changes in the chromatin organization of promoters [1] .", "More recently , efforts have concentrated on elucidating the chromatin dynamics of distal regulatory regions and particularly enhancers ...	[ "While the importance of gene enhancers in transcriptional regulation is well established , the mechanisms and the protein factors that determine enhancers activity have only recently begun to be unravelled .", "Recent studies have shown that progesterone receptor ( PR ) binds regions that display typical feature...	[ "A lot of research has been devoted during the last decades to understand the mechanisms that control gene promoters activity , however , much less is known about enhancers .", "Only recently , the use of genome-wide chromatin immunoprecipitation techniques has revealed the existence of more than 400 , 000 enhanc...	2015
[ "Introduction", "Materials and methods", "Results", "Discussion" ]	[ "ellipses", "classical mechanics", "reaction time", "statistics", "social sciences", "vertebrates", "neuroscience", "animals", "mammals", "geometry", "primates", "multivariate analysis", "cognitive neuroscience", "mathematics", "artificial intelligence", "vision", "kinematics", "re...	Structure and variability of delay activity in premotor cortex	journal.pcbi.1006808	null	[ [ "A central issue in the study of motor preparation has been identifying which aspects of a movement are specified prior to execution and how precisely these aspects are encoded [1–3] .", "Decades of research have addressed this question with a variety of approaches .", "Many studies have carefully ana...	[ "Voluntary movements are widely considered to be planned before they are executed .", "Recent studies have hypothesized that neural activity in motor cortex during preparation acts as an ‘initial condition’ which seeds the proceeding neural dynamics .", "Here , we studied these initial conditions in detail by i...	[ "Early studies of premotor cortex explored how individual neurons directly encode aspects of an upcoming movement during preparation .", "Recent developments have proposed that the dynamics of populations of neurons underlie motor control , and that neural activity during preparation serves to set up these dynami...	2019
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[]	Elimination of Lymphatic Filariasis in The Gambia	journal.pntd.0003642	null	[ [ "The Gambia is among 73 countries currently considered endemic for lymphatic filariasis ( LF ) by the World Health Organization [1] .", "LF , a neglected tropical disease ( NTD ) , is a debilitating mosquito-borne nematode infection that affects 120 million people in low and middle income countries where ...	[ "The prevalence of Wuchereria bancrofti , which causes lymphatic filariasis ( LF ) in The Gambia was among the highest in Africa in the 1950s .", "However , surveys conducted in 1975 and 1976 revealed a dramatic decline in LF endemicity in the absence of mass drug administration ( MDA ) .", "The decline in prev...	[ "The prevalence of lymphatic filariasis ( LF ) , in The Gambia was among the highest in Africa in the 1950s when about 50% of the adult population was positive for microfilaraemia .", "However , surveys conducted in 1975 and 1976 revealed a dramatic decline in LF endemicity in the absence of systematic treatment ...	2015
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "medicine", "public health and epidemiology", "immunology", "parasitic diseases", "pulmonology", "neglected tropical diseases", "asthma", "infectious diseases", "toxocariasis", "epidemiology", "biology", "child health", "public health", "pediatric epidemiology", "clinical immunology", ...	Toxocara Seropositivity, Atopy and Wheezing in Children Living in Poor Neighbourhoods in Urban Latin American	journal.pntd.0001886	null	[ [ "There is evidence that the prevalence of allergic diseases has increased worldwide in recent decades , especially among populations living in large cities and living a Western lifestyle [1] .", "A better understanding of the causes and risk factors associated with this epidemic is important to identify n...	[ "Toxocara canis and T . cati are parasites of dogs and cats , respectively , that infect humans and cause human toxocariasis .", "Infection may cause asthma-like symptoms but is often asymptomatic and is associated with a marked eosinophilia .", "Previous epidemiological studies indicate that T . canis infectio...	[ "Toxocara canis and T . cati are roundworms found in dogs and cats , respectively , that can also infect humans and cause several clinical features , including asthma-like symptoms .", "Human infections with T . canis have been associated with an increased prevalence of atopy and asthma .", "In the present stud...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "microbiology/immunity to infections", "genetics and genomics/genetics of the immune system", "immunology/immune response", "microbiology/innate immunity", "immunology/innate immunity", "genetics and genomics/disease models", "microbiology/parasitology", "infectious diseases/protozoal infections", "...	Anopheles gambiae PGRPLC-Mediated Defense against Bacteria Modulates Infections with Malaria Parasites	journal.ppat.1000542	null	[ [ "Immune signaling is triggered by recognition of molecular patterns that are common in microbes but absent from the host .", "PGN is a cell wall component of Gram+ and Gram− bacteria and bacilli , but its amount , sub-cellular localization and specific composition vary between different bacteria , and may...	[ "Recognition of peptidoglycan ( PGN ) is paramount for insect antibacterial defenses .", "In the fruit fly Drosophila melanogaster , the transmembrane PGN Recognition Protein LC ( PGRP-LC ) is a receptor of the Imd signaling pathway that is activated after infection with bacteria , mainly Gram-negative ( Gram− ) ...	[ "Recognition of peptidoglycan on the bacteria cell wall triggers insect immune responses .", "The fruit fly PGRPLC receptor protein senses the presence of peptidoglycan and activates a pathway that mediates resistance to bacterial infections , mainly Gram-negative .", "We show that the PGRPLC receptor of the ma...	2009
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	mTORC1 Prevents Preosteoblast Differentiation through the Notch Signaling Pathway	journal.pgen.1005426	null	[ [ "The skeleton is a highly specialized and dynamic structure undergoing constant remodeling [1] .", "The remodeling process is executed by temporary cellular structures that comprise teams of coupled osteoblasts and osteoclasts .", "The rate of genesis as well as death of these two cell types is vital ...	[ "The mechanistic target of rapamycin ( mTOR ) integrates both intracellular and extracellular signals to regulate cell growth and metabolism .", "However , the role of mTOR signaling in osteoblast differentiation and bone formation is undefined , and the underlying mechanisms have not been elucidated .", "Here ...	[ "The coordinated activities of osteoblasts and osteoclasts in bone deposition and resorption form the internal structure of bone .", "Disruption of the balance between bone formation and resorption results in loss of bone mass and causes bone diseases such as osteoporosis .", "Current therapies for osteoporosis...	2015
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "infectious diseases/neglected tropical diseases" ]	Marriage, Sex, and Hydrocele: An Ethnographic Study on the Effect of Filarial Hydrocele on Conjugal Life and Marriageability from Orissa, India	journal.pntd.0000414	null	[ [ "Lymphatic filariasis ( LF ) , the second leading cause of permanent and long-term disability [1] , affects 120 million people globally [2] .", "It is a mosquito-borne parasitic disease caused by Wuchereria bancrofti , which accounts for approximately 90% of all LF cases , followed by Brugia malayi and Br...	[ "Lymphatic filariasis ( LF ) , a leading cause of permanent and long-term disability , affects 120 million people globally .", "Hydrocele , one of the chronic manifestations of LF among 27 million people worldwide , causes economic and psychological burdens on patients and their families .", "The present study ...	[ "Lymphatic filariasis , the second leading cause of permanent and long-term disability , affects 120 million people globally .", "Hydrocele , an accumulation of fluid in the scrotum that causes it to swell , is one of the chronic manifestations of LF among men and there are about 27 million men with hydrocele wor...	2009
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genetics", "biology", "genomics", "genetics and genomics" ]	Widespread Site-Dependent Buffering of Human Regulatory Polymorphism	journal.pgen.1002599	null	[ [ "A growing number of studies associate variation within regulatory DNA and risk of human disease [1]–[3] .", "Variation in regulatory DNA may result in modulation of recognition by sequence-specific transcription factors ( TFs ) , resulting in altered gene expression [4]–[6] .", "That the vast majorit...	[ "The average individual is expected to harbor thousands of variants within non-coding genomic regions involved in gene regulation .", "However , it is currently not possible to interpret reliably the functional consequences of genetic variation within any given transcription factor recognition sequence .", "To ...	[ "A comprehensive understanding of the contribution of individual genome sequences to disease and quantitative traits will require the general ability to predict consequences of genetic variation in non-protein-coding regions , particularly those involved in gene regulation .", "Here we tested the power to predict...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	The Type VI Secretion TssEFGK-VgrG Phage-Like Baseplate Is Recruited to the TssJLM Membrane Complex via Multiple Contacts and Serves As Assembly Platform for Tail Tube/Sheath Polymerization	journal.pgen.1005545	null	[ [ "In the environment , bacteria endure an intense warfare .", "Bacteria collaborate or compete to acquire nutrients or to efficiently colonize a niche .", "The outcome of inter-bacteria interactions depends on several mechanisms including cooperative behaviors or antagonistic activities [1] .", "Th...	[ "The Type VI secretion system ( T6SS ) is a widespread weapon dedicated to the delivery of toxin proteins into eukaryotic and prokaryotic cells .", "The 13 T6SS subunits assemble a cytoplasmic contractile structure anchored to the cell envelope by a membrane-spanning complex .", "This structure is evolutionaril...	[ "In the environment , bacteria compete for privileged access to nutrients or to a particular niche .", "Bacteria have therefore evolved mechanisms to eliminate competitors .", "Among them , the Type VI secretion system ( T6SS ) is a contractile machine functionally comparable to a crossbow: an inner tube is wra...	2015
[ "Introduction", "Results/Discussion", "Materials and Methods" ]	[ "physics", "protein folding", "biophysics simulations", "biophysics" ]	The Role of Non-Native Interactions in the Folding of Knotted Proteins	journal.pcbi.1002504	null	[ [ "A much debated problem in the thermodynamics and kinetics of protein folding [1] , [2] is the process of knot formation in proteins [3] , [4] , [5] , [6] , [7] , [8] .", "The topological entanglement found in naturally-occurring proteins presents several differences from that of compact or collapsed flex...	[ "Stochastic simulations of coarse-grained protein models are used to investigate the propensity to form knots in early stages of protein folding .", "The study is carried out comparatively for two homologous carbamoyltransferases , a natively-knotted N-acetylornithine carbamoyltransferase ( AOTCase ) and an unkno...	[ "Knotted proteins provide an ideal ground for examining how amino acid interactions ( which are local ) can favor their folding into a native state of non-trivial topology ( which is a global property ) .", "Some of the mechanisms that can aid knot formation are investigated here by comparing coarse-grained foldi...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "mutagenesis", "genetic mutation", "chromosome biology", "chromosome structure and function", "genetics", "biology", "genomics", "genetics and genomics", "mutational hypotheses" ]	De Novo CNV Formation in Mouse Embryonic Stem Cells Occurs in the Absence of Xrcc4-Dependent Nonhomologous End Joining	journal.pgen.1002981	null	[ [ "The importance of genomic copy number variants ( CNVs ) , defined as submicroscopic deletions or duplications ranging in size from 50 bp to over a megabase [1] , has become better understood in recent years .", "Normal polymorphic CNVs are a major contributor to human genomic variation and phenotypic div...	[ "Spontaneous copy number variant ( CNV ) mutations are an important factor in genomic structural variation , genomic disorders , and cancer .", "A major class of CNVs , termed nonrecurrent CNVs , is thought to arise by nonhomologous DNA repair mechanisms due to the presence of short microhomologies , blunt ends ,...	[ "Copy number variants ( CNVs ) are a major factor in genetic variation and are a common and important class of mutation in genomic disorders , yet there is limited understanding of how many CNVs arise and the risk factors involved .", "One DNA damage response pathway implicated in CNV formation is nonhomologous e...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biochemistry", "bioinformatics", "database and informatics methods", "mathematical and statistical techniques", "genetics", "bayesian method", "biology and life sciences", "dna", "computational biology", "dna modification", "epigenetics", "epigenomics", "dna methylation", "research and an...	A Bayesian Framework to Identify Methylcytosines from High-Throughput Bisulfite Sequencing Data	journal.pcbi.1003853	null	[ [ "DNA methylation is an important epigenetic modification involved in the regulation of gene expression and plays critical roles in cellular processes [1]–[5] .", "Abnormalities in DNA methylation contribute to the dysregulation of gene expression and have been reported to be associated with tumorigenesis ...	[ "High-throughput bisulfite sequencing technologies have provided a comprehensive and well-fitted way to investigate DNA methylation at single-base resolution .", "However , there are substantial bioinformatic challenges to distinguish precisely methylcytosines from unconverted cytosines based on bisulfite sequenc...	[ "High-throughput bisulfite sequencing ( BS-seq ) has advanced tremendously the study of DNA methylation and the determination of methylcytosines at single-base resolution .", "In BS-seq data analysis , sequencing errors , incomplete bisulfite conversion , and cell heterozygosis affect the accuracy of methylcytosi...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods", "Supporting Information" ]	[ "infectious diseases", "immunology", "homo (human)", "eubacteria" ]	Immunodominant Tuberculosis CD8 Antigens Preferentially Restricted by HLA-B	journal.ppat.0030127	null	[ [ "Infection with Mycobacterium tuberculosis ( Mtb ) remains an important cause of infectious disease , morbidity , and mortality worldwide [1] and has emerged as a major opportunistic infection in individuals with HIV/AIDS [2] .", "Control of infection with Mtb relies heavily on the cellular immune system ...	[ "CD8+ T cells are essential for host defense to intracellular bacterial pathogens such as Mycobacterium tuberculosis ( Mtb ) , Salmonella species , and Listeria monocytogenes , yet the repertoire and dominance pattern of human CD8 antigens for these pathogens remains poorly characterized .", "Tuberculosis ( TB ) ...	[ "CD8+ T cells are essential for host defense to intracellular bacterial pathogens such as Mycobacterium tuberculosis ( Mtb ) , Salmonella species , and Listeria monocytogenes , yet little is known about the antigens recognized by human CD8+ T cells in response to tuberculosis ( TB ) .", "TB , the disease caused b...	2007
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Changes in Postural Syntax Characterize Sensory Modulation and Natural Variation of C. elegans Locomotion	journal.pcbi.1004322	null	[ [ "Animal behaviour can be difficult to study because it involves complex movements that vary continuously in time .", "This is especially true for limbed animals such as insects and mammals , because they have many degrees of freedom and can adopt an even larger number of different postures .", "Detail...	[ "Locomotion is driven by shape changes coordinated by the nervous system through time; thus , enumerating an animal's complete repertoire of shape transitions would provide a basis for a comprehensive understanding of locomotor behaviour .", "Here we introduce a discrete representation of behaviour in the nematod...	[ "Technology for recording neural activity is advancing rapidly and whole-brain imaging with single neuron resolution has already been demonstrated for smaller animals .", "To interpret such complex neural recordings , we need comprehensive characterizations of behaviour , which is the principal output of the brai...	2015
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[]	Accelerated Detection of Mycolactone Production and Response to Antibiotic Treatment in a Mouse Model of Mycobacterium ulcerans Disease	journal.pntd.0002618	null	[ [ "Buruli ulcer , a neglected tropical disease caused by Mycobacterium ulcerans , occurs in marshy environments in scattered countries and regions on most of the world's continents [1] .", "While its mode of transmission remains uncertain , it is now known that the principal virulence factor is a secreted c...	[ "Diagnosis of the neglected tropical disease , Buruli ulcer , can be made by acid-fast smear microscopy , specimen culture on mycobacterial growth media , polymerase chain reaction ( PCR ) , and/or histopathology .", "All have drawbacks , including non-specificity and requirements for prolonged culture at 32°C , ...	[ "The diagnosis of Buruli ulcer , caused by infection with Mycobacterium ulcerans , is complicated by its resemblance to other diseases that may also cause ulcers in the skin .", "Clinical diagnosis can be supported by microscopic detection of acid-fast bacilli in the skin , by prolonged culture of at least 8 week...	2014
[ "Introduction", "Materials and methods", "Results", "Discussion" ]	[ "cell death", "leukemias", "medicine and health sciences", "radiation therapy", "dose prediction methods", "cancer treatment", "clinical oncology", "cell processes", "cancers and neoplasms", "mathematical models", "oncology", "hematologic cancers and related disorders", "clinical medicine", ...	Combination therapeutics of Nilotinib and radiation in acute lymphoblastic leukemia as an effective method against drug-resistance	journal.pcbi.1005482	null	[ [ "The persistence of chemo-resistant leukemia-initiating cells in Philadelphia-chromosome positive ( Ph+ ) B-cell Acute Lymphoblastic Leukemia ( B-ALL ) in the bone marrow is a primary mechanism responsible for disease relapse , following treatment , which occurs in the majority of patients .", "B-ALL is d...	[ "Philadelphia chromosome-positive ( Ph+ ) acute lymphoblastic leukemia ( ALL ) is characterized by a very poor prognosis and a high likelihood of acquired chemo-resistance .", "Although tyrosine kinase inhibitor ( TKI ) therapy has improved clinical outcome , most ALL patients relapse following treatment with TKI...	[ "High likelihood of evolution of resistance to therapy is common in most forms of leukemia .", "This issue persists for tyrosine kinase inhibitor drug treatments as well as other forms of therapies .", "In the current work , we suggest a combination therapy where Ph+ acute lymphoblastic leukemic cells are treat...	2017
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "blood cells", "medicine and health sciences", "immune cells", "immune physiology", "spleen", "immunology", "cloning", "neuroscience", "learning and memory", "cell differentiation", "developmental biology", "cognition", "memory", "cytotoxic t cells", "molecular biology techniques", "re...	TCR stimulation strength is inversely associated with establishment of functional brain-resident memory CD8 T cells during persistent viral infection	journal.ppat.1006318	null	[ [ "Following TCR engagement , pathogen-specific naïve CD8 T cells rapidly expand to generate a large effector population to counter primary infection , with a small population of memory CD8 T cells concomitantly generated to provide accelerated immunity to re-infection .", "CD8 T cell activation and differe...	[ "Establishing functional tissue-resident memory ( TRM ) cells at sites of infection is a newfound objective of T cell vaccine design .", "To directly assess the impact of antigen stimulation strength on memory CD8 T cell formation and function during a persistent viral infection , we created a library of mouse po...	[ "Tissue-resident memory ( TRM ) cells are a subset of memory T cells that primarily reside in non-lymphoid tissues and serve as sentinels and effectors against secondary infections .", "TRM cells have been extensively characterized in mucosal barriers , but much less is known about this population in non-barrier ...	2017
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "invertebrates", "medicine and health sciences", "geographical locations", "panama", "animals", "north america", "mathematics", "algebra", "infectious disease control", "insect vectors", "central america", "public and occupational health", "infectious diseases", "aedes aegypti", "epidemi...	Detecting space-time clusters of dengue fever in Panama after adjusting for vector surveillance data	journal.pntd.0007266	null	[ [ "Dengue disease , a viral infection transmitted to humans by Aedes mosquitoes , is endemic to 128 countries , with 3 . 9 billion people considered at-risk globally [1] .", "Dengue disease cases have increased dramatically worldwide throughout the previous several decades [2] , likely a result of urbanizat...	[ "Long term surveillance of vectors and arboviruses is an integral aspect of disease prevention and control systems in countries affected by increasing risk .", "Yet , little effort has been made to adjust space-time risk estimation by integrating disease case counts with vector surveillance data , which may resul...	[ "Dengue cases have increased in tropical regions worldwide owing to urbanization , globalization , and climate change facilitating the spread of Aedes mosquito vectors .", "National surveillance programs monitor trends in dengue fever and inform the public about epidemiological scenarios where outbreak preventive...	2019
[ "Introduction", "Materials and methods", "Results", "Discussion", "Conclusion" ]	[ "medicine and health sciences", "ecology and environmental sciences", "water resources", "pathology and laboratory medicine", "pathogens", "tropical diseases", "geographical locations", "microbiology", "retroviruses", "viruses", "immunodeficiency viruses", "bacterial diseases", "age groups",...	Multi-site cholera surveillance within the African Cholera Surveillance Network shows endemicity in Mozambique, 2011–2015	journal.pntd.0005941	null	[ [ "Cholera is an acute , diarrheal illness caused by infection of the intestine with the bacterium Vibrio cholerae .", "Its epidemics have been continuously reported from Southern Africa since its reintroduction on the continent in 1970 [1 , 2] .", "Today , cholera remains a significant cause of morbidi...	[ "Mozambique suffers recurrent annual cholera outbreaks especially during the rainy season between October to March .", "The African Cholera Surveillance Network ( Africhol ) was implemented in Mozambique in 2011 to generate accurate detailed surveillance data to support appropriate interventions for cholera contr...	[ "Cholera is a major public health problem in many countries in sub-Saharan Africa .", "In Mozambique , annual outbreaks occur but the place and time may vary .", "Africhol was implemented in Mozambique in 2011 to generate more detailed information on disease burden and characteristics to support appropriate int...	2017
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "evolutionary biology/microbial evolution and genomics", "public health and epidemiology", "infectious diseases/antimicrobials and drug resistance", "genetics and genomics/population genetics" ]	Positive Epistasis Drives the Acquisition of Multidrug Resistance	journal.pgen.1000578	null	[ [ "Epistasis occurs when the phenotypic effect of a mutation in a locus depends on which mutations are present at other loci .", "When the phenotype of interest is fitness , the existence of such genetic interactions can constrain the course of evolution .", "The strength and form of epistasis is releva...	[ "The evolution of multiple antibiotic resistance is an increasing global problem .", "Resistance mutations are known to impair fitness , and the evolution of resistance to multiple drugs depends both on their costs individually and on how they interact—epistasis .", "Information on the level of epistasis betwee...	[ "Understanding the nature of genetic interactions , known as epistasis , is crucial in biology .", "The strength and type of epistasis is relevant for the evolution of sex , buffering of genetic variation , speciation , and the topography of fitness landscapes .", "While epistasis between gene deletions has bee...	2009
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "immunology/immunity to infections", "immunology/innate immunity" ]	Pseudomonas aeruginosa Eliminates Natural Killer Cells via Phagocytosis-Induced Apoptosis	journal.ppat.1000561	null	[ [ "Infectious complications are one of the major causes of morbidity and mortality in immunocompromised patients , despite recent advances in therapeutic approaches and supportive care .", "Among the infectious agents , the increasing incidence of PA is a worldwide problem , particularly in patients with le...	[ "Pseudomonas aeruginosa ( PA ) is an opportunistic pathogen that causes the relapse of illness in immunocompromised patients , leading to prolonged hospitalization , increased medical expense , and death .", "In this report , we show that PA invades natural killer ( NK ) cells and induces phagocytosis-induced cel...	[ "Phagocytic leukocytes , including neutrophils and macrophages , are critical for innate immunity against invading bacteria .", "Binding and internalization of bacteria by these immune cells stimulates a variety of anti-microbial activities .", "Although the immune cells are specialized for elimination of bacte...	2009
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "immunology", "host-pathogen interaction", "biology", "microbiology", "parasitology" ]	Sm10.3, a Member of the Micro-Exon Gene 4 (MEG-4) Family, Induces Erythrocyte Agglutination In Vitro and Partially Protects Vaccinated Mice against Schistosoma mansoni Infection	journal.pntd.0002750	null	[ [ "Schistosomiasis occurs primarily in developing countries and is the most important human helminth infection in terms of global mortality .", "This parasitic disease affects more than 200 million people worldwide , causing more than 250 , 000 deaths per year [1] .", "Furthermore , schistosomiasis is r...	[ "The parasitic flatworm Schistosoma mansoni is a blood fluke that causes schistosomiasis .", "Current schistosomiasis control strategies are mainly based on chemotherapy , but many researchers believe that the best long-term strategy to control disease is a combination of drug treatment and immunization with an a...	[ "Schistosomiasis mainly occurs in developing countries and is the most important human helminth infection in terms of global mortality .", "This parasitic disease affects more than 200 million people worldwide and causes more than 250 , 000 deaths per year .", "Current schistosomiasis control strategies are mai...	2014
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "medicine", "infectious diseases", "public health and epidemiology", "global health", "neglected tropical diseases", "trachoma", "public health" ]	Monitoring of Mass Distribution Interventions for Trachoma in Plateau State, Nigeria	journal.pntd.0001995	null	[ [ "Trachoma , caused by infection with the bacterium Chlamydia trachomatis , is the leading cause of infectious blindness worldwide [1] , [2] .", "Over time , repeated infections develop scar tissue on the inside of the eyelid , pulling the eyelashes towards the eye where they abrade the cornea , resulting ...	[ "Mass drug administration ( MDA ) with antibiotics is a key component of the SAFE strategy for trachoma control .", "Guidelines recommend that where MDA is warranted the whole population be targeted with 80% considered the minimum acceptable coverage .", "In other countries , MDA is usually conducted by salarie...	[ "The World Health Organization recommends that mass drug administration for trachoma control reach a minimum of 80% of the target population .", "Previous evaluations of MDA coverage have demonstrated that administrative reports can bias coverage estimates .", "A survey of participation in mass drug administrat...	2013
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "mutagenesis", "mutation", "substitution mutation", "deletion mutation", "genomics", "point mutation", "microbial mutation", "genome evolution", "insertion mutation", "genetics", "biology and life sciences", "molecular evolution", "microbiology", "computational biology", "evolutionary bi...	A shifting mutational landscape in 6 nutritional states: Stress-induced mutagenesis as a series of distinct stress input–mutation output relationships	journal.pbio.2001477	null	[ [ "The notion of stress-induced mutagenesis ( SIM ) [1 , 2] has changed our perspective on the flexibility of mutation rates in organisms .", "The earliest evidence for SIM was that starvation can increase the supply of mutations , presumably increasing the capacity for adaptive changes and evolvability [1 ...	[ "Environmental stresses increase genetic variation in bacteria , plants , and human cancer cells .", "The linkage between various environments and mutational outcomes has not been systematically investigated , however .", "Here , we established the influence of nutritional stresses commonly found in the biosphe...	[ "The importance of this study is in advancing our understanding of mutation supply—of the frequency that beneficial mutations arise in a population—in evolution and the contribution of stress-induced mutagenesis to this process .", "Evolutionary divergences , the emergence of antibiotic resistance in bacteria , a...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine", "genome expression analysis", "infectious diseases", "genome analysis tools", "hiv", "retrovirology and hiv immunopathogenesis", "biology", "genomics", "viral diseases", "genetics and genomics", "transcriptomes" ]	Exon Level Transcriptomic Profiling of HIV-1-Infected CD4+ T Cells Reveals Virus-Induced Genes and Host Environment Favorable for Viral Replication	journal.ppat.1002861	null	[ [ "CD4+ T cells – the primary cellular target of HIV-1 – are progressively depleted over the course of infection .", "This long-term process culminates in the onset of AIDS , a condition in which the immune system is too weak to efficiently mount an effective defence against opportunistic pathogens .", ...	[ "HIV-1 is extremely specialized since , even amongst CD4+ T lymphocytes ( its major natural reservoir in peripheral blood ) , the virus productively infects only a small proportion of cells under an activated state .", "As the percentage of HIV-1-infected cells is very low , most studies have so far failed to cap...	[ "Some previous studies have monitored HIV-1-induced gene expression in various host cell targets and tissues but the discrimination between productively infected cells and uninfected bystander cells represents a technical challenge yet to be solved .", "Consequently , data interpretation has always been biased to...	2012
[ "Introduction", "Methods", "Results", "Discussion", "Conclusion" ]	[ "dengue virus", "medicine and health sciences", "pathology and laboratory medicine", "elderly", "pathogens", "respiratory failure", "tropical diseases", "geographical locations", "microbiology", "pulmonology", "health care", "viruses", "age groups", "rna viruses", "neglected tropical dis...	A Cohort Study of Adult Patients with Severe Dengue in Taiwanese Intensive Care Units: The Elderly and APTT Prolongation Matter for Prognosis	journal.pntd.0005270	null	[ [ "Dengue fever ( DF ) is a mosquito-borne disease that affects at least 50 million people annually worldwide [1 , 2] .", "There have been several outbreaks during the past three decades in Taiwan [3] , most recently , in southern Taiwan in 2015 which involved 43 , 784 cases [4] .", "DF is often conside...	[ "There was a large dengue outbreak in Taiwan in 2015 , in which the ages of the affected individuals were higher than those in other countries .", "The aim of this study was to explore the characteristics and prognostic factors for adults with severe dengue in intensive care units ( ICUs ) .", "All adults admit...	[ "Severe forms of dengue fever ( DF ) are usually considered as a pediatric disease in southern Asia and are graded from dengue hemorrhagic fever ( DHF ) to dengue with shock syndrome ( DSS ) .", "However , the age of affected individuals is increasing in Singapore , Thailand , Mainland China , Taiwan and many oth...	2017
[ "Introduction", "Results and discussion", "Materials and methods" ]	[ "medicine and health sciences", "genetic networks", "protein metabolism", "protein interaction networks", "systems science", "mathematics", "network analysis", "protein structure", "pharmacology", "drug metabolism", "computer and information sciences", "proteins", "proteomics", "molecular ...	Detecting similar binding pockets to enable systems polypharmacology	journal.pcbi.1005522	null	[ [ "Multi-target strategies are a natural approach to tackling complex diseases .", "A fine way to achieve a multi-target effect is through drug polypharmacology , i . e . the simultaneous modulation of several targets by means of one single agent [1 , 2] , which poses pharmacokinetic advantages over drug co...	[ "In the era of systems biology , multi-target pharmacological strategies hold promise for tackling disease-related networks .", "In this regard , drug promiscuity may be leveraged to interfere with multiple receptors: the so-called polypharmacology of drugs can be anticipated by analyzing the similarity of bindin...	[ "Traditionally , the fact that most drugs are promiscuous binders has been a major concern in pharmacology , due to the occurrence of undesired off-target clinical events .", "In the recent years , however , the realization that many diseases are the result of complex biological processes has encouraged rethinkin...	2017
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "blood cells", "medicine and health sciences", "immune cells", "pathology and laboratory medicine", "immunology", "parasitic diseases", "animal models", "colitis", "model organisms", "signs and symptoms", "gastroenterology and hepatology", "experimental organism systems", "inflammatory bowel...	Intestinal helminth infection drives carcinogenesis in colitis-associated colon cancer	journal.ppat.1006649	null	[ [ "A close relationship between inflammation and tumor development has been described for numerous human cancers over the last years [1] .", "In terms of inflammatory bowel diseases ( IBD ) such as ulcerative colitis ( UC ) , it has been clearly demonstrated that patients are predisposed to develop colorect...	[ "Inflammatory bowel diseases ( IBD ) are chronic inflammatory disorders of the gastrointestinal tract , strongly associated with an increased risk of colorectal cancer development .", "Parasitic infections caused by helminths have been shown to modulate the host’s immune response by releasing immunomodulatory mol...	[ "Evidence from epidemiological studies indicates an inverse correlation between the incidence of certain immune-mediated diseases , including inflammatory bowel diseases , and exposure to helminths .", "As a consequence , helminth parasites were tested for treating IBD patients , resulting in clinical amelioratio...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "animal models", "drosophila melanogaster", "animal genetics", "congenital hereditary myopathies", "model organisms", "cellular stress responses", "genetic screens", "genetics", "biology", "human genetics", "molecular cell biology", "autosomal dominant" ]	The NADPH Metabolic Network Regulates Human αB-crystallin Cardiomyopathy and Reductive Stress in Drosophila melanogaster	journal.pgen.1003544	null	[ [ "The maintenance and integrity of specialized functional structures such as sarcomeres , the basic unit of contractile force in striated muscles , are inextricably linked to the cellular machinery of molecular chaperones and protein quality control pathways .", "Evidence for this notion is provided by the...	[ "Dominant mutations in the alpha-B crystallin ( CryAB ) gene are responsible for a number of inherited human disorders , including cardiomyopathy , skeletal muscle myopathy , and cataracts .", "The cellular mechanisms of disease pathology for these disorders are not well understood .", "Among recent advances is...	[ "Cardiomyopathy is a specific form of heart disease that involves progressive restructuring of the heart muscle , resulting in reduced function and increased chance of sudden heart failure .", "Several mutations have been identified that cause inherited cardiomyopathy , including mutations in a gene called alpha ...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genome-wide association studies", "medicine", "public health and epidemiology", "quantitative traits", "glaucoma", "genetic epidemiology", "disease mapping", "epidemiology", "gene expression", "biology", "heredity", "ophthalmology", "genetics", "human genetics", "genetics and genomics" ...	Common Genetic Determinants of Intraocular Pressure and Primary Open-Angle Glaucoma	journal.pgen.1002611	null	[ [ "Primary open-angle glaucoma ( hereafter referred to as glaucoma ) is a progressive optic neuropathy responsible for 12 . 3% of global blindness [1] .", "The evidence for a genetic etiology of glaucoma is well-established [2] .", "However , genes consistently implicated so far ( MYOC , OPTN , WDR36 ) ...	[ "Intraocular pressure ( IOP ) is a highly heritable risk factor for primary open-angle glaucoma and is the only target for current glaucoma therapy .", "The genetic factors which determine IOP are largely unknown .", "We performed a genome-wide association study for IOP in 11 , 972 participants from 4 independe...	[ "Glaucoma is a major eye disease in the elderly and is the second leading cause of blindness worldwide .", "The numerous familial glaucoma cases , as well as evidence from epidemiological and twin studies , strongly support a genetic component in developing glaucoma .", "However , it has proven difficult to ide...	2012
[ "Introduction", "Results/Discussion", "Materials and Methods", "Supporting Information" ]	[ "evolutionary biology", "genetics and genomics", "mammals" ]	The Molecular Basis of High-Altitude Adaptation in Deer Mice	journal.pgen.0030045	null	[ [ "Many long-standing questions about genetic mechanisms of adaptation remain unanswered due to the difficulty of integrating molecular data with evidence for causal effects on organismal fitness .", "In principle , progress could be made by identifying key proteins or key components of protein interaction ...	[ "Elucidating genetic mechanisms of adaptation is a goal of central importance in evolutionary biology , yet few empirical studies have succeeded in documenting causal links between molecular variation and organismal fitness in natural populations .", "Here we report a population genetic analysis of a two-locus α-...	[ "A major goal in evolutionary biology is to identify the specific genetic mechanisms that have enabled organisms to adapt to their environments .", "Variation in deer mouse hemoglobin represents an especially promising system for examining the molecular underpinnings of adaptation because it has been possible to ...	2007
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "material fatigue", "medicine and health sciences", "classical mechanics", "pathology and laboratory medicine", "fatigue", "social sciences", "neuroscience", "learning and memory", "perception", "cognitive psychology", "signs and symptoms", "cognition", "materials science", "memory", "da...	Canonical Cortical Circuit Model Explains Rivalry, Intermittent Rivalry, and Rivalry Memory	journal.pcbi.1004903	null	[ [ "Perceptual rivalry is the subjective experience of alternations between competing percepts when an individual is presented with an ambiguous stimulus .", "It has been suggested that rivalry between neurons may be a ubiquitous property and competition between neural representations occurs throughout the b...	[ "It has been shown that the same canonical cortical circuit model with mutual inhibition and a fatigue process can explain perceptual rivalry and other neurophysiological responses to a range of static stimuli .", "However , it has been proposed that this model cannot explain responses to dynamic inputs such as f...	[ "When the brain is presented with an ambiguous stimulus like the Necker cube or what is known as the quartet illusion , the perception will alternate or rival between the possible interpretations .", "There are neurons in the brain whose activity is correlated with the perception and not the stimulus .", "Hence...	2016
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[]	Modelling the Effects of Electrical Coupling between Unmyelinated Axons of Brainstem Neurons Controlling Rhythmic Activity	journal.pcbi.1004240	null	[ [ "Electrical synapses are widespread in nervous systems from motoneurons to the neocortex and have a long history of study [1–2] .", "In simpler systems , they have been proposed to reduce response latency , synchronise firing , and detect input coincidence [3–8] .", "Electrical coupling is found withi...	[ "Gap junctions between fine unmyelinated axons can electrically couple groups of brain neurons to synchronise ﬁring and contribute to rhythmic activity .", "To explore the distribution and significance of electrical coupling , we modelled a well analysed , small population of brainstem neurons which drive swimmin...	[ "Some groups of nerve cells in the brain are connected to each other electrically where their processes make contact and form specialized “gap” junctions .", "The simplest function of electrical connections is to make activity propagate faster by avoiding the delays resulting from chemical messengers at synaptic ...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	BILBO1 Is a Scaffold Protein of the Flagellar Pocket Collar in the Pathogen Trypanosoma brucei	journal.ppat.1004654	null	[ [ "Trypanosoma brucei is an important parasitic protozoan that is the etiological agent of sleeping sickness in sub-Saharan Africa .", "Related parasites are responsible for Chagas disease and Leishmaniasis in South America and many tropical countries [1 , 2 , 3] .", "At the G1 stage of the T . brucei c...	[ "The flagellar pocket ( FP ) of the pathogen Trypanosoma brucei is an important single copy structure that is formed by the invagination of the pellicular membrane .", "It is the unique site of endo- and exocytosis and is required for parasite pathogenicity .", "The FP consists of distinct structural sub-domain...	[ "Trypanosoma brucei avoids destruction by , in part , changing its surface glycoprotein coat , which is trafficked onto the cell surface via an invagination of the cell surface called the flagellar pocket .", "The pocket is essential for pathogenicity .", "The distal membrane of the pocket is anchored to a cyto...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Ccr4-Not Regulates RNA Polymerase I Transcription and Couples Nutrient Signaling to the Control of Ribosomal RNA Biogenesis	journal.pgen.1005113	null	[ [ "Eukaryotic cells alter gene expression programs in response to changes in their environment , including nutrient availability and the presence of stress , by transmitting this information through nutrient-responsive signaling cascades to the transcriptional machinery [1] .", "This process is critically i...	[ "Ribosomal RNA synthesis is controlled by nutrient signaling through the mechanistic target of rapamycin complex 1 ( mTORC1 ) pathway .", "mTORC1 regulates ribosomal RNA expression by affecting RNA Polymerase I ( Pol I ) -dependent transcription of the ribosomal DNA ( rDNA ) but the mechanisms involved remain obs...	[ "All cells communicate their environmental nutrient status to the gene expression machinery so that transcription occurs in proportion to the nutrients available to support cell growth and proliferation .", "mTORC1 signaling , which is essential for this process , regulates Pol I-dependent rRNA expression .", "...	2015
[ "Introduction", "Methods", "Results", "Discussion" ]	[]	Metapopulation Persistence in Random Fragmented Landscapes	journal.pcbi.1004251	null	[ [ "In an increasingly fragmented and patchy world [1] , species survival critically depends on dispersal , as local populations at high risk of extinction could be rescued by immigration from neighboring populations [2] .", "This intuition forms the core of metapopulation theory: even though local populatio...	[ "Habitat destruction and land use change are making the world in which natural populations live increasingly fragmented , often leading to local extinctions .", "Although local populations might undergo extinction , a metapopulation may still be viable as long as patches of suitable habitat are connected by dispe...	[ "Like the hundreds of paintings of water lilies by Monet , any two landscapes in which a metapopulation dwells are different , as the size , shape and location of the patches of suitable habitat ( the lilies ) , distributed over a inhospitable background ( the water ) vary among landscapes .", "Yet , as all the p...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "oncology", "medicine", "public health and epidemiology", "epidemiology", "genetics and genomics", "clinical genetics" ]	Germline Genetic Variants Disturbing the Let-7/LIN28 Double-Negative Feedback Loop Alter Breast Cancer Susceptibility	journal.pgen.1002259	null	[ [ "MicroRNAs ( miRNAs ) are an abundant class of ∼22 nucleotides ( nt ) long endogenous noncoding RNAs that can guide post-transcriptional gene silencing .", "They have important roles in multiple physiological processes , including developmental timing , cellular proliferation , differentiation , and apopt...	[ "Previous studies have shown that let-7 can repress the post-transcriptional translation of LIN28 , and LIN28 in turn could block the maturation of let-7 , forming a double-negative feedback loop .", "In this study , we investigated the effect of germline genetic variants on regulation of the homeostasis of the l...	[ "Genetic variants are the genetic basis of inter-individual differences in susceptibility to common diseases like cancer .", "Single nucleotide polymorphisms ( SNPs ) are the major type of genetic variation in human beings , and previous studies have linked many SNPs with the risk of suffering human malignancies ...	2011
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biology", "neuroscience" ]	A Structural and Mutagenic Blueprint for Molecular Recognition of Strychnine and d-Tubocurarine by Different Cys-Loop Receptors	journal.pbio.1001034	null	[ [ "Strychnine and d-TC ( Figure 1A ) are alkaloids from poisonous plants .", "Strychnine exerts its lethal effects by antagonizing inhibitory glycine receptors ( GlyR ) in the central nervous system .", "Intoxication with strychnine causes muscle spasms , convulsions and eventually leads to death by res...	[ "Cys-loop receptors ( CLR ) are pentameric ligand-gated ion channels that mediate fast excitatory or inhibitory transmission in the nervous system .", "Strychnine and d-tubocurarine ( d-TC ) are neurotoxins that have been highly instrumental in decades of research on glycine receptors ( GlyR ) and nicotinic acety...	[ "Ligand-gated ion channels play an important role in fast electrochemical signaling in the brain .", "Cys-loop receptors are a class of pentameric ligand-gated ion channels that are activated by specific neurotransmitters , including acetylcholine ( ACh ) , serotonin ( 5-HT ) , glycine ( Gly ) , and γ-aminobutyri...	2011
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "medicine", "infectious diseases", "ecology", "biology", "parasitic diseases" ]	Incrimination of Phlebotomus kandelakii and Phlebotomus balcanicus as Vectors of Leishmania infantum in Tbilisi, Georgia	journal.pntd.0001609	null	[ [ "Historically , visceral leishmaniasis ( VL ) in Georgia has been characterized by sporadic cases chiefly in eastern mountainous districts indicative of an endemic situation [1] , [2] .", "It wasn't until the 1990s that VL due to Leishmania infantum was recognized as a significant public health problem in...	[ "A survey of potential vector sand flies was conducted in the neighboring suburban communities of Vake and Mtatsminda districts in an active focus of visceral Leishmaniasis ( VL ) in Tbilisi , Georgia .", "Using light and sticky-paper traps , 1 , 266 male and 1 , 179 female sand flies were collected during 2006–2...	[ "Visceral Leishmaniasis ( VL ) is a public health problem in Tbilisi , capital of the Republic of Georgia .", "VL is caused by Leishmania parasites and dogs represent the main infection reservoirs .", "VL is transmitted among humans and dogs by sand fly bites .", "Here , we carried out a three-year survey to ...	2012
[ "Introduction", "Results and Discussion", "Materials and Methods" ]	[ "effective population size", "natural selection", "virology", "genetics", "population genetics", "biology", "evolutionary theory", "evolutionary biology", "genomic evolution", "genetics of disease", "evolutionary genetics", "microbiology" ]	Loss and Recovery of Genetic Diversity in Adapting Populations of HIV	journal.pgen.1004000	null	[ [ "Understanding the process of adaptation is one of the basic questions in evolutionary biology .", "The evolution of drug resistance in pathogens such as HIV is a prime example of adaptation and a major clinical and public health concern because it leads to treatment failures .", "The likelihood that ...	[ "The evolution of drug resistance in HIV occurs by the fixation of specific , well-known , drug-resistance mutations , but the underlying population genetic processes are not well understood .", "By analyzing within-patient longitudinal sequence data , we make four observations that shed a light on the underlying...	[ "It is well known that HIV can evolve to become drug resistant if it acquires specific drug-resistance mutations , but the underlying population genetic processes are not well understood .", "We found that the evolution of drug resistance in HIV populations within infected patients occurs by one mutation at a tim...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "infectious diseases/bacterial infections", "microbiology/applied microbiology", "biochemistry/drug discovery", "infectious diseases/antimicrobials and drug resistance" ]	Identification of Small Molecule Inhibitors of Pseudomonas aeruginosa Exoenzyme S Using a Yeast Phenotypic Screen	journal.pgen.1000005	null	[ [ "Microbial resistance flourishes in hospitals and community settings , and represents a major threat to human health worldwide [1] , [2] .", "Despite the threat , drug discovery methods have failed to deliver new effective antibiotics [3] .", "This problem is likely to worsen because major pharmaceuti...	[ "Pseudomonas aeruginosa is an opportunistic human pathogen that is a key factor in the mortality of cystic fibrosis patients , and infection represents an increased threat for human health worldwide .", "Because resistance of Pseudomonas aeruginosa to antibiotics is increasing , new inhibitors of pharmacologicall...	[ "Microbial resistance to antibiotics is a serious and growing threat to human health .", "Here , we used a novel approach that combines chemical and genetic perturbation of bakers yeast to find new targets that might be effective in controlling infections caused by the opportunistic human pathogen Pseudomonas aer...	2008
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "spectrometric identification of proteins", "protein interactions", "gene function", "proteins", "membranes and sorting", "biology", "proteomics", "molecular biology", "biochemistry", "signal transduction", "cell biology", "genetics", "human genetics", "molecular cell biology", "genetics...	A Novel Protein LZTFL1 Regulates Ciliary Trafficking of the BBSome and Smoothened	journal.pgen.1002358	null	[ [ "Primary cilia are microtubule-based subcellular organelles projecting from the surface of cells .", "Studies during the last decade have shown that primary cilia play essential roles in regulating cell cycle , embryonic development , and tissue homeostasis by acting as a cellular antenna transducing extr...	[ "Many signaling proteins including G protein-coupled receptors localize to primary cilia , regulating cellular processes including differentiation , proliferation , organogenesis , and tumorigenesis .", "Bardet-Biedl Syndrome ( BBS ) proteins are involved in maintaining ciliary function by mediating protein traff...	[ "Primary cilia are considered to be a signaling hub coordinating multiple signaling pathways .", "Impairment of ciliary function results in developmental defects in vertebrates and also underlies many human disorders including obesity , polycystic kidney disease , and retinopathy .", "BBS is a prototypical huma...	2011
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[]	Irradiation of Neurons with High-Energy Charged Particles: An In Silico Modeling Approach	journal.pcbi.1004428	null	[ [ "Neuronal cells show great diversity in morphology and are highly organized within the animal brain [1] .", "In general , neurons are differentiated cells with a tree-like structure including the soma which contains the cell nucleus , numerous dendritic branches emanating from the soma unidirectionally or...	[ "In this work , a stochastic computational model of microscopic energy deposition events is used to study for the first time damage to irradiated neuronal cells of the mouse hippocampus .", "An extensive library of radiation tracks for different particle types is created to score energy deposition in small voxels...	[ "Changes to cognition and other central nervous system ( CNS ) effects following charged particle exposures are of concern for medical patients undergoing radiation treatment in cancer therapy and for cosmic ray exposures to astronauts during space travel .", "Neuronal cell injury initiated by ionizing energy dep...	2015
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "blood cells", "flow cytometry", "typhus", "medicine and health sciences", "innate immune system", "immune cells", "immune physiology", "pathology and laboratory medicine", "cytokines", "body fluids", "pathogens", "immunology", "microbiology", "bacterial diseases", "developmental biology...	Activation, Impaired Tumor Necrosis Factor-α Production, and Deficiency of Circulating Mucosal-Associated Invariant T Cells in Patients with Scrub Typhus	journal.pntd.0004832	null	[ [ "Scrub typhus is a mite-borne bacterial infection in humans caused by Orientia tsutsugamushi , an obligate intracellular bacterium , prevalent in Asia , Northern Australia , and the Indian subcontinent .", "With early diagnosis and management , most patients with scrub typhus are able to recover without c...	[ "Mucosal-associated invariant T ( MAIT ) cells contribute to protection against certain microorganism infections .", "However , little is known about the role of MAIT cells in Orientia tsutsugamushi infection .", "Hence , the aims of this study were to examine the level and function of MAIT cells in patients wi...	[ "Scrub typhus is a mite-borne bacterial infection in humans caused by Orientia tsutsugamushi , an obligate intracellular bacterium , prevalent in Asia , Northern Australia , and the Indian subcontinent .", "The pathogenesis of O . tsutsugamushi infection is known to be not only related to the virulence of O . tsu...	2016
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "group-specific staining", "medicine and health sciences", "pathology and laboratory medicine", "hematoxylin staining", "nervous system", "pathogens", "skeletal muscles", "immunology", "microbiology", "neuroscience", "animal models", "viruses", "model organisms", "rna viruses", "signs an...	Neuropathogenesis of Zika Virus in a Highly Susceptible Immunocompetent Mouse Model after Antibody Blockade of Type I Interferon	journal.pntd.0005296	null	[ [ "Zika virus ( ZIKV , Flaviviridae , Flavivirus ) is an arthropod-borne virus ( arbovirus ) that is closely related to dengue , West Nile , Japanese encephalitis and yellow fever viruses [1 , 2] .", "ZIKV was first isolated in Uganda in 1947 from a febrile sentinel rhesus monkey in the Zika forest [3 , 4] ...	[ "Animal models are needed to better understand the pathogenic mechanisms of Zika virus ( ZIKV ) and to evaluate candidate medical countermeasures .", "Adult mice infected with ZIKV develop a transient viremia , but do not demonstrate signs of morbidity or mortality .", "Mice deficient in type I or a combination...	[ "Research addressing the severe clinical complications associated with ZIKV infection , including GBS and congenital ZIKV syndrome , are urgently needed .", "Key to this effort is development of well-characterized animal models that recapitulate human disease .", "Adult wild-type mice infected with ZIKV can dev...	2017
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[]	Within-Host Stochastic Emergence Dynamics of Immune-Escape Mutants	journal.pcbi.1004149	null	[ [ "Parasites and pathogens pose a continuous threat to human , livestock , and plant health since new strains can readily emerge , via mutation or recombination , from pre-existing strains .", "Generally , the focus has been on detection of emerging diseases at the population level , in order to track and c...	[ "Predicting the emergence of new pathogenic strains is a key goal of evolutionary epidemiology .", "However , the majority of existing studies have focussed on emergence at the population level , and not within a host .", "In particular , the coexistence of pre-existing and mutated strains triggers a heightened...	[ "The ongoing evolution of infectious diseases provides a constant health threat .", "This evolution can either result in the production of new pathogens , or new strains of existing pathogens that escape prevailing drug treatments or immune responses .", "The latter process , also known as immune escape , is a ...	2015
[ "Introduction", "Results", "Discussion", "Methods" ]	[]	Learning the Structure of Biomedical Relationships from Unstructured Text	journal.pcbi.1004216	null	[ [ "Biomedical research generates text at an incredible rate .", "Each year , several hundred thousand new articles enter Medline from over 5 , 500 unique journals [1 , 2] .", "The literature’s rapid growth and the rise of interdisciplinary domains like bioinformatics and systems biology are changing how...	[ "The published biomedical research literature encompasses most of our understanding of how drugs interact with gene products to produce physiological responses ( phenotypes ) .", "Unfortunately , this information is distributed throughout the unstructured text of over 23 million articles .", "The creation of st...	[ "Virtually all important biomedical knowledge is described in the published research literature , but Medline currently contains over 23 million articles and is growing at the rate of several hundred thousand new articles each year .", "In this environment , we need computational algorithms that can efficiently e...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "molecular cell biology", "genetics", "cell biology", "biology and life sciences" ]	The Not5 Subunit of the Ccr4-Not Complex Connects Transcription and Translation	journal.pgen.1004569	null	[ [ "The life of an mRNA molecule in eukaryotic cells is considered to be the sum of distinct events separated in time and space .", "Precisely , this separation seems to constitute the characteristic difference distinguishing eukaryotes from prokaryotes , where translation is co-transcriptional and occurs in...	[ "Recent studies have suggested that a sub-complex of RNA polymerase II composed of Rpb4 and Rpb7 couples the nuclear and cytoplasmic stages of gene expression by associating with newly made mRNAs in the nucleus , and contributing to their translation and degradation in the cytoplasm .", "Here we show by yeast two...	[ "In this work we show that , both in the nucleus and in the cytoplasm , Not5 plays a “bridging” role for RNA Polymerase II .", "In the cytoplasm , Not5 interacts with the mRNA encoding the largest subunit of RNA polymerase II Rpb1 and supports the association of a co-chaperone to newly produced protein , to keep ...	2014
[ "Introduction", "Methods", "Results", "Discussion" ]	[]	Discovery of Infection Associated Metabolic Markers in Human African Trypanosomiasis	journal.pntd.0004200	null	[ [ "Human African Trypanosomiasis ( HAT ) is caused by infection with either of two subspecies of Trypanosoma brucei .", "Trypanosoma brucei ( T . b . ) gambiense causes chronic disease ( that can last months or years ) and is endemic in Western Africa while T . b .", "rhodiesiense causes a more acute il...	[ "Human African trypanosomiasis ( HAT ) remains a major neglected tropical disease in Sub-Saharan Africa .", "As clinical symptoms are usually non-specific , new diagnostic and prognostic markers are urgently needed to enhance the number of identified cases and optimise treatment .", "This is particularly import...	[ "Metabolic profiling of biofluids and tissues in disease and healthy individuals is a powerful approach to discover new markers for diagnosis .", "We have applied these techniques to the protozoan infection human African trypanosomiasis ( HAT ) , otherwise known as sleeping sickness .", "The form of HAT endemic...	2015
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "medicine", "immunology", "microbiology", "liver diseases", "infectious hepatitis", "gastroenterology and hepatology", "signaling pathways", "hepatitis c", "stress signaling cascade", "viral immune evasion", "biology", "molecular biology", "signal transduction", "immunity", "virology", ...	Hepatitis C Virus Reveals a Novel Early Control in Acute Immune Response	journal.ppat.1002289	null	[ [ "IFN induction in response to several RNA viruses involves the intracytosolic pathogen recognition receptor ( PRR ) CARD-containing DexD/H RNA helicase RIG-I .", "Following its binding to viral RNA , RIG-I undergoes a change in its conformation through Lys63-type ubiquitination by the E3 ligase TRIM25 .",...	[ "Recognition of viral RNA structures by the intracytosolic RNA helicase RIG-I triggers induction of innate immunity .", "Efficient induction requires RIG-I ubiquitination by the E3 ligase TRIM25 , its interaction with the mitochondria-bound MAVS protein , recruitment of TRAF3 , IRF3- and NF-κB-kinases and transcr...	[ "Hepatitis C Virus ( HCV ) is a poor interferon ( IFN ) inducer , despite recognition of its RNA by the cytosolic RNA helicase RIG-I .", "This is due in part through cleavage of MAVS , a downstream adapter of RIG-I , by the HCV NS3/4A protease and through activation of the eIF2α-kinase PKR to control IFN translat...	2011
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genetics", "epigenetics", "biology", "genetics and genomics" ]	The Dynamics and Prognostic Potential of DNA Methylation Changes at Stem Cell Gene Loci in Women's Cancer	journal.pgen.1002517	null	[ [ "Aberrant DNA methylation is one of the most important cancer hallmarks [1] , yet its precise role in carcinogenesis and clinical prognosis remains ill-defined [2] .", "Indeed , the dynamical changes in DNA methylation that happen during carcinogenesis , in particular those prior to morphological changes ...	[ "Aberrant DNA methylation is an important cancer hallmark , yet the dynamics of DNA methylation changes in human carcinogenesis remain largely unexplored .", "Moreover , the role of DNA methylation for prediction of clinical outcome is still uncertain and confined to specific cancers .", "Here we perform the mo...	[ "DNA methylation is an important chemical modification of DNA that can affect and regulate the activity of genes in human tissue .", "Abnormal DNA methylation and its subsequent effects on gene activity are a hallmark of cancer , yet when precisely these DNA methylation changes occur and how they contribute to th...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	IBR5 Modulates Temperature-Dependent, R Protein CHS3-Mediated Defense Responses in Arabidopsis	journal.pgen.1005584	null	[ [ "Plant growth and development are continuously affected by various environmental stresses , including low temperature and pathogen infection .", "Emerging evidence has shown that the defense responses of plants are regulated by temperatures [1] .", "Temperature modulates the defense responses induced ...	[ "Plant responses to low temperature are tightly associated with defense responses .", "We previously characterized the chilling-sensitive mutant chs3-1 resulting from the activation of the Toll and interleukin 1 receptor-nucleotide binding-leucine-rich repeat ( TIR-NB-LRR ) -type resistance ( R ) protein harborin...	[ "Resistance ( R ) genes play central roles in recognizing pathogens and triggering plant defense responses .", "CHS3 encodes a TIR-NB-LRR-type R protein harboring a C-terminal LIM domain .", "A point mutation in CHS3 activates the defense response under chilling stress .", "Here we identified and characterize...	2015
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "infectious diseases/protozoal infections", "evidence-based healthcare/methods for diagnostic and therapeutic studies", "infectious diseases/tropical and travel-associated diseases" ]	Plasma Superoxide Dismutase-1 as a Surrogate Marker of Vivax Malaria Severity	journal.pntd.0000650	null	[ [ "Severe malaria presents a relevant public health problem worldwide , affecting the socio-economic development of many communities .", "The identification of predictors of disease severity is critical to improve patient care .", "Most of the actual knowledge regarding the immunopathological determinan...	[ "Severe outcomes have been described for both Plasmodium falciparum and P . vivax infections .", "The identification of sensitive and reliable markers of disease severity is fundamental to improving patient care .", "An intense pro-inflammatory response with oxidative stress and production of reactive oxygen sp...	[ "Despite being considered a relatively benign disease , Plasmodium vivax infection has been associated with fatal outcomes due to treatment failure or inadequate health care .", "The identification of sensitive and reliable markers of disease severity is important to improve the quality of patient care .", "Alt...	2010
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "medicine and health sciences", "pathology and laboratory medicine", "influenza", "atmospheric science", "pathogens", "applied mathematics", "microbiology", "orthomyxoviruses", "simulation and modeling", "viruses", "algorithms", "optimization", "seasons", "mathematics", "rna viruses", ...	The use of ambient humidity conditions to improve influenza forecast	journal.pcbi.1005844	null	[ [ "A growing body of evidence indicates that the survival and transmissibility of influenza are affected by ambient humidity conditions .", "Laboratory experiments have shown that aerosolized influenza survival rates increase in low ambient relative humidity ( RH ) , i . e . less than 40% [1–10] .", "Ad...	[ "Laboratory and epidemiological evidence indicate that ambient humidity modulates the survival and transmission of influenza .", "Here we explore whether the inclusion of humidity forcing in mathematical models describing influenza transmission improves the accuracy of forecasts generated with those models .", ...	[ "Laboratory and epidemiological evidence indicate that atmospheric absolute humidity conditions modulate the survival , transmission , incidence and seasonality of influenza .", "Absolute humidity ( AH ) conditions are often incorporated as a forcing factor in mathematical models used to describe and forecast inf...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "acute cardiovascular problems", "genome-wide association studies", "medicine", "coronary artery disease", "arrhythmias", "genetics", "biology", "human genetics", "genetics of disease", "genetics and genomics", "cardiovascular" ]	Identification of a Sudden Cardiac Death Susceptibility Locus at 2q24.2 through Genome-Wide Association in European Ancestry Individuals	journal.pgen.1002158	null	[ [ "Despite recent progress in treatment and prevention of coronary heart disease , sudden cardiac death ( SCD ) remains a major public health problem , with an annual incidence of SCD that ranges from 50 to 100 per 100 , 000 in the general population [1] , [2] .", "While there has been a great deal of focus...	[ "Sudden cardiac death ( SCD ) continues to be one of the leading causes of mortality worldwide , with an annual incidence estimated at 250 , 000–300 , 000 in the United States and with the vast majority occurring in the setting of coronary disease .", "We performed a genome-wide association meta-analysis in 1 , 2...	[ "Family studies have clearly demonstrated a role for genes in modifying risk for sudden cardiac death ( SCD ) , however genetic studies have been limited by available samples .", "Here we have assembled over 4 , 400 SCD cases with >30 , 000 controls , all of European ancestry , and utilize a two-stage study desig...	2011
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "transfer rna", "small nucleolar rnas", "chemical compounds", "gene regulation", "enzymes", "enzymology", "nucleotides", "organic compounds", "fungi", "pyrimidines", "sequence motif analysis", "cellular structures and organelles", "research and analysis methods", "sequence analysis", "bi...	Specialized box C/D snoRNPs act as antisense guides to target RNA base acetylation	journal.pgen.1006804	null	[ [ "Non-coding RNA ( ncRNA ) represents the most abundant form of gene expression in eukaryotic cells [1] .", "Small nucleolar ( sno ) RNAs are a group of well-characterized ncRNA molecules of variable length of 60 to 1000 nts .", "Based on evolutionarily conserved sequence elements , these snoRNAs can b...	[ "Box C/D snoRNAs are known to guide site-specific ribose methylation of ribosomal RNA .", "Here , we demonstrate a novel and unexpected role for box C/D snoRNAs in guiding 18S rRNA acetylation in yeast .", "Our results demonstrate , for the first time , that the acetylation of two cytosine residues in 18S rRNA ...	[ "Base-pairing of box C/D small nucleolar RNAs ( snoRNAs ) with the target RNA guides site-specific ribose methylation by fibrillarin ( Nop1 ) , a highly conserved methyltransferase .", "Some box C/D snoRNAs , like yeast U3 , U14 and U8 in higher eukaryotes are not involved in methylation but are essential for pre...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine", "infectious diseases", "viral diseases", "cytomegalovirus infection" ]	Ablation of the Regulatory IE1 Protein of Murine Cytomegalovirus Alters In Vivo Pro-inflammatory TNF-alpha Production during Acute Infection	journal.ppat.1002901	null	[ [ "The β-herpesvirus human cytomegalovirus ( HCMV ) is a species-specific virus and a clinically important pathogen that can establish both acute and latent infections .", "The murine counterpart ( MCMV ) provides a useful model for studying CMV natural infection in its natural host .", "CMV has a dsDNA...	[ "Little is known about the role of viral genes in modulating host cytokine responses .", "Here we report a new functional role of the viral encoded IE1 protein of the murine cytomegalovirus in sculpting the inflammatory response in an acute infection .", "In time course experiments of infected primary macrophag...	[ "The suppression of the production rather than the blockage of action of the potent inflammatory mediator TNFα is a particular hallmark of anti-TNFα mechanisms associated with microbial and parasitic infections .", "Whether this mode of counter-regulation is an important feature of infection by viruses is not cle...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genetics", "biology and life sciences", "developmental biology" ]	BLMP-1/Blimp-1 Regulates the Spatiotemporal Cell Migration Pattern in C. elegans	journal.pgen.1004428	null	[ [ "Cell migration is important for organogenesis and development of animals .", "Numerous extracellular guidance cues and receptors for the spatial control of cell migration have been identified and characterized [1] .", "However , little is known about the temporal regulation of cell migration and how ...	[ "Spatiotemporal regulation of cell migration is crucial for animal development and organogenesis .", "Compared to spatial signals , little is known about temporal signals and the mechanisms integrating the two .", "In the Caenorhabditis elegans hermaphrodite , the stereotyped migration pattern of two somatic di...	[ "The migratory path of DTCs determines the shape of the C . elegans gonad .", "How the spatiotemporal migration pattern is regulated is not clear .", "We identified a conserved transcription factor BLMP-1 as a central component of a gene regulatory circuit required for the spatiotemporal control of DTC migratio...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "plant biology", "plant cell biology", "gene function", "model organisms", "molecular genetics", "arabidopsis thaliana", "chromosome biology", "plant genetics", "biology", "plant and algal models", "cell biology", "genetics", "molecular cell biology", "genetics and genomics" ]	The DNA Replication Factor RFC1 Is Required for Interference-Sensitive Meiotic Crossovers in Arabidopsis thaliana	journal.pgen.1003039	null	[ [ "Meiosis reduces the genomic complement of the cell by half in preparation for fertilization and is essential for sexual reproduction .", "Recombination is a key event in meiotic prophase I and is important for homolog pairing , bivalent formation and proper homolog segregation [1] , [2] .", "Accordin...	[ "During meiotic recombination , induced double-strand breaks ( DSBs ) are processed into crossovers ( COs ) and non-COs ( NCO ) ; the former are required for proper chromosome segregation and fertility .", "DNA synthesis is essential in current models of meiotic recombination pathways and includes only leading st...	[ "Meiotic recombination is important for pairing and sustained association of homologous chromosomes ( homologs ) , thereby ensuring proper homolog segregation and normal fertility .", "DNA synthesis is thought to be required for meiotic recombination , but few genes coding for DNA synthesis factors have been stud...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	A Structural and Functional Comparison Between Infectious and Non-Infectious Autocatalytic Recombinant PrP Conformers	journal.ppat.1005017	null	[ [ "The conformational conversion of the host-encoded prion protein ( PrP ) is a central pathogenic event in the prion diseases [1] .", "In healthy individuals , PrP adopts a fold that is rich in α-helix , termed PrPC , and is post-translationally modified by the incorporation of N-linked glycans and a C-ter...	[ "Infectious prions contain a self-propagating , misfolded conformer of the prion protein termed PrPSc .", "A critical prediction of the protein-only hypothesis is that autocatalytic PrPSc molecules should be infectious .", "However , some autocatalytic recombinant PrPSc molecules have low or undetectable levels...	[ "A key prediction of the prion hypothesis is that autocatalytic , misfolded PrPSc molecules should be highly infectious .", "Various recombinant PrPSc conformers are able to self-propagate in vitro , yet paradoxically only some of these conformers possess significant levels of specific infectivity in bioassays ."...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "virology/mechanisms of resistance and susceptibility, including host genetics", "virology/animal models of infection", "virology/host invasion and cell entry" ]	Heterologous Replacement of the Supposed Host Determining Region of Avihepadnaviruses: High In Vivo Infectivity Despite Low Infectivity for Hepatocytes	journal.ppat.1000230	null	[ [ "Hepadnaviruses including hepatitis B virus ( HBV ) , the causative agent of B-type hepatitis in humans , are small enveloped hepatotropic DNA viruses that replicate by reverse transcription ( [1]; for reviews see [2] , [3] ) .", "Related viruses have been found in some mammals ( orthohepadnaviruses ) , e...	[ "Hepadnaviruses , including hepatitis B virus ( HBV ) , a highly relevant human pathogen , are small enveloped DNA viruses that replicate via reverse transcription .", "All hepadnaviruses display a narrow tissue and host tropism .", "For HBV , this restricts efficient experimental in vivo infection to chimpanze...	[ "Hepatitis B virus ( HBV ) associated liver disease is a leading cause of death worldwide .", "Host range restrictions limit experimental HBV infections largely to chimpanzees or isolated human hepatocytes .", "A narrow host range is shared by the animal hepadnaviruses , e . g . from ducks ( DHBV ) and herons (...	2008
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biochemistry", "in vitro", "computational biology", "neuroscience", "molecular biology" ]	Exon Silencing by UAGG Motifs in Response to Neuronal Excitation	journal.pbio.0050036	Exon skipping of NMDA R1 receptor exon 21 (CI cassette) is mediated by UAGG-type silencing motifs, presenting a mechanism by which external stimuli communicate to the nuclear splicing machinery in neurons.	[ [ "Alternative pre-mRNA splicing expands protein functional diversity by directing precise nucleotide sequence changes within mRNA coding regions .", "Splicing regulation often involves adjusting the relative levels of exon inclusion and skipping patterns as a function of cell type or stage of development ....	[ "Alternative pre-mRNA splicing plays fundamental roles in neurons by generating functional diversity in proteins associated with the communication and connectivity of the synapse .", "The CI cassette of the NMDA R1 receptor is one of a variety of exons that show an increase in exon skipping in response to cell ex...	[ "The modular features of a protein's architecture are regulated after transcription by the process of alternative pre-mRNA splicing .", "Conditions that excite or stress neurons can induce changes in some splicing patterns , suggesting that cellular pathways can take advantage of the flexibility of splicing to tu...	2007
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "oncology", "biochemistry/experimental biophysical methods", "biophysics/protein folding", "biochemistry/protein folding", "biophysics/theory and simulation", "computational biology/protein structure prediction", "biochemistry/bioinformatics", "biotechnology/bioengineering", "chemical biology/macrom...	Identification and Rational Redesign of Peptide Ligands to CRIP1, A Novel Biomarker for Cancers	journal.pcbi.1000138	null	[ [ "Cysteine-rich intestinal protein 1 ( CRIP1 ) belongs to the LIM/double zinc finger protein family , which includes cysteine- and glycine-rich protein-1 , rhombotin-1 , rhombotin-2 , and rhombotin-3 .", "Human CRIP1 , primarily a cytosolic protein , was cloned in 1997 [1] using RT-PCR of human small intes...	[ "Cysteine-rich intestinal protein 1 ( CRIP1 ) has been identified as a novel marker for early detection of cancers .", "Here we report on the use of phage display in combination with molecular modeling to identify a high-affinity ligand for CRIP1 .", "Panning experiments using a circularized C7C phage library y...	[ "Breast cancer is one of the most frequently diagnosed malignancies in American females and is the second leading cause of cancer deaths in women .", "Several improvements in diagnostic protocols have enhanced our ability for earlier detection of breast cancer , resulting in improvement of therapeutic outcome and...	2008
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "medicine", "immune cells", "immune activation", "immunity to infections", "immunology", "liver diseases", "adaptive immunity", "infectious hepatitis", "hepatitis", "gastroenterology and hepatology", "immunoregulation", "hepatitis c", "infectious diseases", "t cells", "biology", "immun...	Dual Function of the NK Cell Receptor 2B4 (CD244) in the Regulation of HCV-Specific CD8+ T Cells	journal.ppat.1002045	null	[ [ "The outcome of viral infections is dependent on the function of CD8+ T cells .", "The activity of CD8+ T cells is tightly regulated by costimulatory molecules", "which are expressed on the cell surface .", "Upon interaction with their respective", "counterparts , various intracellular signall...	[ "The outcome of viral infections is dependent on the function of CD8+ T cells", "which are tightly regulated by costimulatory molecules .", "The NK cell receptor 2B4", "( CD244 ) is a transmembrane protein belonging to the Ig superfamily which can", "also be expressed by CD8+ T cells .", "The aim of this ...	[ "Infection with the hepatitis C Virus ( HCV ) is a world-wide health burden , the", "infection becomes persistent in the majority of cases .", "In chronic patients", "HCV-specific immune responses are weak , HCV-specific CD8+ T cells were", "shown to be functionally exhausted and to be negatively controlled...	2011
[ "Introduction", "Results/Discussion", "Materials and Methods" ]	[ "genetics and genomics/animal genetics", "genetics and genomics/cancer genetics", "molecular biology/dna repair", "cell biology/cellular death and stress responses" ]	Inactivation of Chk2 and Mus81 Leads to Impaired Lymphocytes Development, Reduced Genomic Instability, and Suppression of Cancer	journal.pgen.1001385	null	[ [ "DNA damage response is a result of the coordinated actions of DNA damage signaling and repair pathways , cell cycle checkpoints , and apoptosis [1] .", "Highlighting the importance of the damage signaling and repair mechanisms , mutations of genes such as ATM , BRCA1 and NBS1 , involved in these mechanis...	[ "Chk2 is an effector kinase important for the activation of cell cycle checkpoints , p53 , and apoptosis in response to DNA damage .", "Mus81 is required for the restart of stalled replication forks and for genomic integrity .", "Mus81Δex3-4/Δex3-4 mice have increased cancer susceptibility that is exacerbated b...	[ "Failure to repair DNA damage has been associated with a number of human syndromes , neurodegenerative diseases , immunodeficiency , and cancer .", "In addition , radiotherapy and many cancer chemotherapeutic drugs induce DNA damage , thus allowing the killing of tumors .", "Recent data indicated Mus81's role i...	2011
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "systems biology", "cell biology", "gene expression", "genetics", "biology and life sciences", "computational biology", "molecular cell biology", "dna transcription" ]	Linear Superposition and Prediction of Bacterial Promoter Activity Dynamics in Complex Conditions	journal.pcbi.1003602	null	[ [ "Bacteria respond to their environment by regulating gene expression [1]–[5] .", "Gene expression is determined by global factors such as the cell's growth rate and overall transcription and translation capacity [6]–[10] , together with specific factors such as transcription regulators that respond to spe...	[ "Bacteria often face complex environments .", "We asked how gene expression in complex conditions relates to expression in simpler conditions .", "To address this , we obtained accurate promoter activity dynamical measurements on 94 genes in E . coli in environments made up of all possible combinations of four ...	[ "Bacteria face complex conditions in important settings such as our body and in biotechnological applications such as biofuel production .", "Understanding how bacteria respond to complex conditions is a hard problem: the number of conditions that need to be tested grows exponentially with the number of nutrients...	2014
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "virology/virus evolution and symbiosis", "microbiology/microbial evolution and genomics", "infectious diseases/viral infections", "microbiology/medical microbiology", "infectious diseases/epidemiology and control of infectious diseases" ]	Geo-spatial Hotspots of Hemorrhagic Fever with Renal Syndrome and Genetic Characterization of Seoul Variants in Beijing, China	journal.pntd.0000945	null	[ [ "Hantaviruses are rodent-borne pathogens with a worldwide distribution .", "More than 50 hantaviruses have been found in the world [1]–[3] , each of which appears to have coevolved with a specific rodent or insectivore host [4] .", "As with other members of the family Bunyaviridae , hantaviruses are e...	[ "Hemorrhagic fever with renal syndrome ( HFRS ) is highly endemic in mainland China , and has extended from rural areas to cities recently .", "Beijing metropolis is a novel affected region , where the HFRS incidence seems to be diverse from place to place .", "The spatial scan analysis based on geographical in...	[ "Hemorrhagic fever with renal syndrome ( HFRS ) is caused by Hantaviruses , the enzootic viruses with a worldwide distribution .", "In China , HFRS is a significant public health problem with more than 10 , 000 human cases reported annually and the endemic areas of the disease have extended from rural to urban ar...	2011
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "plasmid construction", "germ cells", "zygotes", "fungi", "model organisms", "sex pheromones", "experimental organism systems", "dna construction", "molecular biology techniques", "dna", "schizosaccharomyces", "research and analysis methods", "sequence analysis", "pheromone receptors", "...	Asymmetric diversification of mating pheromones in fission yeast	journal.pbio.3000101	An asymmetric pheromone/receptor system in the fission yeast Schizosaccharomyces pombe might allow flexible adaptation of pheromones to mutational changes while maintaining stringent recognition for mating partners, perhaps as a first step toward prezygotic mating isolation.	[ [ "Reproductive isolation , which restricts gene flow between sympatric populations , is one of the key mechanisms of speciation [1] .", "Mating between individuals of closely related species is prevented by a prezygotic barrier , which is mainly caused by changes in signals that enable individuals to appro...	[ "In fungi , mating between partners depends on the molecular recognition of two peptidyl mating pheromones by their respective receptors .", "The fission yeast Schizosaccharomyces pombe ( Sp ) has two mating types , Plus ( P ) and Minus ( M ) .", "The mating pheromones P-factor and M-factor , secreted by P and ...	[ "The emergence of a new species might occur when two groups can no longer mate .", "Although such reproductive isolation is considered a key evolutionary process , the mechanisms by which it actually occurs have been confined to conjecture .", "The two sexes ( Plus [P] and Minus [M] ) of S . pombe each secrete ...	2019
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "rna interference", "vesicles", "cloning", "neuroscience", "molecular motors", "nerve fibers", "epigenetics", "molecular biology techniques", "cellular structures and organelles", "neuronal dendrites", "motor proteins", "endosomes", "research and analysis methods", "animal cells", "genet...	Prd1 associates with the clathrin adaptor α-Adaptin and the kinesin-3 Imac/Unc-104 to govern dendrite pruning in Drosophila	journal.pbio.2004506	null	[ [ "Neuronal remodeling is a pivotal step in the formation of mature nervous systems during animal development .", "Developing neurons often outgrow superfluous axonal or dendritic branches at early developmental stages .", "Selective elimination of the unneeded branches without the death of parent neuro...	[ "Refinement of the nervous system depends on selective removal of excessive axons/dendrites , a process known as pruning .", "Drosophila ddaC sensory neurons prune their larval dendrites via endo-lysosomal degradation of the L1-type cell adhesion molecule ( L1-CAM ) , Neuroglian ( Nrg ) .", "Here , we have iden...	[ "During the maturation of the nervous system , some neurons can selectively eliminate their unnecessary connections , including dendrites and axons , to retain specific connections .", "In Drosophila , a class of sensory neurons lose all their larval dendrites during metamorphosis , when they transition from larv...	2018
[ "Introduction", "Results/Discussion", "Materials and Methods" ]	[ "virology/viral replication and gene regulation", "virology/animal models of infection", "virology/host antiviral responses" ]	Non-Human Primate Model of Kaposi's Sarcoma-Associated Herpesvirus Infection	journal.ppat.1000606	null	[ [ "The most recently described human tumor virus , KSHV is a γ-2 herpesvirus and was first identified in association with KS , the most common neoplasm amongst AIDS patients [1] .", "KS is clinically separated into four different forms: classical KS , endemic KS , iatrogenic KS , and epidemic HIV-associated...	[ "Since Kaposi's sarcoma-associated herpesvirus ( KSHV or human herpesvirus 8 ) was first identified in Kaposi's sarcoma ( KS ) lesions of HIV-infected individuals with AIDS , the basic biological understanding of KSHV has progressed remarkably .", "However , the absence of a proper animal model for KSHV continues...	[ "Kaposi's sarcoma-associated herpesvirus ( KSHV or human herpesvirus 8 ) , the most recently identified human tumor-inducing virus , has been linked to Kaposi's sarcoma , pleural effusion lymphomas and multicentric Castleman's disease .", "In fact , KSHV accounts for a large proportion of the cancer deaths in Afr...	2009

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