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headings list	keywords list	title stringlengths 20 281	id stringlengths 20 20	toc stringlengths 57 522 ⌀	sections list	abstract list	summary list	year stringclasses 13 values
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "microbiology/cellular microbiology and pathogenesis", "microbiology/innate immunity" ]	Staphylococcus aureus Panton-Valentine Leukocidin Is a Very Potent Cytotoxic Factor for Human Neutrophils	journal.ppat.1000715	null	[ [ "Staphylococcus aureus is an important human pathogen that can cause serious diseases [1] .", "In the last few years , there was a dramatic increase in the incidence of community-associated methicillin-resistant S . aureus ( CA-MRSA ) infections in otherwise healthy individuals and resistance to multiple ...	[ "The role of the pore-forming Staphylococcus aureus toxin Panton-Valentine leukocidin ( PVL ) in severe necrotizing diseases is debated due to conflicting data from epidemiological studies of community-associated methicillin-resistant S . aureus ( CA-MRSA ) infections and various murine disease-models .", "In thi...	[ "Staphylococcus aureus can cause serious diseases , including necrotizing pneumonia , which often affects young immunocompetent patients and has a high lethality rate .", "Several clinical studies demonstrated a clear association between this form of pneumonia and S . aureus strains carrying the gene for the pore...	2010
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "biogeography", "taxonomy", "medicine and health sciences", "ecology and environmental sciences", "melioidosis", "population genetics", "geographical locations", "india", "australia", "bacterial diseases", "phylogenetics", "data management", "population biology", "research and analysis met...	Molecular analysis of clinical Burkholderia pseudomallei isolates from southwestern coastal region of India, using multi-locus sequence typing	journal.pntd.0006915	null	[ [ "Melioidosis , caused by soil saprophyte Gram-negative bacterium Burkholderia pseudomallei , is classically characterized by pneumonia , septicemia and multiple abscesses .", "There are various predisposing factors for melioidosis with diabetes mellitus as one of the most important factors .", "Until ...	[ "The Gram-negative soil dwelling bacterium Burkholderia pseudomallei is the etiological agent of melioidosis .", "The disease is endemic in most parts of Southeast Asia and northern Australia .", "Over last few years , there has been an increase in number of melioidosis cases from India; however the disease epi...	[ "Burkholderia pseudomallei , a gram negative bacterium , is the causative agent of melioidosis .", "B . pseudomallei is a soil saprophyte and causes infections in humans by percutaneous inoculation , inhalation or ingestion .", "Melioidosis is a life threatening disease , which requires prolonged antibiotic tre...	2018
[ "Introduction", "Results/Discussion", "Materials and Methods" ]	[ "evolutionary biology/bioinformatics", "genetics and genomics/bioinformatics", "computational biology/genomics" ]	Evolution and Survival on Eutherian Sex Chromosomes	journal.pgen.1000568	null	[ [ "Therian sex chromosomes , X and Y , evolved from a pair of homologous autosomes and thus originally harbored an identical set of genes [1]–[3] .", "Driven by a male-determining locus ( SRY ) , the stepwise suppression of recombination between the Y and the X led to evolutionary strata corresponding to in...	[ "Since the two eutherian sex chromosomes diverged from an ancestral autosomal pair , the X has remained relatively gene-rich , while the Y has lost most of its genes through the accumulation of deleterious mutations in nonrecombining regions .", "Presently , it is unclear what is distinctive about genes that rema...	[ "Using recently available marsupial and monotreme genomes , we investigated nascent sex chromosome evolution in mammals .", "We show that , in eutherian mammals , X and Y genes acquired distinct evolutionary rates and functional constraints immediately after recombination suppression; X-linked genes maintained lo...	2009
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Erosion of Conserved Binding Sites in Personal Genomes Points to Medical Histories	journal.pcbi.1004711	null	[ [ "The advent of high-throughput genotyping spurred the rise of genome-wide association studies ( GWAS ) aimed at identifying the basis of genetic diseases .", "GWAS variants , over 90% of which have been found to localize outside of protein-coding sequences [1] , and the growing body of non-coding genome a...	[ "Although many human diseases have a genetic component involving many loci , the majority of studies are statistically underpowered to isolate the many contributing variants , raising the question of the existence of alternate processes to identify disease mutations .", "To address this question , we collect ance...	[ "A central goal of personal genomics is to interpret an individual’s genome to identify variants that confer disease risk , an aim that has far-reaching implications for personalized , precision medicine .", "Here , we leverage next generation sequencing , health records , and functional genome annotations to dev...	2016
[ "Introduction", "Materials and methods", "Results", "Discussion" ]	[ "medicine and health sciences", "body fluids", "immune physiology", "pathology and laboratory medicine", "european union", "pathogens", "immunology", "geographical locations", "microbiology", "vertebrates", "saliva", "animals", "mammals", "viruses", "animal behavior", "rna viruses", ...	Longitudinal survey of two serotine bat (Eptesicus serotinus) maternity colonies exposed to EBLV-1 (European Bat Lyssavirus type 1): Assessment of survival and serological status variations using capture-recapture models	journal.pntd.0006048	null	[ [ "Chiroptera is the second largest order of mammals after Rodentia .", "They have a worldwide geographical range , with the exception of Antarctica and are represented by more than 1 100 different species [1] , of which 36 are found in Europe .", "Of these 36 , 34 are reported in France , and all of th...	[ "This study describes two longitudinal serological surveys of European Bat Lyssavirus type 1 ( EBLV-1 ) antibodies in serotine bat ( Eptesicus serotinus ) maternity colonies located in the North-East of France .", "This species is currently considered as the main EBLV-1 reservoir .", "Multievent capture-recaptu...	[ "A multi-annual survey of two serotine bat ( Eptesicus serotinus ) maternity colonies previously found exposed to European Bat Lyssavirus type 1 ( EBLV-1 ) was assessed using capture-recapture methodology .", "The two roosting site were located in the North-East of France .", "Animals were trapped , banded , an...	2017
[ "Introduction", "Model", "Results", "Discussion" ]	[ "evolutionary biology/microbial evolution and genomics", "molecular biology/molecular evolution", "microbiology/microbial evolution and genomics", "ecology/population ecology", "genetics and genomics/population genetics" ]	Nasty Viruses, Costly Plasmids, Population Dynamics, and the Conditions for Establishing and Maintaining CRISPR-Mediated Adaptive Immunity in Bacteria	journal.pgen.1001171	null	[ [ "For many species of bacteria , adaptive evolution is through the expression of chromosomal and extrachromosomal ( plasmid- and prophage - borne ) genes or clusters of genes ( pathogenicity and nicer islands ) acquired by horizontal gene transfer ( HGT ) from the same or even quite distant species [1] , [2] ....	[ "Clustered , Regularly Interspaced Short Palindromic Repeats ( CRISPR ) abound in the genomes of almost all archaebacteria and nearly half the eubacteria sequenced .", "Through a genetic interference mechanism , bacteria with CRISPR regions carrying copies of the DNA of previously encountered phage and plasmids a...	[ "CRISPR is the acronym for the adaptive immune system that has been found in almost all archaebacteria and nearly half the eubacteria examined .", "Unlike the other defenses bacteria have for protection from phage and other deleterious DNAs , CRISPR has the virtues of specificity , memory , and the capacity to ab...	2010
[ "Introduction", "Materials and methods", "Results", "Discussion" ]	[ "plant anatomy", "apoplastic space", "cell processes", "hormones", "plant science", "plant hormones", "cellular structures and organelles", "leaf veins", "leaves", "biophysics", "exocytosis", "cell membranes", "physics", "biochemistry", "plant biochemistry", "biochemical simulations", ...	Toward a 3D model of phyllotaxis based on a biochemically plausible auxin-transport mechanism	journal.pcbi.1006896	null	[ [ "In plants , most developmental processes are driven by the spatiotemporal distribution of the growth regulator auxin .", "The versatility of the morphogenetic role played by auxin relies on its self-regulated polar transport , in which auxin transport feedbacks on auxin efflux carriers , the PIN proteins...	[ "Polar auxin transport lies at the core of many self-organizing phenomena sustaining continuous plant organogenesis .", "In angiosperms , the shoot apical meristem is a potentially unique system in which the two main modes of auxin-driven patterning—convergence and canalization—co-occur in a coordinated manner an...	[ "The regularity of leaf arrangement around stems has long puzzled scientists .", "The key role played by the plant hormone auxin is now well established .", "On the surface of the tissue responsible for leaf formation , auxin accumulates at several points , from which new leaves eventually emerge .", "Auxin a...	2019
[ "Introduction", "Materials and methods", "Results", "Discussion" ]	[ "antimicrobials", "dermatology", "typhus", "medicine and health sciences", "pathology and laboratory medicine", "viral transmission and infection", "drugs", "tropical diseases", "microbiology", "bacterial diseases", "signs and symptoms", "antibiotics", "neglected tropical diseases", "pharm...	Causes of acute undifferentiated fever and the utility of biomarkers in Chiangrai, northern Thailand	journal.pntd.0006477	null	[ [ "Acute undifferentiated fever ( AUF ) remains the leading cause of hospitalisation among adults and children in urban and rural regions of Southeast Asia .", "The causes include common diseases such as dengue , scrub typhus , murine typhus , leptospirosis , and enteric fever , which continue to contribute...	[ "Tropical infectious diseases like dengue , scrub typhus , murine typhus , leptospirosis , and enteric fever continue to contribute substantially to the febrile disease burden throughout Southeast Asia while malaria is declining .", "Recently , there has been increasing focus on biomarkers ( i . e . C-reactive pr...	[ "Fever remains an important reason why people are hospitalised in Southeast Asia .", "We do not know the most common causes of fever in many regions of the tropics .", "This knowledge would help doctors decide on the most appropriate treatment in areas where access to diagnostics is difficult .", "Establishin...	2018
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "phylogenetics", "ecology", "biology", "evolutionary biology", "microbiology", "evolutionary systematics", "microbial ecology" ]	Incorporating 16S Gene Copy Number Information Improves Estimates of Microbial Diversity and Abundance	journal.pcbi.1002743	null	[ [ "The SSU rRNA gene ( also known as the 16S rRNA gene , referred to as “16S” hereafter ) is widely used in studies of microbial ecology as a “barcode gene” [1] to quantify microbial community structure and diversity [2] , [3] .", "The widespread adoption of 16S as a microbial barcode gene has been driven b...	[ "The abundance of different SSU rRNA ( “16S” ) gene sequences in environmental samples is widely used in studies of microbial ecology as a measure of microbial community structure and diversity .", "However , the genomic copy number of the 16S gene varies greatly – from one in many species to up to 15 in some bac...	[ "Microbial ecologists cannot observe their study organisms directly , so they use molecular sequencing to measure the abundance of different microbes living in the wild .", "The most commonly used method for measuring the abundance of different microbes is to collect a DNA sample from an environment and sequence ...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "computational biology", "mus (mouse)", "neuroscience" ]	Auditory Cortical Detection and Discrimination Correlates with Communicative Significance	journal.pbio.0050173	Pup calls produce quicker and larger neural responses, which convey more information for pup call detection and discrimination, in the auditory cortex of mother mice compared with virgin female mice.	[ [ "A central question in neuroscience is how behaviorally relevant sensory signals are encoded by the brain .", "In the context of species-specific communication , this issue is complicated by the fact that many sounds with the same meaning are variable in their physical characteristics , such as speech pho...	[ "Plasticity studies suggest that behavioral relevance can change the cortical processing of trained or conditioned sensory stimuli .", "However , whether this occurs in the context of natural communication , where stimulus significance is acquired through social interaction , has not been well investigated , perh...	[ "Like a student in a foreign country immersed in an unfamiliar language or a young mother trying to decipher her baby's cries , we all encounter initially meaningless sounds that in fact carry meaning .", "As these sounds gain significance , we become better at detecting and discriminating between them .", "How...	2007
[ "Introduction", "Models", "Results", "Discussion" ]	[]	Network Events on Multiple Space and Time Scales in Cultured Neural Networks and in a Stochastic Rate Model	journal.pcbi.1004547	null	[ [ "The spontaneous activity of excitable neuronal networks exhibits a spectrum of dynamic regimes ranging from quasi-linear , small fluctuations close to stationary activity , to dramatic events such as abrupt and transient synchronization .", "Understanding the underpinnings of such dynamic versatility is ...	[ "Cortical networks , in-vitro as well as in-vivo , can spontaneously generate a variety of collective dynamical events such as network spikes , UP and DOWN states , global oscillations , and avalanches .", "Though each of them has been variously recognized in previous works as expression of the excitability of th...	[ "The spontaneous neural activity is the dynamic floor on which the cortex builds its response to incoming stimuli and organizes its information processing , thereby the importance of understanding its dynamical underpinnings .", "In-vitro preparations , as well as the intact cortex in deep sleep or anesthesia , d...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "immunology/immunity to infections", "immunology/immune response" ]	Perforin and IL-2 Upregulation Define Qualitative Differences among Highly Functional Virus-Specific Human CD8+ T Cells	journal.ppat.1000798	null	[ [ "Understanding the mechanisms by which human T cells provide effective control of pathogens is important for designing interventions against those that persist to cause severe morbidity and/or mortality .", "T cells generally limit the replication of Epstein Barr virus ( EBV ) [1] , [2] , Cytomegalovirus ...	[ "The prevailing paradigm of T lymphocyte control of viral replication is that the protective capacity of virus-specific CD8+ T cells is directly proportional to the number of functions they can perform , with IL-2 production capacity considered critical .", "Having recently defined rapid perforin upregulation as ...	[ "Although CD8+ T cells are thought to be largely responsible for the control of viral infections , exactly how they mediate protection is uncertain .", "One approach to assessing their protective capacity is to measure several of their functions simultaneously .", "Generally , it is believed the more functions ...	2010
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "oncology", "systems biology", "medicine and health sciences", "cell biology", "molecular biology", "biology and life sciences", "computational biology", "biomechanics" ]	Multiparametric Classification Links Tumor Microenvironments with Tumor Cell Phenotype	journal.pbio.1001995	Tumor microenvironment features are established as predictors of tumor cell behavior and fate.	[ [ "Statistics from 2013 show that more than 90% of breast cancer deaths are a consequence of metastatic disease and that median survival for metastatic breast cancer is 3 years [1] .", "Accordingly , a better understanding of the physiological conditions that help initiate or facilitate metastatic recurrenc...	[ "While it has been established that a number of microenvironment components can affect the likelihood of metastasis , the link between microenvironment and tumor cell phenotypes is poorly understood .", "Here we have examined microenvironment control over two different tumor cell motility phenotypes required for ...	[ "A large proportion of cancer deaths are due to metastasis—the spread of cancer from the primary tumor to other parts of the body .", "Movement of cells may require the formation of protrusions called invadopodia , which degrade extracellular matrix .", "Although some studies have reported on locomotion in prim...	2014
[ "Introduction", "Results", "Discussion", "Materials and method" ]	[ "blood cells", "medicine and health sciences", "immune cells", "enzyme-linked immunoassays", "pathology and laboratory medicine", "hepacivirus", "pathogens", "immunology", "microbiology", "viral structure", "immune receptor signaling", "viruses", "rna viruses", "membrane receptor signaling...	Modulation of calcium signaling pathway by hepatitis C virus core protein stimulates NLRP3 inflammasome activation	journal.ppat.1007593	null	[ [ "HCV continues as a global health problem causing chronic and progressive liver disease [1–5] .", "HCV is a major risk factor for hepatocellular carcinoma , and infection is a consistent cause of liver transplants .", "HCV is a small , enveloped , single-stranded RNA virus that belongs to the Flavivir...	[ "Hepatitis C virus ( HCV ) infection remains a major cause of hepatic inflammation and liver disease .", "HCV triggers NLRP3 inflammasome activation and interleukin-1β ( IL-1β ) production from hepatic macrophages , or Kupffer cells , to drive the hepatic inflammatory response .", "Here we examined HCV activati...	[ "This study deciphers the molecular mechanism of Hepatitis C virus ( HCV ) -induced hepatic inflammation .", "HCV triggers NLRP3 inflammasome activation and IL-1β release from hepatic macrophages , thus driving liver inflammation .", "Using biochemical , virological , and genetic approaches we identified the HC...	2019
[ "Introduction", "Materials and methods", "Results", "Discussion" ]	[ "invertebrates", "livestock", "medicine and health sciences", "african trypanosomiasis", "angola", "geographical locations", "tropical diseases", "parasitic diseases", "animals", "parasitic protozoans", "glossina", "research design", "protozoans", "tanzania", "materials science", "negl...	Standardising visual control devices for Tsetse: East and Central African Savannah species Glossina swynnertoni, Glossina morsitans centralis and Glossina pallidipes	journal.pntd.0006831	null	[ [ "Diseases transmitted by tsetse flies , notably human African trypanosomiasis ( HAT or sleeping sickness ) and African animal trypanosomosis ( AAT or Nagana ) , are caused by the transmission of trypanosomes , and are still a serious health and economic burden in sub-Saharan Africa [1 , 2] .", "After a re...	[ "This study focused on the savannah tsetse species Glossina swynnertoni and G . morsitans centralis , both efficient vectors of human and animal trypanosomiasis in , respectively , East and Central Africa .", "The aim was to develop long-lasting , practical and cost-effective visually attractive devices that indu...	[ "Glossina swynnertoni is restricted to open savannah in northwestern Tanzania and southwestern Kenya whereas G . morsitans centralis has a much wider distribution from western Tanzania/southern Uganda westwards through Zambia and southeast of the Democratic Republic of the Congo ( DRC ) to Angola .", "Both are sa...	2018
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "medicine", "infectious diseases", "public health and epidemiology", "epidemiology", "global health", "public health" ]	Forecast of Dengue Incidence Using Temperature and Rainfall	journal.pntd.0001908	null	[ [ "Previous study by Hii et al . ( 2009 ) has shown that elevated weekly mean temperature and cumulative rainfall influence the risks of dengue cases in Singapore at lag times up to 20 weeks with higher relative risks of dengue cases at time lag of 3–4 months [15] .", "Also , a recent study by Hii et al . (...	[ "An accurate early warning system to predict impending epidemics enhances the effectiveness of preventive measures against dengue fever .", "The aim of this study was to develop and validate a forecasting model that could predict dengue cases and provide timely early warning in Singapore .", "We developed a tim...	[ "Without effective drugs or a vaccine , vector control remains the only method of controlling dengue fever outbreaks in Singapore .", "Based on our previous findings on the effects of weather on dengue cases and optimal timing for issuing dengue early warning in Singapore , the purpose of this study was to develo...	2012
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "medicine", "infectious diseases", "neglected tropical diseases" ]	Successful Outcomes with Oral Fluoroquinolones Combined with Rifampicin in the Treatment of Mycobacterium ulcerans: An Observational Cohort Study	journal.pntd.0001473	null	[ [ "In recent years the treatment of Mycobacterium ulcerans ( M . ulcerans ) has radically changed , evolving from a predominantly surgically [1] , [2] to a predominantly medically treated disease [3] .", "This resulted from clinical experience supported by scientific data showing superior outcomes when anti...	[ "The World Health Organization currently recommends combined streptomycin and rifampicin antibiotic treatment as first-line therapy for Mycobacterium ulcerans infections .", "Alternatives are needed when these are not tolerated or accepted by patients , contraindicated , or neither accessible nor affordable .", ...	[ "Buruli ulcer is a necrotizing infection of skin and subcutaneous tissue caused by Mycobacterium ulcerans and is the third most common mycobacterial disease worldwide ( after tuberculosis and leprosy ) .", "In recent years its treatment has radically changed , evolving from a predominantly surgically to a predomi...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "organismal evolution", "viral transmission and infection", "microbial evolution", "virology", "biology and life sciences", "microbiology", "evolutionary biology", "viral evolution" ]	Genetics, Receptor Binding Property, and Transmissibility in Mammals of Naturally Isolated H9N2 Avian Influenza Viruses	journal.ppat.1004508	null	[ [ "Avian influenza viruses of several subtypes continue to present challenges to human health .", "The H5N1 influenza viruses have caused 380 fatal cases among the 641 documented human infections in 16 countries [1] , and several studies have documented the transmission potential of H5N1 mutants or reassort...	[ "H9N2 subtype influenza viruses have been detected in different species of wild birds and domestic poultry in many countries for several decades .", "Because these viruses are of low pathogenicity in poultry , their eradication is not a priority for animal disease control in many countries , which has allowed the...	[ "Avian influenza viruses continue to present challenges to human health .", "Recently the H7N9 and H10N8 viruses that are of low pathogenicity for poultry have caused human infections and deaths in China .", "H9N2 influenza virus have been isolated worldwide from wild and domestic avian species for several deca...	2014
[ "Introduction", "Methods", "Results", "Discussion", "Conclusion" ]	[ "schistosoma", "invertebrates", "schistosoma mansoni", "medicine and health sciences", "education", "helminths", "sociology", "tropical diseases", "geographical locations", "social sciences", "malawi", "parasitic diseases", "animals", "health care", "mathematics", "statistics (mathemat...	Optimising cluster survey design for planning schistosomiasis preventive chemotherapy	journal.pntd.0005599	null	[ [ "Schistosomiasis is a major global health problem , and is estimated to infect 230 million people , cause at least 11 , 000 deaths per year [1 , 2] and 3 . 3 million Disability Adjusted Life Years in 2010 [3] .", "While various tools are used to control the disease , population-level preventive chemothera...	[ "The cornerstone of current schistosomiasis control programmes is delivery of praziquantel to at-risk populations .", "Such preventive chemotherapy requires accurate information on the geographic distribution of infection , yet the performance of alternative survey designs for estimating prevalence and converting...	[ "Many countries are currently scaling up efforts to control schistosomiasis , a helminthic disease for which preventive chemotherapy with praziquantel is the main control tool .", "In order to apply WHO guidelines on how frequently to treat a given district or similar geographic unit for schistosomiasis , survey-...	2017
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "humoral immunity", "infectious disease immunology", "clinical immunology", "immunity", "biology and life sciences", "immunology", "humoral immune response" ]	Protective Efficacy of a Plasmodium vivax Circumsporozoite Protein-Based Vaccine in Aotus nancymaae Is Associated with Antibodies to the Repeat Region	journal.pntd.0003268	null	[ [ "The range of Plasmodium vivax transmission spans 95 countries putting 2 . 86 billion people at risk for this malaria parasite [1] and causes an estimated 132–391 million infections each year [2] .", "In addition to its widespread distribution , P . vivax also has the propensity to form dormant hypnozoite...	[ "We have previously reported that Vivax Malaria Protein 001 ( VMP001 ) , a vaccine candidate based on the circumsporozoite protein of Plasmodium vivax , is immunogenic in mice and rhesus monkeys in the presence of various adjuvants .", "In the present study , we evaluated the immunogenicity and efficacy of VMP001...	[ "Plasmodium vivax is responsible for causing malaria in large parts of the globe , including regions with temperate climates not suited for the transmission of other Plasmodium species .", "In addition , P . vivax has the propensity to form dormant forms , known as hypnozoites , that can remain latent for weeks t...	2014
[ "Introduction", "Results and Discussion", "Materials and Methods" ]	[ "invertebrates", "medicine and health sciences", "caenorhabditis", "gene regulation", "regulatory proteins", "endoplasmic reticulum", "cell processes", "dna-binding proteins", "neuroscience", "animals", "animal models", "physiological processes", "developmental biology", "caenorhabditis el...	Reduced Insulin/Insulin-Like Growth Factor Receptor Signaling Mitigates Defective Dendrite Morphogenesis in Mutants of the ER Stress Sensor IRE-1	journal.pgen.1006579	null	[ [ "During their development neurons can form complex dendritic branching patterns .", "The specific arbor morphologies of different neuron types are thought to have evolved to mediate the acquisition and processing of distinct inputs [1] .", "Defective arbor morphologies in brain neurons are a common ce...	[ "Neurons receive excitatory or sensory inputs through their dendrites , which often branch extensively to form unique neuron-specific structures .", "How neurons regulate the formation of their particular arbor is only partially understood .", "In genetic screens using the multidendritic arbor of PVD somatosens...	[ "Sensory neurons sample their environment through highly branched structures termed dendritic arbors or trees .", "The precise patterning of dendritic arbors is important for the proper functioning of the nervous system , and evidence indicates an involvement of sensory neurons in neuropsychiatric disease such as...	2017
[ "Introduction", "Methods", "Results" ]	[ "genetic networks", "gene regulation", "brassica", "light", "electromagnetic radiation", "circadian oscillators", "model organisms", "network analysis", "experimental organism systems", "chronobiology", "plants", "arabidopsis thaliana", "research and analysis methods", "computer and inform...	Dynamical differential expression (DyDE) reveals the period control mechanisms of the Arabidopsis circadian oscillator	journal.pcbi.1006674	null	[ [ "The synchronization of physiological rhythms with the external environment is important for nearly all organisms .", "Circadian oscillators are internal timing devices that produce rhythms with a period of about 24 hours to regulate a wide range of biological processes .", "Circadian rhythms maintain...	[ "The circadian oscillator , an internal time-keeping device found in most organisms , enables timely regulation of daily biological activities by maintaining synchrony with the external environment .", "The mechanistic basis underlying the adjustment of circadian rhythms to changing external conditions , however ...	[ "Circadian oscillators are internal timing devices that produce rhythms with a period of about 24 hours to regulate a wide range of biological processes for nearly all organisms .", "Circadian oscillators adjust phase and period in response to external cues such as light and temperatures and internal cues such as...	2019
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Neural Substrates Related to Motor Memory with Multiple Timescales in Sensorimotor Adaptation	journal.pbio.1002312	A model-based functional MRI study reveals the existence of brain regions associated with four distinct timescales in motor adaptation.	[ [ "Behavioral and computational modeling studies , on the one hand , and neuroimaging studies , on the other hand , have greatly advanced our understanding of motor adaptation .", "In particular , recent behavioral and computational modeling studies have shed light on the temporal structure of motor adaptat...	[ "Recent computational and behavioral studies suggest that motor adaptation results from the update of multiple memories with different timescales .", "Here , we designed a model-based functional magnetic resonance imaging ( fMRI ) experiment in which subjects adapted to two opposing visuomotor rotations .", "A ...	[ "Motor adaptation , a form of motor learning in which motor commands are modified to compensate for disturbances in the external environment , usually proceeds at a rapid pace initially and is then followed by more gradual adjustments .", "This suggests that at least two learning processes are involved , but litt...	2015
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "cell walls", "fluorescence imaging", "cell cycle and cell division", "cell processes", "membrane staining", "light microscopy", "membrane proteins", "microscopy", "cellular structures and organelles", "cytoskeleton", "research and analysis methods", "specimen preparation and treatment", "st...	The bacterial Sec system is required for the organization and function of the MreB cytoskeleton	journal.pgen.1007017	null	[ [ "Internal organization of bacterial cells is a complex process coordinated spatiotemporally by several molecular machineries .", "In most rod-shaped bacteria , the actin-homolog , MreB , functions as an intracellular organizer controlling cell wall synthesis , cell shape maintenance , cell polarity , cell...	[ "The Sec system is responsible for protein insertion , translocation and secretion across membranes in all cells .", "The bacterial actin homolog MreB controls various processes , including cell wall synthesis , membrane organization and polarity establishment .", "Here we show that the two systems genetically ...	[ "The notion that bacterial cells have intricate spatial organization , which affects many vital processes , is relatively new and , hence , the underlying mechanisms are largely unknown .", "The general secretion system and the cytoskeleton are central systems , each known to organize functions associated with ce...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "cell biology/microbial growth and development", "microbiology/microbial evolution and genomics", "genetics and genomics/chromosome biology", "molecular biology/centromeres" ]	Neocentromeres Form Efficiently at Multiple Possible Loci in Candida albicans	journal.pgen.1000400	null	[ [ "Centromeres , the DNA regions at which microtubules attach to and segregate daughter chromosomes , are essential for genome integrity .", "Point centromeres have been characterized extensively because of their small size and relative simplicity , especially in Saccharomyces cerevisiae .", "They are c...	[ "Centromeres are critically important for chromosome stability and integrity .", "Most eukaryotes have regional centromeres that include long tracts of repetitive DNA packaged into pericentric heterochromatin .", "Neocentromeres , new sites of functional kinetochore assembly , can form at ectopic loci because n...	[ "Centromere function is essential for proper chromosomal segregation .", "Most organisms , including humans , have regional centromeres in which centromere function is not strictly dependent on DNA sequence .", "Upon alteration of chromosomes , new functional centromeres ( neocentromeres ) can form at ectopic p...	2009
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	RFX2 Is a Major Transcriptional Regulator of Spermiogenesis	journal.pgen.1005368	null	[ [ "Reproductive failure affects 10–15% of couples worldwide , with responsibility distributed about equally between males and females [1 , 2] .", "Failure of spermatogenesis is a common cause of male infertility .", "A large fraction of such cases is believed to result from genetic causes .", "The a...	[ "Spermatogenesis consists broadly of three phases: proliferation of diploid germ cells , meiosis , and finally extensive differentiation of the haploid cells into effective delivery vehicles for the paternal genome .", "Despite detailed characterization of many haploid developmental steps leading to sperm , only ...	[ "Failure of spermatogenesis , which is presumed to often result from genetic defects , is a common cause of male sterility .", "Although numerous genes associated with defects in male spermatogenesis have been identified , numerous cases of genetic male infertility remain unelucidated .", "We report here that t...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genome-wide association studies", "medicine and health sciences", "population genetics", "immunology", "ethnicities", "clinical medicine", "genome analysis", "population biology", "chromosome 6", "genomic signal processing", "lipids", "major histocompatibility complex", "chromosome biology"...	Strong Selection at MHC in Mexicans since Admixture	journal.pgen.1005847	null	[ [ "In 1492 Columbus discovered America .", "Europeans , led by the Spaniards , and armed with horses , wheels , germs , and steel , rapidly conquered the New World [1] , and promptly Africans were brought there as slave labor .", "During the past 500 or so years , three populations—Amerindians , Europea...	[ "Mexicans are a recent admixture of Amerindians , Europeans , and Africans .", "We performed local ancestry analysis of Mexican samples from two genome-wide association studies obtained from dbGaP , and discovered that at the MHC region Mexicans have excessive African ancestral alleles compared to the rest of the...	[ "Whether or not there exists recent selection since admixture in Latinos has been a subject of debate .", "To detect selection signal , a method uniquely applicable to recently admixed samples is local ancestry analysis .", "We infer local ancestry of admixed samples ( in our study , Mexicans ) , and look for r...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "mutation", "mycology", "fungi", "plant microbiology", "evolutionary biology", "plant biology", "crops", "population genetics", "crop diseases", "biology", "microbiology", "host-pathogen interaction", "agriculture" ]	Genome Structure and Reproductive Behaviour Influence the Evolutionary Potential of a Fungal Phytopathogen	journal.ppat.1003020	null	[ [ "Fungi are the most important pathogens of cultivated plants , with significant economic , food security and environmental impacts , the latter being due to the large quantities of fungicides used to control plant diseases [1] .", "In contrast to fungicide use , genetic resistance against pathogens in cro...	[ "Modern agriculture favours the selection and spread of novel plant diseases .", "Furthermore , crop genetic resistance against pathogens is often rendered ineffective within a few years of its commercial deployment .", "Leptosphaeria maculans , the cause of phoma stem canker of oilseed rape , develops gene-for...	[ "Plant disease resistance often relies on simple “gene-for-gene” systems and , in the pathogen , a mutation in a single “avirulence” gene matching the plant resistance gene is sufficient to render the resistance ineffective .", "In agricultural systems , breeding for resistance is challenged by both the high evol...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "animal genetics", "cell differentiation", "gene function", "animal models", "developmental biology", "model organisms", "gene expression", "biology", "systems biology", "zebrafish", "genetics", "gene networks", "genetics and genomics", "cell fate determination" ]	An Iterative Genetic and Dynamical Modelling Approach Identifies Novel Features of the Gene Regulatory Network Underlying Melanocyte Development	journal.pgen.1002265	null	[ [ "Understanding the mechanisms of generation of differentiated cell-types from multipotent precursors is a fundamental aspect of development , with profound implications for the therapeutic use of stem cells .", "Whilst numerous transcription factors mediating fate choice from stem cells have been characte...	[ "The mechanisms generating stably differentiated cell-types from multipotent precursors are key to understanding normal development and have implications for treatment of cancer and the therapeutic use of stem cells .", "Pigment cells are a major derivative of neural crest stem cells and a key model cell-type for...	[ "In a multicellular organism , one genome is used to make numerous different cell-types .", "This must require the activity of all these genes to be configured into multiple distinct and stable active states , each corresponding to one of the different cell-types characteristic of a tissue .", "The stable activ...	2011
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	A Rapid Screening Assay Identifies Monotherapy with Interferon-ß and Combination Therapies with Nucleoside Analogs as Effective Inhibitors of Ebola Virus	journal.pntd.0004364	null	[ [ "As of December 13 , 2015 , the current outbreak of Ebola virus disease ( EVD ) in West Africa has resulted in 28 , 633 cumulative cases and 11 , 314 deaths [1] .", "Two potential vaccine candidates , rVSVΔG-ZEBOV and ChAd3-EBO Z , have shown durable protection from lethal Ebola challenge in mice [2] and ...	[ "To date there are no approved antiviral drugs for the treatment of Ebola virus disease ( EVD ) .", "While a number of candidate drugs have shown limited efficacy in vitro and/or in non-human primate studies , differences in experimental methodologies make it difficult to compare their therapeutic effectiveness ....	[ "Studies to evaluate the effectiveness of candidate antiviral drugs to inhibit Ebola virus infection have been hampered by the availability and access to level 4 containment facilities .", "Using a mini-genome model system that generates Ebola virus-like particles that infect cells , we have been able to screen a...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	The Cannabinoid Receptor CB1 Interacts with the WAVE1 Complex and Plays a Role in Actin Dynamics and Structural Plasticity in Neurons	journal.pbio.1002286	A proteomic study reveals the actin nucleation complex WAVE1 as a hitherto unknown binding partner of cannabinoid receptor 1 and explores the functional role of this interaction in regulating pain-related structural plasticity.	[ [ "Psychoactive cannabinoids derived from marijuana as well as diverse endocannabinoids , such as anandamide and 2-arachidonylglycerol ( 2-AG ) bind to and activate signaling via cannabinoid type 1 and type 2 ( CB1 and CB2 ) receptors , which belong to the G-protein coupled receptor ( GPCR ) family .", "Gen...	[ "The molecular composition of the cannabinoid type 1 ( CB1 ) receptor complex beyond the classical G-protein signaling components is not known .", "Using proteomics on mouse cortex in vivo , we pulled down proteins interacting with CB1 in neurons and show that the CB1 receptor assembles with multiple members of t...	[ "One of the most interesting features of the endocannabinoid system ( a group of neuromodulatory lipids and their receptors , which promotes homeostasis in a variety of physiological processes ) is its ability to counteract nociception or pain .", "This function is largely mediated by the receptor component of th...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "developmental biology/germ cells", "molecular biology/recombination", "cell biology/cell growth and division", "cell biology", "genetics and genomics/nuclear structure and function", "molecular biology/chromosome structure", "genetics and genomics/chromosome biology", "genetics and genomics/gene func...	Csm4, in Collaboration with Ndj1, Mediates Telomere-Led Chromosome Dynamics and Recombination during Yeast Meiosis	journal.pgen.1000188	null	[ [ "Classical cytological studies have shown that during the zygotene stage of meiosis , chromosome ends are tightly and specifically associated with the nuclear envelope ( NE ) and move coordinately into a “bouquet” configuration such that they are localized within a sub-area of the nuclear periphery .", "U...	[ "Chromosome movements are a general feature of mid-prophase of meiosis .", "In budding yeast , meiotic chromosomes exhibit dynamic movements , led by nuclear envelope ( NE ) -associated telomeres , throughout the zygotene and pachytene stages .", "Zygotene motion underlies the global tendency for colocalization...	[ "In meiosis , cells specified to become gametes ( eggs or sperm ) undergo a single round of DNA replication followed by two consecutive chromosomal divisions .", "In most organisms , the proper segregation of chromosomes at the first meiotic division is mechanically dependent upon genetic exchange , or crossing o...	2008
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "medicine and health sciences", "diagnostic radiology", "functional magnetic resonance imaging", "brain", "vertebrates", "social sciences", "neuroscience", "animals", "mammals", "cerebral hemispheres", "magnetic resonance imaging", "primates", "right hemisphere", "brain mapping", "vision...	Posterior Parietal Cortex Drives Inferotemporal Activations During Three-Dimensional Object Vision	journal.pbio.1002445	A study in which monkeys examined images of three-dimensional shapes, showing that reversible inactivation of a dorsal stream area affects functional activation in the ventral visual stream.	[ [ "The primate visual cortex consists of a large number of cortical areas that collaborate to compute neural representations of the external world .", "In both the dorsal and the ventral visual stream of the macaque monkey , these cortical networks are organized into distinct hierarchies that provide progre...	[ "The primate visual system consists of a ventral stream , specialized for object recognition , and a dorsal visual stream , which is crucial for spatial vision and actions .", "However , little is known about the interactions and information flow between these two streams .", "We investigated these interactions...	[ "Many different areas of the brain are utilized to analyze the three-dimensional shape of the objects we see and grasp ( e . g . , a sphere compared to a disk ) .", "In this study , we temporarily inactivated one of these areas in the monkey parietal cortex and measured the effect on the network of brain areas in...	2016
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "mathematics/statistics", "computational biology/computational neuroscience", "computational biology/metabolic networks", "computational biology", "computational biology/signaling networks", "neuroscience", "neuroscience/theoretical neuroscience" ]	Efficient Network Reconstruction from Dynamical Cascades Identifies Small-World Topology of Neuronal Avalanches	journal.pcbi.1000271	null	[ [ "Cascade-like dynamics is characterized by the succession of events , or processes ,", "that are causally related , and is frequently encountered in many complex systems", "( networks ) across disciplines .", "For example , single cells in living organisms", "maintain metabolic , protein and g...	[ "Cascading activity is commonly found in complex systems with directed", "interactions such as metabolic networks , neuronal networks , or disease spreading", "in social networks .", "Substantial insight into a system's organization", "can be obtained by reconstructing the underlying functional network arch...	[ "In many complex systems found across disciplines , such as biological cells and", "organisms , social networks , economic systems , and the Internet , individual", "elements interact with each other , thereby forming large networks whose", "structure is often not known .", "In these complex networks , loca...	2009
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "physiology/sensory systems", "neuroscience/sensory systems", "physiology/neuronal signaling mechanisms", "biophysics/theory and simulation", "computational biology/computational neuroscience", "neuroscience/neuronal signaling mechanisms", "neuroscience/theoretical neuroscience" ]	Dendritic Spikes Amplify the Synaptic Signal to Enhance Detection of Motion in a Simulation of the Direction-Selective Ganglion Cell	journal.pcbi.1000899	null	[ [ "The On-Off direction-selective ganglion cell ( DSGC ) of the mammalian retina spikes vigorously to moving stimuli , but only weakly to stationary light spots .", "It responds most strongly over a limited range of stimulus directions , and the direction producing the maximal response is called the “prefer...	[ "The On-Off direction-selective ganglion cell ( DSGC ) in mammalian retinas responds most strongly to a stimulus moving in a specific direction .", "The DSGC initiates spikes in its dendritic tree , which are thought to propagate to the soma with high probability .", "Both dendritic and somatic spikes in the DS...	[ "The On-Off direction-selective ganglion cell ( DSGC ) found in mammalian retinas generates a directional signal , responding most strongly to a stimulus moving in a specific direction .", "The DSGC initiates spikes in its dendritic tree which are thought to propagate to the soma and brain with high probability ....	2010
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "medicine", "infectious diseases", "pediatrics and child health", "pediatrics" ]	Cross-reactive Neutralizing Antibody Responses to Enterovirus 71 Infections in Young Children: Implications for Vaccine Development	journal.pntd.0002067	null	[ [ "Human enteroviruses include over 100 serotypes and usually cause self-limited infections , except polioviruses and enterovirus 71 ( EV71 ) which frequently involve neurological complications [1] , [2] .", "Although EV71 was first described in 1969 , a retrospective analysis shows that this virus circulat...	[ "Recently , enterovirus 71 ( EV71 ) has caused life-threatening outbreaks involving neurological and cardiopulmonary complications in Asian children with unknown mechanism .", "EV71 has one single serotype but can be phylogenetically classified into 3 main genogroups ( A , B and C ) and 11 genotypes ( A , B1∼B5 a...	[ "Recently , enterovirus 71 ( EV71 ) has caused life-threatening outbreaks in tropical Asia .", "EV71 has one single serotype but can be phylogenetically classified into 3 main genogroups and 11 genotypes ( A , B1∼B5 and C1∼C5 ) .", "In Taiwan , nationwide EV71 epidemics with different predominant genotypes occu...	2013
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[]	Trends in Animal Rabies Surveillance in the Endemic State of Minas Gerais, Brazil	journal.pntd.0003591	null	[ [ "Rabies is a viral zoonosis due to a Lyssavirus infection associated with neurological expression due to encephalitis or meningoencephalitis .", "It is one of the oldest known infectious diseases in the world but remains a neglected zoonotic disease , insufficiently addressed by governments and the intern...	[ "Rabies is a viral zoonosis affecting mammal species and causes large economic losses .", "Included among the neglected diseases , it is still insufficiently addressed by governments and the international community , despite formal surveillance and control programs .", "This study used a dataset of 10 , 112 rab...	[ "The approach proposed in this study can provide a valuable contribution to strengthen the efforts to reduce rabies incidence , a relevant public health problem worldwide .", "In Brazil during the period from 2001–2012 , 129 human cases of rabies were notified , with 128 deaths .", "It is imperative to decrease...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "developmental biology", "molecular cell biology", "molecular development", "genetics", "molecular genetics", "biology", "morphogenesis", "neuroscience", "genetics and genomics" ]	The Caenorhabditis elegans Eph Receptor Activates NCK and N-WASP, and Inhibits Ena/VASP to Regulate Growth Cone Dynamics during Axon Guidance	journal.pgen.1002513	null	[ [ "During development , axons navigate to their final destination by interpreting extracellular guidance cues through their growth cone .", "The Eph receptor tyrosine kinases ( RTKs ) and their ephrin ligands are involved in directing axons to their proper location [1] , [2] .", "Studies in vertebrate s...	[ "The Eph receptor tyrosine kinases ( RTKs ) are regulators of cell migration and axon guidance .", "However , our understanding of the molecular mechanisms by which Eph RTKs regulate these processes is still incomplete .", "To understand how Eph receptors regulate axon guidance in Caenorhabditis elegans , we sc...	[ "The correct wiring of the nervous system depends on the ability of axons to properly interpret extracellular cues that guide them to their targets .", "The Eph receptor tyrosine kinases ( RTKs ) have roles in guiding axons , but their signaling pathways are not completely understood .", "In this study , we use...	2012
[ "Introduction", "Results", "Methods", "Discussion" ]	[ "evolutionary biology", "theoretical biology", "biology and life sciences", "microbiology" ]	Geometry Shapes Evolution of Early Multicellularity	journal.pcbi.1003803	null	[ [ "Organisms have increased in complexity through a series of major evolutionary transitions , in which formerly autonomous entities become parts of a novel higher-level entity [1]–[5] .", "Examples of this transition include the evolution of multicellular organisms from unicellular ancestors and eusocial “...	[ "Organisms have increased in complexity through a series of major evolutionary transitions , in which formerly autonomous entities become parts of a novel higher-level entity .", "One intriguing feature of the higher-level entity after some major transitions is a division of reproductive labor among its lower-lev...	[ "A major transition in evolution occurs when previously autonomous entities become co-dependent in the context of a higher-level entity .", "Such transitions include the evolution of multicellular organisms from unicellular ancestors and eusocial “superorganisms” from multicellular ancestors .", "The evolution ...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "physics", "systems biology", "molecular cell biology", "statistical mechanics", "theoretical biology", "protein translation", "gene expression", "biology", "computational biology", "molecular biology" ]	Ribosome Traffic on mRNAs Maps to Gene Ontology: Genome-wide Quantification of Translation Initiation Rates and Polysome Size Regulation	journal.pcbi.1002866	null	[ [ "The expression of genes can be considered as a two-stage process , beginning with transcription and the production of an mRNA , followed by translation of that mRNA into protein by the cell's ribosome population .", "Gene expression must be tightly regulated to control protein composition , enabling the ...	[ "To understand the complex relationship governing transcript abundance and the level of the encoded protein , we integrate genome-wide experimental data of ribosomal density on mRNAs with a novel stochastic model describing ribosome traffic dynamics during translation elongation .", "This analysis reveals that co...	[ "Gene expression regulation is central to all living systems .", "Here we introduce a new framework and methodology to study the last stage of protein production in cells , where the genetic information encoded in the mRNAs is translated from the language of nucleotides into functional proteins .", "The process...	2013
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "peroxidases", "chemical compounds", "quantitative trait loci", "enzymes", "gene regulation", "regulatory proteins", "enzymology", "dna-binding proteins", "organic compounds", "fungi", "transcription factors", "alcohols", "proteins", "gene expression", "chemistry", "ethanol", "geneti...	Linkage mapping of yeast cross protection connects gene expression variation to a higher-order organismal trait	journal.pgen.1007335	null	[ [ "A fundamental question in genetics is how individuals with extremely similar genetic makeups can have dramatically different characteristics .", "One hypothesis is that a small number of regulatory polymorphisms can have large effects on gene expression , leading to the extensive phenotypic variation we ...	[ "Gene expression variation is extensive in nature , and is hypothesized to play a major role in shaping phenotypic diversity .", "However , connecting differences in gene expression across individuals to higher-order organismal traits is not trivial .", "In many cases , gene expression variation may be evolutio...	[ "A major goal in genetics is to understand how individuals with different genetic makeups respond to their environment .", "Understanding these “gene-environment interactions” is important for the development of personalized medicine .", "For example , gene-environment interactions can explain why some people a...	2018
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "invertebrates", "medicine and health sciences", "cloning", "animals", "drug screening", "complementary dna cloning", "age groups", "fungi", "adults", "model organisms", "brugia", "forms of dna", "pharmacology", "dna", "molecular biology techniques", "dna cloning", "research and anal...	Yeast-Based High-Throughput Screens to Identify Novel Compounds Active against Brugia malayi	journal.pntd.0004401	null	[ [ "Lymphatic filariasis is a neglected tropical disease caused primarily by the parasitic nematodes Wuchereria bancrofti and Brugia malayi .", "The painful and disfiguring manifestations of this disease , also known as elephantiasis , can lead to permanent disability , causing an annual loss of approximatel...	[ "Lymphatic filariasis is caused by the parasitic worms Wuchereria bancrofti , Brugia malayi or B . timori , which are transmitted via the bites from infected mosquitoes .", "Once in the human body , the parasites develop into adult worms in the lymphatic vessels , causing severe damage and swelling of the affecte...	[ "We have developed and validated a yeast-based high-throughput screening assay for the identification of specific inhibitors of filarial targets .", "We engineered yeast strains to functionally express parasite and human enzymes , labeling these with fluorescent proteins and growing them in competition in the pre...	2016
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "medicine", "public health and epidemiology", "clinical research design", "behavioral and social aspects of health", "infectious disease epidemiology", "parasitic diseases", "preventive medicine", "skin infections", "global health", "cohort studies", "neglected tropical diseases", "lymphatic f...	Impact of Community-Based Lymphedema Management on Perceived Disability among Patients with Lymphatic Filariasis in Orissa State, India	journal.pntd.0002100	null	[ [ "Lymphatic filariasis ( LF ) is a parasitic infection that leads to damage of the lymphatic system , causing lymphedema of the legs , arms , breast , or genitals .", "These symptoms affect an estimated 40 million people , making LF the second-leading cause of disability globally [1] , [2] .", "Despite...	[ "Lymphatic filariasis ( LF ) infects approximately 120 million people worldwide .", "As many as 40 million have symptoms of LF disease , including lymphedema , elephantiasis , and hydrocele .", "India constitutes approximately 45% of the world's burden of LF .", "The Indian NGO Church's Auxiliary for Social A...	[ "Lymphatic filariasis ( LF ) is the world's second-leading cause of disability and causes limb lymphedema and elephantiasis in up to 15 million people and lymphedema or hydrocele in over 40 million people , worldwide .", "A massive global effort has been undertaken to eliminate LF as a public health problem .", ...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "rna viruses", "viral classification", "virology", "biology", "microbiology", "viral evolution" ]	Cell Tropism Predicts Long-term Nucleotide Substitution Rates of Mammalian RNA Viruses	journal.ppat.1003838	null	[ [ "RNA viruses are responsible for a disproportionate number of emerging human diseases , including influenza , ebola hemorrhagic fever , hantavirus pulmonary syndrome , and Middle East respiratory syndrome , which place tremendous health and economic burdens on both the developing and developed world [1] , [2]...	[ "The high rates of RNA virus evolution are generally attributed to replication with error-prone RNA-dependent RNA polymerases .", "However , these long-term nucleotide substitution rates span three orders of magnitude and do not correlate well with mutation rates or selection pressures .", "This substitution ra...	[ "RNA viruses are the fastest evolving human pathogens , making their treatment and control difficult .", "Compared to DNA viruses , RNA viruses replicate with much lower fidelity , which can explain why RNA viruses evolve significantly faster than most DNA viruses .", "However , there is tremendous variation am...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "molecular cell biology", "genetic screens", "gene expression", "genetics", "gene regulation", "epigenetics", "biology", "molecular genetics", "chromatin", "genetics and genomics", "dna transcription", "histone modification" ]	Mutations in the Transcription Elongation Factor SPT5 Disrupt a Reporter for Dosage Compensation in Drosophila	journal.pgen.1003073	null	[ [ "Drosophila dosage compensation is widely used as a model system to investigate how transcription is regulated by large scale chromatin modifications [1] .", "To equalize the expression of the X-linked genes between XY males and XX females , the single X-chromosome in males is hypertranscribed a modest , ...	[ "In Drosophila , the MSL ( Male Specific Lethal ) complex up regulates transcription of active genes on the single male X-chromosome to equalize gene expression between sexes .", "One model argues that the MSL complex acts upon the elongation step of transcription rather than initiation .", "In an unbiased forw...	[ "Drosophila males hypertranscribe most of the genes along their single X chromosome to match the output of females with two X chromosomes .", "It had been difficult to imagine how the MSL dosage compensation complex could impose a modest , but essential , ∼two-fold increase by interacting with hundreds of differe...	2012
[ "Introduction", "Results", "Discusion", "Materials and methods" ]	[ "ecology and environmental sciences", "medicine and health sciences", "engineering and technology", "sleep", "cell phones", "physiological processes", "probability distribution", "mathematics", "longitude", "chronobiology", "geography", "cartography", "probability theory", "communication e...	Tracking urban human activity from mobile phone calling patterns	journal.pcbi.1005824	null	[ [ "The daily activity of people varies across space and time from place to place , date to date , and hour to hour as a result of biological , societal , economic , and environmental factors , shaping the society where they live .", "Roughly speaking , each day humans do certain activities at specific times...	[ "Timings of human activities are marked by circadian clocks which in turn are entrained to different environmental signals .", "In an urban environment the presence of artificial lighting and various social cues tend to disrupt the natural entrainment with the sunlight .", "However , it is not completely unders...	[ "For humans living in urban areas , the modern daily life is very different from that of people who lived in ancient times , from which todays’ societies evolved .", "Mainly due to the availability of artificial lighting , modern humans have been able to modify their natural daily cycles .", "In addition , soci...	2017
[ "Introduction", "Models and Methods", "Results", "Discussion" ]	[ "invertebrates", "gene regulation", "animals", "blastulas", "animal models", "developmental biology", "drosophila melanogaster", "model organisms", "systems science", "mathematics", "experimental organism systems", "molecular development", "embryos", "morphogenesis", "pattern formation",...	Dynamic Maternal Gradients Control Timing and Shift-Rates for Drosophila Gap Gene Expression	journal.pcbi.1005285	null	[ [ "Biological systems depend on time .", "Like everything else that persists for more than an instant , there is a temporal dimension to their existence .", "This much is obvious .", "What is less obvious , however , is the active role that time plays in altering the rules governing biological proce...	[ "Pattern formation during development is a highly dynamic process .", "In spite of this , few experimental and modelling approaches take into account the explicit time-dependence of the rules governing regulatory systems .", "We address this problem by studying dynamic morphogen interpretation by the gap gene n...	[ "Animal development is a highly dynamic process .", "Biochemical or environmental signals can cause the rules that shape it to change over time .", "We know little about the effects of such changes .", "For the sake of simplicity , we usually leave them out of our models and experimental assays .", "Here , ...	2017
[ "Introduction", "Results/Discussion", "Methods" ]	[]	Native Contact Density and Nonnative Hydrophobic Effects in the Folding of Bacterial Immunity Proteins	journal.pcbi.1004260	null	[ [ "The study of proteins that fold in an apparent two-state-like manner [1] has led to tremendous advances in protein folding biophysics [2 , 3] .", "In line with the consistency [4] and minimal frustration [5] principles , the energy landscapes of these proteins may be pictured as smooth funnels with littl...	[ "The bacterial colicin-immunity proteins Im7 and Im9 fold by different mechanisms .", "Experimentally , at pH 7 . 0 and 10°C , Im7 folds in a three-state manner via an intermediate but Im9 folding is two-state-like .", "Accordingly , Im7 exhibits a chevron rollover , whereas the chevron arm for Im9 folding is l...	[ "In order to fold correctly , a globular protein must avoid being trapped in wrong , i . e . , nonnative conformations .", "Thus a biophysical account of how attractive nonnative interactions are bypassed by some amino acid sequences but not others is key to deciphering protein structure and function .", "We ex...	2015
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "cell death", "medicine and health sciences", "pathology and laboratory medicine", "gene regulation", "immunology", "cell processes", "tropical diseases", "fascioliasis", "parasitic diseases", "regulator genes", "gene types", "neglected tropical diseases", "immune system proteins", "protei...	Transcriptomic Study on Ovine Immune Responses to Fasciola hepatica Infection	journal.pntd.0005015	null	[ [ "The trematode parasite Fasciola hepatica ( liver fluke ) is the causative agent of a global disease ( fasciolosis ) that is of major health , welfare and economic importance in domestic animals ( cattle , sheep ) [1] .", "This parasite can also infect and complete its lifecycle in a wide range of other m...	[ "Fasciola hepatica is not only responsible for major economic losses in livestock farming , but is also a major food-borne zoonotic agent , with 180 million people being at risk of infection worldwide .", "This parasite is sophisticated in manipulating the hosts’ immune system to benefit its own survival .", "A...	[ "Fasciola hepatica ( liver fluke ) is not only of major health , welfare and economic importance in ruminants , but also an emerging zoonosis .", "This parasite is sophisticated in manipulating the host’s immune system to benefit its own survival .", "In this study we investigated global gene expression changes...	2016
[ "Introduction", "Results/Discussion", "Materials and Methods" ]	[ "genetics and genomics/genomics", "genetics and genomics/gene discovery", "computer science/applications", "developmental biology/stem cells", "evolutionary biology/evolutionary and comparative genetics", "genetics and genomics/functional genomics", "genetics and genomics/gene expression", "genetics a...	A Scalable Approach for Discovering Conserved Active Subnetworks across Species	journal.pcbi.1001028	null	[ [ "Developments in genomic and proteomic technologies in recent years have given us numerous methods for capturing high resolution snapshots of cellular processes .", "The end result of a genome-scale experiment is typically a long list of candidate genes that provide a basis for further , more detailed , f...	[ "Overlaying differential changes in gene expression on protein interaction networks has proven to be a useful approach to interpreting the cell's dynamic response to a changing environment .", "Despite successes in finding active subnetworks in the context of a single species , the idea of overlaying lists of dif...	[ "Microarrays are a powerful tool for discovering genes whose expression is associated with a particular biological process or phenotype .", "Differential expression analysis can often generate a list of several hundred or even thousands of significant genes .", "While these genes represent real expression diffe...	2010
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "infectious diseases", "veterinary diseases", "zoonoses", "medicine and health sciences", "leishmaniasis", "biology and life sciences", "immunology", "protozoan infections", "parasitic diseases", "veterinary science", "parasitology" ]	CD8+ T cells Are Preferentially Activated during Primary Low Dose Leishmania major Infection but Are Completely Dispensable during Secondary Anti-Leishmania Immunity	journal.pntd.0003300	null	[ [ "The spectrum of disease collectively known as leishmaniasis continues to be a major threat to global health in many regions of the world .", "According to the World Health Organization ( WHO ) estimate , about 15–20 million people are afflicted with the disease and close to 2 million new cases occur annu...	[ "We previously showed that CD8+ T cells are required for optimal primary immunity to low dose Leishmania major infection .", "However , it is not known whether immunity induced by low dose infection is durable and whether CD8+ T cells contribute to secondary immunity following recovery from low dose infection .",...	[ "It is known that CD8+ T cells are important for primary immunity to low dose L . major infection , but whether low dose-induced immunity is long lasting and whether CD8+ T cells are also important for memory immune response to low dose L . major is unknown .", "We studied whether infectious dose affects primary ...	2014
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "cognitive science", "medicine and health sciences", "neural networks", "nervous system", "electrophysiology", "neuroscience", "learning and memory", "mathematics", "algebra", "cognition", "computational neuroscience", "memory", "neuronal tuning", "computer and information sciences", "an...	Slow diffusive dynamics in a chaotic balanced neural network	journal.pcbi.1005505	null	[ [ "The question of whether balanced networks can produce persistent activity has attracted considerable interest in recent years .", "Several works explored architectures which give rise to slow dynamics in balanced networks , characterized by the coexistence of multiple discrete balanced states [22] .", ...	[ "It has been proposed that neural noise in the cortex arises from chaotic dynamics in the balanced state: in this model of cortical dynamics , the excitatory and inhibitory inputs to each neuron approximately cancel , and activity is driven by fluctuations of the synaptic inputs around their mean .", "It remains ...	[ "This work studies the effects of chaotic dynamics , a prominent feature of the balanced state model , on storage of continuous parameters in working memory .", "We propose a simple model of a balanced network with mutual inhibition , and show that it possesses a continuum of steady states , a commonly proposed m...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Molecular Basis of Gene-Gene Interaction: Cyclic Cross-Regulation of Gene Expression and Post-GWAS Gene-Gene Interaction Involved in Atrial Fibrillation	journal.pgen.1005393	null	[ [ "Genome-wide association studies ( GWAS ) have been highly successful in identifying common genomic variants that are associated with complex human diseases or traits .", "However , these common variants have small effects , and in aggregate explain only a small fraction of heritability for most diseases ...	[ "Atrial fibrillation ( AF ) is the most common cardiac arrhythmia at the clinic .", "Recent GWAS identified several variants associated with AF , but they account for <10% of heritability .", "Gene-gene interaction is assumed to account for a significant portion of missing heritability .", "Among GWAS loci fo...	[ "Gene-gene interaction is assumed to be critical to the pathogenesis of human disease , but its contribution to human disease phenotype needs definitive documentation .", "Moreover , the underlying molecular mechanism for gene-gene interaction is unknown .", "Here we use atrial fibrillation ( AF ) as a model to...	2015
[ "Introduction", "Results/Discussion", "Methods" ]	[ "organismal evolution", "computer science", "biology", "evolutionary biology", "computerized simulations", "evolutionary processes" ]	Environmental Influence on the Evolution of Morphological Complexity in Machines	journal.pcbi.1003399	null	[ [ "The “arrow of complexity” hypothesis [1] posits that the most complex products of open-ended evolutionary systems tend to increase in complexity over evolutionary time .", "Whether such a tendency exists is a long standing open question [2]–[6] .", "While it seems evident that more complex organisms ...	[ "Whether , when , how , and why increased complexity evolves in biological populations is a longstanding open question .", "In this work we combine a recently developed method for evolving virtual organisms with an information-theoretic metric of morphological complexity in order to investigate how the complexity...	[ "The evolution of complexity , a central issue of evolutionary theory since Darwin's time , remains a controversial topic .", "One particular question of interest is how the complexity of an organism's body plan ( morphology ) is influenced by the complexity of the environment in which it evolved .", "Ideally ,...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "microbiology/plant-biotic interactions", "plant biology/plant-biotic interactions", "genetics and genomics/gene expression", "genetics and genomics/functional genomics", "infectious diseases/fungal infections", "genetics and genomics/gene function" ]	Combining ChIP-chip and Expression Profiling to Model the MoCRZ1 Mediated Circuit for Ca2+/Calcineurin Signaling in the Rice Blast Fungus	journal.ppat.1000909	null	[ [ "Rice blast , caused by the fungal pathogen Magnaporthe oryzae , is a recurrent and devastating problem worldwide [1] .", "Severe disease outbreaks can destroy upwards of 90% of rice yields for an entire field , region , or country resulting in a dramatic impact on human welfare and regional economies .",...	[ "Significant progress has been made in defining the central signaling networks in many organisms , but collectively we know little about the downstream targets of these networks and the genes they regulate .", "To reconstruct the regulatory circuit of calcineurin signal transduction via MoCRZ1 , a Magnaporthe ory...	[ "All organisms have the innate ability to perceive their environment and respond to it , largely through controlling gene expression .", "Tailored specificity of a response is primarily achieved through signal cascades involving unique receptors , downstream transcription factors ( proteins that bind to DNA to re...	2010
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "taxonomy", "medicine and health sciences", "immune cells", "markov models", "statistics", "split-decomposition method", "antigen-presenting cells", "immunology", "multiple alignment calculation", "phylogenetics", "data management", "mathematics", "forecasting", "phylogenetic analysis", ...	Synthetic protein alignments by CCMgen quantify noise in residue-residue contact prediction	journal.pcbi.1006526	null	[ [ "In the course of evolution , proteins are under selective pressure to maintain their function and correspondingly their structure .", "A possible mechanism to maintain structural integrity is the compensation of deleterious mutations between residue pairs in physical contact , known as compensatory mutat...	[ "Compensatory mutations between protein residues in physical contact can manifest themselves as statistical couplings between the corresponding columns in a multiple sequence alignment ( MSA ) of the protein family .", "Conversely , large coupling coefficients predict residue contacts .", "Methods for de-novo p...	[ "Knowledge about the three-dimensional structure of proteins is key to understanding their function and role in biological processes and diseases .", "The experimental structure determination techniques , such as X-ray crystallography or electron cryo-microscopy , are labour intensive , time-consuming and expensi...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "evolutionary biology/microbial evolution and genomics", "computer science/applications", "genetics and genomics/comparative genomics", "computational biology/comparative sequence analysis", "infectious diseases/bacterial infections", "microbiology/medical microbiology" ]	Generation of Genic Diversity among Streptococcus pneumoniae Strains via Horizontal Gene Transfer during a Chronic Polyclonal Pediatric Infection	journal.ppat.1001108	null	[ [ "Horizontal gene transfer ( HGT ) is a fundamental process in bacterial genome evolution [1] .", "In the context of infections it can provide pathogenic bacteria with ready access to crucial resistance determinants or virulence factors .", "Analysis of whole genome sequences ( WGS ) of multiple isolat...	[ "Although there is tremendous interest in understanding the evolutionary roles of horizontal gene transfer ( HGT ) processes that occur during chronic polyclonal infections , to date there have been few studies that directly address this topic .", "We have characterized multiple HGT events that most likely occurr...	[ "Bacterial infections have long been studied using Koch's postulates wherein the paradigm is that a single clone leads to a given infection .", "Over the past decade , it has become clear that chronic bacterial infections often do not fit this paradigm .", "Instead these are associated with the presence of mult...	2010
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "medicine", "infectious diseases", "adaptive immunity", "immune cells", "clinical immunology", "immunity", "t cells", "immunity to infections", "immune tolerance", "malaria", "plasmodium falciparum", "parasitic diseases", "immune response" ]	IFNγ/IL-10 Co-producing Cells Dominate the CD4 Response to Malaria in Highly Exposed Children	journal.ppat.1003864	null	[ [ "Clinical immunity to malaria eventually develops in endemic populations , but only after repeated infections with significant morbidity to both individuals and their communities [1] .", "Studies in regions of high malaria transmission intensity have consistently shown that the incidence of severe disease...	[ "Although evidence suggests that T cells are critical for immunity to malaria , reliable T cell correlates of exposure to and protection from malaria among children living in endemic areas are lacking .", "We used multiparameter flow cytometry to perform a detailed functional characterization of malaria-specific ...	[ "Despite reports of decreasing malaria morbidity across many parts of Africa , the incidence of malaria among children continues to be very high in Uganda , even in the setting of insecticide-treated bednets and artemisinin-based combination therapy .", "Additional control measures , including a vaccine , are sor...	2014
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "neuroscience/theoretical neuroscience" ]	How Noisy Adaptation of Neurons Shapes Interspike Interval Histograms and Correlations	journal.pcbi.1001026	null	[ [ "The firing of action potentials of a neuron in vivo is a genuine stochastic process due to the presence of several sources of noise [1] .", "The spontaneous neural activity ( e . g . the firing of a sensory cell in absence of sensory stimuli ) [2] , [3] as well as the response of neurons to stimuli canno...	[ "Channel noise is the dominant intrinsic noise source of neurons causing variability in the timing of action potentials and interspike intervals ( ISI ) .", "Slow adaptation currents are observed in many cells and strongly shape response properties of neurons .", "These currents are mediated by finite populatio...	[ "Neurons of sensory systems encode signals from the environment by sequences of electrical pulses — so-called spikes .", "This coding of information is fundamentally limited by the presence of intrinsic neural noise .", "One major noise source is “channel noise” that is generated by the random activity of vario...	2010
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "transfection", "medicine and health sciences", "senescence", "gene regulation", "cancer treatment", "biomarkers", "oncology", "physiological processes", "developmental biology", "organism development", "molecular biology techniques", "research and analysis methods", "small interfering rnas"...	A ‘synthetic-sickness’ screen for senescence re-engagement targets in mutant cancer backgrounds	journal.pgen.1006942	null	[ [ "Cellular senescence , often described as the irreversible arrest of cell proliferation , can be induced by a variety of signals [1 , 2] .", "It is a complex phenotype , consisting of various effector mechanisms including the DNA damage response ( DDR ) , chromatin modification , autophagy and the senesce...	[ "Senescence is a universal barrier to immortalisation and tumorigenesis .", "As such , interest in the use of senescence-induction in a therapeutic context has been gaining momentum in the past few years; however , senescence and immortalisation remain underserved areas for drug discovery owing to a lack of robus...	[ "Cellular senescence is an irreversible arrest of cell proliferation .", "Senescence is understood to be a universal barrier that all cancers must overcome during their evolution .", "Developing ways to induce senescence in cancer cells is therefore an attractive strategy to identify targets for cancer therapy ...	2017
[ "Introduction", "Results", "Discussion" ]	[ "mutation", "plant microbiology", "genetic polymorphism", "effective population size", "disease dynamics", "microbial evolution", "virology", "natural selection", "genetics", "population dynamics", "population genetics", "host-pathogen interaction", "biology", "microbiology", "evolutiona...	Within-Host Spatiotemporal Dynamics of Plant Virus Infection at the Cellular Level	journal.pgen.1004186	null	[ [ "For obligate intra-cellular micro-parasites such as viruses , the cell is the fundamental and minimal unit of infection .", "Important macro-scale phenomena in viral infection – immunity , virulence , transmission , and evolution – all depend on the infection outcome in individual cells .", "The bioc...	[ "A multicellular organism is not a monolayer of cells in a flask; it is a complex , spatially structured environment , offering both challenges and opportunities for viruses to thrive .", "Whereas virus infection dynamics at the host and within-cell levels have been documented , the intermediate between-cell leve...	[ "A great deal is understood about how a virus infects an individual cell and manages to replicate .", "Patterns of disease progression in plant and animal hosts , such as virus titers and the appearance of symptoms , have also been described in great detail .", "On other hand , very little is known about what i...	2014
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "evolutionary biology", "ecology" ]	Effects of Selection for Honey Bee Worker Reproduction on Foraging Traits	journal.pbio.0060056	A new study lends support to the model of social insect evolution, in which a gene regulatory network linked to the reproductive and foraging phases of ancestral solitary insects gave rise to queen and worker castes. But the study challenges the notion that genes related to reproduction also regulate the foraging behav...	[ [ "Two of the most challenging questions to students of social insects are the evolutionary origins of the worker caste [e . g . , 1–6] and the regulation of division of labour within the worker caste [e . g . , 7–13] .", "It has been suggested that the solution to both these puzzles may lie in modification...	[ "The “reproductive ground plan” hypothesis ( RGPH ) proposes that reproductive division of labour in social insects had its antecedents in the ancient gene regulatory networks that evolved to regulate the foraging and reproductive phases of their solitary ancestors .", "Thus , queens express traits that are chara...	[ "In social insects , the evolution of the worker caste and the regulation of reproductive behaviour by workers are poorly understood .", "Evolution is conservative and often proceeds by adapting an existing gene network to a new function .", "The “reproductive ground plan” hypothesis ( RGPH ) suggests that soci...	2008
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "medicine and health sciences", "immune physiology", "pathology and laboratory medicine", "pathogens", "immunology", "tropical diseases", "microbiology", "vertebrates", "geographical locations", "animals", "mammals", "dogs", "indonesia", "viruses", "rabies", "rna viruses", "neglected...	Development and validation of an immunoperoxidase antigen detection test for improved diagnosis of rabies in Indonesia	journal.pntd.0006079	null	[ [ "Rabies is a lethal zoonotic viral disease caused by a member of the Lyssavirus genus within the Rhabdoviridae family .", "Dog bites are responsible for transmission of rabies to humans in 99% of all mortalities and for 90% of post-exposure prophylaxis ( PEP ) globally .", "Rabies was first reported i...	[ "Rabies continues to pose a significant threat to human and animal health in regions of Indonesia .", "Indonesia has an extensive network of veterinary diagnostic laboratories and the 8 National laboratories are equipped to undertake diagnostic testing for rabies using the commercially-procured direct fluorescent...	[ "In Indonesia , veterinary diagnostic laboratories conduct tests for rabies on brain samples from animals suspected of being infected with rabies virus .", "National laboratories use internationally recommended tests for rabies virus that require expensive materials and equipment .", "Remote and smaller Provinc...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "carbohydrate metabolism", "invertebrates", "medicine and health sciences", "chemical compounds", "diabetic endocrinology", "hyperglycemia", "carbohydrates", "glucose metabolism", "animals", "organic compounds", "glucose", "hormones", "endocrine physiology", "animal models", "physiologic...	Sir2 Acts through Hepatocyte Nuclear Factor 4 to maintain insulin Signaling and Metabolic Homeostasis in Drosophila	journal.pgen.1005978	null	[ [ "The incidence of complex metabolic disorders has been on the rise for the past three decades , comprising an epidemic of ever-increasing severity .", "Much of this can be attributed to an increase in the prevalence of type 2 diabetes accompanied by insulin resistance , the development of which is complex...	[ "SIRT1 is a member of the sirtuin family of NAD+-dependent deacetylases , which couple cellular metabolism to systemic physiology .", "Although studies in mouse models have defined a central role for SIRT1 in maintaining metabolic health , the molecular mechanisms remain unclear .", "Here we show that loss of t...	[ "The sirtuins are a highly conserved family of deacetylases with targets that range from DNA-associated histones to transcription factors .", "The activities of these enzymes are dependent upon the energetic state of the cell as they utilize the coenzyme NAD+ , an important electron carrier in central metabolic p...	2016
[ "Introduction", "Results/Discussion", "Materials and methods" ]	[ "flow cytometry", "medicine and health sciences", "split-decomposition method", "random variables", "covariance", "simulation and modeling", "bone marrow cells", "multiple alignment calculation", "lymph nodes", "mathematics", "lymphatic system", "cytometry", "research and analysis methods", ...	Scalable multi-sample single-cell data analysis by Partition-Assisted Clustering and Multiple Alignments of Networks	journal.pcbi.1005875	null	[ [ "Analyses of CyTOF data rely on many of the tools and ideas from flow cytometry ( FC ) data analysis , as CyTOF datasets are essentially higher dimensional versions of flow cytometry datasets .", "Currently , the most widely used method in FC is still human hand-gating , as other methods often fail to ext...	[ "Mass cytometry ( CyTOF ) has greatly expanded the capability of cytometry .", "It is now easy to generate multiple CyTOF samples in a single study , with each sample containing single-cell measurement on 50 markers for more than hundreds of thousands of cells .", "Current methods do not adequately address the ...	[ "Recently , the cytometry field has experienced rapid advancement in the development of mass cytometry ( CyTOF ) .", "CyTOF enables a significant increase in the ability to monitor 50 or more cellular markers for millions of cells at the single-cell level .", "Initial studies with CyTOF focused on few samples ,...	2017
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "infectious diseases/helminth infections", "molecular biology", "genetics and genomics/functional genomics" ]	Functional Analysis of the Cathepsin-Like Cysteine Protease Genes in Adult Brugia malayi Using RNA Interference	journal.pntd.0000377	null	[ [ "Human lymphatic filariasis ( LF ) , caused by the filarial parasites Brugia malayi , Brugia timori and Wuchereria bancrofti , infects 120 million people worldwide , of which 40 million people show chronic disease symptoms ( www . globalnetwork . org ) [1] .", "The disease is estimated to be responsible f...	[ "Cathepsin-like enzymes have been identified as potential targets for drug or vaccine development in many parasites , as their functions appear to be essential in a variety of important biological processes within the host , such as molting , cuticle remodeling , embryogenesis , feeding and immune evasion .", "Fu...	[ "Filarial nematodes are an important group of human pathogens , causing lymphatic filariasis and onchocerciasis , and infecting around 150 million people throughout the tropics with more than 1 . 5 billion at risk of infection .", "Control of filariasis currently relies on mass drug administration ( MDA ) program...	2009
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "synapses", "neurotransmitters", "sensory systems", "biology", "neuroscience", "neurophysiology" ]	Experience-Dependent Rewiring of Specific Inhibitory Connections in Adult Neocortex	journal.pbio.1001798	Optogenetic mapping of connectivity in the primary somatosensory cortex shows that mature cortical circuits adapt to sensory deprivation by selectively altering specific network motifs.	[ [ "Neocortex has a similar multilayered histology throughout [1] , [2] , and different cortical areas are able to adapt , depending on their inputs , to the normal function of other regions [3] .", "This versatility may reflect the existence of a “canonical” information-processing architecture , underpinned...	[ "Although neocortical connectivity is remarkably stereotyped , the abundance of some wiring motifs varies greatly between cortical areas .", "To examine if regional wiring differences represent functional adaptations , we have used optogenetic raster stimulation to map the laminar distribution of GABAergic intern...	[ "Many natural and engineered networks contain recurring patterns of local connectivity .", "Although these so-called network motifs are thought to have functional significance , direct tests of the idea that network topology reflects function remain scarce .", "We have performed such a test in the area of mamma...	2014
[ "Introduction", "Methods", "Results", "Discussion", "Supporting Information" ]	[ "homo (human)", "immunology" ]	T Cell Responses to Human Endogenous Retroviruses in HIV-1 Infection	journal.ppat.0030165	null	[ [ "Human endogenous retroviruses ( HERV ) are the remnants of ancient infectious agents that successfully entered the germ-line , established a truce with the host , and now make up 8 . 29% of the human genome [1 , 2] .", "Most HERVs are normally quiescent , either because the sequences are truncated and fu...	[ "Human endogenous retroviruses ( HERVs ) are remnants of ancient infectious agents that have integrated into the human genome .", "Under normal circumstances , HERVs are functionally defective or controlled by host factors .", "In HIV-1-infected individuals , intracellular defense mechanisms are compromised .",...	[ "The human genome contains a number of remnants or fossils of ancient viral infections referred to as human endogenous retroviruses ( HERV ) .", "Like fossils , these HERV are considered to be dead or inert in most cases .", "However , we demonstrate that T cells in the human immune system respond to HERV when ...	2007
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "medicine and health sciences", "vacuoles", "pathology and laboratory medicine", "hela cells", "pathogens", "immunology", "biological cultures", "microbiology", "physiological processes", "inflammasomes", "cell cultures", "caco-2 cells", "cellular structures and organelles", "bacterial pat...	Dysregulated hemolysin liberates bacterial outer membrane vesicles for cytosolic lipopolysaccharide sensing	journal.ppat.1007240	null	[ [ "The host innate immune system can sense invading bacteria by detecting pathogen-associated molecular patterns ( PAMPs ) [1] .", "Lipopolysaccharide ( LPS ) , a component of the outer cell membrane of Gram-negative bacteria , is one of the strongest immune activators [2] .", "Extracellular and endocyt...	[ "Inflammatory caspase-11/4/5 recognize cytosolic LPS from invading Gram-negative bacteria and induce pyroptosis and cytokine release , forming rapid innate antibacterial defenses .", "Since extracellular or vacuole-constrained bacteria are thought to rarely access the cytoplasm , how their LPS are exposed to the ...	[ "Sensing of lipopolysaccharide ( LPS ) in the cytosol triggers non-canonical inflammasome-mediated innate responses .", "Recent work revealed that bacterial outer membrane vesicles ( OMVs ) enables LPS to access the cytosol for extracellular bacteria .", "However , since intracellular OMVs are generally constra...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "telomeres", "cell biology", "chromosome biology", "biology", "molecular cell biology" ]	Ku Must Load Directly onto the Chromosome End in Order to Mediate Its Telomeric Functions	journal.pgen.1002233	null	[ [ "Eukaryotic telomeres are comprised of repetitive G-rich sequence arrays and a host of proteins that associate with the repeats directly or as part of a complex [1] , [2] .", "These proteins maintain telomeres by facilitating the replication of telomeric DNA and by protecting the natural chromosomal ends ...	[ "The Ku heterodimer associates with the Saccharomyces cerevisiae telomere , where it impacts several aspects of telomere structure and function .", "Although Ku avidly binds DNA ends via a preformed channel , its ability to associate with telomeres via this mechanism could be challenged by factors known to bind d...	[ "The telomeric cap modulates telomere replication and prevents natural chromosome ends from being processed as DNA double-strand breaks ( DSBs ) .", "In multiple species , including budding yeast , a detailed picture exists of the factors that comprise the telomeric cap and how they associate with telomeric DNA ....	2011
[ "Introduction", "Results/Discussion", "Methods" ]	[ "biochemistry", "computer and information sciences", "medicinal chemistry", "computer modeling", "biology and life sciences", "chemistry", "physical sciences", "chemical biology" ]	Chemical, Target, and Bioactive Properties of Allosteric Modulation	journal.pcbi.1003559	null	[ [ "The generation of drug-like lead and candidate molecules against a specific molecular target remains a major challenge in drug discovery .", "We are now in a position to partially understand the factors behind this , and they fall into two basic themes – 1 ) the diversity and size of the set of compounds...	[ "Allosteric modulators are ligands for proteins that exert their effects via a different binding site than the natural ( orthosteric ) ligand site and hence form a conceptually distinct class of ligands for a target of interest .", "Here , the physicochemical and structural features of a large set of allosteric a...	[ "The physicochemistry and topography of ligand binding sites is generally conserved amongst related proteins , however , comparisons of the pharmacology of related targets ( and even the same target ) are often confounded by the existence of multiple , distinct , binding sites within the same protein .", "Importa...	2014
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[]	Deltamethrin Resistance Mechanisms in Aedes aegypti Populations from Three French Overseas Territories Worldwide	journal.pntd.0004226	null	[ [ "Aedes ( Stegomyia ) aegypti ( Linnaeus , 1762 ) is a mosquito species of high medical importance due to its widespread distribution and ability to transmit a variety of arboviruses .", "For decades its control has involved mechanical elimination of breeding sites as well as larvicidal applications and ad...	[ "Aedes aegypti is a cosmopolite mosquito , vector of arboviruses .", "The worldwide studies of its insecticide resistance have demonstrated a strong loss of susceptibility to pyrethroids , the major class of insecticide used for vector control .", "French overseas territories such as French Guiana ( South Ameri...	[ "Aedes aegypti is vector of Dengue , Chikungunya and Zika viruses , all causing emerging or re-emerging diseases worldwide .", "Fighting these diseases relies on the control of the vector .", "Therefore , insecticides have been extensively used worldwide , resulting in the development of insecticide resistance ...	2015
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "cellular structures", "cell biology", "biology", "microbiology", "molecular cell biology" ]	The Legionella pneumophila Effector VipA Is an Actin Nucleator That Alters Host Cell Organelle Trafficking	journal.ppat.1002546	null	[ [ "The gram-negative bacterium Legionella pneumophila is the causative agent of a severe type of pneumonia known as Legionnaires' disease [1] .", "Infection of mammalian alveolar macrophages is believed to be largely accidental and occurs after inhalation of aerosols originating from contaminated water sour...	[ "Legionella pneumophila , the causative agent of Legionnaires' disease , invades and replicates within macrophages and protozoan cells inside a vacuole .", "The type IVB Icm/Dot secretion system is necessary for the translocation of effector proteins that modulate vesicle trafficking pathways in the host cell , t...	[ "Legionella pneumophila is a facultative intracellular bacterium that can cause an often fatal type of pneumonia known as Legionnaires' disease .", "In nature , L . pneumophila is found in both fresh water and soil where it parasitizes free-living protists .", "Upon inhalation of contaminated aerosols , L . pne...	2012
[ "Introduction", "Results", "Discussion", "Methods and models" ]	[ "glycosylamines", "medicine and health sciences", "mitochondrial dna", "cardiovascular anatomy", "computational biology", "developmental biology", "inosine", "genome analysis", "forms of dna", "energy-producing organelles", "mammalian genomics", "dna", "bioenergetics", "mitochondria", "e...	ITPase deficiency causes a Martsolf-like syndrome with a lethal infantile dilated cardiomyopathy	journal.pgen.1007605	null	[ [ "It is 40 years since two brothers were reported with severely delayed neurocognitive development , spasticity , postnatal microcephaly , short stature , congenital cataracts and primary hypogonadism[1] , characterising a disorder that is now termed Martsolf syndrome ( MIM 212720 ) .", "Warburg Micro synd...	[ "Typical Martsolf syndrome is characterized by congenital cataracts , postnatal microcephaly , developmental delay , hypotonia , short stature and biallelic hypomorphic mutations in either RAB3GAP1 or RAB3GAP2 .", "Genetic analysis of 85 unrelated “mutation negative” probands with Martsolf or Martsolf-like syndro...	[ "Nucleotide triphosphate bases containing inosine , ITP and dITP , are continually produced within the cell as a consequence of various essential biosynthetic reactions .", "The enzyme inosine triphosphate pyrophosphatase ( ITPase ) scavenges ITP and dITP to prevent their incorporation into RNA and DNA .", "Her...	2019
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "bacteriology", "medicine and health sciences", "pathology and laboratory medicine", "chemical compounds", "oxidative stress", "oxygen", "pathogens", "microbiology", "nucleotides", "organic compounds", "purines", "helicobacter", "bacterial genetics", "bioassays and physiological analysis",...	Genetic Diversity as Consequence of a Microaerobic and Neutrophilic Lifestyle	journal.ppat.1005626	null	[ [ "The human stomach is a hostile niche .", "After overcoming the acid barrier , bacterial colonization at the gastric mucosa represents a constant battle with the host immune system .", "In particular , the pathogen is confronted with ROS-mediated oxidative stress produced by NADPH oxidases that releas...	[ "As a neutrophilic bacterium , Helicobacter pylori is growth deficient under extreme acidic conditions .", "The gastric pathogen is equipped with an acid survival kit , regulating urease activity by a pH-gated urea channel , opening below pH 6 . 5 .", "After overcoming acid stress , the bacterium’s multiplicati...	[ "Natural transformation , i . e . the capacity to take up DNA from the environment , is one of the crucial means for horizontal gene transfer and genetic diversity in bacteria .", "The human gastric pathogen Helicobacter pylori is confronted with acid stress before entering its multiplication site , the gastric m...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "blood cells", "medicine and health sciences", "immune cells", "markov models", "immunology", "mathematics", "genome analysis", "genomic signal processing", "genomic libraries", "white blood cells", "animal cells", "chromosome biology", "hidden markov models", "t cells", "probability the...	4C-ker: A Method to Reproducibly Identify Genome-Wide Interactions Captured by 4C-Seq Experiments	journal.pcbi.1004780	null	[ [ "Understanding the 3D organization of the genome and the intricacies of chromatin dynamics has been the focus of studies aimed at characterizing gene regulation in physiological processes and disease states [1 , 2] .", "Microscopy based studies provided the first snapshots of nuclear organization , reveal...	[ "4C-Seq has proven to be a powerful technique to identify genome-wide interactions with a single locus of interest ( or “bait” ) that can be important for gene regulation .", "However , analysis of 4C-Seq data is complicated by the many biases inherent to the technique .", "An important consideration when deali...	[ "Circularized chromosome conformation capture , or 4C-Seq is a technique developed to identify regions of the genome that are in close spatial proximity to a single locus of interest ( ‘bait’ ) .", "This technique is used to detect regulatory interactions between promoters and enhancers and to characterize the nu...	2016
[ "Introduction", "Results/Discussion", "Materials and Methods", "Supporting Information" ]	[ "evolutionary biology", "genetics and genomics", "eubacteria" ]	Adaptive Diversification in Genes That Regulate Resource Use in Escherichia coli	journal.pgen.0030015	null	[ [ "Adaptive diversification describes the splitting of an ancestral lineage into two derived groups due to frequency-dependent ecological interactions [1] .", "During this process , disruptive selection on a common ancestral type drives the creation of diversified ecotypes through a series of adaptive genet...	[ "While there has been much recent focus on the ecological causes of adaptive diversification , we know less about the genetic nature of the trade-offs in resource use that create and maintain stable , diversified ecotypes .", "Here we show how a regulatory genetic change can contribute to sympatric diversificatio...	[ "Understanding the origin of diversity is a fundamental problem in evolutionary biology .", "The past decade has seen a shift in our understanding of speciation , away from considering geographical isolation as the main cause and towards elucidating how ecological interactions can drive diversification in populat...	2007
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "sequencing techniques", "medicine and health sciences", "gut bacteria", "pathology and laboratory medicine", "statistics", "pathogens", "microbiology", "pseudomonas aeruginosa", "genome sequencing", "antibiotic resistance", "mathematics", "forecasting", "genome analysis", "pharmacology", ...	A k-mer-based method for the identification of phenotype-associated genomic biomarkers and predicting phenotypes of sequenced bacteria	journal.pcbi.1006434	null	[ [ "The falling cost of sequencing has made genome sequencing affordable to a large number of labs , and therefore , there has been a dramatic increase in the number of genome sequences available for comparison in the public domain [1] .", "These developments have facilitated the genomic analysis of bacteria...	[ "We have developed an easy-to-use and memory-efficient method called PhenotypeSeeker that", "( a ) identifies phenotype-specific k-mers ,", "( b ) generates a k-mer-based statistical model for predicting a given phenotype and", "( c ) predicts the phenotype from the sequencing data of a given bacterial isolat...	[ "Predicting phenotypic properties of bacterial isolates from their genomic sequences has numerous potential applications .", "A good example would be prediction of antimicrobial resistance and virulence phenotypes for use in medical diagnostics .", "We have developed a method that is able to predict phenotypes ...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "microbiology/microbial growth and development", "microbiology/microbial evolution and genomics", "microbiology" ]	Tight Regulation of the intS Gene of the KplE1 Prophage: A New Paradigm for Integrase Gene Regulation	journal.pgen.1001149	null	[ [ "Temperate bacteriophages are characterized by their ability to maintain their genome into the host , a process called lysogeny .", "Most temperate phages integrate their genome into the host's chromosome , becoming prophages .", "Alternatively , circularized phage genomes are maintained as episomes ....	[ "Temperate phages have the ability to maintain their genome in their host , a process called lysogeny .", "For most , passive replication of the phage genome relies on integration into the host's chromosome and becoming a prophage .", "Prophages remain silent in the absence of stress and replicate passively wit...	[ "Temperate bacteriophages are widespread bacterial viruses that have the ability to replicate passively in their hosts as long as no stressful conditions are encountered , a process called lysogeny .", "Prophage-encoded genes may benefit the host in several ways such as providing resistance to antibiotics , incre...	2010
[ "Introduction", "Materials and methods", "Results", "Discussion" ]	[ "invertebrates", "livestock", "medicine and health sciences", "ruminants", "geographical locations", "tropical diseases", "vertebrates", "fascioliasis", "parasitic diseases", "animals", "mammals", "genetic mapping", "physiological processes", "gastropods", "neglected tropical diseases", ...	DNA multigene characterization of Fasciola hepatica and Lymnaea neotropica and its fascioliasis transmission capacity in Uruguay, with historical correlation, human report review and infection risk analysis	journal.pntd.0005352	null	[ [ "The impact of climate change and global change is putting trematodiases in one of the main focuses of infectious disease actuality [1–4] .", "Among the food-borne trematodiases emphasized in the recent WHO Roadmap for neglected tropical diseases 2020 [5] , fascioliasis depicts a specific place due to its...	[ "Fascioliasis is a pathogenic disease transmitted by lymnaeid snails and recently emerging in humans , in part due to effects of climate changes , anthropogenic environment modifications , import/export and movements of livestock .", "South America is the continent presenting more human fascioliasis hyperendemic ...	[ "Fascioliasis is a highly pathogenic zoonotic disease emerging in recent decades , in part due to the effects of climate and global changes .", "South America is the continent presenting more numerous human fascioliasis endemic areas and the highest Fasciola hepatica infection prevalences and intensities known in...	2017
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "sequencing techniques", "invertebrates", "medicine and health sciences", "geographical locations", "vertebrates", "india", "parasitic diseases", "dogs", "animals", "mammals", "necator americanus", "physiological processes", "developmental biology", "molecular biology techniques", "resea...	Molecular Identification of Hookworm Isolates in Humans, Dogs and Soil in a Tribal Area in Tamil Nadu, India	journal.pntd.0004891	null	[ [ "Infections with hookworms ( Necator americanus and Ancylostoma duodenale ) remain a major public health problem in several low and middle-income countries [1 , 2] .", "It is estimated that ~439 million people are infected , resulting in a global disease burden of ~3 . 5 million disability adjusted life y...	[ "Hookworms ( Necator americanus and Ancylostoma duodenale ) remain a major public health problem worldwide .", "Infections with hookworms ( e . g . , A . caninum , A . ceylanicum and A . braziliense ) are also prevalent in dogs , but the role of dogs as a reservoir for zoonotic hookworm infections in humans needs...	[ "Hookworm infections remain a major public health problem in both tropical and subtropical parts of the world .", "To control the disease burden attributable to hookworms , large-scale deworming programs , in which drugs are administered to schoolchildren regardless of their infection status , are currently being...	2016
[ "Introduction", "Methods", "Discussion" ]	[ "medicine and health sciences", "midwives", "medical personnel", "tropical diseases", "parasitic diseases", "developmental biology", "neglected tropical diseases", "infectious disease control", "public and occupational health", "infectious diseases", "protozoan infections", "congenital disorde...	Towards Chagas disease elimination: Neonatal screening for congenital transmission in rural communities	journal.pntd.0005783	null	[ [ "Chagas disease is a vector-borne illness that can also be transmitted congenitally , via blood transfusion , organ donation , lab accidents or ingestion [1] .", "With the implementation of vector control programs , insect transmission of Trypanosoma cruzi has become less common [2] and vertical transmiss...	[ "Chagas disease is a neglected tropical disease that continues to affect populations living in extreme poverty in Latin America .", "After successful vector control programs , congenital transmission remains as a challenge to disease elimination .", "We used the PRECEDE-PROCEED planning model to develop strateg...	[ "Chagas disease is caused by a parasite transmitted by insects that infest households living in extreme poverty conditions .", "The parasite can also be transmitted from mother to child during pregnancy .", "If detected at birth , the infection can be treated effectively with available drugs .", "However , ac...	2017
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "medicine", "public health and epidemiology", "computer science", "mathematical computing", "mathematics", "epidemiology", "statistics", "genetics", "biology", "computational biology", "computerized simulations", "genetics and genomics", "numerical analysis" ]	Improved Statistics for Genome-Wide Interaction Analysis	journal.pgen.1002625	null	[ [ "Genome-wide association studies ( GWAS ) have been remarkably successful at identifying the genomic locations of variants involved in a variety of complex diseases [2]–[7] .", "In spite of this success , some researchers have expressed disquiet at the issue of the ‘missing heritability’ [8] , namely the ...	[ "Recently , Wu and colleagues [1] proposed two novel statistics for genome-wide interaction analysis using case/control or case-only data .", "In computer simulations , their proposed case/control statistic outperformed competing approaches , including the fast-epistasis option in PLINK and logistic regression an...	[ "Gene–gene interactions are a topic of great interest to geneticists carrying out studies of how genetic factors influence the development of common , complex diseases .", "Genes that interact may not only make important biological contributions to underlying disease processes , but also be more difficult to dete...	2012
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "sequencing techniques", "taxonomy", "medicine and health sciences", "pathology and laboratory medicine", "pathogens", "microbiology", "salmonellosis", "sequence assembly tools", "bacterial diseases", "phylogenetics", "data management", "enterobacteriaceae", "phylogenetic analysis", "genom...	A Phylogenetic and Phenotypic Analysis of Salmonella enterica Serovar Weltevreden, an Emerging Agent of Diarrheal Disease in Tropical Regions	journal.pntd.0004446	null	[ [ "Salmonella enterica is a globally distributed Gram-negative enteric bacterial species that is responsible for significant levels of morbidity and mortality in both humans and animals [1] .", "S . enterica is currently classified into six subspecies and >2 , 500 serovars on the basis of the White- Kauffma...	[ "Salmonella enterica serovar Weltevreden ( S . Weltevreden ) is an emerging cause of diarrheal and invasive disease in humans residing in tropical regions .", "Despite the regional and international emergence of this Salmonella serovar , relatively little is known about its genetic diversity , genomics or virulen...	[ "Organisms belonging to the species Salmonella enterica are a major cause of infection globally .", "Such infections can be zoonotic in origin or transmitted between humans .", "One of the most notable features of the genus Salmonella is that the dominant serovars that cause human infections change over time , ...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Carcinogenic Parasite Secretes Growth Factor That Accelerates Wound Healing and Potentially Promotes Neoplasia	journal.ppat.1005209	null	[ [ "Approximately 10 million people in Thailand and Laos are infected with the South East Asian liver fluke Opisthorchis viverrini [1 , 2] .", "Infection with O . viverrini , a one-centimeter long flatworm that inhabits the bile ducts , is strongly associated with the induction of cholangiocarcinoma ( CCA ) ...	[ "Infection with the human liver fluke Opisthorchis viverrini induces cancer of the bile ducts , cholangiocarcinoma ( CCA ) .", "Injury from feeding activities of this parasite within the human biliary tree causes extensive lesions , wounds that undergo protracted cycles of healing , and re-injury over years of ch...	[ "The oriental liver fluke Opisthorchis viverrini infects millions of people in SE-Asia and kills 26 , 000 people each year due to parasite-induced liver cancer .", "The mechanisms by which the parasite causes cancer are complex , but a role for excessive wound healing in response to feeding parasites in the bile ...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine", "bacterial diseases", "pathogenesis", "infectious diseases", "enterococcus infection", "medical microbiology", "microbial pathogens", "biology", "microbiology", "bacterial pathogens", "gram positive" ]	AsrR Is an Oxidative Stress Sensing Regulator Modulating Enterococcus faecium Opportunistic Traits, Antimicrobial Resistance, and Pathogenicity	journal.ppat.1002834	null	[ [ "Enterococci are commensal Gram-positive cocci of intestinal origin .", "First reported as a cause of infective endocarditis in 1899 , enterococci have also become , over the past 20 years , the 2nd–3rd most common organisms isolated from healthcare-associated infections [1] , [2] .", "In the USA , th...	[ "Oxidative stress serves as an important host/environmental signal that triggers a wide range of responses in microorganisms .", "Here , we identified an oxidative stress sensor and response regulator in the important multidrug-resistant nosocomial pathogen Enterococcus faecium belonging to the MarR family and ca...	[ "Multiple antibiotic‐resistant isolates of the opportunistic pathogen Enterococcus faecium have emerged and spread worldwide .", "However , studies aimed at identifying mechanisms that underlie the transformation of E . faecium from its commensal nature into a nosocomial pathogen are scarce .", "We report pleio...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "developmental biology/cell differentiation", "neuroscience/neurodevelopment", "developmental biology/neurodevelopment", "developmental biology/molecular development", "developmental biology/organogenesis" ]	Generation of Functional Eyes from Pluripotent Cells	journal.pbio.1000174	The directed differentiation of pluripotent cells into specific cell-types is a major hurdle in regenerative medicine. This study shows the eye field transcription factor factors can direct pluripotent cells into functioning frog eyes.	[ [ "Every body organ consists of tissue groups with multiple cell types .", "Therefore , recovery from organ damage requires the replacement of a variety of distinct cell types .", "The retina is the light detecting tissue of the eye , and consists of seven major cell classes .", "All retinal cell cl...	[ "Pluripotent cells such as embryonic stem ( ES ) and induced pluripotent stem ( iPS ) cells are the starting point from which to generate organ specific cell types .", "For example , converting pluripotent cells to retinal cells could provide an opportunity to treat retinal injuries and degenerations .", "In th...	[ "The goal of regenerative medicine is to replace dead or dying cells .", "Successful cell replacement depends on the ability of donor cells to differentiate into all functional cell types lost in the target organ .", "Blindness resulting from retinal disease or damage , for example , would require the replaceme...	2009
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "medicine", "infectious diseases", "trichinellosis", "parasitic diseases" ]	Trichinella spiralis Paramyosin Binds to C8 and C9 and Protects the Tissue-Dwelling Nematode from Being Attacked by Host Complement	journal.pntd.0001225	null	[ [ "Trichinellosis is one of the common parasitic zoonoses and is a serious public threat in both developing and developed countries [1]-[6] .", "Trichinella spiralis ( T . spiralis ) infection is initiated by the consumption of meat contaminated with infective muscle larvae ( ML ) .", "With the aid of h...	[ "Paramyosin is a thick myofibrillar protein found exclusively in invertebrates .", "Evidence suggested that paramyosin from helminths serves not only as a structural protein but also as an immunomodulatory agent .", "We previously reported that recombinant Trichinella spiralis paramyosin ( Ts-Pmy ) elicited a p...	[ "Trichinellosis is a serious food borne parasitic disease caused by the consumption of meat contaminated with the infective larvae of Trichinella spiralis .", "The ability of the tissue-dwelling parasite to evade the host complement attack is essential for its survival and for establishing infection in the host ....	2011
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "bacteriology", "medicine and health sciences", "gut bacteria", "toxins", "pathology and laboratory medicine", "gene regulation", "pathogens", "bacillus", "microbiology", "vertebrates", "animals", "mammals", "toxicology", "toxic agents", "bacterial sporulation", "prokaryotic models", ...	Pleiotropic roles of Clostridium difficile sin locus	journal.ppat.1006940	null	[ [ "Clostridium difficile , a major nosocomial pathogen , is the causative agent of antibiotic-associated diarrhea and pseudomembranous colitis [1 , 2] .", "Every year , nearly half a million cases of C . difficile infections ( CDI ) occur in the United States and result in approximately 14 , 000 deaths [3] ...	[ "Clostridium difficile is the primary cause of nosocomial diarrhea and pseudomembranous colitis .", "It produces dormant spores , which serve as an infectious vehicle responsible for transmission of the disease and persistence of the organism in the environment .", "In Bacillus subtilis , the sin locus coding S...	[ "In Bacillus subtilis , sporulation , competence and biofilm formation are regulated by a pleiotropic regulator called SinR .", "Two sinR homologs are present in C . difficile genome as an operon and henceforth labeled as sinR and sinR’ .", "Our detailed investigation revealed that in C . difficile , the SinR a...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Simulations Meet Experiment to Reveal New Insights into DNA Intrinsic Mechanics	journal.pcbi.1004631	null	[ [ "Binding of DNA to proteins or small molecules is modulated by subtle sequence-dependent variations inherent to the structure and dynamics of free DNA , which facilitate or disfavor the structural fit with cognate partners [1–4] .", "Given the many DNA targets , a purely experimental characterization of t...	[ "The accurate prediction of the structure and dynamics of DNA remains a major challenge in computational biology due to the dearth of precise experimental information on DNA free in solution and limitations in the DNA force-fields underpinning the simulations .", "A new generation of force-fields has been develop...	[ "The ability to simulate computationally the structure and dynamics of biomolecules is a major goal of structural biology .", "Such simulations require the calculation of the forces and energy of the system , typically with extensively parametrized functions called “force-fields” .", "Developing reliable force-...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genome evolution", "evolutionary modeling", "biology and life sciences", "molecular evolution", "computational biology", "evolutionary biology", "genomics statistics", "evolutionary theory" ]	A Comparative Study and a Phylogenetic Exploration of the Compositional Architectures of Mammalian Nuclear Genomes	journal.pcbi.1003925	null	[ [ "Human and cow genomes have been shown to possess a complex architecture , in which compositionally homogeneous and nonhomogeneous domains of varying lengths and nucleotide composition are interspersed with one another [1] , [2] .", "These empirically derived compositional architectures are mostly incompa...	[ "For the past four decades the compositional organization of the mammalian genome posed a formidable challenge to molecular evolutionists attempting to explain it from an evolutionary perspective .", "Unfortunately , most of the explanations adhered to the “isochore theory , ” which has long been rebutted .", "...	[ "The non-uniformity of DNA composition in mammalian genomes has been known for over four decades .", "Many attempts have been made to provide a concise description of this heterogeneity and to identify the evolutionary driving forces behind this compositional phenomenology .", "The first concise description of ...	2014
[ "Introduction", "Methods", "Results", "Discussion" ]	[]	Sustaining Control of Schistosomiasis Mansoni in Western Côte d’Ivoire: Results from a SCORE Study, One Year after Initial Praziquantel Administration	journal.pntd.0004329	null	[ [ "Schistosomiasis is a neglected tropical disease that exerts a considerable public health problem in 78 tropical and subtropical countries [1] .", "In 2013 , it was estimated that schistosomiasis affected more than 250 million people worldwide with 90% of the reported cases concentrated in sub-Saharan Afr...	[ "The Schistosomiasis Consortium for Operational Research and Evaluation ( SCORE ) has launched several large-scale trials to determine the best strategies for gaining and sustaining control of schistosomiasis and transitioning toward elimination .", "In Côte d’Ivoire , a 5-year cluster-randomized trial is being i...	[ "Schistosomiasis is a parasitic worm disease that is widespread in sub-Saharan Africa .", "To better understand how to gain and sustain the control of schistosomiasis and how to eliminate this disease in different epidemiologic settings , the Schistosomiasis Consortium for Operational Research and Evaluation ( SC...	2016
[ "Introduction", "Results", "Discussion", "Methods" ]	[]	Nonconsensus Protein Binding to Repetitive DNA Sequence Elements Significantly Affects Eukaryotic Genomes	journal.pcbi.1004429	null	[ [ "Binding of TFs to their target sites on the DNA is a key step during gene activation and repression .", "An existing paradigm assumes that the main mechanism responsible for specific TF-DNA recognition is TF binding to short ( typically 6–20 bp long ) DNA sequences called specific consensus motifs , or s...	[ "Recent genome-wide experiments in different eukaryotic genomes provide an unprecedented view of transcription factor ( TF ) binding locations and of nucleosome occupancy .", "These experiments revealed that a large fraction of TF binding events occur in regions where only a small number of specific TF binding si...	[ "Interactions between proteins and DNA trigger many important biological processes .", "Therefore , to fully understand how the information encoded on the DNA transcribes into RNA , which in turn translates into proteins in the cell , we need to unravel the molecular design principles of protein-DNA interactions ...	2015
[ "Introduction", "Results", "Discussion", "Methods and Materials" ]	[ "algorithms", "computer and information sciences", "mathematics", "applied mathematics", "biology and life sciences", "physical sciences", "computational biology" ]	Negative Example Selection for Protein Function Prediction: The NoGO Database	journal.pcbi.1003644	null	[ [ "Despite the recent influx of machine learning algorithms applied to function prediction , there has been relatively little study devoted to the issue of class imbalance in function labels .", "This imbalance stems from the fact that the current standard set of labels for protein functions , the Gene Onto...	[ "Negative examples – genes that are known not to carry out a given protein function – are rarely recorded in genome and proteome annotation databases , such as the Gene Ontology database .", "Negative examples are required , however , for several of the most powerful machine learning methods for integrative prote...	[ "Many machine learning methods have been applied to the task of predicting the biological function of proteins based on a variety of available data .", "The majority of these methods require negative examples: proteins that are known not to perform a function , in order to achieve meaningful predictions , but neg...	2014
[ "Introduction", "Conclusions" ]	[ "nucleic acid synthesis", "non-coding rna sequences", "nucleases", "enzymes", "dna-binding proteins", "enzymology", "polynucleotides", "nucleotides", "review", "mitochondria", "bioenergetics", "rna synthesis", "cellular structures and organelles", "chemical synthesis", "research and anal...	Polynucleotide phosphorylase: Not merely an RNase but a pivotal post-transcriptional regulator	journal.pgen.1007654	null	[ [ "In bacteria and eukaryotes , PNPase has an important function in RNA decay .", "PNPase catalyzes the processive degradation of single-stranded RNA in the 3ʹ to 5ʹ direction using inorganic phosphate as the nucleophile to attack the 3ʹ phosphodiester bond releasing a ribonucleoside diphosphate ( NDP ) .",...	[ "Almost 60 years ago , Severo Ochoa was awarded the Nobel Prize in Physiology or Medicine for his discovery of the enzymatic synthesis of RNA by polynucleotide phosphorylase ( PNPase ) .", "Although this discovery provided an important tool for deciphering the genetic code , subsequent work revealed that the pred...	[ "Widely distributed among bacteria and eukaryotes , including humans , polynucleotide phosphorylase ( PNPase ) is a critical enzyme in RNA metabolism that functions in most organisms as a 3ʹ to 5ʹ exoribonuclease .", "In bacteria , inactivation of the gene encoding PNPase results in a wide range of consequences ,...	2018
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "computational biology/molecular dynamics", "biophysics/biomacromolecule-ligand interactions", "cell biology/cell adhesion", "infectious diseases/hiv infection and aids" ]	Organization of Cellular Receptors into a Nanoscale Junction during HIV-1 Adhesion	journal.pcbi.1000855	null	[ [ "Strategies for antiretroviral therapy have recently focused on inhibiting human immunodeficiency virus ( HIV ) adhesion , fusion , and entry .", "The biochemical properties of the dynamic binding interactions between host cell and viral receptors have been well characterized [1] , [2] .", "However , ...	[ "The fusion of the human immunodeficiency virus type 1 ( HIV-1 ) with its host cell is the target for new antiretroviral therapies .", "Viral particles interact with the flexible plasma membrane via viral surface protein gp120 which binds its primary cellular receptor CD4 and subsequently the coreceptor CCR5 .", ...	[ "The entry of human immunodeficiency virus ( HIV ) into cells is the target for new therapies preventing HIV infection .", "While intermediate steps of viral entry have been characterized , the progression between these steps and how they result in productive infection are not well understood .", "By using stoc...	2010
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "invertebrates", "medicine and health sciences", "pathology and laboratory medicine", "pathogens", "microbiology", "vertebrates", "parasitic protozoans", "animals", "mammals", "organisms", "protozoans", "phylogenetic analysis", "molecular biology techniques", "bacteria", "bacterial patho...	Detection of a Potential New Bartonella Species “Candidatus Bartonella rondoniensis” in Human Biting Kissing Bugs (Reduviidae; Triatominae)	journal.pntd.0005297	null	[ [ "Triatomine bugs ( order Hemiptera , family Reduviidae , subfamily Triatominae ) are blood-sucking arthropods ( “kissing bugs” ) , most of which can feed both on animals and humans .", "All stages from first instar to male and female adults are strictly hematophagous and responsible for a relatively large...	[ "Among the Reduviidae family , triatomines are giant blood-sucking bugs .", "They are well known in Central and South America where they transmit Trypanosoma cruzi to mammals , including humans , through their feces .", "This parasitic protozoan is the causative agent of Chagas disease , a major public health i...	[ "Triatomines are hematophagous insects including vectors of T . cruzi , the agent of Chagas disease , a huge public health issue , especially in South America .", "Whether these arthropods carry other pathogenic microorganisms is currently unknown .", "We investigated the presence of different arthropod-borne p...	2017
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "medicine and health sciences", "vesicles", "immune cells", "chemical compounds", "crystal structure", "viral transmission and infection", "antigen-presenting cells", "immunology", "condensed matter physics", "microbiology", "parasitic diseases", "organic compounds", "amino acids", "crysta...	Structural basis of Toxoplasma gondii perforin-like protein 1 membrane interaction and activity during egress	journal.ppat.1007476	null	[ [ "Cellular egress from the host is a crucial step in the infectious cycle of intracellular pathogens .", "Accordingly , such pathogens have evolved multiple exit strategies , which can be divided into those that leave the host cell intact and those that rupture the host cell .", "Several bacterial path...	[ "Intracellular pathogens must egress from the host cell to continue their infectious cycle .", "Apicomplexans are a phylum of intracellular protozoans that have evolved members of the membrane attack complex and perforin ( MACPF ) family of pore forming proteins to disrupt cellular membranes for traversing cells ...	[ "The intracellular parasite Toxoplasma gondii infects many hosts including humans .", "Infected people with a weak immune system can suffer severe disease when the parasite replicates uncontrolled via repeated cycles of cell invasion , intracellular growth , and exit , resulting in cell death .", "Previous stud...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "circuit models", "computational neuroscience", "single neuron function", "biology and life sciences", "computational biology", "coding mechanisms" ]	Dendritic Nonlinearities Reduce Network Size Requirements and Mediate ON and OFF States of Persistent Activity in a PFC Microcircuit Model	journal.pcbi.1003764	null	[ [ "Small , tightly interconnected “clusters” of cortical neurons have recently been discovered in regions such as the visual , somatosensory and prefrontal cortex ( PFC ) [1]–[6] , yet their role in cognitive processes remains unexplored .", "In the PFC , such microcircuits have been suggested to participat...	[ "Technological advances have unraveled the existence of small clusters of co-active neurons in the neocortex .", "The functional implications of these microcircuits are in large part unexplored .", "Using a heavily constrained biophysical model of a L5 PFC microcircuit , we recently showed that these structures...	[ "Working memory , the ability to retain information for a short period of time , is a fundamental cognitive function that shapes behavior .", "The cellular correlate of working memory is the prolonged spiking ( persistent ) activity of neurons in the prefrontal cortex .", "Impairments of prefrontal cortex funct...	2014
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "immunopathology", "medicine", "cerebrovascular diseases", "emerging infectious diseases", "neurological disorders", "neurology", "immunology", "biology", "microbiology", "host-pathogen interaction" ]	Changes in Gene Expression of Pial Vessels of the Blood Brain Barrier during Murine Neurocysticercosis	journal.pntd.0002099	null	[ [ "The blood brain barrier ( BBB ) separates the peripheral circulation from the CNS and plays a critical role in homeostasis of the CNS environment .", "In the healthy brain BBB selectively restricts molecular and cellular trafficking between the blood and brain tissue and between blood and cerebrospinal f...	[ "In murine neurocysticercosis ( NCC ) , caused by infection with the parasite Mesocestoides corti , the breakdown of the Blood Brain Barrier ( BBB ) and associated leukocyte infiltration into the CNS is dependent on the anatomical location and type of vascular bed .", "Prior studies of NCC show that the BBB compr...	[ "Neurocysticercosis ( NCC ) is one of the most common parasitic diseases of the CNS caused by the metacestode ( larva ) of the tapeworm Taenia solium .", "Epidemiological studies show that among the various forms of NCC , subarachnoid NCC is associated with poor prognosis , more resistance to anti-helminthic drug...	2013

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