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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", "Material and Methods" ]	[ "medicine", "rheumatology", "public health and epidemiology", "cytokines", "immunology", "rheumatoid arthritis", "genetic epidemiology", "systemic lupus erythematosus", "inflammatory and psoriatic arthritis", "disease mapping", "scleroderma", "connective tissue diseases", "major histocompati...	Genome-Wide Scan Identifies TNIP1, PSORS1C1, and RHOB as Novel Risk Loci for Systemic Sclerosis	journal.pgen.1002091	null	[ [ "Systemic sclerosis ( MIM181750 ) is a connective tissue disease characterized by generalized microangiopathy , severe immunologic alterations and massive deposits of matrix components in the connective tissue .", "Being an orphan disease , SSc presents a major medical challenge and is recognized as the m...	[ "Systemic sclerosis ( SSc ) is an orphan , complex , inflammatory disease affecting the immune system and connective tissue .", "SSc stands out as a severely incapacitating and life-threatening inflammatory rheumatic disease , with a largely unknown pathogenesis .", "We have designed a two-stage genome-wide ass...	[ "Systemic sclerosis ( SSc ) is a connective tissue disease characterized by generalized microangiopathy , severe immunologic alterations , and massive deposits of matrix components in the connective tissue .", "Epidemiological investigations indicate that SSc follows a pattern of multifactorial inheritance; howev...	2011
[ "Introduction", "Materials and methods", "Results", "Discussion" ]	[ "medicine and health sciences", "myoclonus", "pathology and laboratory medicine", "neurodegenerative diseases", "membrane potential", "brain electrophysiology", "electrophysiology", "neuroscience", "surgical and invasive medical procedures", "deep-brain stimulation", "functional electrical stimu...	Quantitative theory of deep brain stimulation of the subthalamic nucleus for the suppression of pathological rhythms in Parkinson’s disease	journal.pcbi.1006217	null	[ [ "Deep brain stimulation ( DBS ) has become an effective treatment for a number of neurological disorders such as Parkinson’s disease ( PD ) and essential tremor [1 , 2] .", "In Parkinson’s disease DBS treatments , a macroelectrode is chronically implanted in a target nucleus , typically either the globus ...	[ "Deep brain stimulation ( DBS ) of the subthalamic nucleus ( STN ) is modeled to explore the mechanisms of this effective , but poorly understood , treatment for motor symptoms of drug-refractory Parkinson’s disease and dystonia .", "First , a neural field model of the corticothalamic-basal ganglia ( CTBG ) syste...	[ "Pathological 13-30 Hz ( beta ) oscillations within the basal ganglia are a characteristic feature of human Parkinson’s disease which seem to correlate with symptom severity .", "The origin of these oscillations and the suppressive mechanism of effective deep brain stimulation treatments remains to be shown .", ...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "infectious diseases", "medicine and health sciences", "protozoans", "malarial parasites", "clinical immunology", "biology and life sciences", "immunology", "microbiology", "protozoology", "plasmodium falciparum", "parasitic diseases", "immunomodulation", "parasitic protozoans", "malaria",...	Exposure-Dependent Control of Malaria-Induced Inflammation in Children	journal.ppat.1004079	null	[ [ "In previously unexposed individuals , blood-stage Plasmodium falciparum parasites rapidly replicate and almost invariably induce fever and other symptoms of malaria [1] through the production of pro-inflammatory cytokines and chemokines [2]–[4] .", "Although the initial systemic inflammatory response is ...	[ "In malaria-naïve individuals , Plasmodium falciparum infection results in high levels of parasite-infected red blood cells ( iRBCs ) that trigger systemic inflammation and fever .", "Conversely , individuals in endemic areas who are repeatedly infected are often asymptomatic and have low levels of iRBCs , even y...	[ "Malaria remains a major cause of disease and death worldwide .", "When mosquitoes infect people with malaria parasites for the first time , the parasite rapidly multiplies in the blood and the body responds by producing molecules that cause inflammation and fever , and sometimes the infection progresses to life-...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "molecular biology/histone modification", "genetics and genomics/gene expression", "genetics and genomics/functional genomics", "genetics and genomics/epigenetics", "genetics and genomics" ]	A Comprehensive Map of Insulator Elements for the Drosophila Genome	journal.pgen.1000814	null	[ [ "The spatiotemporal regulation of transcription is controlled by the binding of transcription factors to their target cis-regulatory modules ( CRM ) and their resulting interactions with promoters .", "Such regulatory interactions between CRMs and promoters can occur over short distances when regulatory s...	[ "Insulators are DNA sequences that control the interactions among genomic regulatory elements and act as chromatin boundaries .", "A thorough understanding of their location and function is necessary to address the complexities of metazoan gene regulation .", "We studied by ChIP–chip the genome-wide binding sit...	[ "The spatiotemporal specificity of gene expression is controlled by interactions among regulatory proteins , cis-regulatory elements , chromatin modifications , and genes .", "These interactions can occur over large distances , and the mechanisms by which they are controlled are poorly understood .", "Insulator...	2010
[ "Introduction", "Results/Discussion", "Materials and Methods" ]	[ "biochemistry", "developmental biology", "none", "cell biology", "mammals", "eukaryotes", "vertebrates", "mus (mouse)", "genetics and genomics" ]	Argonaute2 Is Essential for Mammalian Gastrulation and Proper Mesoderm Formation	journal.pgen.0030227	null	[ [ "Argonaute proteins comprise a highly conserved gene family necessary for a range of physiological and developmental processes .", "These proteins are defined by the presence of PAZ and PIWI domains , which modulate protein−protein interactions , nucleic acid binding , and , in some cases , mRNA cleavage ...	[ "Mammalian Argonaute proteins ( EIF2C1−4 ) play an essential role in RNA-induced silencing .", "Here , we show that the loss of eIF2C2 ( Argonaute2 or Ago2 ) results in gastrulation arrest , ectopic expression of Brachyury ( T ) , and mesoderm expansion .", "We identify a genetic interaction between Ago2 and T ...	[ "Gastrulation is a developmental phase that delineates the three embryonic germ layers: ectoderm , endoderm , and mesoderm .", "The gene Brachyury is essential for mesoderm development , and short-tail mice , which were later found to be carrying a Brachyury mutation , have been known since 1927 .", "In this st...	2007
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "population ecology", "mathematics", "ecology", "population modeling", "statistics", "theoretical ecology", "biology", "computational biology", "infectious disease modeling", "statistical methods" ]	Statistical Inference for Multi-Pathogen Systems	journal.pcbi.1002135	null	[ [ "Studies of infectious disease systems typically focus solely on the interaction between the host and the causative agent .", "This approach has served epidemiologists well , especially for antigenically stable pathogens , such as measles or chickenpox [1]–[4] .", "It is becoming increasingly evident ...	[ "There is growing interest in understanding the nature and consequences of interactions among infectious agents .", "Pathogen interactions can be operational at different scales , either within a co-infected host or in host populations where they co-circulate , and can be either cooperative or competitive .", "...	[ "It is becoming increasingly evident that pathogens associated with infectious diseases interact amongst themselves .", "Pathogen interactions can occur in a co-infected host , or in host populations where they co-circulate , and they can be cooperative or competitive .", "Four serotypes of dengue virus , for e...	2011
[ "Introduction", "Results/Discussion", "Materials and Methods", "Supporting Information" ]	[ "none", "molecular biology", "computational biology" ]	Ligand Binding and Circular Permutation Modify Residue Interaction Network in DHFR	journal.pcbi.0030117	null	[ [ "Extensive experimental studies of dihydrofolate reductase ( DHFR ) have provided rich data toward the structure–function relationship in proteins .", "Escherichia coli DHFR is a 159–amino acid , monomeric , two-domain protein that is well characterized in terms of structure and function .", "DHFR cat...	[ "Residue interaction networks and loop motions are important for catalysis in dihydrofolate reductase ( DHFR ) .", "Here , we investigate the effects of ligand binding and chain connectivity on network communication in DHFR .", "We carry out systematic network analysis and molecular dynamics simulations of the ...	[ "The cooperative movements within a protein concerning the binding and dissociation of the reactants and products could be important for protein function .", "Communication among the various parts of an enzyme can be achieved by the networks connecting amino acids through peptide backbone connections and nonbonde...	2007
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genetics", "biology", "molecular cell biology", "genetics and genomics" ]	Histone H3K56 Acetylation, CAF1, and Rtt106 Coordinate Nucleosome Assembly and Stability of Advancing Replication Forks	journal.pgen.1002376	null	[ [ "Problems in DNA replication are a direct cause of genetic instability and are associated with early tumor development [1] .", "This instability is linked to a high susceptibility of the replication forks to become stalled , damaged or even broken , and for this reason understanding of the scenarios that ...	[ "Chromatin assembly mutants accumulate recombinogenic DNA damage and are sensitive to genotoxic agents .", "Here we have analyzed why impairment of the H3K56 acetylation-dependent CAF1 and Rtt106 chromatin assembly pathways , which have redundant roles in H3/H4 deposition during DNA replication , leads to genetic...	[ "Loss of replication fork integrity is a primary source of genetic instability .", "In eukaryotes DNA synthesis is rapidly followed by its assembly into chromatin , and these two processes are tightly connected .", "Defective chromatin assembly mutants accumulate DNA damage and are sensitive to genotoxic agents...	2011
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "blood cells", "medicine and health sciences", "c-reactive proteins", "immune cells", "protein interactions", "built structures", "engineering and technology", "immunology", "random variables", "covariance", "simulation and modeling", "mathematics", "research and analysis methods", "white ...	Joint genetic analysis using variant sets reveals polygenic gene-context interactions	journal.pgen.1006693	null	[ [ "Understanding genetic interactions with external context ( GxC ) , including environment , is a major challenge in quantitative genetics .", "Linear mixed models ( LMMs ) have emerged as the framework of choice for many genetic analyses , mainly because the random effect component in this class of models...	[ "Joint genetic models for multiple traits have helped to enhance association analyses .", "Most existing multi-trait models have been designed to increase power for detecting associations , whereas the analysis of interactions has received considerably less attention .", "Here , we propose iSet , a method based...	[ "Genetic effects on phenotypes can depend on external contexts , including environment .", "Statistical tests for identifying such interactions are important to understand how individual genetic variants may act in different contexts .", "Interaction effects can either be studied using measurements of a given p...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genetics and genomics/epigenetics", "microbiology/microbial evolution and genomics", "infectious diseases/antimicrobials and drug resistance", "microbiology" ]	SOS Response Induces Persistence to Fluoroquinolones in Escherichia coli	journal.pgen.1000760	null	[ [ "Persistence is the ability of a subpopulation of susceptible bacteria to survive lethal doses of antibiotics .", "It is a transient and non-hereditary phenotype unlike resistance , which is due to genetic modification .", "The transient nature of persistence makes it inherently difficult to study the...	[ "Bacteria can survive antibiotic treatment without acquiring heritable antibiotic resistance .", "We investigated persistence to the fluoroquinolone ciprofloxacin in Escherichia coli .", "Our data show that a majority of persisters to ciprofloxacin were formed upon exposure to the antibiotic , in a manner depen...	[ "The frequent failure of antibiotic treatments is an acute public health problem .", "Bacteria can escape the lethal action of antibiotics by a mutation in the cell's DNA , leading to antibiotic resistance .", "Alternatively , they can enter a physiological state in which the antibiotics do not affect them .", ...	2009
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "ecology and environmental sciences", "c3 photosynthesis", "genetic networks", "water resources", "chemical compounds", "carbohydrates", "departures from diploidy", "organic compounds", "circadian oscillators", "plant science", "tetraploidy", "network analysis", "chronobiology", "photosynt...	Time of day and network reprogramming during drought induced CAM photosynthesis in Sedum album	journal.pgen.1008209	null	[ [ "Drought is the most pervasive abiotic stress and plants have evolved diverse strategies to mitigate the effects of water deficit [1] .", "Most water loss in plants occurs through transpiration as a byproduct of daytime stomata mediated CO2 uptake .", "Crassulacean acid metabolism ( CAM ) plants have ...	[ "Plants with facultative crassulacean acid metabolism ( CAM ) maximize performance through utilizing C3 or C4 photosynthesis under ideal conditions while temporally switching to CAM under water stress ( drought ) .", "While genome-scale analyses of constitutive CAM plants suggest that time of day networks are shi...	[ "Crassulacean acid metabolism ( CAM ) photosynthesis represents an important adaptation to arid environments as CAM plants take up CO2 at night when evapotranspiration rates are lower .", "Genomes and large-scale datasets are available for several plants with constitutive CAM activity , but they provided little i...	2019
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "medicine and health sciences", "genetic networks", "breast tumors", "statistics", "protein interaction networks", "cancers and neoplasms", "oncology", "mathematics", "forecasting", "network analysis", "genome analysis", "research and analysis methods", "computer and information sciences", ...	A data-driven interactome of synergistic genes improves network-based cancer outcome prediction	journal.pcbi.1006657	null	[ [ "Metastases at distant sites ( e . g . in bone , lung , liver and brain ) is the major cause of death in breast cancer patients [1] .", "However , it is currently difficult to assess tumor progression in these patients using common clinical variables ( e . g . tumor size , lymph-node status , etc . ) [2] ...	[ "Robustly predicting outcome for cancer patients from gene expression is an important challenge on the road to better personalized treatment .", "Network-based outcome predictors ( NOPs ) , which considers the cellular wiring diagram in the classification , hold much promise to improve performance , stability and...	[ "Cancer is caused by disrupted activity of several pathways .", "Therefore , to predict cancer patient prognosis from gene expression profiles , it may be beneficial to consider the cellular interactome ( e . g . the protein interaction network ) .", "These so-called Network based Outcome Predictors ( NOPs ) ho...	2019
[ "Introduction", "Results", "Discussion" ]	[]	Mechanism for Collective Cell Alignment in Myxococcus xanthus Bacteria	journal.pcbi.1004474	null	[ [ "Myxococcus xanthus is a model organism for studying self-organization behavior in bacteria [1] .", "These rod-shaped bacteria are known for their ability to collectively move on solid surfaces .", "Depending on environmental conditions , this collective movement allows cells to self-organize into a v...	[ "Myxococcus xanthus cells self-organize into aligned groups , clusters , at various stages of their lifecycle .", "Formation of these clusters is crucial for the complex dynamic multi-cellular behavior of these bacteria .", "However , the mechanism underlying the cell alignment and clustering is not fully under...	[ "Many bacterial species are capable of collectively moving and reorganizing themselves into a variety of multi-cellular structures .", "However , the mechanisms behind this self-organization behavior are not completely understood .", "The majority of previous studies focused on biochemical signaling among cells...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "developmental biology", "growth control", "organism development", "regeneration", "biology", "morphogenesis", "cell fate determination", "limb development" ]	Tissue Homeostasis in the Wing Disc of Drosophila melanogaster: Immediate Response to Massive Damage during Development	journal.pgen.1003446	null	[ [ "During the development or during the adult life organisms may suffer different kinds of insults , ranging from minor injuries to massive tissue damage or physical amputations .", "In consequence they have developed response mechanisms to reconstruct the damaged tissue .", "The phenomenon of regenerat...	[ "All organisms have developed mechanisms to respond to organ or tissue damage that may appear during development or during the adult life .", "This process of regeneration is a major long-standing problem in Developmental Biology .", "We are using the Drosophila melanogaster wing imaginal disc to study the resp...	[ "The study of how organs or tissues regenerate after damage is a classic topic in Developmental Biology .", "We are studying this process in the developing wing imaginal disc of Drosophila melanogaster , using genetic methods to inflict massive damage in the region destined to form the wing blade .", "We find t...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genetics", "biology", "genomics", "genetics and genomics" ]	Cryptic Transcription Mediates Repression of Subtelomeric Metal Homeostasis Genes	journal.pgen.1002163	null	[ [ "A large fraction of eukaryotic genomes is transcribed , even in the non-coding regions ( reviewed in [1] ) .", "One of the major questions that arise from these observations is to understand whether the RNAs expressed from these regions serve any functional purpose or whether they correspond to genomic n...	[ "Nonsense-mediated mRNA decay ( NMD ) prevents the accumulation of transcripts bearing premature termination codons .", "Here we show that Saccharomyces cerevisiae NMD mutants accumulate 5′–extended RNAs ( CD-CUTs ) of many subtelomeric genes .", "Using the subtelomeric ZRT1 and FIT3 genes activated in response...	[ "Precise expression of genes relies on their accurate and timely transcription and on turning off these genes when production of the proteins is not required .", "Our study describes that in the baker's yeast , S . cerevisiae , repression of many genes relies on transcription of long extended RNAs upstream from w...	2011
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biology and life sciences" ]	Heterodimerization of p45–p75 Modulates p75 Signaling: Structural Basis and Mechanism of Action	journal.pbio.1001918	The formation of a p45-p75 heterodimer overrides p75â€™s inhibition of nerve regeneration by stopping p75 homodimers from forming and creating a complex with the Nogo receptor.	[ [ "The neurotrophin receptor p75 is a member of the tumor necrosis factor receptor ( TNFR ) superfamily and has four extracellular cysteine rich domains , a single transmembrane ( TM ) domain , and an intracellular domain ( ICD ) comprising a juxtamembrane and a death domain ( DD ) [1]–[5] .", "Depending on...	[ "The p75 neurotrophin receptor , a member of the tumor necrosis factor receptor superfamily , is required as a co-receptor for the Nogo receptor ( NgR ) to mediate the activity of myelin-associated inhibitors such as Nogo , MAG , and OMgp .", "p45/NRH2/PLAIDD is a p75 homologue and contains a death domain ( DD ) ...	[ "Injuries to the brain and spinal cord often result in paralysis due to the fact that the injured nerves cannot regrow to reach their normal targets and carry out their functions .", "At the injury sites , there are proteins released from the damaged myelin that bind the Nogo receptor ( NgR ) on the nerve and inh...	2014
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "biology" ]	Detection, Isolation and Confirmation of Crimean-Congo Hemorrhagic Fever Virus in Human, Ticks and Animals in Ahmadabad, India, 2010–2011	journal.pntd.0001653	null	[ [ "Crimean-Congo hemorrhagic fever ( CCHF ) is a severe acute febrile illness caused by the CCHF virus ( CCHFV , family Bunyaviridae , genus Nairovirus ) , with overall case fatality of 9–50% [1] .", "CCHF was first recognized in the Crimean peninsula in the mid-1940s , [2] , but the virus was first isolate...	[ "In January 2011 , human cases with hemorrhagic manifestations in the hospital staff were reported from a tertiary care hospital in Ahmadabad , India .", "This paper reports a detailed epidemiological investigation of nosocomial outbreak from the affected area of Ahmadabad , Gujarat , India .", "Samples from 3 ...	[ "A nosocomial outbreak of CCHFV occurred in January 2011 , in a tertiary care hospital in Ahmadabad , Gujarat State in western India .", "Out of a total five cases reported , contact transmission occurred to three treating medical professionals , all of whom succumbed to the disease .", "The only survivor was t...	2012
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "molecular biology/bioinformatics", "mathematics/statistics", "computational biology/sequence motif analysis", "computational biology/transcriptional regulation" ]	Using Sequence-Specific Chemical and Structural Properties of DNA to Predict Transcription Factor Binding Sites	journal.pcbi.1001007	null	[ [ "An important step in characterizing the genetic regulatory network of a cell is to identify the DNA binding sites recognized by each transcription factor ( TF ) protein encoded in the genome .", "A TF typically activates and/or represses genes by associating with specific DNA sequences .", "Although ...	[ "An important step in understanding gene regulation is to identify the DNA binding sites recognized by each transcription factor ( TF ) .", "Conventional approaches to prediction of TF binding sites involve the definition of consensus sequences or position-specific weight matrices and rely on statistical analysis...	[ "An important step in characterizing the genetic regulatory network of a cell is to identify the DNA binding sites recognized by each transcription factor ( TF ) protein encoded in the genome .", "Current computational approaches to TF binding site prediction rely exclusively on DNA sequence analysis .", "In th...	2010
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biology", "genomics", "evolutionary biology", "genetics and genomics" ]	Rapid Evolution of Enormous, Multichromosomal Genomes in Flowering Plant Mitochondria with Exceptionally High Mutation Rates	journal.pbio.1001241	A pair of species within the genus Silene have evolved the largest known mitochondrial genomes, coinciding with extreme changes in mutation rate, recombination activity, and genome structure.	[ [ "Explaining the origins of variation in genome size and complexity has become the defining challenge for the field of molecular evolution in the genomic era .", "Historically , numerous evolutionary models have been developed , involving mechanisms such as insertion and deletion ( indel ) bias [1] , [2] ,...	[ "Genome size and complexity vary tremendously among eukaryotic species and their organelles .", "Comparisons across deeply divergent eukaryotic lineages have suggested that variation in mutation rates may explain this diversity , with increased mutational burdens favoring reduced genome size and complexity .", ...	[ "A fundamental challenge in evolutionary biology is to explain why organisms exhibit dramatic variation in genome size and complexity .", "One hypothesis predicts that high rates of mutation in DNA sequence create selection against large and complex genomes , which are more susceptible to mutational disruption ."...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biotechnology", "chemistry", "neuroscience", "molecular biology" ]	Solid-State, Dye-Labeled DNA Detects Volatile Compounds in the Vapor Phase	journal.pbio.0060009	Short sequences of solid-state DNA can selectively signal their interactions with small molecules in the vapor phase. These observations have been implemented in odor sensing in an electronic "nose" and further suggest that in vivo responses to small molecules may represent new, nongenetic attributes of DNA.	[ [ "Odor sensor arrays composed of materials that are cross-reactive have advantages over narrowly tuned receptor systems .", "These include combinatorial responses to sets of compounds that exceed the number of receptor or sensor types , tolerance to partial system failure , and an ability to be flexibly tr...	[ "This paper demonstrates a previously unreported property of deoxyribonucleic acid—the ability of dye-labeled , solid-state DNA dried onto a surface to detect odors delivered in the vapor phase by changes in fluorescence .", "This property is useful for engineering systems to detect volatiles and provides a way f...	[ "Biological systems can provide engineering guidance on how evolution has solved particular problems .", "In the context of detecting chemicals in either the aqueous or vapor phase , two general biological approaches have emerged .", "The first relies on individual highly specific single receptors ( sensors ) ,...	2008
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "cell death", "medicine and health sciences", "cardiovascular physiology", "in situ hybridization", "molecular probe techniques", "cardiovascular anatomy", "cardiac ventricles", "cell processes", "developmental biology", "molecular biology techniques", "embryos", "research and analysis methods...	Hand factor ablation causes defective left ventricular chamber development and compromised adult cardiac function	journal.pgen.1006922	null	[ [ "The left ventricle ( LV ) of the heart drives systemic circulation .", "Because the LV must be large enough to support adequate cardiac output but not hypertrophic or hypoplastic , such that it obstructs blood flow , congenital heart defects ( CHDs ) and acquired diseases that impact LV morphology or cel...	[ "Coordinated cardiomyocyte growth , differentiation , and morphogenesis are essential for heart formation .", "We demonstrate that the bHLH transcription factors Hand1 and Hand2 play critical regulatory roles for left ventricle ( LV ) cardiomyocyte proliferation and morphogenesis .", "Using an LV-specific Cre a...	[ "The left ventricle of the heart drives blood flow throughout the body .", "Impaired left ventricle function , associated either with heart failure or with certain , severe cardiac birth defects , constitutes a significant cause of mortality .", "Understanding how heart muscle grows is vital to developing impro...	2017
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "schistosoma", "invertebrates", "schistosoma mansoni", "medicine and health sciences", "enzyme-linked immunoassays", "immune physiology", "pathology and laboratory medicine", "viral transmission and infection", "helminths", "pathogens", "immunology", "tropical diseases", "microbiology", "p...	Schistosomiasis is associated with incident HIV transmission and death in Zambia	journal.pntd.0006902	null	[ [ "Of the more than 200 million persons who have schistosomiasis worldwide , more than 90% live in Africa , and the disease causes tens to hundreds of thousands of deaths annually [1] .", "Of the parasitic diseases , the health impact of schistosomiasis is second only to malaria [2] .", "Common species ...	[ "We examined relationships between schistosome infection , HIV transmission or acquisition , and all-cause death .", "We retrospectively tested baseline sera from a heterosexual HIV-discordant couple cohort in Lusaka , Zambia with follow-up from 1994–2012 in a nested case-control design .", "Schistosome-specifi...	[ "This study explored the association between schistosome infections ( a disease caused by parasitic flatworms , also known as ‘snail fever’ , which is very common throughout sub-Saharan Africa ) and human immunodeficiency virus ( HIV ) .", "We found in Lusaka , the capital of Zambia , that schistosome infections ...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "microbiology/immunity to infections", "microbiology/innate immunity", "immunology/immunity to infections", "microbiology", "microbiology/cellular microbiology and pathogenesis" ]	Yersinia enterocolitica Targets Cells of the Innate and Adaptive Immune System by Injection of Yops in a Mouse Infection Model	journal.ppat.1000551	null	[ [ "Yersinia enterocolitica ( Ye ) is an enteropathogenic bacterium that causes gastrointestinal disorders such as enteritis and enterocolitis as well as extraintestinal manifestations such as lymphadenitis , reactive arthritis , and septicemia [1] , [2] .", "Ye has been demonstrated to multiply extracellula...	[ "Yersinia enterocolitica ( Ye ) evades the immune system of the host by injection of Yersinia outer proteins ( Yops ) via a type three secretion system into host cells .", "In this study , a reporter system comprising a YopE-β-lactamase hybrid protein and a fluorescent staining sensitive to β-lactamase cleavage w...	[ "An important strategy of Yersinia enterocolitica ( Ye ) to suppress the immune defense is to inject bacterial proteins ( Yersinia outer proteins , Yops ) after cell contact directly into host cells , which affects their functions .", "However , tracking of cells in which Yop injection occurred has only been desc...	2009
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "taxonomy", "invertebrates", "medicine and health sciences", "typhus of rickettsiae", "animals", "animal phylogenetics", "phylogenetics", "emerging infectious diseases", "fleas", "veterinary science", "infectious diseases", "veterinary diseases", "zoonoses", "epidemiology", "evolutionary...	Fleas of Small Mammals on Reunion Island: Diversity, Distribution and Epidemiological Consequences	journal.pntd.0003129	null	[ [ "Reunion is a small oceanic island of volcanic origin located in the Indian Ocean , Southern Hemisphere ( 21°6′S and 55°36′E ) that forms , together with Mauritius and Rodrigues Islands , the Mascarene archipelago .", "This oceanic island is geographically isolated from continental landmasses and located ...	[ "The diversity and geographical distribution of fleas parasitizing small mammals have been poorly investigated on Indian Ocean islands with the exception of Madagascar where endemic plague has stimulated extensive research on these arthropod vectors .", "In the context of an emerging flea-borne murine typhus outb...	[ "Fleas are blood-feeding parasites involved in the transmission of several arthropod borne pathogens .", "Rat-fleas ( Xenopsylla spp . ) are known vectors of bubonic plague together with other human diseases receiving less attention such as murine typhus .", "This latter disease was recorded for the first time ...	2014
[ "Introduction", "Materials and methods", "Results", "Discussion" ]	[ "action potentials", "medicine and health sciences", "diagnostic radiology", "functional magnetic resonance imaging", "neural networks", "nervous system", "membrane potential", "vertebrates", "electrophysiology", "neuroscience", "animals", "mammals", "magnetic resonance imaging", "primates...	A multi-scale layer-resolved spiking network model of resting-state dynamics in macaque visual cortical areas	journal.pcbi.1006359	null	[ [ "Cortical activity has distinct but interdependent features on local and global scales , molded by multi-scale connectivity .", "Data from multiple species including macaque indicate that the ground state of cortex locally features asynchronous irregular spiking with low pairwise correlations [1] and low ...	[ "Cortical activity has distinct features across scales , from the spiking statistics of individual cells to global resting-state networks .", "We here describe the first full-density multi-area spiking network model of cortex , using macaque visual cortex as a test system .", "The model represents each area by ...	[ "The mammalian cortex fulfills its complex tasks by operating on multiple temporal and spatial scales from single cells to entire areas comprising millions of cells .", "These multi-scale dynamics are supported by specific network structures at all levels of organization .", "Since models of cortex hitherto ten...	2018
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "infectious diseases/protozoal infections", "infectious diseases/neglected tropical diseases", "infectious diseases/epidemiology and control of infectious diseases" ]	Control of Visceral Leishmaniasis in Latin America—A Systematic Review	journal.pntd.0000584	null	[ [ "Visceral leishmaniasis ( VL ) in Latin America is a severe systemic disease caused by an intracellular protozoon , Leishmania infantum ( syn . L . chagasi ) .", "VL is a zoonosis: the domestic dog is the main animal reservoir , while foxes and other wild animals play a role in sylvatic transmission [1]–[...	[ "While three countries in South Asia decided to eliminate anthroponotic visceral leishmaniasis ( VL ) by 2015 , its control in other regions seems fraught with difficulties .", "Is there a scope for more effective VL control in the Americas where transmission is zoonotic ?", "We reviewed the evidence on VL cont...	[ "Visceral leishmaniasis is a vector-borne disease characterized by fever , spleen and liver enlargement , and low blood cell counts .", "In the Americas VL is zoonotic , with domestic dogs as main animal reservoirs , and is caused by the intracellular parasite Leishmania infantum ( syn . Leishmania chagasi ) .", ...	2010
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "bacteriology", "antimicrobials", "medicine and health sciences", "pathology and laboratory medicine", "pathogens", "drugs", "microbiology", "bacterial diseases", "physiological processes", "mutation", "secretion systems", "immunoprecipitation", "antibiotics", "enterobacteriaceae", "phar...	Role of SpaO in the assembly of the sorting platform of a Salmonella type III secretion system	journal.ppat.1007565	null	[ [ "Type III protein secretion systems ( T3SSs ) are highly specialized multiprotein molecular machines with the capacity to inject bacterially-encoded proteins into target eukaryotic cells .", "Encoded by a large variety of gram-negative bacteria , T3SSs are central to the interactions of many pathogens and...	[ "Many bacterial pathogens and symbionts use type III secretion machines to interact with their hosts by injecting bacterial effector proteins into host target cells .", "A central component of this complex machine is the cytoplasmic sorting platform , which orchestrates the engagement and preparation of type III ...	[ "Many pathogenic and symbiotic gram-negative bacteria utilize type III secretion systems to deliver bacterial proteins , known as effectors , directly into the host cell cytosol to promote their survival and the colonization of tissues .", "Type III secretion systems or injectisomes are large , multiprotein compl...	2019
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "protons", "medicine and health sciences", "neurochemistry", "pathology and laboratory medicine", "chemical compounds", "respiratory infections", "enzymes", "pathogens", "microbiology", "enzymology", "carbohydrates", "neuroscience", "staphylococcus aureus", "organic compounds", "glucose"...	Genetic requirements for Staphylococcus aureus nitric oxide resistance and virulence	journal.ppat.1006907	null	[ [ "Staphylococcus aureus is a highly invasive human pathogen that is responsible for significant morbidity each year[1] .", "Treatment of S . aureus infections has become increasingly difficult due to the propensity of S . aureus to quickly evolve antibiotic resistance .", "Methicillin resistant S . aur...	[ "Staphylococcus aureus exhibits many defenses against host innate immunity , including the ability to replicate in the presence of nitric oxide ( NO· ) .", "S . aureus NO· resistance is a complex trait and hinges on the ability of this pathogen to metabolically adapt to the presence of NO· .", "Here , we employ...	[ "The human pathogen Staphylococcus aureus is remarkably resistant to many facets of the host immune response , including the antibacterial radical nitric oxide ( NO· ) .", "The mechanism underlying this resistance is complex and comprises many gene products .", "Here we employ an approach that involves transpos...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine and health sciences", "lysosomes", "vesicles", "pathology and laboratory medicine", "hek 293 cells", "influenza", "pathogens", "biological cultures", "microbiology", "retroviruses", "viruses", "immunodeficiency viruses", "immune receptor signaling", "rna viruses", "membrane rec...	CD4 Receptor is a Key Determinant of Divergent HIV-1 Sensing by Plasmacytoid Dendritic Cells	journal.ppat.1005553	null	[ [ "Type I interferon ( IFN ) plays a dichotomous role in chronic viral infections such as Human Immunodeficiency Virus-1 ( HIV ) , contributing to the control of viral replication during the earliest stages of infection , yet fueling disease progression by activating target cells for infection , decreasing anti...	[ "Plasmacytoid dendritic cells ( pDC ) are innate immune cells that sense viral nucleic acids through endosomal Toll-like receptor ( TLR ) 7/9 to produce type I interferon ( IFN ) and to differentiate into potent antigen presenting cells ( APC ) .", "Engagement of TLR7/9 in early endosomes appears to trigger the I...	[ "Plasmacytoid dendritic cells ( pDC ) are innate immune cells that are specialized to produce type I interferon ( IFN ) and to activate adaptive immune responses .", "Although IFN is an anti-viral cytokine , it may contribute more to pathogenesis than to protection during chronic viral infections , including chro...	2016
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "medicine and health sciences", "pathology and laboratory medicine", "china", "pathogens", "immunology", "tropical diseases", "geographical locations", "microbiology", "vertebrates", "animals", "mammals", "dogs", "viruses", "preventive medicine", "age groups", "rabies", "rna viruses"...	Human Rabies in China, 1960-2014: A Descriptive Epidemiological Study	journal.pntd.0004874	null	[ [ "Rabies is a zoonotic disease caused by viruses of genus Lyssavirus , it’s also a vaccine-preventable viral disease which occurs in more than 150 countries and territories .", "Although a number of carnivore and bat species serve as natural reservoirs , worldwide rabies in dogs is the source more than 95%...	[ "Rabies in China remains a public health problem .", "In 2014 , nearly one thousand rabies-related deaths were reported while rabies geographic distribution has expanded for the recent years .", "This report used surveillance data to describe the epidemiological characteristics of human rabies in China includin...	[ "China is a high-risk environment for rabies , with human rabies cases second only to India globally .", "This paper reviews 55 years of rabies epidemiology in mainland China , and detailed analysis of data in recent years .", "In this study , notifiable surveillance data were analyzed and found that rabies sti...	2016
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "medicine and health sciences", "pathology and laboratory medicine", "togaviruses", "chikungunya infection", "economic analysis", "pathogens", "tropical diseases", "microbiology", "geographical locations", "social sciences", "alphaviruses", "health care", "viruses", "chikungunya virus", ...	Chikungunya outbreak (2017) in Bangladesh: Clinical profile, economic impact and quality of life during the acute phase of the disease	journal.pntd.0006561	null	[ [ "Chikungunya is a mosquito-borne ( Aedes species ) , self-limiting , febrile illness with severe debilitating arthropathy caused by chikungunya virus ( CHIKV ) .", "This virus was first identified during an epidemic of febrile polyarthralgia in Tanzania in 1953 [1] .", "Since then , CHIKV has been rep...	[ "Chikungunya virus causes mosquito-transmitted infection that leads to extensive morbidity affecting substantial quality of life .", "Disease associated morbidity , quality of life , and financial loss are seldom reported in resources limited countries , such as Bangladesh .", "We reported the acute clinical pr...	[ "A major outbreak of chikungunya virus occurred for the first time in Dhaka , Bangladesh between May and September 2017 .", "In this study , a face-to-face interview with a structured questionnaire was conducted to collect data to investigate the clinical symptoms , quality of life , and economic aspects of 1 , 3...	2018
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "infectious diseases", "subcutaneous mycoses", "medicine and health sciences", "mycetoma", "neglected tropical diseases", "tropical diseases", "fungal diseases" ]	Mycetoma: Experience of 482 Cases in a Single Center in Mexico	journal.pntd.0003102	null	[ [ "Mycetoma is a chronic granulomatous disease , associated with a progressive , inflammatory reaction that clinically presents as tumor-like soft tissue swelling with sinus tract formation that drains purulent material containing grains .", "Mycetoma usually results of traumatic implantation of soil organi...	[ "Mycetoma is a chronic granulomatous disease .", "It is classified into eumycetoma caused by fungi and actinomycetoma due to filamentous actinomycetes .", "Mycetoma can be found in geographic areas in close proximity to the Tropic of Cancer .", "Mexico is one of the countries in which this disease is highly e...	[ "Mycetoma is a chronic , subcutaneous granulomatous disease that usually begins after traumatic inoculation with causative microorganisms .", "Based on its etiology , mycetoma is referred to eumycetoma when the infection is caused by filamentous fungi , and actinomycetoma when the infection is due to aerobic acti...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "hematologic cancers and related disorders", "medicine", "infectious diseases", "myelomas and lymphoproliferative diseases", "lymphomas", "viral diseases", "hematology", "epstein-barr virus infectious mononucleosis" ]	Novel Mouse Xenograft Models Reveal a Critical Role of CD4+ T Cells in the Proliferation of EBV-Infected T and NK Cells	journal.ppat.1002326	null	[ [ "Epstein-Barr virus ( EBV ) is a ubiquitous γ-herpesvirus that infects more than 90% of the adult population in the world .", "EBV is occasionally involved in the pathogenesis of malignant tumors , such as Burkitt lymphoma , Hodgkin lymphoma , and nasopharyngeal carcinoma , along with the post-transplanta...	[ "Epstein-Barr virus ( EBV ) , a ubiquitous B-lymphotropic herpesvirus , ectopically infects T or NK cells to cause severe diseases of unknown pathogenesis , including chronic active EBV infection ( CAEBV ) and EBV-associated hemophagocytic lymphohistiocytosis ( EBV-HLH ) .", "We developed xenograft models of CAEB...	[ "Epstein-Barr virus ( EBV ) is a ubiquitous human herpesvirus that infects more than 90% of the adult human population in the world .", "EBV usually infects B lymphocytes and does not produce symptoms in infected individuals , but in rare occasions it infects T or NK lymphocytes and causes severe diseases such as...	2011
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "immunopathology", "pathogenesis", "inflammation", "immune cells", "cytokines", "monocytes", "immunity", "immune activation", "t cells", "immune defense", "immunology", "immunity to infections", "biology", "microbiology", "host-pathogen interaction", "microbial control", "immune resp...	TREM-1 Deficiency Can Attenuate Disease Severity without Affecting Pathogen Clearance	journal.ppat.1003900	null	[ [ "Innate immune cells express several cell surface receptors and intracellular sensing molecules that allow for autonomous recognition of pathogen- and danger-associated molecular patterns ( PAMPs and DAMPs ) and initiation of pro-inflammatory anti-microbial reponses .", "Toll-like receptors ( TLR ) and nu...	[ "Triggering receptor expressed on myeloid cells-1 ( TREM-1 ) is a potent amplifier of pro-inflammatory innate immune reactions .", "While TREM-1-amplified responses likely aid an improved detection and elimination of pathogens , excessive production of cytokines and oxygen radicals can also severely harm the host...	[ "Triggering receptor expressed on myeloid cells-1 ( TREM-1 ) is an immune receptor expressed by myeloid cells that has the capacity to augment pro-inflammatory responses in the context of a microbial infection .", "While a TREM-1-amplified response likely serves the efficient clearance of pathogens , it also bear...	2014
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "biophysics/cell signaling and trafficking structures", "biophysics/theory and simulation", "computational biology/systems biology" ]	Predicting the Distribution of Spiral Waves from Cell Properties in a Developmental-Path Model of Dictyostelium Pattern Formation	journal.pcbi.1000422	null	[ [ "The slime mold Dictyostelium discoideum is a model organism for the study of pattern formation and excitable media dynamics in biological systems [1] .", "Several stages of its life cycle exhibit self-organized formation of structures successively building up on one another .", "Here we are exclusive...	[ "The slime mold Dictyostelium discoideum is one of the model systems of biological pattern formation .", "One of the most successful answers to the challenge of establishing a spiral wave pattern in a colony of homogeneously distributed D . discoideum cells has been the suggestion of a developmental path the cell...	[ "Spatio-temporal pattern formation is a core discipline of theoretical biology .", "Formation of large-scale patterns from local interactions can very prominently be observed in the swarming behavior of fish and birds , in animal markings or bacterial growth patterns .", "It also plays a critical role in the li...	2009
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "sequencing techniques", "taxonomy", "horizontal gene transfer", "split-decomposition method", "microbiology", "gene transfer", "multiple alignment calculation", "phylogenetics", "data management", "phylogenetic analysis", "genetic elements", "molecular biology techniques", "research and ana...	Phylogeny Reconstruction with Alignment-Free Method That Corrects for Horizontal Gene Transfer	journal.pcbi.1004985	null	[ [ "Learning how to obtain complete genomes was a critical step to understanding biology and was achieved as early as 1977 for the genome of bacteriophage ɸX174 [1] .", "Since then , methods for obtaining full genome sequences have advanced tremendously [2–4] , leading to a second critical transition , when ...	[ "Advances in sequencing have generated a large number of complete genomes .", "Traditionally , phylogenetic analysis relies on alignments of orthologs , but defining orthologs and separating them from paralogs is a complex task that may not always be suited to the large datasets of the future .", "An alternativ...	[ "Due to their lack of distinct morphological features , bacteria and archaea were extremely difficult to classify until technology was developed to obtain their DNA sequences; these sequences could then be compared to estimate evolutionary relationships .", "Now , due to technological advances , there is a flood ...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "viruses", "infectious diseases", "public health and epidemiology", "virology", "yeast and fungi", "in vitro", "immunology", "mus (mouse)", "homo (human)" ]	Methamphetamine Inhibits Antigen Processing, Presentation, and Phagocytosis	journal.ppat.0040028	null	[ [ "Chronic methamphetamine ( Meth ) abuse has reached epidemic proportion throughout the United States , where a 2003 survey indicated that approximately 5% of the population over 12 years of age has tried Meth and the rate of treatment admissions for primary Meth abuse increased over 3-fold ( The DASIS Report ...	[ "Methamphetamine ( Meth ) is abused by over 35 million people worldwide .", "Chronic Meth abuse may be particularly devastating in individuals who engage in unprotected sex with multiple partners because it is associated with a 2-fold higher risk for obtaining HIV and associated secondary infections .", "We rep...	[ "There is a new population of HIV+ men who are developing AIDS over months instead of years as typical .", "It has recently become popular among gay and bisexual men to consume very high levels of Meth .", "Unsafe sex together with Meth abuse has been suspected to lead to rapid disease progression .", "While ...	2008
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "infectious diseases/neglected tropical diseases" ]	Risk Factors for Ocular Infection with Chlamydia trachomatis in Children 6 Months following Mass Treatment in Tanzania	journal.pntd.0000978	null	[ [ "Trachoma is a blinding chronic conjunctivitis caused by repeated episodes of ocular Chlamydia trachomatis infection .", "It continues to be the leading infectious cause of blindness in the world , largely in the most resource poor countries [1] .", "The World Health Organization ( WHO ) has made a co...	[ "Trachoma is the leading infectious cause of blindness in the world , and for endemic communities , mass treatment with azithromycin reduces the pool of infection .", "High coverage is essential , especially in children as they are the infectious reservoir .", "However , infection remains post-mass treatment ."...	[ "Trachoma control programs aim for high coverage of endemic communities with oral azithromycin to reduce the pool of infection with Chlamydia trachomatis .", "However , even with high coverage , infection is seen following treatment .", "In four communities in Tanzania , we followed every child aged under ten y...	2011
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "computational biology/molecular dynamics", "computational biology/macromolecular structure analysis", "diabetes and endocrinology/endocrinology" ]	Active Nuclear Receptors Exhibit Highly Correlated AF-2 Domain Motions	journal.pcbi.1000111	null	[ [ "The nuclear receptor ( NR ) superfamily of ligand-regulated transcription factors controls the expression of genes essential to metabolism , development and systemic homeostasis [1]–[3] .", "NRs are modular proteins typically composed of a conserved N- terminal Zn-module DNA binding domain ( DBD ) that t...	[ "Nuclear receptor ligand binding domains ( LBDs ) convert ligand binding events into changes in gene expression by recruiting transcriptional coregulators to a conserved activation function-2 ( AF-2 ) surface .", "While most nuclear receptor LBDs form homo- or heterodimers , the human nuclear receptor pregnane X ...	[ "Long-range motions play essential roles in protein function but are difficult to appreciate from static crystal structures .", "We sought to understand how macromolecular motion affects the formation of transcriptional complexes central to controlling gene expression .", "Using 20- to 30-ns molecular dynamics ...	2008
[ "Introduction", "Methods", "Results and Discussion" ]	[]	Altered Hypercoagulability Factors in Patients with Chronic Chagas Disease: Potential Biomarkers of Therapeutic Response	journal.pntd.0004269	null	[ [ "Chagas disease ( CD ) is one of 17 neglected tropical diseases recognized by the World Health Organization .", "Caused by the protozoan parasite Trypanosoma cruzi , it mainly affects people with poor socioeconomic status and limited health care access in endemic and nonendemic countries .", "[1 , 2] ...	[ "Thromboembolic events were described in patients with Chagas disease without cardiomyopathy .", "We aim to confirm if there is a hypercoagulable state in these patients and to determine if there is an early normalization of hemostasis factors after antiparasitic treatment .", "Ninety-nine individuals from Chag...	[ "The manuscript describes the results of a study whose aim was to assess the tendency to coagulate in people suffering from a parasitic infection frequent in Latin America named T . cruzi infection or Chagas disease , by the study of several coagulation factors .", "According to the state of the art in this topic...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "bacteriology", "medicine and health sciences", "pathology and laboratory medicine", "host-pathogen interactions", "medical microbiology", "microbial pathogens", "biology and life sciences", "microbiology", "pathogenesis" ]	Reorganization of the Endosomal System in Salmonella-Infected Cells: The Ultrastructure of Salmonella-Induced Tubular Compartments	journal.ppat.1004374	null	[ [ "Bacterial pathogens have evolved sophisticated mechanisms to modify host cell functions in order to avoid antimicrobial defense or to use host cell-derived material for their own proliferation .", "Intracellular pathogens evade humoral immune responses of the host by hiding inside cells of the host organ...	[ "During the intracellular life of Salmonella enterica , a unique membrane-bound compartment termed Salmonella-containing vacuole , or SCV , is formed .", "By means of translocated effector proteins , intracellular Salmonella also induce the formation of extensive , highly dynamic membrane tubules termed Salmonell...	[ "Salmonella enterica is an invasive , facultative intracellular bacterial pathogen .", "Within mammalian host cells , Salmonella inhabits a specialized membrane-bound compartment , the Salmonella-containing vacuole ( SCV ) , redirects host cell vesicular transport and massively remodels the endosomal system .", ...	2014
[ "Introduction", "Methods", "Results", "Discussion" ]	[]	Predicted Role of NAD Utilization in the Control of Circadian Rhythms during DNA Damage Response	journal.pcbi.1004144	null	[ [ "Circadian rhythms are biological oscillations occurring with an approximately 24-hour period affecting many processes .", "In mammals , these oscillations are centrally controlled in the brain by the suprachiasmatic nuclei ( SCN ) .", "The SCN synchronizes the peripheral circadian clocks that exist i...	[ "The circadian clock is a set of regulatory steps that oscillate with a period of approximately 24 hours influencing many biological processes .", "These oscillations are robust to external stresses , and in the case of genotoxic stress ( i . e . DNA damage ) , the circadian clock responds through phase shifting ...	[ "Many physiological processes are regulated by the circadian clock , and we are continuing to learn about the role of the circadian clock in disease .", "Research in recent years has begun to shed light on the feedback mechanisms that exist between circadian regulation and other processes , including metabolism a...	2015
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "cardiomyopathies", "medicine and health sciences", "population genetics", "tropical diseases", "variant genotypes", "parasitic diseases", "parasitic protozoans", "genetic mapping", "genetic predisposition", "protozoans", "neglected tropical diseases", "population biology", "cardiology", "...	IL18 Gene Variants Influence the Susceptibility to Chagas Disease	journal.pntd.0004583	null	[ [ "Host genetic factors have been suggested to play an important role in the susceptibility to human infectious diseases [1] .", "An example of such conditions is Chagas disease , which is caused by infection of the protozoan Trypanosoma cruzi .", "Recent estimations indicate that more than 70 million p...	[ "Chagas disease is a parasitic disorder caused by the infection with the flagellated protozoan Trypanosoma cruzi .", "According to the World Health Organization , more than six million people are currently infected in endemic regions .", "Genetic factors have been proposed to influence predisposition to infecti...	[ "Chagas disease is a parasitic disorder caused by the infection with the protozoan Trypanosoma cruzi .", "In Latin America , this disease represents a major public health concern , as almost 6 million people are currently infected .", "During the last years , great efforts have been made in health policy to con...	2016
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "medicine and health sciences", "diagnostic radiology", "functional magnetic resonance imaging", "markov models", "neural networks", "random variables", "neuroscience", "covariance", "simulation and modeling", "magnetic resonance imaging", "regression analysis", "mathematics", "statistics (m...	Simulations to benchmark time-varying connectivity methods for fMRI	journal.pcbi.1006196	null	[ [ "Time-varying connectivity ( TVC ) is being applied to an increasing number of topics studying the brain’s networks .", "Topics that have been explored with TVC include development [1] , various pathologies [2 , 3] , affect [4] , attention [5] , levels of consciousness [6] , and temporal properties of the...	[ "There is a current interest in quantifying time-varying connectivity ( TVC ) based on neuroimaging data such as fMRI .", "Many methods have been proposed , and are being applied , revealing new insight into the brain’s dynamics .", "However , given that the ground truth for TVC in the brain is unknown , many c...	[ "Time-varying connectivity attempts to quantify the fluctuating covariance relationship between two or more regions through time .", "In recent years , it has become popular to do this with fMRI neuroimaging data .", "There have been many methods proposed to quantify time-varying connectivity , but very few att...	2018
[ "Introduction", "Materials and methods", "Results", "Discussion" ]	[ "genome-wide association studies", "variant genotypes", "random variables", "covariance", "genetic mapping", "mathematics", "statistics (mathematics)", "genome analysis", "research and analysis methods", "genome complexity", "genomics", "mathematical and statistical techniques", "genetic loc...	Proper conditional analysis in the presence of missing data: Application to large scale meta-analysis of tobacco use phenotypes	journal.pgen.1007452	null	[ [ "Meta-analysis has become a critical tool for genetic association studies in human genetics .", "Meta-analysis increases sample sizes , empowers association studies , and has led to many exciting discoveries in the past decade [1–5] .", "Many of these genetic discoveries have informed new biology , pr...	[ "Meta-analysis of genetic association studies increases sample size and the power for mapping complex traits .", "Existing methods are mostly developed for datasets without missing values , i . e . the summary association statistics are measured for all variants in contributing studies .", "In practice , genoty...	[ "It is of great interest to estimate the joint effects of multiple variants from large scale meta-analyses , in order to fine-map causal variants and understand the genetic architecture for complex traits .", "The summary association statistics from participating studies in a meta-analysis often contain missing v...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "computational biology/systems biology", "genetics and genomics/gene expression", "computational biology/genomics", "genetics and genomics/bioinformatics", "diabetes and endocrinology/type 2 diabetes" ]	Using Pre-existing Microarray Datasets to Increase Experimental Power: Application to Insulin Resistance	journal.pcbi.1000718	null	[ [ "Since their inception over 13 years ago [1] , DNA microarrays have become a staple experimental tool used primarily for exploring the effects of biological interventions on gene expression .", "Microarrays have enabled a range of experimental queries , including a survey of gene expression across dozens ...	[ "Although they have become a widely used experimental technique for identifying differentially expressed ( DE ) genes , DNA microarrays are notorious for generating noisy data .", "A common strategy for mitigating the effects of noise is to perform many experimental replicates .", "This approach is often costly...	[ "Though the use of microarrays to identify differentially expressed ( DE ) genes has become commonplace , it is still not a trivial task .", "Microarray data are notorious for being noisy , and current DE gene methods do not fully utilize pre-existing biological knowledge to help control this noise .", "One suc...	2010
[ "Introduction", "Model", "Results", "Discussion", "Methods" ]	[ "neuroscience/theoretical neuroscience", "computational biology/computational neuroscience" ]	Parallel Computational Subunits in Dentate Granule Cells Generate Multiple Place Fields	journal.pcbi.1000500	null	[ [ "Neurons possess highly branched , complex dendritic trees , but the relationship between the structure of the dendritic arbor and underlying neural function is poorly understood [1] .", "Recent studies suggest that dendritic branches form independent computational subunits: Individual branches function a...	[ "A fundamental question in understanding neuronal computations is how dendritic events influence the output of the neuron .", "Different forms of integration of neighbouring and distributed synaptic inputs , isolated dendritic spikes and local regulation of synaptic efficacy suggest that individual dendritic bran...	[ "Neurons were originally divided into three morphologically distinct compartments: the dendrites receive the synaptic input , the soma integrates it and communicates the output of the cell to other neurons via the axon .", "Although several lines of evidence challenged this oversimplified view , neurons are still...	2009
[ "Introduction", "Results", "Discussion", "Materials and Methods", "Supporting Information" ]	[]	Temporal Expression Profiling Identifies Pathways Mediating Effect of Causal Variant on Phenotype	journal.pgen.1005195	null	[ [ "Identifying the causative genetic variants associated with complex human diseases is only the first step [1] .", "The major challenge is to understand how these genetic variants cause the disease .", "The mediating molecular pathways connecting these variants to phenotypes have been more systematical...	[ "Even with identification of multiple causal genetic variants for common human diseases , understanding the molecular processes mediating the causal variants’ effect on the disease remains a challenge .", "This understanding is crucial for the development of therapeutic strategies to prevent and treat disease .",...	[ "The causal path from a genetic variant to a complex phenotype such as disease progression is often not known .", "Studying gene expression variation is one approach to identify the mediating genes , however , it is difficult to distinguish causative from correlative genes .", "This becomes a challenge especial...	2015
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "developmental biology", "computational biology/transcriptional regulation", "mathematics", "developmental biology/pattern formation", "computational biology", "evolutionary biology", "computational biology/systems biology" ]	Canalization of Gene Expression and Domain Shifts in the Drosophila Blastoderm by Dynamical Attractors	journal.pcbi.1000303	null	[ [ "Canalization refers to the constancy of the wild type phenotype under varying developmental conditions [1]–[4] .", "In order to explain canalization , C . H . Waddington hypothesized that there must only be a finite number of distinct developmental trajectories possible , since cells make discrete fate d...	[ "The variation in the expression patterns of the gap genes in the blastoderm of the fruit fly Drosophila melanogaster reduces over time as a result of cross regulation between these genes , a fact that we have demonstrated in an accompanying article in PLoS Biology ( see Manu et al . , doi:10 . 1371/journal . pbio ...	[ "C . H . Waddington predicted in 1942 that networks of chemical reactions in embryos can counteract the effects of variable developmental conditions to produce reliable outcomes .", "The experimental signature of this process , called “canalization , ” is the reduction of the variation of the concentrations of mo...	2009
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "pharmacology/drug development", "computer science/numerical analysis and theoretical computing", "pharmacology/drug interactions", "oncology/gastrointestinal cancers", "computational biology/signaling networks", "computational biology", "computational biology/systems biology" ]	Identifying Drug Effects via Pathway Alterations using an Integer Linear Programming Optimization Formulation on Phosphoproteomic Data	journal.pcbi.1000591	null	[ [ "Target-based drug discovery is a predominant focus of the pharmaceutical industry .", "The primary objective is to selectively target protein ( s ) within diseased cells in order to ameliorate an undesired phenotype , e . g . , unrestrained cell proliferation or inflammatory cytokine release .", "Ide...	[ "Understanding the mechanisms of cell function and drug action is a major endeavor in the pharmaceutical industry .", "Drug effects are governed by the intrinsic properties of the drug ( i . e . , selectivity and potency ) and the specific signaling transduction network of the host ( i . e . , normal vs . disease...	[ "Cells are complex functional units .", "Signal transduction refers to the underlying mechanism that regulates cell function , and it is usually depicted on signaling pathways maps .", "Each cell type has distinct signaling transduction mechanisms , and several diseases arise from alterations on the signaling p...	2009
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "crystal structure", "condensed matter physics", "crystals", "materials science", "protein structure", "crystallography", "materials by structure", "lipids", "computer and information sciences", "solid state physics", "protein structure determination", "proteins", "molecular biology", "phy...	Vaccinia Virus Immunomodulator A46: A Lipid and Protein-Binding Scaffold for Sequestering Host TIR-Domain Proteins	journal.ppat.1006079	null	[ [ "Viral infection depends not only on the rate and precision of viral reproduction , but also requires a simultaneously efficient inhibition of host immune responses .", "Viruses have evolved varied strategies to interfere with immune responses of the host , including production of secreted molecules that ...	[ "Vaccinia virus interferes with early events of the activation pathway of the transcriptional factor NF-kB by binding to numerous host TIR-domain containing adaptor proteins .", "We have previously determined the X-ray structure of the A46 C-terminal domain; however , the structure and function of the A46 N-termi...	[ "Viruses possess mechanisms to interfere with the host immune system to enhance their replication .", "Vaccinia virus , the viral vaccine used to eradicate smallpox , synthesizes many such proteins .", "The vaccinia virus protein A46 is one of a series of proteins preventing expression of host proteins that ind...	2016
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[]	Bartonella spp. in Fruit Bats and Blood-Feeding Ectoparasites in Madagascar	journal.pntd.0003532	null	[ [ "The role of bats as reservoirs for viral pathogens—including several responsible for severe human disease—has received increasing attention in recent years [1] .", "The extent to which this pattern is mirrored by bats’ abilities to host and transmit other zoonotic agents , including bacteria , is less wi...	[ "We captured , ectoparasite-combed , and blood-sampled cave-roosting Madagascan fruit bats ( Eidolon dupreanum ) and tree-roosting Madagascan flying foxes ( Pteropus rufus ) in four single-species roosts within a sympatric geographic foraging range for these species in central Madagascar .", "We describe infectio...	[ "Bartonella spp .", "are bacteria that inhabit the red blood cells of both human and animal hosts .", "Among humans , Bartonella spp .", "are known to cause several febrile illnesses , including Carrion’s disease ( Bartonella bacilliformis ) , trench fever ( Bartonella quintana ) , and cat scratch fever ( Bar...	2015
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "transfection", "phosphorylation", "medicine and health sciences", "luciferase", "pathology and laboratory medicine", "hepacivirus", "pathogens", "enzymes", "microbiology", "enzymology", "viruses", "rna viruses", "molecular biology techniques", "research and analysis methods", "proteins"...	Hepatitis E virus persists in the presence of a type III interferon response	journal.ppat.1006417	null	[ [ "The hepatitis E virus ( HEV ) causes significant morbidity and mortality worldwide [1 , 2] .", "Although HEV is known for causing acute hepatitis in developing countries , cases of chronic HEV infection have been reported in recent years in industrialized countries in persons with an immune system compro...	[ "The RIG-I-like RNA helicase ( RLR ) -mediated interferon ( IFN ) response plays a pivotal role in the hepatic antiviral immunity .", "The hepatitis A virus ( HAV ) and the hepatitis C virus ( HCV ) counter this response by encoding a viral protease that cleaves the mitochondria antiviral signaling protein ( MAVS...	[ "HEV infection is a common cause for acute viral hepatitis worldwide .", "Approximately 20 millions of people are infected annually .", "In immunocompetent hosts the infection is self-limited and mostly asymptomatic , but the virus frequently persists when immunity is compromised leading to increased risk for c...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "molecular biology/bioinformatics", "molecular biology/recombination", "microbiology/microbial evolution and genomics" ]	The λ Red Proteins Promote Efficient Recombination between Diverged Sequences: Implications for Bacteriophage Genome Mosaicism	journal.pgen.1000065	null	[ [ "Bacterial viruses ( bacteriophages ) are the most abundant and diverse life form and exhibit high levels of evolvability and adaptability [1] .", "Moreover , bio-informatic studies suggest that they contribute substantially to bacterial genome evolution .", "For example , in γ Proteobacteria , most g...	[ "Genome mosaicism in temperate bacterial viruses ( bacteriophages ) is so great that it obscures their phylogeny at the genome level .", "However , the precise molecular processes underlying this mosaicism are unknown .", "Illegitimate recombination has been proposed , but homeologous recombination could also b...	[ "Temperate bacterial viruses alternate between a dormant state , during which viral DNA remains integrated in the host genome , and a lytic state of phage multiplication .", "Temperate viruses have a characteristic genome organisation known as ‘mosaic’ – they contain ‘foreign’ segments that originate from related...	2008
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "action potentials", "medicine and health sciences", "neural networks", "nervous system", "membrane potential", "social sciences", "electrophysiology", "neuroscience", "animal anatomy", "interneurons", "zoology", "computer and information sciences", "animal cells", "neural pathways", "to...	Mechanisms underlying a thalamocortical transformation during active tactile sensation	journal.pcbi.1005576	null	[ [ "Thalamocortical circuits represent model systems for multi-area computations [1] .", "Sensory information enters the cortex through the thalamus .", "Transformations in thalamocortical circuits have mostly been studied in anesthetized animals with passive sensory stimuli [2–8] or with artificial whis...	[ "During active somatosensation , neural signals expected from movement of the sensors are suppressed in the cortex , whereas information related to touch is enhanced .", "This tactile suppression underlies low-noise encoding of relevant tactile features and the brain’s ability to make fine tactile discriminations...	[ "We study how information is transformed between connected brain areas: the thalamus , the gateway to the cortex , and layer 4 ( L4 ) in cortex , which is the first station to process sensory input from the thalamus .", "When mice perform an active object localization task with their whiskers , thalamic neurons a...	2017
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "community ecology", "population metrics", "ecological metrics", "ecology and environmental sciences", "ecological niches", "species diversity", "ecology", "species delimitation", "community structure", "speciation", "habitats", "biology and life sciences", "population biology", "evolution...	Generalizing clusters of similar species as a signature of coexistence under competition	journal.pcbi.1006688	null	[ [ "Competition is a driving force in nature , and a central question in ecology is how it shapes community structure .", "Species traits mediate their interactions with the environment and each other , and therefore determine how they compete .", "As such , patterns of trait distribution among co-occurr...	[ "Patterns of trait distribution among competing species can potentially reveal the processes that allow them to coexist .", "It has been recently proposed that competition may drive the spontaneous emergence of niches comprising clusters of similar species , in contrast with the dominant paradigm of greater-than-...	[ "Species traits determine how they compete with each other .", "As such , patterns in the distributions of traits in a community of competing species may reveal the processes responsible for coexistence .", "One central idea in theoretical ecology is that the strength of competition relates to similarity in spe...	2019
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "crystal structure", "chemical compounds", "aliphatic amino acids", "condensed matter physics", "vertebrates", "organic compounds", "animals", "xenopus", "germ cells", "animal models", "mutation", "oocytes", "model organisms", "amphibians", "amino acids", "protein structure", "crysta...	Signal Transduction at the Domain Interface of Prokaryotic Pentameric Ligand-Gated Ion Channels	journal.pbio.1002393	Interacting residues at the interface between the extracellular domain and the pore of prokaryotic pentameric ligand-gated ion channels play an important role in the transduction of conformational changes that lead to channel activation.	[ [ "During activation of a pentameric ligand-gated ion channel ( pLGIC ) , the binding of agonists promotes the opening of a selective ion conduction pore at a distance of more than 50 Å away from the binding sites [1 , 2] .", "This process has been described by means of the Monod Weyman Changeux ( MWC ) mec...	[ "Pentameric ligand-gated ion channels are activated by the binding of agonists to a site distant from the ion conduction path .", "These membrane proteins consist of distinct ligand-binding and pore domains that interact via an extended interface .", "Here , we have investigated the role of residues at this int...	[ "The pentameric ligand-gated ion channels constitute a large family of membrane proteins that are expressed in animals and certain bacteria .", "Their molecular architecture and function is conserved throughout the family .", "In mammals , they operate as receptors of the neurotransmitters acetylcholine , serot...	2016
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "microbiology/environmental microbiology", "microbiology/microbial evolution and genomics" ]	The Core and Accessory Genomes of Burkholderia pseudomallei: Implications for Human Melioidosis	journal.ppat.1000178	null	[ [ "Melioidosis is a potentially fatal infectious disease of humans and animals caused by the Gram-negative bacterium Burkholderia pseudomallei ( Bp ) [1] .", "An environmental saphrophyte found in South East Asia , Bp infections in endemic areas may be responsible for up to 20% of deaths due to septicemia [...	[ "Natural isolates of Burkholderia pseudomallei ( Bp ) , the causative agent of melioidosis , can exhibit significant ecological flexibility that is likely reflective of a dynamic genome .", "Using whole-genome Bp microarrays , we examined patterns of gene presence and absence across 94 South East Asian strains is...	[ "Melioidosis is a serious infectious disease of humans caused by Burkholderia pseudomallei , a soil bacterium endemic to many areas in South East Asia .", "Besides humans , B . pseudomallei is also capable of infecting many other species and can be isolated from diverse environmental sources including soil , wate...	2008
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "blood cells", "schistosoma", "invertebrates", "schistosoma mansoni", "medicine and health sciences", "immune cells", "immune physiology", "enzyme-linked immunoassays", "helminths", "spleen", "immunology", "tropical diseases", "parasitic diseases", "animals", "animal models", "model or...	Host regulation of liver fibroproliferative pathology during experimental schistosomiasis via interleukin-4 receptor alpha	journal.pntd.0005861	null	[ [ "Schistosomiasis is a parasitic disease caused by blood-dwelling parasitic flatworms of the genus Schistosoma , mainly , Schistosoma mansoni ( S . mansoni ) , S . japonicum and S . haematobium that are infective to humans and the most clinically relevant [1] .", "Schistosomiasis is estimated to affect mor...	[ "Interleukin-4 receptor ( IL-4Rα ) is critical for the initiation of type-2 immune responses and implicated in the pathogenesis of experimental schistosomiasis .", "IL-4Rα mediated type-2 responses are critical for the control of pathology during acute schistosomiasis .", "However , type-2 responses tightly ass...	[ "Liver fibroproliferative diseases drive a considerable fraction of the overall human mortality .", "This is closely linked to the absence of efficient control measures against such diseases .", "Schistosomiasis , a chronic disease that affects humans , preferentially causes liver fibrosis and is responsible fo...	2017
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "infectious diseases", "veterinary diseases", "zoonoses", "medicine and health sciences", "clinical medicine", "drug research and development", "leishmaniasis", "neglected tropical diseases", "biology and life sciences", "pharmacology", "drug discovery", "tropical diseases", "veterinary scie...	Antileishmanial Activity of the Estrogen Receptor Modulator Raloxifene	journal.pntd.0002842	null	[ [ "With an incidence of two million new cases per year , leishmaniasis is endemic in 98 countries and territories , representing an area where more than 350 million people are at risk of acquiring the infection [1] .", "The treatment of leishmaniasis relies mostly on parenteral drugs and involves high costs...	[ "The treatment of leishmaniasis relies mostly on parenteral drugs with potentially serious adverse effects .", "Additionally , parasite resistance in the treatment of leishmaniasis has been demonstrated for the majority of drugs available , making the search for more effective and less toxic drugs and treatment r...	[ "Cutaneous and visceral leishmaniasis are part of the group we call neglected diseases .", "They are serious conditions that afflict millions in vast regions of the world .", "These diseases are very difficult to treat .", "This is due to the scanty choice of effective drugs together with their potentially se...	2014
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "invertebrates", "medicine and health sciences", "engineering and technology", "cancer treatment", "clinical oncology", "tropical diseases", "parasitic diseases", "animals", "health care", "oncology", "control engineering", "clinical medicine", "gastropods", "pharmaceutics", "neglected t...	Global Assessment of Schistosomiasis Control Over the Past Century Shows Targeting the Snail Intermediate Host Works Best	journal.pntd.0004794	null	[ [ "Can we do better at controlling schistosomiasis ?", "Despite effective drug treatment options and large-scale drug distribution programs , most endemic areas have not yet achieved satisfactory schistosomiasis control .", "Today , schistosomiasis remains prevalent in Africa , Asia , and South America ...	[ "Despite control efforts , human schistosomiasis remains prevalent throughout Africa , Asia , and South America .", "The global schistosomiasis burden has changed little since the new anthelmintic drug , praziquantel , promised widespread control .", "We evaluated large-scale schistosomiasis control attempts ov...	[ "Schistosomiasis is a parasitic disease infecting more than 250 million people worldwide , with almost 800 million at risk .", "Over the past century , nations undertook schistosomiasis control programs , with outcomes varying from little effect to elimination .", "The biggest hope for elimination began about 4...	2016
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "blood cells", "sequencing techniques", "medicine and health sciences", "immune cells", "nucleases", "enzymes", "immunology", "dna-binding proteins", "enzymology", "next-generation sequencing", "mutation", "dna replication", "genome analysis", "dna", "molecular biology techniques", "ex...	Topoisomerases I and III inhibit R-loop formation to prevent unregulated replication in the chromosomal Ter region of Escherichia coli	journal.pgen.1007668	null	[ [ "DNA topoisomerases ( topos ) are nicking-closing enzymes that solve the topological problems inherent to the double-helical structure of the DNA [1] .", "Such problems arise during DNA transactions including replication , transcription and recombination and must be solved in order for these processes to ...	[ "Type 1A topoisomerases ( topos ) are the only ubiquitous topos .", "E . coli has two type 1A topos , topo I ( topA ) and topo III ( topB ) .", "Topo I relaxes negative supercoiling in part to inhibit R-loop formation .", "To grow , topA mutants acquire compensatory mutations , base substitutions in gyrA or g...	[ "DNA topoisomerases are nicking closing enzymes with strand passage activity that solves the topological problems inherent to the double-helical structure of DNA .", "Topos of the type 1A family are the only ubiquitous topos .", "They are classified in two subfamilies , topo I and topo III respectively found in...	2018
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "biotechnology", "medicine and health sciences", "genome evolution", "simulation and modeling", "optimization", "methylation", "mathematics", "algebra", "pacemakers", "epigenetics", "dna", "dna methylation", "chromatin", "polynomials", "research and analysis methods", "genomics", "ch...	A Statistical Framework to Identify Deviation from Time Linearity in Epigenetic Aging	journal.pcbi.1005183	null	[ [ "DNA methylation is an important component of the epigenetic code that defines and maintains the state of cells [1–3] .", "Mammalian cells contain three DNA methyltransferases that preferentially methylate CpG dinucleotides .", "These enzymes faithfully maintain cytosine methylation patterns during ce...	[ "In multiple studies DNA methylation has proven to be an accurate biomarker of age .", "To develop these biomarkers , the methylation of multiple CpG sites is typically linearly combined to predict chronological age .", "By contrast , in this study we apply the Universal PaceMaker ( UPM ) model to investigate c...	[ "DNA methylation is an important component of the epigenetic code that defines and maintains the state of cells .", "Recently , it has been found that certain sites in the genome undergo methylation changes at different rates during aging .", "The seminal work of Steve Horvath found that the methylation of a co...	2016
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "death rates", "reverse transcriptase-polymerase chain reaction", "taxonomy", "invertebrates", "livestock", "sequencing techniques", "medicine and health sciences", "ixodes", "crimean-congo hemorrhagic fever", "tropical diseases", "geographical locations", "animals", "organisms", "phylogen...	Clinical and molecular epidemiology of Crimean-Congo hemorrhagic fever in Oman	journal.pntd.0007100	null	[ [ "Crimean-Congo hemorrhagic fever ( CCHF ) is a serious and often fatal infection caused by the CCHF virus ( CCHFV ) .", "Ixodid ticks , especially Hyalomma spp , act as both reservoirs and vectors .", "This virus has the greatest geographic range of any tick-borne virus and there are reports of viral ...	[ "Crimean-Congo hemorrhagic fever ( CCHF ) is a serious disease with a high fatality rate reported in many countries .", "The first case of CCHF in Oman was detected in 1995 and serosurveys have suggested widespread infection of humans and livestock throughout the country .", "Cases of CCHF reported to the Minis...	[ "Crimean-Congo hemorrhagic fever , an often fatal tick-borne viral disease , has made an impact in the Sultanate of Oman—affecting nationals and expatriates alike—for the past 20 years .", "In this retrospective review of the epidemiology and outcomes of cases in Oman from 1995 to 2017 , we identified 4 sporadic ...	2019
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "infectious diseases/fungal infections", "microbiology/medical microbiology" ]	SREB, a GATA Transcription Factor That Directs Disparate Fates in Blastomyces dermatitidis Including Morphogenesis and Siderophore Biosynthesis	journal.ppat.1000846	null	[ [ "The endemic dimorphic fungi are comprised of seven ascomycetes that include Blastomyces dermatitidis , Histoplasma capsulatum , Coccidioides immitis , Coccidioides posadasii , Paracoccidioides brasiliensis , Sporothrix schenckii , and Penicillium marneffei .", "These fungi possess the unique ability to s...	[ "Blastomyces dermatitidis belongs to a group of human pathogenic fungi that exhibit thermal dimorphism .", "At 22°C , these fungi grow as mold that produce conidia or infectious particles , whereas at 37°C they convert to budding yeast .", "The ability to switch between these forms is essential for virulence in...	[ "The dimorphic fungi are the most common cause of invasive fungal disease worldwide .", "In the soil , these fungi grow as mold that produce infectious spores; when inhaled into the warmer lungs of a mammalian host , the spores convert into yeast , which cause infection .", "The change in shape between mold and...	2010
[ "Introduction", "Models", "Results", "Discussion" ]	[ "medicine and health sciences", "neurochemistry", "nervous system", "astrocytes", "membrane potential", "ions", "electrophysiology", "neuroscience", "macroglial cells", "sodium", "neurotransmitters", "cations", "physical chemistry", "animal cells", "chemistry", "glial cells", "glutam...	Potassium and sodium microdomains in thin astroglial processes: A computational model study	journal.pcbi.1006151	null	[ [ "Astroglia determine the architecture of neural tissue and maintain central nervous system ( CNS ) homeostasis [1–3] .", "Astrocytes are organised into functional syncytia that show anatomical specialisation [4 , 5] , which allow intercellular diffusion of ions , second messengers and metabolites .", ...	[ "A biophysical model that captures molecular homeostatic control of ions at the perisynaptic cradle ( PsC ) is of fundamental importance for understanding the interplay between astroglial and neuronal compartments .", "In this paper , we develop a multi-compartmental mathematical model which proposes a novel mech...	[ "During periods of neuronal activity , ionic homeostasis in the surrounding extracellular space ( ECS ) is disturbed .", "To provide a healthy environment for continued neuronal function , excess ions such as potassium must be buffered away from the ECS; a vital supportive role provided by astrocyte cells .", "...	2018
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "sequencing techniques", "cellular stress responses", "anaphase", "gene regulation", "cell cycle and cell division", "cell processes", "cloning", "dna damage", "mitosis", "molecular biology techniques", "dna", "rna sequencing", "research and analysis methods", "small interfering rnas", "...	Spontaneously slow-cycling subpopulations of human cells originate from activation of stress-response pathways	journal.pbio.3000178	Single-cell time-lapse imaging and transcriptomic analysis reveal why some human cells proliferate more slowly than the majority of the population, with cellular stress responses triggering entry into a slow-cycling state to promote cellular survival in unpredictable environments.	[ [ "From an evolutionary perspective , individuals that give rise to the highest number of progeny are considered to be the fittest .", "However , proliferation rate is often highly variable , even in a genetically identical population in optimal growth conditions .", "This heterogeneity is marked by the...	[ "Slow-cycling subpopulations exist in bacteria , yeast , and mammalian systems .", "In the case of cancer , slow-cycling subpopulations have been proposed to give rise to drug resistance .", "However , the origin of slow-cycling human cells is poorly studied , in large part due to lack of markers to identify th...	[ "Even within a genetically identical population , some cells proliferate more slowly than others .", "Slow-cycling cells have been implicated in resistance to antibiotics , antifungals , and cancer therapies , yet the origin of the slow-cycling state remains poorly understood .", "Here , we isolate a naturally ...	2019
[ "Introduction", "Population and methods", "Results", "Discussion", "Conclusion" ]	[ "neonatology", "children", "medicine and health sciences", "milk", "breast milk", "body fluids", "maternal health", "liquid chromatography", "tropical diseases", "diet", "parasitic diseases", "pediatrics", "age groups", "nutrition", "women's health", "infants", "neglected tropical di...	Negligible exposure to nifurtimox through breast milk during maternal treatment for Chagas Disease	journal.pntd.0007647	null	[ [ "Chagas disease ( CD ) or American trypanosomiasis , is a parasitic zoonosis caused by infection with Trypanosome cruzi of worldwide distribution , endemic to the Americas , predominantly affecting the poor and medically underserved [1 , 2 , 3] .", "Most CD patients are asymptomatic during the acute phase...	[ "Treatment with nifurtimox ( NF ) for Chagas disease is discouraged during breast-feeding because no information on NF transfer into breast milk is available .", "NF is safe and effective for paediatric and adult Chagas disease .", "We evaluated the degree of NF transfer into breast milk in lactating women with...	[ "It is not known whether Nifurtimox , a drug for Chagas disease , is significantly transferred into breast milk , and no clinical trials were conducted to evaluate this topic .", "Treatment with nifurtimox is safe and effective in children and newborns with Chagas disease .", "Treatment of young women before pr...	2019
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "medicine and health sciences", "microbial mutation", "immune physiology", "pathology and laboratory medicine", "pathogens", "immunology", "microbiology", "cloning", "retroviruses", "viruses", "immunodeficiency viruses", "mutation", "substitution mutation", "rna viruses", "molecular biol...	Diverse pathways of escape from all well-characterized VRC01-class broadly neutralizing HIV-1 antibodies	journal.ppat.1007238	null	[ [ "A large number of potent broadly neutralizing antibodies ( bNAbs ) have been generated from HIV-1-infected individuals ( reviewed in [1–5] ) .", "Many of these bNAbs , including 2F5 , 4E10 , PGT121 , VRC01 , 3BNC117 and 10–1074 , have been or will be evaluated in clinical trials [6–12] .", "A number ...	[ "Many broadly neutralizing antibodies ( bNAbs ) against human immunodeficiency virus type 1 ( HIV-1 ) were shown effective in animal models , and are currently evaluated in clinical trials .", "However , use of these antibodies in humans is hampered by the rapid emergence of resistant viruses .", "Here we show ...	[ "Several potent antibodies against human immunodeficiency virus type 1 ( HIV-1 ) have been evaluated in clinical trials .", "Use of these antibodies in humans , however , is problematic , because easy viral escape remains a major concern .", "To gain greater insights , we sought to develop an approach to rapidl...	2018
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "medicine", "infectious diseases", "public health and epidemiology", "epidemiology", "global health", "neglected tropical diseases", "infectious disease control", "infectious disease modeling", "public health" ]	Optimal Lead Time for Dengue Forecast	journal.pntd.0001848	null	[ [ "This study aims to identify the optimal timing for issuing a dengue early warning that will allow sufficient time for the local authority in Singapore to execute preventive measures to mitigate the potential risks .", "Our objectives are to", "1 ) establish links between the estimated forecast lead t...	[ "A dengue early warning system aims to prevent a dengue outbreak by providing an accurate prediction of a rise in dengue cases and sufficient time to allow timely decisions and preventive measures to be taken by local authorities .", "This study seeks to identify the optimal lead time for warning of dengue cases ...	[ "A dengue early warning system that would provide an accurate forecast could enhance the effectiveness of dengue control , but only if it is given in sufficient time for local authorities to implement those control operations .", "In this study , we have suggested the optimal timing for issuing a warning of a den...	2012
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "biotechnology", "medicine and health sciences", "chemical compounds", "pneumococcus", "pathology and laboratory medicine", "small molecules", "pathogens", "metabolic networks", "microbiology", "organic compounds", "pseudomonas aeruginosa", "network analysis", "genome analysis", "pharmacol...	Managing uncertainty in metabolic network structure and improving predictions using EnsembleFBA	journal.pcbi.1005413	null	[ [ "Metabolism is the driving force behind the wondrous flurry of biological activity carpeting our planet .", "An organism’s metabolism is determined by the metabolic enzymes encoded in its genome , the chemical reactions catalyzed by those enzymes , and whether or not those enzymes are actively expressed [...	[ "Genome-scale metabolic network reconstructions ( GENREs ) are repositories of knowledge about the metabolic processes that occur in an organism .", "GENREs have been used to discover and interpret metabolic functions , and to engineer novel network structures .", "A major barrier preventing more widespread use...	[ "Metabolism is the driving force behind all biological activity .", "Genome-scale metabolic network reconstructions ( GENREs ) are representations of metabolic systems that can be analyzed mathematically to make predictions about how a system will behave , as well as to design systems with new properties .", "G...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Brain Connectivity Dissociates Responsiveness from Drug Exposure during Propofol-Induced Transitions of Consciousness	journal.pcbi.1004669	null	[ [ "Understanding how the human brain reversibly generates and loses consciousness , through complex interactions of neural activity at multiple spatial and temporal scales , is a grand challenge for modern neuroscience .", "Recent theoretical advances have argued that consciousness changes when the balance ...	[ "Accurately measuring the neural correlates of consciousness is a grand challenge for neuroscience .", "Despite theoretical advances , developing reliable brain measures to track the loss of reportable consciousness during sedation is hampered by significant individual variability in susceptibility to anaesthetic...	[ "Though scientific understanding of how brain networks generate consciousness has seen rapid advances in recent years , application of this knowledge to accurately track transitions to unconsciousness during general anaesthesia has proven difficult due to considerable variability in this gradual process across indi...	2016
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "medicine and health sciences", "enzyme-linked immunoassays", "immune physiology", "pathology and laboratory medicine", "immunology", "tropical diseases", "parasitic diseases", "parasitic protozoans", "age groups", "protozoans", "leishmania", "neglected tropical diseases", "antibodies", "i...	Age trends in asymptomatic and symptomatic Leishmania donovani infection in the Indian subcontinent: A review and analysis of data from diagnostic and epidemiological studies	journal.pntd.0006803	null	[ [ "The Indian subcontinent ( ISC ) appears to be on course to reach the target of elimination of visceral leishmaniasis ( VL ) as a public health problem ( less than 1 case/10 , 000 people/year at sub-district level ) in most sub-districts by 2020 [1–3] .", "Once this goal has been achieved , surveillance m...	[ "Age patterns in asymptomatic and symptomatic infection with Leishmania donovani , the causative agent of visceral leishmaniasis ( VL ) in the Indian subcontinent ( ISC ) , are currently poorly understood .", "Age-stratified serology and infection incidence have been used to assess transmission levels of other di...	[ "As the elimination target for visceral leishmaniasis ( VL ) in the Indian subcontinent ( <1 case/10 , 000 people/year ) is approached , there is a growing need for surveillance tools with which to monitor transmission to ensure the target is sustained , especially given the large proportion of infections which are...	2018
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "learning", "acoustics", "vocalization", "linguistics", "linear discriminant analysis", "social sciences", "vertebrates", "neuroscience", "animals", "mammals", "learning and memory", "animal signaling and communication", "cognitive psychology", "animal behavior", "mathematics", "statis...	Crowd vocal learning induces vocal dialects in bats: Playback of conspecifics shapes fundamental frequency usage by pups	journal.pbio.2002556	null	[ [ "Vocal learning , the ability to learn to produce vocalizations by hearing , is essential in human language acquisition , but only a few other mammals appear to possess this capability [1–8] .", "Some indications for the existence of vocal learning in nonhuman animals arise from the observation of group-s...	[ "Vocal learning , the substrate of human language acquisition , has rarely been described in other mammals .", "Often , group-specific vocal dialects in wild populations provide the main evidence for vocal learning .", "While social learning is often the most plausible explanation for these intergroup differenc...	[ "The spontaneous acquisition of speech by human infants is considered a keystone of human language , but the ability to reproduce vocalizations acquired by hearing is not commonly described in other mammals .", "This skill , termed vocal learning , is challenging to study in nonhuman animals since such investigat...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine", "neurological disorders", "neurology", "cerebellar disorders" ]	MicroRNA-277 Modulates the Neurodegeneration Caused by Fragile X Premutation rCGG Repeats	journal.pgen.1002681	null	[ [ "Fragile X syndrome ( FXS ) , the most common form of inherited mental retardation , is caused by expansion of the rCGG trinucleotide repeat in the 5′ untranslated region ( 5′ UTR ) of the fragile X mental retardation 1 ( FMR1 ) gene , which leads to silencing of its transcript and the loss of the encoded fra...	[ "Fragile X-associated tremor/ataxia syndrome ( FXTAS ) , a late-onset neurodegenerative disorder , has been recognized in older male fragile X premutation carriers and is uncoupled from fragile X syndrome .", "Using a Drosophila model of FXTAS , we previously showed that transcribed premutation repeats alone are ...	[ "Fragile X–associated tremor/ataxia syndrome ( FXTAS ) is an adult-onset neurodegenerative disorder , usually affecting males over 50 years of age .", "FXTAS patients are the carriers of fragile X premutation alleles .", "Using a FXTAS Drosophila model , we previously demonstrated that fragile X premutation rCG...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine", "enzymes", "microbiology", "hepatitis", "lipid metabolism", "hepatitis c", "infectious diseases", "lipids", "virulence factors and mechanisms", "proteins", "enzyme regulation", "membranes and sorting", "biology", "viral replication complex", "viral replication", "biochemist...	The Lipid Kinase Phosphatidylinositol-4 Kinase III Alpha Regulates the Phosphorylation Status of Hepatitis C Virus NS5A	journal.ppat.1003359	null	[ [ "Worldwide about 170 million people are chronically infected with hepatitis C virus ( HCV ) , a positive-strand RNA virus belonging to the Flaviviridae family , frequently leading to severe liver disease .", "The viral genome encompasses 9 . 6 kb and encodes mainly for a polyprotein of about 3 , 000 amino...	[ "The lipid kinase phosphatidylinositol 4-kinase III alpha ( PI4KIIIα ) is an essential host factor of hepatitis C virus ( HCV ) replication .", "PI4KIIIα catalyzes the synthesis of phosphatidylinositol 4-phosphate ( PI4P ) accumulating in HCV replicating cells due to enzyme activation resulting from its interacti...	[ "Hepatitis C virus ( HCV ) infections affect about 170 million people worldwide and often result in severe chronic liver disease .", "HCV is a positive-strand RNA virus inducing massive rearrangements of intracellular membranes to generate the sites of genome replication , designated the membranous web .", "The...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "blood cells", "hiv infections", "medicine and health sciences", "immune cells", "pathology and laboratory medicine", "viral transmission and infection", "pathogens", "immunology", "microbiology", "cloning", "neuroscience", "learning and memory", "retroviruses", "viruses", "immunodeficie...	Temporal Dynamics of CD8+ T Cell Effector Responses during Primary HIV Infection	journal.ppat.1005805	null	[ [ "CD8+ T cells play a central role in the control of HIV replication .", "During acute infection the emergence of HIV-specific CD8+ T cells correlates with resolution of peak viremia [1 , 2] , and in the nonhuman primate model experimental depletion of CD8+ T cells prior to infection with simian immunodefi...	[ "The loss of HIV-specific CD8+ T cell cytolytic function is a primary factor underlying progressive HIV infection , but whether HIV-specific CD8+ T cells initially possess cytolytic effector capacity , and when and why this may be lost during infection , is unclear .", "Here , we assessed CD8+ T cell functional e...	[ "Previous studies have demonstrated that HIV-specific CD8+ T cells are critical for the initial control of HIV infection .", "However , this control is typically incomplete , being able to neither clear infection nor maintain plasma viremia below undetectable levels .", "Mounting evidence has implicated CD8+ T ...	2016
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "blood cells", "flow cytometry", "medicine and health sciences", "immune physiology", "immune cells", "viral transmission and infection", "immunology", "cell processes", "microbiology", "viral structure", "fluorophotometry", "antibodies", "research and analysis methods", "immune system pro...	Asymmetric antiviral effects of ebolavirus antibodies targeting glycoprotein stem and glycan cap	journal.ppat.1007204	null	[ [ "Filoviruses are enveloped , filamentous-like viruses with non-segmented RNA genome of negative polarity .", "The Ebolavirus genus of the Filoviridae family includes five species: Ebola ( EBOV ) , Sudan ( SUDV ) , Bundibugyo ( BDBV ) , Taï Forest ( TAFV ) and Reston ( RESTV ) viruses .", "Most of thes...	[ "Recent studies suggest that some monoclonal antibodies ( mAbs ) specific for ebolavirus glycoprotein ( GP ) can protect experimental animals against infections .", "Most mAbs isolated from ebolavirus survivors appeared to target the glycan cap or the stalk region of the viral GP , which is the envelope protein a...	[ "Recent progress in isolation of mAbs from survivors of filovirus infections suggests that the human adaptive immune system is capable of producing strong antibody responses .", "However , the effects of mAbs with different epitope specificity on individual steps of filovirus infection are still unclear .", "We...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "molecular cell biology", "genetics", "biology", "model organisms" ]	Budding Yeast Greatwall and Endosulfines Control Activity and Spatial Regulation of PP2ACdc55 for Timely Mitotic Progression	journal.pgen.1003575	null	[ [ "Entry into mitosis in eukaryotic cells is driven by cyclin-dependent kinases ( CDKs ) bound to B-type cyclins .", "Many targets of cyclinB/CDKs have been identified in different organisms and include proteins involved in mitotic spindle formation/elongation , nuclear envelope breakdown , chromosome conde...	[ "Entry into mitosis is triggered by cyclinB/Cdk1 , whose activity is abruptly raised by a positive feedback loop .", "The Greatwall kinase phosphorylates proteins of the endosulfine family and allows them to bind and inhibit the main Cdk1-counteracting PP2A-B55 phosphatase , thereby promoting mitotic entry .", ...	[ "In all eukaryotic cells chromosome partition during mitosis requires a number of processes , including the formation of the mitotic spindle , i . e . the machinery that drives chromosome segregation to the daughter cells .", "Mitotic entry requires a delicate balance between protein phosphorylation , driven by c...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "blood cells", "medicine and health sciences", "immune cells", "pathology and laboratory medicine", "evolutionary biology", "gene regulation", "pathogens", "endothelial cells", "focal adhesions", "population genetics", "microbiology", "immunology", "gene pool", "epithelial cells", "devel...	Endothelial Cells Use a Formin-Dependent Phagocytosis-Like Process to Internalize the Bacterium Listeria monocytogenes	journal.ppat.1005603	null	[ [ "Vascular endothelial cells prevent free movement of material from the bloodstream into underlying tissues by tight regulation of cellular internalization pathways and robust cell-cell junctions .", "Nonetheless , in a process termed “angiophagy” , endothelial cells lining small-diameter capillaries in th...	[ "Vascular endothelial cells act as gatekeepers that protect underlying tissue from blood-borne toxins and pathogens .", "Nevertheless , endothelial cells are able to internalize large fibrin clots and apoptotic debris from the bloodstream , although the precise mechanism of such phagocytosis-like uptake is unknow...	[ "Vascular endothelial cells , which line the lumen of blood vessels , are conventionally viewed as a restrictive barrier that protects underlying tissue from blood-borne toxins and pathogens .", "Nonetheless , even highly restrictive endothelial cells can internalize micron-sized objects , such as blood clots , r...	2016
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "plant anatomy", "chemical compounds", "plant growth and development", "ethylene signaling cascade", "ethylene", "plant embryo anatomy", "brassica", "organic compounds", "hormones", "developmental biology", "plant science", "model organisms", "plant hormones", "experimental organism system...	Triplin, a small molecule, reveals copper ion transport in ethylene signaling from ATX1 to RAN1	journal.pgen.1006703	null	[ [ "The phytohormone ethylene ( C2H4 ) plays important roles in plant growth and development .", "When exposed to ethylene gas for 3 days , dark-grown Arabidopsis seedling shows a typical triple response phenotype including a short hypocotyl and root , larger diameter hypocotyl , and an exaggerated apical ho...	[ "Copper ions play an important role in ethylene receptor biogenesis and proper function .", "The copper transporter RESPONSIVE-TO-ANTAGONIST1 ( RAN1 ) is essential for copper ion transport in Arabidopsis thaliana .", "However it is still unclear how copper ions are delivered to RAN1 and how copper ions affect e...	[ "Copper ions are cofactors of protein functions , and their disorder is closely related to many human diseases which drive to develop new copper chelator related drugs .", "In plants , copper ions are essential for ethylene receptors , but many details are unclear .", "Researchers need novel specific copper che...	2017
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "typhus", "medicine and health sciences", "liver", "immunology", "tropical diseases", "microbiology", "lungs", "bacterial diseases", "histology", "respiratory system", "immunochemistry", "emerging infectious diseases", "population modeling", "neglected tropical diseases", "animal models ...	A Hematogenously Disseminated Orientia tsutsugamsushi-Infected Murine Model of Scrub Typhus	journal.pntd.0002966	null	[ [ "Orientia tsutsugamushi , a gram-negative obligately intracellular coccobacillus , is the etiologic agent of scrub typhus [1] .", "Scrub typhus is a serious public health problem in Asia , northern Australia , and islands of the western Pacific and Indian Oceans including Korea , Japan , China , Taiwan , ...	[ "Orientia tsutsugamushi , the etiologic agent of scrub typhus , is a mite-borne rickettsia transmitted by the parasitic larval stage of trombiculid mites .", "Approximately one-third of the world's population is at risk of infection with Orientia tsutsugamushi , emphasizing its importance in global health .", "...	[ "Scrub typhus is a disease found in Southeast Asia that infects over 1 million people each year .", "This disease is caused by the intracellular pathogen Orientia tsutsugamushi transmitted by the bite of chigger mites .", "Scrub typhus is characterized by pulmonary disease and in severe cases , multiorgan syste...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "virology", "biology", "microbiology" ]	Super-Resolution Microscopy Reveals Specific Recruitment of HIV-1 Envelope Proteins to Viral Assembly Sites Dependent on the Envelope C-Terminal Tail	journal.ppat.1003198	null	[ [ "Human immunodeficiency virus type 1 ( HIV-1 ) acquires its lipid envelope by budding through the plasma membrane of an infected cell .", "Virus morphogenesis is directed by the viral Gag polyprotein , which is sufficient for release of virus-like particles , and also facilitates the incorporation of the ...	[ "The inner structural Gag proteins and the envelope ( Env ) glycoproteins of human immunodeficiency virus ( HIV-1 ) traffic independently to the plasma membrane , where they assemble the nascent virion .", "HIV-1 carries a relatively low number of glycoproteins in its membrane , and the mechanism of Env recruitme...	[ "Newly formed HIV-1 particles assemble at the plasma membrane of virus producing cells .", "The inner structural protein Gag and the envelope glycoprotein Env , which are both essential components of infectious virus particles , traffic to the membrane via different pathways .", "Attached to the inner side of t...	2013
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "infectious diseases/viral infections", "virology/viruses and cancer", "oncology/hematological malignancies", "microbiology/cellular microbiology and pathogenesis" ]	Epstein-Barr Virus Nuclear Antigen 3C Facilitates G1-S Transition by Stabilizing and Enhancing the Function of Cyclin D1	journal.ppat.1001275	null	[ [ "Epstein–Barr virus ( EBV ) is a B-lymphotropic human herpes virus that persists indefinitely in latently infected B-cells .", "EBV infection occurs early in life for most people and is associated with a broad spectrum of benign and malignant diseases including Burkitt's lymphoma ( BL ) , nasopharyngeal c...	[ "EBNA3C , one of the Epstein-Barr virus ( EBV ) -encoded latent antigens , is essential for primary B-cell transformation .", "Cyclin D1 , a key regulator of G1 to S phase progression , is tightly associated and aberrantly expressed in numerous human cancers .", "Previously , EBNA3C was shown to bind to Cyclin ...	[ "Epstein-Barr virus ( EBV ) , a ubiquitous human herpesvirus , is linked to the development of multiple cancers , including lymphomas and epithelial carcinomas .", "EBNA3C , one of its essential latent antigens encoded by EBV , is expressed in EBV-associated lymphomas and contributes to aberrant cell growth after...	2011
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biochemistry", "cell biology", "nucleic acids", "biology and life sciences", "dna", "dna recombination", "molecular cell biology" ]	Branch Migration Prevents DNA Loss during Double-Strand Break Repair	journal.pgen.1004485	null	[ [ "Homologous recombination ( HR ) is a mechanism of DNA double-strand break repair ( DSBR ) that is conserved from bacteria to humans [1] .", "It involves resection of the broken DNA ends to generate single-stranded DNA overhangs , coated in a recombinase , which search the genome for homologous sequences ...	[ "The repair of DNA double-strand breaks must be accurate to avoid genomic rearrangements that can lead to cell death and disease .", "This can be accomplished by promoting homologous recombination between correctly aligned sister chromosomes .", "Here , using a unique system for generating a site-specific DNA d...	[ "Genetic recombination is critically important for the repair of DNA double-strand breaks and is the only repair mechanism available to the bacterium Escherichia coli .", "Repair requires that the appropriate location on an unbroken sister chromosome is recognised as a repair template , and this can be accomplish...	2014
[ "Introduction", "Results", "Discussion", "Material and methods" ]	[ "flow cytometry", "cell physiology", "chitin", "cell walls", "cryptococcus neoformans", "medicine and health sciences", "cryptococcus", "yeast infections", "pathology and laboratory medicine", "pathogens", "microbiology", "cell formation", "fungi", "materials science", "fungal diseases",...	Titan cells formation in Cryptococcus neoformans is finely tuned by environmental conditions and modulated by positive and negative genetic regulators	journal.ppat.1006982	null	[ [ "The ubiquitous environmental yeast Cryptococcus neoformans is a basidiomycetous yeast that has been estimated to cause over 200 , 000 new cases of meningoencephalitis with greater than 180 , 000 deaths per year worldwide [1] , occurring mostly in immunocompromised individuals with acquired immunodeficiency s...	[ "The pathogenic fungus Cryptococcus neoformans exhibits morphological changes in cell size during lung infection , producing both typical size 5 to 7 μm cells and large titan cells ( > 10 μm and up to 100 μm ) .", "We found and optimized in vitro conditions that produce titan cells in order to identify the ancest...	[ "Cryptococcus neoformans is a yeast that is capable of morphological change upon interaction with the host .", "Particularly , in the lungs of infected mice , a subpopulation of yeast enlarges , producing cells up to 100 μm in cell body diameter–referred to as titan cells .", "Along with their large size , the ...	2018
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "biotechnology", "infectious diseases/helminth infections", "molecular biology", "immunology" ]	Schistosoma mansoni Stomatin Like Protein-2 Is Located in the Tegument and Induces Partial Protection against Challenge Infection	journal.pntd.0000597	null	[ [ "Schistosomiasis is an important parasitic disease , caused by trematode worms of the genus Schistosoma; it affects approximately 200 million of individuals primarily in developing countries and an estimated additional 500 to 600 million are at risk .", "The digenetic blood fluke , Schistosoma mansoni , i...	[ "Schistosomiasis affects more than 200 million individuals worldwide , with a further 650 million living at risk of infection , constituting a severe health problem in developing countries .", "Even though an effective treatment exists , it does not prevent re-infection , and the development of an effective vacci...	[ "Schistosomiasis is a parasitic disease causing serious chronic morbidity in tropical countries .", "Together with the publication of the transcriptome database , a series of new vaccine candidates were proposed based on their functional classification .", "However , the prediction of vaccine candidates from se...	2010
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "innate immune system", "medicine and health sciences", "immune physiology", "cytokines", "pathology and laboratory medicine", "cardiovascular physiology", "pathogens", "immunology", "microbiology", "cancers and neoplasms", "viral structure", "angiogenesis", "viruses", "oncology", "devel...	An APE1 inhibitor reveals critical roles of the redox function of APE1 in KSHV replication and pathogenic phenotypes	journal.ppat.1006289	null	[ [ "Kaposi’s sarcoma-associated herpesvirus ( KSHV ) , also termed human herpesvirus type 8 ( HHV8 ) , is a member of the γ-herpesviridae subfamily .", "This virus has been proven to be the etiological agent of Kaposi’s sarcoma ( KS ) [1] .", "Almost 100% of KS lesions , regardless of their source or cli...	[ "APE1 is a multifunctional protein with a DNA base excision repair function in its C-terminal domain and a redox activity in its N-terminal domain .", "The redox function of APE1 converts certain transcription factors from inactive oxidized to active reduced forms .", "Given that among the APE1-regulated transc...	[ "As a major AIDS-associated malignancy , Kaposi’s sarcoma ( KS ) is caused by Kaposi’s sarcoma-associated herpesvirus ( KSHV ) .", "Currently there is no definitive cure for KS .", "In this study , we identified a cellular protein , namely APE1 , as an effective therapeutic target for blocking KSHV replication ...	2017
[ "Introduction", "Results", "Methods" ]	[]	Evaluating the Performance of Fine-Mapping Strategies at Common Variant GWAS Loci	journal.pgen.1005535	null	[ [ "As a result of linkage disequilibrium ( LD ) , loci identified by common variant genome-wide association analyses are often large and may contain hundreds of variants .", "Characterization of the specific variants driving these signals has clear benefits , most obviously through highlighting the specific...	[ "The growing availability of high-quality genomic annotation has increased the potential for mechanistic insights when the specific variants driving common genome-wide association signals are accurately localized .", "A range of fine-mapping strategies have been advocated , and specific successes reported , but t...	[ "Over the last few years , several approaches for fine-mapping genome-wide association studies ( GWAS ) loci have been proposed and used to localize potential causal variants .", "However , the performance of these types of tests is often poorly characterized .", "In this study , we used extensive simulations t...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "oncology", "medicine", "epigenetic therapy", "gene expression", "genetics", "cancer treatment", "epigenetics", "biology", "dna modification", "molecular cell biology", "chromatin", "dna transcription", "histone modification" ]	Reassembly of Nucleosomes at the MLH1 Promoter Initiates Resilencing Following Decitabine Exposure	journal.pgen.1003636	null	[ [ "The DNA hypomethylating agents decitabine ( 5-aza-2′deoxycytidine ) and azacitidine ( 5-azacytidine ) are established therapies for myeloid malignancies and show promise in treating solid tumors [1] .", "These drugs are cytidine analogs that covalently trap the DNA methyltransferase I ( DNMT1 [NP_0011242...	[ "Hypomethylating agents reactivate tumor suppressor genes that are epigenetically silenced in cancer .", "Inevitably these genes are resilenced , leading to drug resistance .", "Using the MLH1 tumor suppressor gene as a model , we showed that decitabine-induced re-expression was dependent upon demethylation and...	[ "Hypomethylating agents are emerging as effective cancer therapies .", "However , their therapeutic effects are transient and drug resistance inevitably develops .", "While resistance is associated with resilencing of genes initially demethylated by the drug , the mechanism underlying this resilencing is unknow...	2013
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "death rates", "organismal evolution", "cell division analysis", "cell cycle and cell division", "cell processes", "developmental biology", "bioassays and physiological analysis", "population biology", "fecundity", "research and analysis methods", "cell analysis", "life cycles", "population ...	Fragmentation modes and the evolution of life cycles	journal.pcbi.1005860	null	[ [ "A requirement for evolution—and a defining feature of life—is reproduction [1–4] .", "Perhaps the simplest mode of reproduction is binary fission in unicellular bacteria , whereby a single cell divides and produces two offspring cells .", "In more complex organisms , such as colonial bacteria , repro...	[ "Reproduction is a defining feature of living systems .", "To reproduce , aggregates of biological units ( e . g . , multicellular organisms or colonial bacteria ) must fragment into smaller parts .", "Fragmentation modes in nature range from binary fission in bacteria to collective-level fragmentation and the ...	[ "Mode of reproduction is a defining trait of all organisms , including colonial bacteria and multicellular organisms .", "To produce offspring , aggregates must fragment by splitting into two or more groups .", "The particular way that a given group fragments defines the life cycle of the organism .", "For in...	2017
[ "Introduction", "Materials and methods", "Discussion" ]	[ "medicine and health sciences", "oxygen", "integrative physiology", "simulation and modeling", "oxygen metabolism", "systems science", "mathematics", "physiological parameters", "near-infrared spectroscopy", "research and analysis methods", "computer and information sciences", "spectrum analys...	A Bayesian framework for the analysis of systems biology models of the brain	journal.pcbi.1006631	null	[ [ "Systems biology models are used to understand complex biological and physiological systems comprised of large numbers of individual elements that give rise to emergent behaviours .", "These complex systems are dependent on both the properties of the whole network and on the individual elements [1] .", ...	[ "Systems biology models are used to understand complex biological and physiological systems .", "Interpretation of these models is an important part of developing this understanding .", "These models are often fit to experimental data in order to understand how the system has produced various phenomena or behav...	[ "Systems biology models are mathematical representations of biological processes that reproduce the overall behaviour of a biological system .", "They are comprised by a number of parameters representing biological information .", "We use them to understand the behaviour of biological systems , such as the brai...	2019
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "virology/viral replication and gene regulation", "virology/virus evolution and symbiosis", "virology/animal models of infection", "virology/emerging viral diseases", "virology", "virology/viruses and cancer", "virology/effects of virus infection on host gene expression" ]	The Canine Papillomavirus and Gamma HPV E7 Proteins Use an Alternative Domain to Bind and Destabilize the Retinoblastoma Protein	journal.ppat.1001089	null	[ [ "Human papillomaviruses ( HPVs ) mediate the initiation and maintenance of cervical cancer [1] , [2] .", "Based upon DNA sequence homology , there are more than 150 different HPV genotypes , 40 of which infect anogenital and oral mucosa [3] .", "In addition to genotyping , HPVs can also be classified ...	[ "The high-risk HPV E6 and E7 proteins cooperate to immortalize primary human cervical cells and the E7 protein can independently transform fibroblasts in vitro , primarily due to its ability to associate with and degrade the retinoblastoma tumor suppressor protein , pRb .", "The binding of E7 to pRb is mediated b...	[ "Human papillomaviruses ( HPVs ) are estimated to cause the most common sexually transmitted infection in the world , and these infections are recognized as the major cause of cervical cancer .", "One of the papillomavirus oncoproteins , E7 , plays a major role in both the viral life cycle and progression to canc...	2010
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "cellular stress responses", "cell biology", "gene expression", "genetics", "cellular types", "biology and life sciences", "cell processes", "molecular cell biology" ]	De-Differentiation Confers Multidrug Resistance Via Noncanonical PERK-Nrf2 Signaling	journal.pbio.1001945	Upregulation of PERK-Nrf2 signaling is a key mechanism by which de-differentiated cancer cells gain multi-drug resistance.	[ [ "Multidrug resistance ( MDR ) is the primary obstacle to treating malignant tumors [1] .", "Cancer cells develop MDR by overexpressing antioxidant enzymes that neutralize the reactive oxygen species ( ROS ) required for chemotherapy toxicity or by up-regulating drug efflux pumps [2] , [3] .", "In many...	[ "Malignant carcinomas that recur following therapy are typically de-differentiated and multidrug resistant ( MDR ) .", "De-differentiated cancer cells acquire MDR by up-regulating reactive oxygen species ( ROS ) –scavenging enzymes and drug efflux pumps , but how these genes are up-regulated in response to de-dif...	[ "The development of multidrug resistance is the primary obstacle to treating cancers .", "High-grade tumors that are less differentiated typically respond poorly to therapy and carry a much worse prognosis than well-differentiated low-grade tumors .", "Therapy-resistant cancer cells often overexpress antioxidan...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Photoreceptor Specificity in the Light-Induced and COP1-Mediated Rapid Degradation of the Repressor of Photomorphogenesis SPA2 in Arabidopsis	journal.pgen.1005516	null	[ [ "As sessile organisms plants continuously monitor the ambient light conditions and adjust their growth and development with the aim to optimize growth and—ultimately—seed production in a competitive environment .", "Plants sense the intensity , color , direction and periodicity of light .", "Responses...	[ "The Arabidopsis COP1/SPA E3 ubiquitin ligase is a key negative regulator that represses light signaling in darkness by targeting transcription factors involved in the light response for degradation .", "The COP1/SPA complex consists of COP1 and members of the four-member SPA protein family ( SPA1-SPA4 ) .", "G...	[ "Plants have evolved photoreceptors that initiate a signaling cascade to adjust growth and development to the ambient light environment .", "The CUL4-dependent COP1/SPA E3 ubiquitin ligase is a key negative regulator of light signaling whose function is repressed by light .", "Recent research has identified mec...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genome-wide association studies", "genetic polymorphism", "natural selection", "genome analysis", "genetics", "biology and life sciences", "evolutionary adaptation", "population genetics", "computational biology", "evolutionary biology", "evolutionary processes", "genetic drift", "human gen...	A Population Genetic Signal of Polygenic Adaptation	journal.pgen.1004412	null	[ [ "Population and quantitative genetics were in large part seeded by Fisher's insight [1] that the inheritance and evolution of quantitative characters could be explained by small contributions from many independent Mendelian loci [2] .", "While still theoretically aligned [3] , these two fields have often ...	[ "Adaptation in response to selection on polygenic phenotypes may occur via subtle allele frequencies shifts at many loci .", "Current population genomic techniques are not well posed to identify such signals .", "In the past decade , detailed knowledge about the specific loci underlying polygenic traits has beg...	[ "The process of adaptation is of fundamental importance in evolutionary biology .", "Within the last few decades , genotyping technologies and new statistical methods have given evolutionary biologists the ability to identify individual regions of the genome that are likely to have been important in this process ...	2014
[ "Introduction", "Materials and Methods", "Results", "Discussion", "Data Deposition" ]	[ "invertebrates", "medicine and health sciences", "enzymes", "enzymology", "diet", "animals", "physiological processes", "developmental biology", "nutrition", "insect vectors", "bacteria", "digestive system", "molting", "aedes aegypti", "proteins", "epidemiology", "gene expression", ...	Transcriptome Sequencing Reveals Large-Scale Changes in Axenic Aedes aegypti Larvae	journal.pntd.0005273	null	[ [ "Like most animals , mosquitoes host communities of microbes in their digestive tract that consist primarily of bacteria [1–3] .", "Both field and laboratory studies indicate that most of these bacteria are aerobes or facultative anaerobes [3–12] .", "Analysis of 16S rRNA gene amplicons of select spec...	[ "Mosquitoes host communities of microbes in their digestive tract that consist primarily of bacteria .", "We previously reported that Aedes aegypti larvae colonized by a native community of bacteria and gnotobiotic larvae colonized by only Escherichia coli develop very similarly into adults , whereas axenic larva...	[ "Several mosquito species including Aedes aegypti transmit pathogens as adults that cause disease in humans and other vertebrates .", "It has also long been known that mosquitoes host bacteria in their digestive tract , which are primarily acquired during the larval stage and transstadially transmitted to adults ...	2017
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "acoustics", "medicine and health sciences", "engineering and technology", "ears", "vertebrates", "robots", "animals", "mammals", "echoes", "remote sensing", "robotics", "bioacoustics", "head", "physics", "mechanical engineering", "eukaryota", "anatomy", "bats", "biology and life...	A fully autonomous terrestrial bat-like acoustic robot	journal.pcbi.1006406	null	[ [ "The growing use of autonomous robots emphasizes the need for new sensory approaches to facilitate tasks such as obstacle avoidance , object recognition and path planning .", "One of the most challenging tasks , faced by many robots , is the problem of generating a map of an unknown environment , while si...	[ "Echolocating bats rely on active sound emission ( echolocation ) for mapping novel environments and navigating through them .", "Many theoretical frameworks have been suggested to explain how they do so , but few attempts have been made to build an actual robot that mimics their abilities .", "Here , we presen...	[ "Many animals are able of mapping a new environment even while moving through it for the first time .", "Bats can do this by emitting sound and extracting information from the echoes reflected from objects in their surroundings .", "In this study , we mimicked this ability by developing a robot that emits sound...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "cell biology/cell signaling", "biophysics/theory and simulation", "mathematics/statistics", "biophysics/cell signaling and trafficking structures", "computational biology/systems biology" ]	A Dual Receptor Crosstalk Model of G-Protein-Coupled Signal Transduction	journal.pcbi.1000185	null	[ [ "The G-protein-coupled signal transduction system integrates a wide range of intercellular signals and actuates downstream pathways .", "G-protein-coupled receptors ( GPCRs ) are composed of seven α-helices that span the plasma membrane , an extracellular domain that is activated by an agonist and an intr...	[ "Macrophage cells that are stimulated by two different ligands that bind to G-protein-coupled receptors ( GPCRs ) usually respond as if the stimulus effects are additive , but for a minority of ligand combinations the response is synergistic .", "The G-protein-coupled receptor system integrates signaling cues fro...	[ "The G protein signal transduction system transmits a wide variety of extracellular signals including light , odors , and hormones , to intracellular effectors in diverse cell types in eukaryotes .", "G-protein-coupled receptors are involved in many diseases including inflammation , cardiac dysfunction , and diab...	2008
[ "Introduction", "Results", "Discussion", "Materials and Methods", "Supporting Information" ]	[ "viruses", "infectious diseases", "virology", "immunology", "mus (mouse)", "homo (human)", "mammals" ]	Coronavirus Non-Structural Protein 1 Is a Major Pathogenicity Factor: Implications for the Rational Design of Coronavirus Vaccines	journal.ppat.0030109	null	[ [ "Coronaviruses are vertebrate pathogens mainly associated with respiratory and enteric diseases [1] .", "They can cause severe diseases in livestock animals and lead thereby to high economic losses .", "In humans , coronavirus infections manifest usually as mild respiratory tract disease ( common cold...	[ "Attenuated viral vaccines can be generated by targeting essential pathogenicity factors .", "We report here the rational design of an attenuated recombinant coronavirus vaccine based on a deletion in the coding sequence of the non-structural protein 1 ( nsp1 ) .", "In cell culture , nsp1 of mouse hepatitis vir...	[ "Prevention of viral diseases by vaccination aims for controlled induction of protective immune responses against viral pathogens .", "Live viral vaccines consist of attenuated , replication-competent viruses that are believed to be superior in the induction of broad immune responses , including cell-mediated imm...	2007

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