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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", "Materials and methods", "Results", "Discussion" ]	[ "cdna libraries", "rna interference", "gene regulation", "animals", "small nuclear rna", "genome analysis", "forms of dna", "dna libraries", "epigenetics", "dna", "amphioxus", "small interfering rnas", "genomic libraries", "genomics", "antisense rna", "genetic interference", "gene ex...	Functional lability of RNA-dependent RNA polymerases in animals	journal.pgen.1007915	null	[ [ "Small interfering RNAs ( siRNAs ) play a central role in the RNA interference ( RNAi ) response .", "Usually loaded on a protein of the AGO subfamily of the Argonaute family , they recognize specific target RNAs by sequence complementarity and typically trigger their degradation by the AGO protein [1] ."...	[ "RNA interference ( RNAi ) requires RNA-dependent RNA polymerases ( RdRPs ) in many eukaryotes , and RNAi amplification constitutes the only known function for eukaryotic RdRPs .", "Yet in animals , classical model organisms can elicit RNAi without possessing RdRPs , and only nematode RNAi was shown to require Rd...	[ "RNA interference ( RNAi ) is a conserved gene regulation system in eukaryotes .", "In non-animal eukaryotes , it necessitates RNA-dependent RNA polymerases ( “RdRPs” ) .", "Among animals , only nematodes appear to require RdRPs for RNAi .", "Yet additional animal clades have RdRPs and it is assumed that they...	2019
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine", "infectious diseases", "neurological disorders", "neurology", "biology", "neuroscience" ]	Plasmacytoid Dendritic Cells Sequester High Prion Titres at Early Stages of Prion Infection	journal.ppat.1002538	null	[ [ "Transmissible spongiform encephalopathies ( TSE ) or prion diseases are infectious and fatal degenerative disorders of the central nervous system including Creutzfeldt-Jakob disease ( CJD ) in humans , bovine spongiform encephalopathy ( BSE ) in cattle and scrapie in sheep and goats [1] .", "Prions , the...	[ "In most transmissible spongiform encephalopathies prions accumulate in the lymphoreticular system ( LRS ) long before they are detectable in the central nervous system .", "While a considerable body of evidence showed that B lymphocytes and follicular dendritic cells play a major role in prion colonization of ly...	[ "Prions , rogue proteins that cause the fatal brain disease CJD in humans and BSE in cattle are not only found in the brain , but also in other tissues , particularly in lymphoid organs , long before they are detectable in the central nervous system .", "It is of great interest to better characterize how prions c...	2012
[ "Introduction", "Results", "Discussion", "Methods" ]	[]	The Encoding of Decision Difficulty and Movement Time in the Primate Premotor Cortex	journal.pcbi.1004502	null	[ [ "The information about the difficulty of a decision can be very valuable to properly allocate cognitive resources or to develop complex plans .", "Indeed , not only humans but even very simple form of life like honey bees are able to selectively avoid difficult decisions [1] .", "Moreover the degree o...	[ "Estimating the difficulty of a decision is a fundamental process to elaborate complex and adaptive behaviour .", "In this paper , we show that the movement time of behaving monkeys performing a decision-making task is correlated with decision difficulty and that the activity of a population of neurons in ventral...	[ "Understanding how the brain produces complex cognitive functions has been a crucial question since ancient philosophical inquiries .", "The encoding of decision difficulty in the brain is fundamental for complex and adaptive behaviour , and can provide valuable information in uncertain environments where the fut...	2015
[ "Introduction", "Results and Discussion", "Materials and Methods" ]	[ "fungal genetics", "computational biology", "microbiology", "fungi", "agarose gel electrophoresis", "genome analysis", "sequence motif analysis", "gel electrophoresis", "microbial genomics", "research and analysis methods", "sequence analysis", "viral genomics", "mycology", "electrophoreti...	Studies on the Virome of the Entomopathogenic Fungus Beauveria bassiana Reveal Novel dsRNA Elements and Mild Hypervirulence	journal.ppat.1006183	null	[ [ "Beauveria bassiana ( Balsamo ) Vuillemin is an entomopathogenic ascomycete belonging to the family Clavicipitaceae , order Hypocreales .", "It has a wide host range of approximately 750 arthropod species and a widespread geographical distribution .", "B . bassiana isolates have also been recovered fr...	[ "The entomopathogenic fungus Beauveria bassiana has a wide host range and is used as a biocontrol agent against arthropod pests .", "Mycoviruses have been described in phytopathogenic fungi while in entomopathogenic fungi their presence has been reported only rarely .", "Here we show that 21 . 3% of a collectio...	[ "Virus diversity is constantly increasing and the findings often challenge our perceptions of the virosphere , enhance our understanding of the global ecology and evolution of viruses and virus-like elements and offer a range of new tools .", "Here we describe a fungal viral family , provisionally designated as P...	2017
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "biology", "microbiology", "parasitology" ]	Novel Structural Components of the Ventral Disc and Lateral Crest in Giardia intestinalis	journal.pntd.0001442	null	[ [ "Giardia intestinalis is a widespread zoonotic parasitic protist .", "Infection with this parasite results in giardiasis , a common protozoan intestinal disease .", "Both chronic and acute giardiasis contribute to high morbidity rates in developed [1] and developing countries [2] .", "Due to a con...	[ "Giardia intestinalis is a ubiquitous parasitic protist that is the causative agent of giardiasis , one of the most common protozoan diarrheal diseases in the world .", "Giardia trophozoites attach to the intestinal epithelium using a specialized and elaborate microtubule structure , the ventral disc .", "Surro...	[ "Giardia is a unicellular intestinal parasite that infects millions of people worldwide each year .", "Colonization of the small intestine is a critical stage in Giardia infection .", "Giardia colonizes the intestinal wall using a specialized suction cup-like structure , the ventral disc .", "Little is known ...	2011
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "public health", "medicine", "biochemistry", "infectious diseases", "public health and epidemiology", "drug research and development", "drugs and devices", "global health", "neglected tropical diseases", "pharmacology", "biology", "microbiology", "parasitic diseases" ]	Targeting the Wolbachia Cell Division Protein FtsZ as a New Approach for Antifilarial Therapy	journal.pntd.0001411	null	[ [ "Filarial nematode parasites are responsible for a number of devastating diseases in humans and animals .", "These include lymphatic filariasis and onchocerciasis that afflict 150 million people in the tropics and threaten the health of over one billion .", "Unlike other nematodes , the majority of fi...	[ "The use of antibiotics targeting the obligate bacterial endosymbiont Wolbachia of filarial parasites has been validated as an approach for controlling filarial infection in animals and humans .", "Availability of genomic sequences for the Wolbachia ( wBm ) present in the human filarial parasite Brugia malayi has...	[ "Filarial nematode parasites are responsible for a number of devastating diseases in humans and animals .", "These include lymphatic filariasis and onchocerciasis that afflict 150 million people in the tropics and threaten the health of over one billion .", "The parasites possess intracellular bacteria , Wolbac...	2011
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "caenorhabditis", "immunology", "microbiology", "eubacteria" ]	Staphylococcal Biofilm Exopolysaccharide Protects against Caenorhabditis elegans Immune Defenses	journal.ppat.0030057	null	[ [ "Staphylococci are a predominant cause of hospital-acquired infections , particularly those associated with implanted medical devices and catheters .", "The ability of staphylococci , particularly Staphylococcus epidermidis , to form biofilm on biotic and abiotic surfaces appears to be critical for the es...	[ "Staphylococcus epidermidis and Staphylococcus aureus are leading causes of hospital-acquired infections that have become increasingly difficult to treat due to the prevalence of antibiotic resistance in these organisms .", "The ability of staphylococci to produce biofilm is an important virulence mechanism that ...	[ "Biofilm is an agglomeration of microbes bound together by a slimy matrix composed of excreted proteins and polysaccharide polymers .", "Most bacteria in the environment reside in biofilms , as do 80% or more of those causing human infections , according to some estimates .", "During infection , biofilm matrix ...	2007
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "carbohydrate metabolism", "medicine and health sciences", "diabetic endocrinology", "gene regulation", "brown adipose tissue", "glucose metabolism", "hormones", "animal models", "glucose tolerance", "diabetes mellitus", "micrornas", "model organisms", "endocrine disorders", "molecular bio...	MiR-155 Enhances Insulin Sensitivity by Coordinated Regulation of Multiple Genes in Mice	journal.pgen.1006308	null	[ [ "Diabetes is recognized as one of the most important health threats of our time[1–4] .", "However , the major mechanisms underlying the pathogenesis of diabetes remain unclear .", "microRNAs ( miRNAs ) are involved in glucose homeostasis , insulin sensitivity and pancreatic β-cell function , and the p...	[ "miR-155 plays critical roles in numerous physiological and pathological processes , however , its function in the regulation of blood glucose homeostasis and insulin sensitivity and underlying mechanisms remain unknown .", "Here , we reveal that miR-155 levels are downregulated in serum from type 2 diabetes ( T2...	[ "In the present study , we provide evidence for the first time showing that miR-155 is a positive regulator of insulin sensitivity in mice .", "Here , we determine that miR-155 levels are downregulated in serum from type 2 diabetes ( T2D ) patients , and shows a negative correlation with HOMA-IR , suggesting that...	2016
[ "Introduction", "Methods", "Results/Discussion" ]	[ "computational biology/molecular dynamics", "biophysics", "biochemistry/membrane proteins and energy transduction", "biophysics/membrane proteins and energy transduction" ]	Modeling and Dynamics of the Inward-Facing State of a Na+/Cl− Dependent Neurotransmitter Transporter Homologue	journal.pcbi.1000905	null	[ [ "Leucine transporter ( LeuT ) is a bacterial amino acid transporter , homologous to / dependent neurotransmitter transporters of the solute carrier 6 ( SLC6 ) family , which is also known as the neurotransmitter:sodium symporter ( NSS ) family [1]–[3] .", "This family of transporters includes several clin...	[ "The leucine transporter ( LeuT ) has recently commanded exceptional attention due mainly to two distinctions; it provides the only crystal structures available for a protein homologous to the pharmacologically relevant neurotransmitter: sodium symporters ( NSS ) , and , it exhibits a hallmark 5-TM inverted repeat ...	[ "Elucidating the mechanism of active transport across the membrane is relevant not only to the understanding of physiological processes but also to the rational design of drugs that modulate these processes .", "In the cell membrane , specialized proteins known as secondary transporters utilize the energy stored ...	2010
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "medicine and health sciences", "methods and resources", "quantitative trait loci", "sleep", "brain electrophysiology", "electrophysiology", "neuroscience", "physiological processes", "clinical medicine", "metabolites", "brain mapping", "bioassays and physiological analysis", "electroencepha...	A systems genetics resource and analysis of sleep regulation in the mouse	journal.pbio.2005750	null	[ [ "Insufficient or disrupted sleep characterizes the 24 h lifestyle of modern society and represents a serious public health concern , as it is associated with increased risk for , e . g . , obesity , diabetes , and high blood pressure , and impairs cognitive performance , which in turn increases the likelihood...	[ "Sleep is essential for optimal brain functioning and health , but the biological substrates through which sleep delivers these beneficial effects remain largely unknown .", "We used a systems genetics approach in the BXD genetic reference population ( GRP ) of mice and assembled a comprehensive experimental know...	[ "Sleep is essential for optimal brain functioning and health , but the biological substrates through which sleep delivers these beneficial effects remain largely unknown .", "We used a systems genetics approach in a large , diverse reference population of mice and assembled a comprehensive experimental knowledge ...	2018
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "cell death", "autophagic cell death", "medicine and health sciences", "microtubules", "pathology and laboratory medicine", "pathogens", "cell processes", "parasitic protozoans", "protozoans", "leishmania", "molecular biology techniques", "tubulins", "cellular structures and organelles", "...	(De)glutamylation and cell death in Leishmania parasites	journal.pntd.0007264	null	[ [ "Microtubules are key components of the eukaryotic cytoskeleton that dynamically assemble from heterodimers of α- and β-tubulin , and whose structure and protein sequence are highly conserved in evolution .", "Microtubules are involved in intracellular transport , organelle positioning , cell shape , mito...	[ "Trypanosomatids are flagellated protozoan parasites that are very unusual in terms of cytoskeleton organization but also in terms of cell death .", "Most of the Trypanosomatid cytoskeleton consists of microtubules , forming different substructures including a subpellicular corset .", "Oddly , the actin network...	[ "Leishmania are unique unicellular organisms in terms of cytoskeleton organization and mechanisms of cell death .", "For example , the major cytoskeletal components of these parasites are microtubules , which form a subpellicular corset .", "In terms of cell death , an apoptotic phenotype has been characterized...	2019
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "luciferase", "gene regulation", "enzymes", "enzymology", "microbiology", "sequence motif analysis", "mammalian genomics", "dna", "microbial genetics", "promoter regions", "research and analysis methods", "sequence analysis", "bioinformatics", "proteins", "gene expression", "oxidoreduc...	Genome-wide analysis of regulatory G-quadruplexes affecting gene expression in human cytomegalovirus	journal.ppat.1007334	null	[ [ "Repetitive guanosine-rich ( G-rich ) sequences connected by short stretches of nucleotides in the genome of an organism can fold into a distinct type of tertiary structure known as a G-quadruplex ( G4 ) .", "Four guanine bases connected with each other through Hoogsteen hydrogen bonding form a square pla...	[ "G-quadruplex ( G4 ) , formed by repetitive guanosine-rich sequences , is known to play various key regulatory roles in cells .", "Herpesviruses containing a large double-stranded DNA genome show relatively higher density of G4-forming sequences in their genomes compared to human and mouse .", "However , it rem...	[ "Although a number of G4-forming sequences are predicted in the herpesviral genomes and some G4s are characterized individually , why so many G4s are present in the genome and whether they are all functional are not yet clear .", "Our genome-wide bioinformatic sequence analyses and biophysical stability and struc...	2018
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "infectious diseases/prion diseases" ]	Highly Efficient Protein Misfolding Cyclic Amplification	journal.ppat.1001277	null	[ [ "Protein misfolding cyclic amplification ( PMCA ) 2 provides faithful amplification of mammalian prions in vitro and , since its introduction in 2001 [1] , has become an important tool in prion research .", "To date , PMCA provides the most sensitive approach for detecting miniscule amounts of prion infec...	[ "Protein misfolding cyclic amplification ( PMCA ) provides faithful replication of mammalian prions in vitro and has numerous applications in prion research .", "However , the low efficiency of conversion of PrPC into PrPSc in PMCA limits the applicability of PMCA for many uses including structural studies of inf...	[ "Protein misfolding cyclic amplification ( PMCA ) provides faithful replication of mammalian prions in vitro .", "While PMCA has become an important tool in prion research , its application is limited because of low yield , poor efficiency and , sometimes , stochastic behavior .", "The current study introduces ...	2011
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "molecular cell biology", "rna interference", "gene expression", "biology", "microbiology", "molecular biology", "parasitology" ]	Molecular Characterization of a Tetraspanin from the Human Liver Fluke, Opisthorchis viverrini	journal.pntd.0001939	null	[ [ "The human liver fluke Opisthorchis viverrini has been classified by the World Health Organization's International Agency for Research on Cancer as a Group 1 carcinogen [1] .", "Approximately 10 million people in Southeast Asia are infected with this neglected parasite [2] , and a further 15–20 million ar...	[ "The human liver fluke , Opisthorchis viverrini , is designated as a group 1 carcinogen , and is the major risk factor for cholangiocarcinoma in endemic countries throughout Southeast Asia .", "Proteins in the excretory-secretory products and tegumental surface membranes of the fluke have been proposed to play pi...	[ "Liver fluke infection is a fish borne disease that afflicts millions of residents in Thailand and Laos .", "Infection results from eating undercooked freshwater fish contaminated with larvae of the worm Opisthorchis viverrini .", "Infection can lead to cancer of the bile ducts ( cholangiocarcinoma ) .", "Ind...	2012
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "medicine", "infectious diseases", "neglected tropical diseases", "immunology", "biology", "parasitic diseases", "immunomodulation", "immune response" ]	Local Increase of Arginase Activity in Lesions of Patients with Cutaneous Leishmaniasis in Ethiopia	journal.pntd.0001684	null	[ [ "The leishmaniases are a complex of vector-borne diseases caused by the parasite Leishmania .", "They are neglected tropical diseases , that affect the poorest population and cause major morbidity and mortality , estimated to 2 . 4 million disability-adjusted life-years [1] .", "Currently , these dise...	[ "Cutaneous leishmaniasis is a vector-borne disease that is in Ethiopia mainly caused by the parasite Leishmania aethiopica .", "This neglected tropical disease is common in rural areas and causes serious morbidity .", "Persistent nonhealing cutaneous leishmaniasis has been associated with poor T cell mediated r...	[ "The leishmaniases are a complex of diseases caused by Leishmania parasites .", "Currently , the diseases affect an estimated 12 million people in 88 countries , and approximately 350 million more people are at risk .", "The leishmaniases belong to the most neglected tropical diseases , affecting the poorest po...	2012
[ "Introduction", "Results/Discussion", "Methods" ]	[ "applied mathematics", "synthetic biology", "algorithms", "mathematical computing", "probability distribution", "mathematics", "algebra", "stochastic processes", "biophysics simulations", "biochemistry simulations", "probability density", "regulatory networks", "computing methods", "biolog...	Direct Solution of the Chemical Master Equation Using Quantized Tensor Trains	journal.pcbi.1003359	null	[ [ "In spite of the success of continuous-variable deterministic models in describing many biological phenomena , discrete stochastic models are often necessary to describe biological phenomena inside living cells where random motion of reacting species introduces randomness in both the order and timing of bioch...	[ "The Chemical Master Equation ( CME ) is a cornerstone of stochastic analysis and simulation of models of biochemical reaction networks .", "Yet direct solutions of the CME have remained elusive .", "Although several approaches overcome the infinite dimensional nature of the CME through projections or other mea...	[ "Stochastic models of chemical networks are necessary to quantitatively describe random fluctuations and other probabilistic phenomena within living cells .", "The Chemical Master Equation ( CME ) describes the time evolution of molecular abundance probabilities in these models , and is a basis for many stochasti...	2014
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "chemical bonding", "cell motility", "parasite groups", "actin filaments", "plasmodium", "cell processes", "parasitology", "developmental biology", "apicomplexa", "hydrogen bonding", "physical chemistry", "contractile proteins", "polymer chemistry", "actins", "actin polymerization", "p...	A unique profilin-actin interface is important for malaria parasite motility	journal.ppat.1006412	null	[ [ "Motility of adherent cells is important for both uni- and multicellular organisms .", "In higher eukaryotic cells , motility plays a key role in , for example embryo- and organogenesis [1] , immune responses [2] , and cancer metastasis [3] .", "Cell motility depends on an actin-myosin motor that is l...	[ "Profilin is an actin monomer binding protein that provides ATP-actin for incorporation into actin filaments .", "In contrast to higher eukaryotic cells with their large filamentous actin structures , apicomplexan parasites typically contain only short and highly dynamic microfilaments .", "In apicomplexans , p...	[ "The malaria parasite Plasmodium has two invasive forms that migrate across different tissue barriers , the ookinete and the very rapidly migrating sporozoite .", "Previous work has shown that the motility of these and related parasites ( e . g . Toxoplasma gondii ) depends on a highly dynamic actin cytoskeleton ...	2017
[ "Introduction", "Model and methods", "Results", "Discussion" ]	[ "classical mechanics", "statistics", "random variables", "covariance", "amino acid sequence analysis", "multivariate analysis", "mathematics", "algebra", "damage mechanics", "research and analysis methods", "sequence analysis", "sequence alignment", "bioinformatics", "mathematical and stat...	Revealing evolutionary constraints on proteins through sequence analysis	journal.pcbi.1007010	null	[ [ "Proteins play crucial roles in all cellular processes , acting as enzymes , motors , receptors , regulators , and more .", "The function of a protein is encoded in its amino-acid sequence .", "In evolution , random mutations affect the sequence , while natural selection acts at the level of function ...	[ "Statistical analysis of alignments of large numbers of protein sequences has revealed “sectors” of collectively coevolving amino acids in several protein families .", "Here , we show that selection acting on any functional property of a protein , represented by an additive trait , can give rise to such a sector ...	[ "Proteins play crucial parts in all cellular processes , and their functions are encoded in their amino-acid sequences .", "Recently , statistical analyses of protein sequence alignments have demonstrated the existence of “sectors” of collectively correlated amino acids .", "What is the origin of these sectors ...	2019
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "bacteriology", "microbial mutation", "microbial evolution", "microbial pathogens", "biology", "evolutionary biology", "microbiology", "bacterial evolution", "evolutionary processes", "bacterial pathogens", "host-pathogen interaction", "pathogenesis" ]	Evolution of Salmonella enterica Virulence via Point Mutations in the Fimbrial Adhesin	journal.ppat.1002733	null	[ [ "Salmonella enterica is comprised of six subspecies ( I , II , IIIa , IIIb , IV and VI ) further subdivided into ∼2 , 500 serovars based on the presence of distinct surface antigens ( somatic O , flagellar H and capsular Vi ) .", "The vast majority of Salmonella strains pathogenic to humans belong to subs...	[ "Whereas the majority of pathogenic Salmonella serovars are capable of infecting many different animal species , typically producing a self-limited gastroenteritis , serovars with narrow host-specificity exhibit increased virulence and their infections frequently result in fatal systemic diseases .", "In our stud...	[ "The process of Salmonella host-adaptation is traditionally considered to involve acquisition of novel genetic elements encoding specific virulence factors or loss of genes representing liability for the more pathogenic strains .", "Here , by analysis of the mannose-sensitive fimbrial adhesin FimH , we demonstrat...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods", "Supporting Information" ]	[ "viruses", "homo (human)", "infectious diseases", "virology" ]	Identification of a Novel Polyomavirus from Patients with Acute Respiratory Tract Infections	journal.ppat.0030064	null	[ [ "Viral infections of the respiratory tract are responsible for significant mortality and morbidity worldwide [1] .", "Despite extensive studies in the past decades that have identified a number of etiologic agents , including rhinoviruses , coronaviruses , influenzaviruses , parainfluenzaviruses , respira...	[ "We report the identification of a novel polyomavirus present in respiratory secretions from human patients with symptoms of acute respiratory tract infection .", "The virus was initially detected in a nasopharyngeal aspirate from a 3-year-old child from Australia diagnosed with pneumonia .", "A random library ...	[ "We have identified a novel virus , referred to as WU virus , in the family Polyomaviridae by screening of human respiratory secretions .", "Two human polyomaviruses , BK and JC , were identified in 1971 and infect the majority of humans around the world .", "These two viruses are closely related to each other ...	2007
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "genetics and genomics/genetics of disease", "genetics and genomics/complex traits" ]	Multiple Independent Loci at Chromosome 15q25.1 Affect Smoking Quantity: a Meta-Analysis and Comparison with Lung Cancer and COPD	journal.pgen.1001053	null	[ [ "Smoking is associated with many different diseases .", "Lung cancer is the illness most identified with smoking , and its prevalence over time mirrors per capita tobacco consumption [1] .", "There has been a reduction in smoking in the United States , and a concomitant decline in the incidence of lun...	[ "Recently , genetic association findings for nicotine dependence , smoking behavior , and smoking-related diseases converged to implicate the chromosome 15q25 . 1 region , which includes the CHRNA5-CHRNA3-CHRNB4 cholinergic nicotinic receptor subunit genes .", "In particular , association with the nonsynonymous C...	[ "Nicotine binds to cholinergic nicotinic receptors , which are composed of a variety of subunits .", "Genetic studies for smoking behavior and smoking-related diseases have implicated a genomic region that encodes the alpha5 , alpha3 , and beta4 subunits .", "We examined genetic data across this region for over...	2010
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "cell biology", "developmental biology" ]	The ECM Moves during Primitive Streak Formation—Computation of ECM Versus Cellular Motion	journal.pbio.0060247	Detailed in vivo video microscopy of the motion of cells and connective tissue in the primitive streak of avian embryos undergoing gastrulation reveals that the connective tissue moves in concert with the cells.	[ [ "Well-recognized bilateral , countercurrent , vortical patterns of epiblast cellular movements accompany formation of the amniote primitive streak ( PS ) —the organizing center for gastrulation [1–3] .", "Two recent time-lapse microscopy studies of chicken PS formation have provided the first descriptions...	[ "Galileo described the concept of motion relativity—motion with respect to a reference frame—in 1632 .", "He noted that a person below deck would be unable to discern whether the boat was moving .", "Embryologists , while recognizing that embryonic tissues undergo large-scale deformations , have failed to accou...	[ "Swirling dance-like patterns of cellular motion accompany the formation of a vital embryonic structure in birds and mammals called the primitive streak , which is located where the future vertebral column will form .", "The primitive streak is considered the “organizing center” of the embryo , because during ear...	2008
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Contribution of Large Region Joint Associations to Complex Traits Genetics	journal.pgen.1005103	null	[ [ "It is widely accepted [1 , 2] that a large fraction of the variance of complex traits is explained by common genetic variants , yet a relatively small number have been associated at genome-wide significance and they collectively explain only a minor fraction of the total predicted heritability .", "The d...	[ "A polygenic model of inheritance , whereby hundreds or thousands of weakly associated variants contribute to a trait’s heritability , has been proposed to underlie the genetic architecture of complex traits .", "However , relatively few genetic variants have been positively identified so far and they collectivel...	[ "It is widely accepted that genetics influences a broad range of human traits and diseases , yet only a few genetic variants are known to determine these traits and their impact is modest .", "In this report , we made the hypothesis that combining information from a large number of genetic variants would help bet...	2015
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "urology", "medicine and health sciences", "genetics", "epigenetics", "biology and life sciences", "infertility" ]	Age-Associated Sperm DNA Methylation Alterations: Possible Implications in Offspring Disease Susceptibility	journal.pgen.1004458	null	[ [ "The effects of advanced paternal age have only recently become of interest to the scientific community as a whole .", "This interest has likely arisen as a result of recent studies that suggest an association with increased incidence of diseases and abnormalities in the offspring of older fathers .", ...	[ "Recent evidence demonstrates a role for paternal aging on offspring disease susceptibility .", "It is well established that various neuropsychiatric disorders ( schizophrenia , autism , etc . ) , trinucleotide expansion associated diseases ( myotonic dystrophy , Huntington's , etc . ) and even some forms of canc...	[ "There is a striking trend of delayed parenthood in developed countries due to secular and socioeconomic pressures .", "As a result , physicians commonly consult with concerned patients inquiring about the impact of advanced age on their ability to conceive healthy offspring .", "The concern has more frequently...	2014
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "fluorescence imaging", "invertebrates", "cell death", "medicine and health sciences", "rna interference", "hela cells", "biological cultures", "cell processes", "animals", "animal models", "drosophila melanogaster", "model organisms", "experimental organism systems", "cell cultures", "m...	Drosophila ADCK1 is critical for maintaining mitochondrial structures and functions in the muscle	journal.pgen.1008184	null	[ [ "The ADCK family proteins have common structural signatures of protein serine/threonine or tyrosine kinase and the evolutionarily conserved AarF domain .", "Among the family proteins , ADCK3 ( also known as COQ8A ) is well-known for its functions related to production of coenzyme Q ubiquinone , which is a...	[ "The function of AarF domain-containing kinase 1 ( ADCK1 ) has not been thoroughly revealed .", "Here we identified that ADCK1 utilizes YME1-like 1 ATPase ( YME1L1 ) to control optic atrophy 1 ( OPA1 ) and inner membrane mitochondrial protein ( IMMT ) in regulating mitochondrial dynamics and cristae structure .",...	[ "Mitochondria function as energy producing factories in the cell , and thus the malfunctioning of mitochondria becomes the causes of many diseases .", "Especially in muscles that continuously require a vast amount of energy , dysfunction of mitochondria leads to abnormalities in muscles .", "Mitochondria mainta...	2019
[ "Introduction", "Results/Discussion", "Materials and Methods" ]	[ "sequence analysis", "biochemistry", "virology", "peptide mapping", "biology", "microbiology", "viral replication", "viral structure", "host-pathogen interaction", "proteomics" ]	Mapping the Phosphoproteome of Influenza A and B Viruses by Mass Spectrometry	journal.ppat.1002993	null	[ [ "Influenza viruses cause serious and widespread disease in humans and livestock .", "Influenza A viruses can infect a wide range of birds and mammals , including humans [1] .", "Adaptation of novel influenza A viruses to humans appears to have caused pandemics for much of recorded history , including ...	[ "Protein phosphorylation is a common post-translational modification in eukaryotic cells and has a wide range of functional effects .", "Here , we used mass spectrometry to search for phosphorylated residues in all the proteins of influenza A and B viruses – to the best of our knowledge , the first time such a co...	[ "Eukaryotic cells regulate the function of many of their proteins through the reversible phosphorylation of serine , threonine or tyrosine residues .", "It is known that some influenza virus proteins are phosphorylated , but few sites of phosphorylation have been identified .", "We used mass spectrometry to ide...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "evolutionary biology/evolutionary ecology", "evolutionary biology/evolutionary and comparative genetics", "molecular biology/molecular evolution", "evolutionary biology", "ecology/physiological ecology" ]	The Eyes Have It: Regulatory and Structural Changes Both Underlie Cichlid Visual Pigment Diversity	journal.pbio.1000266	Differential gene expression and coding sequence evolution play complementary roles in the adaptive diversification of cichlid sensory systems.	[ [ "A very large body of literature has been dedicated to the geography , ecology , and genetics of adaptive diversification and speciation [1]–[5] .", "Yet , the proximate mechanisms responsible for diversification have been characterized for only a few traits in a few systems [3] .", "The molecular gen...	[ "A major goal of evolutionary biology is to unravel the molecular genetic mechanisms that underlie functional diversification and adaptation .", "We investigated how changes in gene regulation and coding sequence contribute to sensory diversification in two replicate radiations of cichlid fishes .", "In the cle...	[ "The molecular mechanisms that generate biodiversity remain largely elusive .", "We examined how two of these mechanisms , changes in gene expression and changes in gene coding sequence , have generated an incredibly diverse set of visual systems in rapidly speciating African cichlids .", "We found large differ...	2009
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "immunology/cellular microbiology and pathogenesis", "microbiology/immunity to infections", "immunology/immunity to infections", "immunology/innate immunity", "microbiology/cellular microbiology and pathogenesis" ]	Production of Extracellular Traps against Aspergillus fumigatus In Vitro and in Infected Lung Tissue Is Dependent on Invading Neutrophils and Influenced by Hydrophobin RodA	journal.ppat.1000873	null	[ [ "Aspergillus fumigatus is the most important airborne fungal pathogen causing life-threatening infections in immunocompromised patients .", "Conidia , the asexually produced small fungal spores , are inhaled and reach the lung alveoli , where they are confronted with the first line of defence which is bui...	[ "Aspergillus fumigatus is the most important airborne fungal pathogen causing life-threatening infections in immunocompromised patients .", "Macrophages and neutrophils are known to kill conidia , whereas hyphae are killed mainly by neutrophils .", "Since hyphae are too large to be engulfed , neutrophils posses...	[ "The fungus Aspergillus fumigatus grows on decaying organic matter and produces large numbers of spores , called conidia , which are constantly inhaled by humans .", "This is harmless , because we have a functioning defence system of immune cells called neutrophil granulocytes , but people with too few or non-fun...	2010
[ "Introduction", "Methods", "Results", "Discussion" ]	[]	Assessment and Treatment of Pain during Treatment of Buruli Ulcer	journal.pntd.0004076	null	[ [ "Buruli ulcer ( BU ) is a Neglected Tropical Disease for which the World Health Organization ( WHO ) stressed the need to improve treatment [1] .", "BU remains endemic in areas in West Africa , especially in Benin and Ghana [2 , 3] .", "In Benin , prevalence rates between 5 . 4 and 60 . 7 per 10 . 000...	[ "Buruli ulcer ( BU ) is described as a relatively painless condition; however clinical observations reveal that patients do experience pain during their treatment .", "Knowledge on current pain assessment and treatment in BU is necessary to develop and implement a future guideline on pain management in BU .", "...	[ "Buruli ulcer ( BU ) is considered relatively painless .", "Nevertheless , observations suggested that patients experience pain during wound care dressings .", "This study explored views on pain , along with pain assessment and treatment practices .", "Medical records were reviewed on prescribed pain medicati...	2015
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "phosphorylation", "chemical compounds", "metabolic processes", "carbohydrates", "organic compounds", "glucose", "plasmid construction", "fermentation", "xylose", "fungi", "hypoxia", "dna construction", "molecular biology techniques", "alcohols", "research and analysis methods", "prote...	Rewired cellular signaling coordinates sugar and hypoxic responses for anaerobic xylose fermentation in yeast	journal.pgen.1008037	null	[ [ "Engineering microbes for non-native metabolic capabilities is a major goal in strain engineering .", "Introducing new genes , gene sets , and now complex pathways [1–3] is relatively facile in modern genetics to imbue strains with novel metabolic capacity .", "But producing strains that make sufficie...	[ "Microbes can be metabolically engineered to produce biofuels and biochemicals , but rerouting metabolic flux toward products is a major hurdle without a systems-level understanding of how cellular flux is controlled .", "To understand flux rerouting , we investigated a panel of Saccharomyces cerevisiae strains w...	[ "An important strategy for sustainable energy is microbial production of biofuels from non-food plant material .", "However , many microbes , including yeast , cannot use the xylose comprising ~30% of hemicellulosic sugars , especially under anaerobic conditions .", "Although cells can be engineered with requir...	2019
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biology and life sciences" ]	DNA Topoisomerase 1α Promotes Transcriptional Silencing of Transposable Elements through DNA Methylation and Histone Lysine 9 Dimethylation in Arabidopsis	journal.pgen.1004446	null	[ [ "DNA methylation and histone H3 lysine 9 ( H3K9 ) methylation are two chromatin modifications widely employed by eukaryotes to maintain genome stability [1] , [2] .", "H3K9 methylation and DNA methylation are targeted via small interfering RNAs ( siRNAs ) to repeats and transposable elements ( TEs ) and a...	[ "RNA-directed DNA methylation ( RdDM ) and histone H3 lysine 9 dimethylation ( H3K9me2 ) are related transcriptional silencing mechanisms that target transposable elements ( TEs ) and repeats to maintain genome stability in plants .", "RdDM is mediated by small and long noncoding RNAs produced by the plant-specif...	[ "DNA topoisomerase is an enzyme that releases the torsional stress in DNA generated during DNA replication or transcription .", "Here , we uncovered an unexpected role of DNA topoisomerase 1α ( TOP1α ) in the maintenance of genome stability .", "Eukaryotic genomes are usually littered with transposable elements...	2014
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "heterozygosity", "deletion mutation", "genome evolution", "population genetics", "vertebrates", "animals", "mammals", "mutation", "effective population size", "mammalian genomics", "population biology", "molecular evolution", "comparative genomics", "animal genomics", "elephants", "po...	Excess of genomic defects in a woolly mammoth on Wrangel island	journal.pgen.1006601	null	[ [ "Woolly mammoths ( Mammuthus primigenius ) were among the most populous large herbivores in North America , Siberia , and Beringia during the Pleistocene and early Holocene [1] .", "However warming climates and human predation led to extinction on the mainland roughly 10 , 000 years ago [2] .", "Lone ...	[ "Woolly mammoths ( Mammuthus primigenius ) populated Siberia , Beringia , and North America during the Pleistocene and early Holocene .", "Recent breakthroughs in ancient DNA sequencing have allowed for complete genome sequencing for two specimens of woolly mammoths ( Palkopoulou et al . 2015 ) .", "One mammoth...	[ "We observe an excess of detrimental mutations , consistent with genomic meltdown in woolly mammoths on Wrangel Island just prior to extinction .", "We observe an excess of deletions , an increase in the proportion of deletions affecting gene sequences , and an excess of premature stop codons in response to evolu...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "immune cells", "t cells", "immunology", "biology", "immune response" ]	The Initial Draining Lymph Node Primes the Bulk of the CD8 T Cell Response and Influences Memory T Cell Trafficking after a Systemic Viral Infection	journal.ppat.1003054	null	[ [ "Lymph nodes ( LN ) play a critical role in initiating the adaptive immune response following viral infections .", "For example , intravenous ( i . v . ) vesicular stomatitis virus infection of splenectomized ( SplnX ) mice yields a similar number of virus-specific CD8 T cells as control mice .", "In ...	[ "Lymphocytic choriomeningitis virus ( LCMV ) causes a systemic infection in mice with virus replication occurring in both peripheral tissues and secondary lymphoid organs .", "Because of the rapid systemic dissemination of the virus , the secondary lymphoid organs responsible for the induction of the LCMV-specifi...	[ "CD8 T cells are required for the elimination of infected host cells following an acute virus infection .", "In addition , memory CD8 T cells provide immunity to the host against a secondary infection .", "Much is known about the priming of CD8 T cells towards viruses that induce a localized infection , however...	2012
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "biochemistry", "gene expression", "biology", "molecular cell biology", "molecular biology", "dna transcription", "histone modification" ]	Nuclear Myosin 1c Facilitates the Chromatin Modifications Required to Activate rRNA Gene Transcription and Cell Cycle Progression	journal.pgen.1003397	null	[ [ "Actin and myosin are involved in many nuclear functions in eukaryotic cells , including chromatin remodelling , transcription by all three RNA polymerases , biogenesis of ribonucleoprotein complexes and the repositioning of active gene loci [1]–[4] .", "There is evidence that actin interacts with the lar...	[ "Actin and nuclear myosin 1c ( NM1 ) cooperate in RNA polymerase I ( pol I ) transcription .", "NM1 is also part of a multiprotein assembly , B-WICH , which is involved in transcription .", "This assembly contains the chromatin remodeling complex WICH with its subunits WSTF and SNF2h .", "We report here that ...	[ "Actin and myosin are key regulators of several processes that occur in the cell nucleus .", "In rRNA biogenesis , actin in complex with nuclear myosin 1c ( NM1 ) is involved in several phases of rDNA transcription .", "Further , NM1 interacts with the chromatin remodelling complex WICH , with the subunits WSTF...	2013
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "medicine and health sciences", "body fluids", "diagnostic radiology", "pathology and laboratory medicine", "maternal health", "obstetrics and gynecology", "pathogens", "microbiology", "vertebrates", "animals", "mammals", "magnetic resonance imaging", "primates", "viruses", "animal model...	Highly efficient maternal-fetal Zika virus transmission in pregnant rhesus macaques	journal.ppat.1006378	null	[ [ "Zika Virus ( ZIKV; Flaviviridae , Flavivirus ) is spread by Aedes mosquitoes [1 , 2] and sexual contact [3–9] .", "ZIKV , first detected in the Americas in early 2015 , is now endemic .", "In utero infection with ZIKV circulating in Oceania and the Americas has been associated with increased incidenc...	[ "Infection with Zika virus ( ZIKV ) is associated with human congenital fetal anomalies .", "To model fetal outcomes in nonhuman primates , we administered Asian-lineage ZIKV subcutaneously to four pregnant rhesus macaques .", "While non-pregnant animals in a previous study contemporary with the current report ...	[ "Maternal ZIKV infection in pregnancy is associated with severe fetal anomalies , including microcephaly .", "It has been shown that infection manifests differently in pregnancy than in the non-pregnant state , with prolonged maternal viremia .", "ZIKV is spread by mosquitos and through sexual contact and since...	2017
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "blood cells", "flow cytometry", "leukemias", "medicine and health sciences", "immune cells", "gene regulation", "regulatory proteins", "immunology", "cancers and neoplasms", "dna-binding proteins", "paired box", "cell differentiation", "oncology", "hematologic cancers and related disorder...	Activating PAX gene family paralogs to complement PAX5 leukemia driver mutations	journal.pgen.1007642	null	[ [ "Pre-B acute lymphoblastic leukemia ( ALL ) is a common pediatric malignancy often successfully treated with chemotherapy [1] .", "Unfortunately , chemotherapy is not without side effects , including risk for secondary malignancies and other long-term complications [2] .", "Additionally , adolescents ...	[ "PAX5 , one of nine members of the mammalian paired box ( PAX ) family of transcription factors , plays an important role in B cell development .", "Approximately one-third of individuals with pre-B acute lymphoblastic leukemia ( ALL ) acquire heterozygous inactivating mutations of PAX5 in malignant cells , and h...	[ "Mutations inactivating PAX5 disrupt B cell differentiation and occur frequently in ALL .", "Others have previously shown that restoring PAX5 expression normalizes B cell differentiation and leads to disease remission in a mouse model of ALL .", "We found that exogenous expression of PAX5’s intact and closely r...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine and health sciences", "diagnostic radiology", "pathology and laboratory medicine", "immunology", "tropical diseases", "brain", "parasitic diseases", "microglial cells", "magnetic resonance imaging", "signs and symptoms", "edema", "neuroblasts", "research and analysis methods", "i...	Experimental Cerebral Malaria Spreads along the Rostral Migratory Stream	journal.ppat.1005470	null	[ [ "Malaria remains among the most frequent and fatal infectious diseases worldwide .", "The WHO reported 207 million cases of malaria in 2013 .", "Most of the 584 , 000 estimated deaths related to the disease occurred in children under 5 years of age [1] and were mainly a sequel of cerebral malaria ( CM...	[ "It is poorly understood how progressive brain swelling in experimental cerebral malaria ( ECM ) evolves in space and over time , and whether mechanisms of inflammation or microvascular sequestration/obstruction dominate the underlying pathophysiology .", "We therefore monitored in the Plasmodium berghei ANKA-C57...	[ "Brain swelling is difficult to detect ex vivo and has recently been identified as a strong predictor of death not only in experimental cerebral malaria ( ECM ) , but also in human cerebral malaria .", "As whole-brain in-vivo imaging methods have been widely underutilized in this disease model , little is known a...	2016
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "public and occupational health", "helminth infections", "infectious diseases", "schistosomiasis", "medicine and health sciences", "global health", "neglected tropical diseases", "tropical diseases", "parasitic diseases" ]	Eosinophil Granule Proteins ECP and EPX as Markers for a Potential Early-Stage Inflammatory Lesion in Female Genital Schistosomiasis (FGS)	journal.pntd.0002974	null	[ [ "The poverty associated disease uro-genital schistosomiasis caused by Schistosoma haematobium affects millions of people in the Sub-Saharan region resulting in a substantial morbidity burden ranging from subtle to severe in individuals [1] .", "The main burden of morbidity ascribed to uro-genital schistos...	[ "Genital granulomas induced by Schistosoma haematobium eggs can manifest as different lesion types visible by colposcopy; rubbery papules ( RP ) , homogenous sandy patches ( HSP ) and grainy sandy patches ( GSP ) .", "Pronounced tissue eosinophilia is a candidate marker for active S . haematobium pathology , as v...	[ "The blood-dwelling fluke Schistosoma haematobium produce eggs which can inflict lesions both in the urinary and genital tract .", "Lesions in the female genital tract have been hypothesised to confer higher risk of contraction of HIV and other genital infections .", "These epithelial genital lesions are visibl...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "infectious diseases/viral infections", "immunology/immunity to infections", "virology/new therapies, including antivirals and immunotherapy", "virology/animal models of infection" ]	Lethal Antibody Enhancement of Dengue Disease in Mice Is Prevented by Fc Modification	journal.ppat.1000790	null	[ [ "The four serotypes of dengue virus ( DV ) are mosquito-borne flaviviruses responsible for 50–100 million human infections annually .", "Primary infection in individuals over the age of one year with any DV serotype is usually asymptomatic or results in self-limited dengue fever ( DF ) , but secondary inf...	[ "Immunity to one of the four dengue virus ( DV ) serotypes can increase disease severity in humans upon subsequent infection with another DV serotype .", "Serotype cross-reactive antibodies facilitate DV infection of myeloid cells in vitro by promoting virus entry via Fcγ receptors ( FcγR ) , a process known as a...	[ "Dengue is the most common vector-borne viral disease of humans , with over 3 billion people at risk for infection and 50–100 million infections in tropical and subtropical regions each year .", "Dengue virus ( DV ) causes a spectrum of clinical disease ranging from an acute debilitating , self-limited febrile il...	2010
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "neurobiology of disease and regeneration", "neuroscience", "homeostatic mechanisms", "ion channels", "computational neuroscience", "neurotransmitters", "biophysics simulations", "theoretical biology", "biophysics theory", "biology", "biophysics", "biochemical simulations", "cellular neurosc...	Efficacy of Synaptic Inhibition Depends on Multiple, Dynamically Interacting Mechanisms Implicated in Chloride Homeostasis	journal.pcbi.1002149	null	[ [ "In the central nervous system , fast inhibition is mediated by GABAA and glycine receptor-gated Cl− channels ( GABAAR and GlyR ) .", "Influx of Cl− through these channels produces outward currents that cause hyperpolarization or prevent depolarization caused by concurrent excitatory input ( i . e . shunt...	[ "Chloride homeostasis is a critical determinant of the strength and robustness of inhibition mediated by GABAA receptors ( GABAARs ) .", "The impact of changes in steady state Cl− gradient is relatively straightforward to understand , but how dynamic interplay between Cl− influx , diffusion , extrusion and intera...	[ "Fast synaptic inhibition relies on chloride current to hyperpolarize the neuron or to prevent depolarization caused by concurrent excitatory input .", "Both scenarios necessarily involve chloride flux into the cell and , thus , a change in intracellular chloride concentration .", "The vast majority of models n...	2011
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "meiosis", "cell cycle and cell division", "variant genotypes", "cell processes", "chromatids", "genetic mapping", "dna", "homologous recombination", "chromosome biology", "biochemistry", "cell biology", "nucleic acids", "heredity", "genetics", "biology and life sciences", "dna repair"...	Extensive Recombination of a Yeast Diploid Hybrid through Meiotic Reversion	journal.pgen.1005781	null	[ [ "Genetic diversity relies on diversification of the parental genome information .", "Besides spontaneous and environmentally induced de novo mutations , sexual reproduction is the prominent source of genetic diversity: it reshuffles the genetic information among individuals from a given species , creating...	[ "In somatic cells , recombination between the homologous chromosomes followed by equational segregation leads to loss of heterozygosity events ( LOH ) , allowing the expression of recessive alleles and the production of novel allele combinations that are potentially beneficial upon Darwinian selection .", "Howeve...	[ "The genetic diversity of eukaryotes relies on the diversification of the parental information , mostly occurring by recombination during gamete formation .", "Homologous chromosomes also recombine in somatic cells , though much less frequently .", "Here , we sequenced the genome of S . cerevisiae hybrid diploi...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "microbiology/environmental microbiology", "microbiology/microbial growth and development", "microbiology/microbial evolution and genomics", "microbiology/cellular microbiology and pathogenesis" ]	Burkholderia Type VI Secretion Systems Have Distinct Roles in Eukaryotic and Bacterial Cell Interactions	journal.ppat.1001068	null	[ [ "Bacteria have evolved many mechanisms of defense against competitors and predators in their environment .", "Some of these , such as type III secretion systems ( T3SSs ) and bacteriocins , provide specialized protection against eukaryotic or bacterial cells , respectively [1] , [2] .", "Gene clusters...	[ "Bacteria that live in the environment have evolved pathways specialized to defend against eukaryotic organisms or other bacteria .", "In this manuscript , we systematically examined the role of the five type VI secretion systems ( T6SSs ) of Burkholderia thailandensis ( B . thai ) in eukaryotic and bacterial cel...	[ "Many bacteria encounter both eukaryotic cells and other bacterial species as a part of their lifestyles .", "In order to compete and survive , these bacteria have evolved specialized pathways that target these distinct cell types .", "Type VI secretion systems ( T6SSs ) are bacterial protein export machines po...	2010
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "cell death", "autophagic cell death", "medicine and health sciences", "lysosomes", "pathology and laboratory medicine", "intracellular pathogens", "molecular probe techniques", "gene regulation", "pathogens", "cell processes", "immunoblotting", "microbiology", "neisseria gonorrhoeae", "ep...	Neisseria gonorrhoeae evades autophagic killing by downregulating CD46-cyt1 and remodeling lysosomes	journal.ppat.1007495	null	[ [ "Autophagy is critical for cellular homeostasis [1] .", "Highly conserved from yeast to man , this catabolic process sequesters aging or damaged cytoplasmic contents and organelles in a structure called the autophagosome [2–4] .", "The autophagosome then fuses with the lysosome to form the autophagoly...	[ "The Gram-negative human pathogen N . gonorrhoeae ( Ngo ) quickly attaches to epithelial cells , and large numbers of the bacteria remain on the cell surface for prolonged periods .", "Ngo invades cells but few viable intracellular bacteria are recovered until later stages of infection , leading to the assumption...	[ "Neisseria gonorrhoeae ( Ngo ) , which causes the sexually transmitted disease of gonorrhea , primarily infects the uorgenital epithelium .", "It attaches to the epithelial surface for lengthy periods .", "It also invades epithelial cells , but few viable intracellular bacteria are recovered until later stages ...	2019
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "invertebrates", "medicine and health sciences", "engineering and technology", "helminths", "tropical diseases", "hookworms", "geographical locations", "parasitic diseases", "animals", "cell phones", "neuroscience", "artificial neural networks", "ascaris", "ascaris lumbricoides", "pharma...	Kankanet: An artificial neural network-based object detection smartphone application and mobile microscope as a point-of-care diagnostic aid for soil-transmitted helminthiases	journal.pntd.0007577	null	[ [ "Soil-transmitted helminths ( STH ) such as Ascaris lumbricoides , hookworm , and Trichuris trichiura affect more than a billion people worldwide [1–3] .", "However , due to lack of access to fecal processing materials , diagnostic equipment , and trained personnel for diagnosis , the mainstay of STH cont...	[ "Endemic areas for soil-transmitted helminthiases often lack the tools and trained personnel necessary for point-of-care diagnosis .", "This study pilots the use of smartphone microscopy and an artificial neural network-based ( ANN ) object detection application named Kankanet to address those two needs .", "A ...	[ "For rainforest-enshrouded rural villages of Madagascar , soil-transmitted helminthiases are more the rule than the exception .", "However , the microscopy equipment and lab technicians needed for diagnosis are a distance of several days’ hike away .", "We piloted a solution for these communities by leveraging ...	2019
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "infectious diseases", "rabies", "veterinary diseases", "zoonoses", "medicine and health sciences", "epidemiology", "neglected tropical diseases", "biology and life sciences", "tropical diseases", "veterinary science" ]	Rabies in Nonhuman Primates and Potential for Transmission to Humans: A Literature Review and Examination of Selected French National Data	journal.pntd.0002863	null	[ [ "Among wildlife , nonhuman primates ( NHPs ) are known to harbor a large diversity of zoonotic pathogens and are among the primary mammals targeted for zoonotic disease surveillance [1] .", "They are the principal host and sometimes an important intermediate host of many zoonotic RNA viruses .", "Amon...	[ "The nonhuman primate ( NHP ) -related injuries in rabies-enzootic countries is a public health problem of increasing importance .", "The aims of this work are to collect data concerning rabies transmission from NHPs to humans; to collate medical practices regarding rabies postexposure prophylaxis ( PEP ) in diff...	[ "No international consensus or even a consensus among existing national recommendations about rabies postexposure prophylaxis ( PEP ) following a nonhuman primate ( NHP ) -related injury currently exists .", "Epidemiologic studies and reports collated in this review indicate that the number of rabies case reporte...	2014
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "invertebrates", "metaphase", "cell cycle and cell division", "cell processes", "animals", "invertebrate genomics", "animal models", "developmental biology", "drosophila melanogaster", "model organisms", "experimental organism systems", "embryos", "cellular structures and organelles", "dro...	Differentially-dimensioned furrow formation by zygotic gene expression and the MBT	journal.pgen.1007174	null	[ [ "Furrow ingression is an obligatory step in animal cells during cell division , and is a critical mechanism that underlies the ability of animal cells to divide and provide new cells for tissue homeostasis and development .", "While much of our knowledge of how plasma membrane furrows form and ingress com...	[ "Despite extensive work on the mechanisms that generate plasma membrane furrows , understanding how cells are able to dynamically regulate furrow dimensions is an unresolved question .", "Here , we present an in-depth characterization of furrow behaviors and their regulation in vivo during early Drosophila morpho...	[ "One of the primary events that must occur repeatedly throughout a complex animal’s lifetime is the ingression of a plasma membrane furrow .", "Furrow formation and ingression are requisite elements of cell division , and drive the physical separation of one cell into two cells .", "However , the mechanisms tha...	2018
[ "Introduction", "Methods", "Results", "Discussion" ]	[]	Repurposing Auranofin as a Lead Candidate for Treatment of Lymphatic Filariasis and Onchocerciasis	journal.pntd.0003534	null	[ [ "River blindness and lymphatic filariasis ( LF ) are two major neglected diseases caused by filariid nematodes that , together , affect an estimated 145 million people worldwide in mostly poor , developing countries [1 , 2] .", "River blindness , caused by the filariid nematode Onchocerca volvulus , is a ...	[ "Two major human diseases caused by filariid nematodes are onchocerciasis , or river blindness , and lymphatic filariasis , which can lead to elephantiasis .", "The drugs ivermectin , diethylcarbamazine ( DEC ) , and albendazole are used in control programs for these diseases , but are mainly effective against th...	[ "Onchocerciasis or river blindness , and lymphatic filariasis , which can lead to disfiguring elephantiasis , are two neglected tropical diseases that affect millions of people , primarily in developing countries .", "Both diseases are caused by filariid nematodes; onchocerciasis is caused by Onchocerca volvulus ...	2015
[ "Introduction", "Results", "Discussion" ]	[ "macromolecular assemblies", "protein folding", "protein structure", "biophysics simulations", "physical chemistry", "biophysics theory", "chemistry", "biology", "biophysics", "physics", "biochemistry", "biophysic al simulations", "computational chemistry", "chemical physics", "computati...	The Effect of Macromolecular Crowding, Ionic Strength and Calcium Binding on Calmodulin Dynamics	journal.pcbi.1002114	null	[ [ "Calmodulin ( CaM ) is a highly acidic protein composed of 148 amino acid residues [1] , [2] .", "It has four helix-loop-helix calcium binding motifs commonly named EF-hands ( Figure 1 ) .", "Two EF-hands form a lobe and the two lobes ( termed N and C ) are connected by a helical linker .", "The l...	[ "The flexibility in the structure of calmodulin ( CaM ) allows its binding to over 300 target proteins in the cell .", "To investigate the structure-function relationship of CaM , we combined methods of computer simulation and experiments based on circular dichroism ( CD ) to investigate the structural characteri...	[ "Proteins are workhorses for driving biological functions inside cells .", "Calmodulin ( CaM ) is a protein that can carry cellular signals by triggered conformational changes due to calcium binding that alters target binding .", "Interestingly , CaM is able to bind over 300 targets .", "One of the challenges...	2011
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "medicine", "biology", "veterinary science", "agriculture" ]	The Salivary Secretome of the Tsetse Fly Glossina pallidipes (Diptera: Glossinidae) Infected by Salivary Gland Hypertrophy Virus	journal.pntd.0001371	null	[ [ "Tsetse flies ( Glossina sp . ) are found exclusively in sub-Saharan Africa and are efficient vectors of African trypanosomes , causative agents of sleeping sickness in humans and nagana in domesticated animals [1]–[3] .", "Sleeping sickness is invariably fatal if untreated and , until now , the available...	[ "The competence of the tsetse fly Glossina pallidipes ( Diptera; Glossinidae ) to acquire salivary gland hypertrophy virus ( SGHV ) , to support virus replication and successfully transmit the virus depends on complex interactions between Glossina and SGHV macromolecules .", "Critical requisites to SGHV transmiss...	[ "Tsetse fly ( Diptera; Glossinidae ) transmits two devastating diseases to farmers ( human African Trypanosomiasis; HAT ) and their livestock ( Animal African Trypanosomiasis; AAT ) in 37 sub-Saharan African countries .", "During the rainy seasons , vast areas of fertile , arable land remain uncultivated as farme...	2011
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "computational biology/macromolecular structure analysis", "computational biology/comparative sequence analysis", "computational biology/macromolecular sequence analysis", "evolutionary biology/bioinformatics", "computational biology" ]	A Combinatorial Approach to Detect Coevolved Amino Acid Networks in Protein Families of Variable Divergence	journal.pcbi.1000488	null	[ [ "The function and mechanical properties of a protein demand strong evolutionary pressures along evolution which are directed on the one hand , to conserve residues involved in catalytic sites and in interactions with amino acids of other proteins [1]–[4] , and on the other hand , to mutually conserve residues...	[ "Communication between distant sites often defines the biological role of a protein: amino acid long-range interactions are as important in binding specificity , allosteric regulation and conformational change as residues directly contacting the substrate .", "The maintaining of functional and structural coupling...	[ "Fine analyses of families of protein sequences reveal the existence of networks of coevolved amino acids .", "These networks are clusters of residues often entering in physical contact one with the other , and they relate residues which are located far apart on the three dimensional structure .", "Coevolved re...	2009
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genetics and genomics/microbial evolution and genomics", "infectious diseases/urological infections", "infectious diseases", "genetics and genomics/comparative genomics", "genetics and genomics/functional genomics", "microbiology/microbial evolution and genomics", "genetics and genomics/genome projects...	Host Imprints on Bacterial Genomes—Rapid, Divergent Evolution in Individual Patients	journal.ppat.1001078	null	[ [ "Microbes have adapted many fascinating strategies to co-evolve with their hosts .", "The specific immune response to surface antigens drives the structural changes in influenza virus hemagglutinin and serotype [1] , the antigenic drift in trypanosomes [2] and the immune evasion mechanisms in malaria [3] ...	[ "Bacteria lose or gain genetic material and through selection , new variants become fixed in the population .", "Here we provide the first , genome-wide example of a single bacterial strain's evolution in different deliberately colonized patients and the surprising insight that hosts appear to personalize their m...	[ "Bacterial virulence results from the interaction between bacteria and their hosts .", "This interaction provides selection pressure for bacterial adaptation towards increased fitness or virulence .", "Basic mechanisms involved in bacterial adaptation at the genetic level are point mutations and recombination ....	2010
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Immunostimulatory Defective Viral Genomes from Respiratory Syncytial Virus Promote a Strong Innate Antiviral Response during Infection in Mice and Humans	journal.ppat.1005122	null	[ [ "According to current paradigms , the host immune response to viral infection is initiated upon recognition of molecular motifs generally present as part of the viral genome ( reviewed in [1–3] ) .", "However , most viruses of clinical significance interfere with the host innate immune response allowing t...	[ "Human respiratory syncytial virus ( RSV ) is a major cause of severe respiratory illness in children and susceptible adults .", "RSV blocks the development of the innate antiviral immune response and can grow to high titers in the respiratory tract .", "Here we demonstrate that immunostimulatory defective vira...	[ "Respiratory syncytial virus is a major cause of chronic lung damage , asthma exacerbations , and hospitalizations of infants , elders , and high-risk adults .", "Currently , there is no effective vaccine or treatment available to protect the general population from RSV infection .", "Here , we demonstrate that...	2015
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "blood cells", "medicine and health sciences", "immune cells", "respiratory infections", "molecular probe techniques", "immunology", "marker genes", "parasitic diseases", "parasitic protozoans", "pulmonology", "monomers (chemistry)", "protozoans", "molecular biology techniques", "cellular ...	Aquaglyceroporin-null trypanosomes display glycerol transport defects and respiratory-inhibitor sensitivity	journal.ppat.1006307	null	[ [ "African trypanosomes are parasitic protozoa and the causative agents of human and animal African trypanosomiasis ( HAT and AAT , respectively ) .", "These parasites are typically transmitted by tsetse-flies , which are restricted to sub-Saharan Africa .", "HAT is typically fatal without treatment , c...	[ "Aquaglyceroporins ( AQPs ) transport water and glycerol and play important roles in drug-uptake in pathogenic trypanosomatids .", "For example , AQP2 in the human-infectious African trypanosome , Trypanosoma brucei gambiense , is responsible for melarsoprol and pentamidine-uptake , and melarsoprol treatment-fail...	[ "Protein channels in cell membranes transport specific molecules in and out of cells , and can also facilitate drug-uptake .", "One such protein , known as an aquaglyceroporin ( AQP ) , allows parasitic African trypanosomes , the cause of lethal diseases in humans and livestock , to accumulate an arsenic-based dr...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "bacteriology", "cell motility", "medicine and health sciences", "pathology and laboratory medicine", "gene regulation", "pathogens", "microbiology", "dna transcription", "bacterial sporulation", "regulator genes", "gene types", "microbial physiology", "proteins", "gene expression", "gen...	A Minimal Threshold of c-di-GMP Is Essential for Fruiting Body Formation and Sporulation in Myxococcus xanthus	journal.pgen.1006080	null	[ [ "Bacteria synthesize a variety of nucleotide-based second messengers that have important functions in adaptation and differentiation processes in response to environmental changes .", "Among these bis- ( 3’-5’ ) -cyclic dimeric GMP ( c-di-GMP ) has emerged as ubiquitous and highly versatile .", "Regul...	[ "Generally , the second messenger bis- ( 3’-5’ ) -cyclic dimeric GMP ( c-di-GMP ) regulates the switch between motile and sessile lifestyles in bacteria .", "Here , we show that c-di-GMP is an essential regulator of multicellular development in the social bacterium Myxococcus xanthus .", "In response to starvat...	[ "The nucleotide-based second messenger c-di-GMP is ubiquitous in bacteria and generally regulates the switch between motile and sessile lifestyles .", "We show that c-di-GMP regulates multicellular morphogenesis and cellular differentiation during the starvation-induced developmental program that culminates in fr...	2016
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "public health and epidemiology", "infectious disease epidemiology", "population genetics", "microbiology", "marine biology", "model organisms", "population biology", "veterinary science", "veterinary diseases", "veterinary epidemiology", "veterinary parasitology", "epidemiology", "marine an...	Polyparasitism Is Associated with Increased Disease Severity in Toxoplasma gondii-Infected Marine Sentinel Species	journal.pntd.0001142	null	[ [ "A single individual often plays host to not only one , but to an entire community of parasites [1]–[3] , and this polyparasitism has been identified as a critical factor in determining the virulence of an infection [4]–[6] .", "The study of host-parasite interactions has accordingly come to question the ...	[ "In 1995 , one of the largest outbreaks of human toxoplasmosis occurred in the Pacific Northwest region of North America .", "Genetic typing identified a novel Toxoplasma gondii strain linked to the outbreak , in which a wide spectrum of human disease was observed .", "For this globally-distributed , water-born...	[ "Severity of toxoplasmosis , a water-borne zoonosis , varies widely from chronic and benign to acutely fatal .", "Here , we investigate polyparasitism ( infection with multiple parasite species ) as one factor governing the spectrum of disease in Toxoplasma gondii infections .", "This study utilized wild marine...	2011
[ "Introduction", "Methods", "Results/Discussion" ]	[]	Inflow/Outflow Boundary Conditions for Particle-Based Blood Flow Simulations: Application to Arterial Bifurcations and Trees	journal.pcbi.1004410	null	[ [ "Blood is a biological fluid that delivers nutrients and oxygen to living cells and removes their waste products .", "The two major components of whole blood are red blood cells ( RBCs ) and plasma , i . e . , RBCs constitute approximately 40% of the total blood volume , plasma around 55% , while the rest...	[ "When blood flows through a bifurcation , red blood cells ( RBCs ) travel into side branches at different hematocrit levels , and it is even possible that all RBCs enter into one branch only , leading to a complete separation of plasma and RBCs .", "To quantify this phenomenon via particle-based mesoscopic simula...	[ "Blood tests , which provide a wealth of information on the state of human health , are often performed on cell-free samples .", "Therefore , blood-plasma separation needs to be achieved .", "A simple but effective solution for isolating plasma from blood utilizes capillary bifurcations .", "In a particle-bas...	2015
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "children", "medicine and health sciences", "pathology and laboratory medicine", "education", "sociology", "tropical diseases", "geographical locations", "social sciences", "pediatrics", "bacterial diseases", "age groups", "signs and symptoms", "benin", "neglected tropical diseases", "af...	The paediatric participation scale measuring participation restrictions among former Buruli Ulcer patients under the age of 15 in Ghana and Benin: Development and first validation results	journal.pntd.0007273	null	[ [ "Buruli Ulcer ( BU ) , caused by infection with Mycobacterium ulcerans ( M . ulcerans ) is a neglected tropical disease that has been reported in 33 countries , predominantly tropical and subtropical regions , but is mostly prevalent in sub-Saharan countries [1] .", "In 2016 , almost 80% of all new BU cas...	[ "Buruli Ulcer ( BU ) is a neglected tropical disease caused by Mycobacterium ulcerans .", "Former BU patients may experience participation restrictions due to physical limitations , stigmatization and other social factors .", "A scale that measures participation restrictions among children , who represent almos...	[ "Buruli Ulcer is a neglected tropical disease caused by infection with Mycobacterium ulcerans .", "While treatment has largely improved , former BU patients may experience participation restrictions after treatment , due to physical limitations , stigmatization or other social factors .", "With more than half o...	2019
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biochemistry", "biophysics", "molecular biology" ]	Identification of COUP-TFII Orphan Nuclear Receptor as a Retinoic Acid–Activated Receptor	journal.pbio.0060227	Structural and functional studies reveal that the orphan nuclear receptor COUP-TFII is a low-affinity receptor for retinoic acids. paving the way to finding the endogenous ligands that may ultimately link retinoic acid and COUP-TF signaling pathways.	[ [ "Nuclear receptors ( NRs ) are ligand-inducible transcription factors that transmit physiological signals of a wide variety of ligands , such as classical steroid hormones , retinoic acid , thyroid hormone , and vitamin D [1 , 2] .", "The NR family also includes a large number of orphan receptors for whic...	[ "The chicken ovalbumin upstream promoter-transcription factors ( COUP-TFI and II ) make up the most conserved subfamily of nuclear receptors that play key roles in angiogenesis , neuronal development , organogenesis , cell fate determination , and metabolic homeostasis .", "Although the biological functions of CO...	[ "Unlike other classes of receptors , nuclear receptors can bind directly to DNA and act as transcription factors , playing key roles in embryonic development and cellular metabolism .", "Most nuclear receptors are activated by signal-triggering molecules ( ligands ) and can regulate their activity by recruiting c...	2008
[ "Introduction", "Results", "Materials and methods", "Discussion" ]	[ "taxonomy", "children", "ecology and environmental sciences", "microbiome", "community structure", "statistics", "microbiology", "multivariate analysis", "age groups", "phylogenetics", "data management", "non-coding rna", "mathematics", "infants", "cellular structures and organelles", ...	Modeling the temporal dynamics of the gut microbial community in adults and infants	journal.pcbi.1006960	null	[ [ "There is increasing recognition that the human gut microbiome is a contributor to many aspects of human physiology and health including obesity , non-alcoholic fatty liver disease , inflammatory diseases , cancer , metabolic diseases , aging , and neurodegenerative disorders [1–14] .", "This suggests tha...	[ "Given the highly dynamic and complex nature of the human gut microbial community , the ability to identify and predict time-dependent compositional patterns of microbes is crucial to our understanding of the structure and functions of this ecosystem .", "One factor that could affect such time-dependent patterns ...	[ "The ability to characterize and predict temporal trajectories of the microbial community in the human gut is crucial to our understanding of the structure and functions of this ecosystem .", "In this study we develop MTV-LMM , a method for modeling time-series microbial community data .", "Using MTV-LMM we fin...	2019
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "skin", "medicine and health sciences", "pruritus", "integumentary system", "fijians", "tropical diseases", "geographical locations", "social sciences", "neuroscience", "habits", "ethnicities", "bacterial diseases", "eye diseases", "neglected tropical diseases", "eyes", "fiji", "infe...	Eyelash Epilation in the Absence of Trichiasis: Results of a Population-Based Prevalence Survey in the Western Division of Fiji	journal.pntd.0005277	null	[ [ "Trachoma is the leading infectious cause of blindness globally , responsible for the irreversible loss of vision in 1 . 9 million people . [1]", "It is caused by repeated bouts of conjunctival Chlamydia trachomatis infection and resolution during childhood , resulting in the gradual accumulation of trach...	[ "The WHO definition of trachomatous trichiasis ( TT ) is “at least one eyelash touching the globe , or evidence of recent epilation of in-turned eyelashes” , reflecting the fact that epilation is used as a self-management tool for TT .", "In Fiji’s Western Division , a high TT prevalence ( 8 . 7% in those aged ≥1...	[ "Trachoma , caused by infection with ocular strains of Chlamydia trachomatis , represents a major public health issue , and is targeted for global elimination as a public health problem by the year 2020 .", "Until recently , data on trachoma in the Pacific Island states have been sparse , with marked variability ...	2017
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "invertebrates", "livestock", "medicine and health sciences", "pathology and laboratory medicine", "pig models", "immunology", "tropical diseases", "vertebrates", "parasitic diseases", "animals", "mammals", "simulation and modeling", "animal models", "preventive medicine", "model organis...	CystiSim – An Agent-Based Model for Taenia solium Transmission and Control	journal.pntd.0005184	null	[ [ "The zoonotic tapeworm Taenia solium is a problem in both health and agricultural sectors in many developing countries in North and South America [1] , sub-Saharan Africa [2] , and Asia [3] .", "Taenia solium is transmitted between humans and pigs , but detailed knowledge about the transmission dynamics i...	[ "Taenia solium taeniosis/cysticercosis was declared eradicable by the International Task Force for Disease Eradication in 1993 , but remains a neglected zoonosis .", "To assist in the attempt to regionally eliminate this parasite , we developed cystiSim , an agent-based model for T . solium transmission and contr...	[ "Taenia solium is the leading cause of preventable epilepsy and the highest ranking foodborne parasite in terms of disease burden worldwide .", "Currently there are no large scale control programmes implemented against T . solium , but efficacious intervention tools are there , making control programmes the next ...	2016
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "infectious diseases/neglected tropical diseases" ]	Application and Validation of PFGE for Serovar Identification of Leptospira Clinical Isolates	journal.pntd.0000824	null	[ [ "Leptospirosis is a zoonotic infection found all over the world . [1]", "There is a wide range of animal hosts that maintain Leptospira organisms in their renal tubules and contaminate the environment . [2]", "Human cases usually occur due to contact with water or other environmental sources that have...	[ "Serovar identification of clinical isolates of Leptospira is generally not performed on a routine basis , yet the identity of an infecting serovar is valuable from both epidemiologic and public health standpoints .", "Only a small number of reference laboratories worldwide have the capability to perform the cros...	[ "Leptospirosis is an infection caused by Leptospira bacteria , and is probably the most widespread zoonosis in the world .", "It is carried by a wide range of animals that contaminate the environment by shedding organisms in their urine .", "Humans become infected when they come into contact with contaminated u...	2010
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "medicine and health sciences", "toxins", "immune physiology", "pathology and laboratory medicine", "animal models of disease", "immunology", "microbiology", "parasitic diseases", "parasitic protozoans", "toxicology", "toxic agents", "animal models", "trypanosoma brucei", "model organisms"...	A single dose of antibody-drug conjugate cures a stage 1 model of African trypanosomiasis	journal.pntd.0007373	null	[ [ "Infection with African trypanosomes causes disease in humans , livestock and wild animals .", "At least seven species are able to infect livestock but only Trypanosoma brucei subspecies normally infect humans: T . b .", "gambiense and T . b .", "rhodesiense cause chronic or acute Human African Tr...	[ "Infections of humans and livestock with African trypanosomes are treated with drugs introduced decades ago that are not always fully effective and often have severe side effects .", "Here , the trypanosome haptoglobin-haemoglobin receptor ( HpHbR ) has been exploited as a route of uptake for an antibody-drug con...	[ "Here we show that antibody-drug conjugates ( ADCs ) can be re-purposed from cancer immunotherapeutics to anti-protozoals by changing the specificity of the immunoglobulin to target a trypanosome cell surface receptor .", "Trypanosomes were used as a model system due to the availability of receptor null cell line...	2019
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine", "infectious diseases", "drug research and development", "drugs and devices", "hiv", "pharmacology", "viral diseases" ]	LEDGF/p75-Independent HIV-1 Replication Demonstrates a Role for HRP-2 and Remains Sensitive to Inhibition by LEDGINs	journal.ppat.1002558	null	[ [ "Integration of viral DNA into the host cell genome is a critical step during HIV replication .", "A stably inserted provirus is essential for productive infection and archives the genetic information of HIV in the host cell .", "The presence of a permanent viral reservoir that evades the immune syste...	[ "Lens epithelium–derived growth factor ( LEDGF/p75 ) is a cellular cofactor of HIV-1 integrase ( IN ) that interacts with IN through its IN binding domain ( IBD ) and tethers the viral pre-integration complex to the host cell chromatin .", "Here we report the generation of a human somatic LEDGF/p75 knockout cell ...	[ "Like other viruses , HIV has a limited genome and needs to exploit the machinery of the host cell to complete its replication cycle .", "The elucidation of virus-host interactions not only sheds light on pathogenesis but also provides opportunities in a limited number of cases to develop novel antiviral drugs ."...	2012
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "medicine and health sciences", "microbial mutation", "pathology and laboratory medicine", "evolutionary biology", "enzymes", "pathogens", "microbiology", "enzymology", "retroviruses", "viruses", "immunodeficiency viruses", "mutation", "rna viruses", "nonsense mutation", "epigenetics", ...	Within-patient mutation frequencies reveal fitness costs of CpG dinucleotides and drastic amino acid changes in HIV	journal.pgen.1007420	null	[ [ "The human immunodeficiency virus ( HIV ) replicates with an extremely high mutation rate and exhibits significant genetic diversity within an infected host , often referred to as a “mutant cloud” or “quasispecies” [1–7] .", "Although mutations are crucial for all adaptive processes , they can have fitnes...	[ "HIV has a high mutation rate , which contributes to its ability to evolve quickly .", "However , we know little about the fitness costs of individual HIV mutations in vivo , their distribution and the different factors shaping the viral fitness landscape .", "We calculated the mean frequency of transition muta...	[ "HIV’s high mutation rate allows it to evolve quickly .", "However , most mutations probably reduce the virus’ ability to replicate —they are costly to the virus .", "Until now , the actual cost of mutations is not well understood .", "We used within-patient mutation frequencies to estimate the cost of 870 HI...	2018
[ "Introduction", "Materials and methods", "Results", "Discussion" ]	[ "invertebrates", "gene regulation", "animals", "animal models", "developmental biology", "drosophila melanogaster", "model organisms", "sense organ development", "organism development", "eye development", "experimental organism systems", "embryos", "drosophila", "research and analysis meth...	Predicting gene regulatory interactions based on spatial gene expression data and deep learning	journal.pcbi.1007324	null	[ [ "Over the past decades , the advances of high-throughput technologies have led to a rapid accumulation of genomic , transcriptomic , proteomic and metabolomics data , and enabled the studies of gene regulation and gene-gene interactions at genome scale [1 , 2] .", "Especially , the reconstruction of gene ...	[ "Reverse engineering of gene regulatory networks ( GRNs ) is a central task in systems biology .", "Most of the existing methods for GRN inference rely on gene co-expression analysis or TF-target binding information , where the determination of co-expression is often unreliable merely based on gene expression lev...	[ "Gene expression images , with abundant spatial expression patterns , have become an important resource for identifying gene regulatory networks ( GRNs ) , while the computational methods for image-based GRN reconstruction have been very few .", "In spite of the difference in experimental types and conditions , w...	2019
[ "Introduction", "Results/Discussion", "Materials and Methods" ]	[ "biochemistry", "genetics", "biology", "microbiology", "genetics and genomics" ]	Principles of Carbon Catabolite Repression in the Rice Blast Fungus: Tps1, Nmr1-3, and a MATE–Family Pump Regulate Glucose Metabolism during Infection	journal.pgen.1002673	null	[ [ "Fungi cause recalcitrant diseases of humans , animals and plants .", "In order to survive in environments with limited and variable resources , they have developed elegant and efficient genetic regulatory systems to enable them to respond rapidly to fluctuating nutritional conditions , but little is know...	[ "Understanding the genetic pathways that regulate how pathogenic fungi respond to their environment is paramount to developing effective mitigation strategies against disease .", "Carbon catabolite repression ( CCR ) is a global regulatory mechanism found in a wide range of microbial organisms that ensures the pr...	[ "To succeed as pathogens , fungi such as the rice blast fungus M . oryzae must adapt their metabolism to nutrient availability within the host , but little is known about the genetic regulatory mechanisms involved .", "M . oryzae destroys enough rice to feed 60 million people annually , and understanding how the ...	2012
[ "Introduction", "Results/Discussion", "Materials and Methods", "Supporting Information" ]	[ "homo (human)", "genetics and genomics", "immunology" ]	Deletion of Complement Factor H–Related Genes CFHR1 and CFHR3 Is Associated with Atypical Hemolytic Uremic Syndrome	journal.pgen.0030041	null	[ [ "Atypical hemolytic uremic syndrome ( aHUS ) is characterized by a triad consisting of microangiopathic hemolytic anemia , thrombocytopenia , and acute renal failure in the absence of a preceding diarrheal illness .", "aHUS can be either sporadic or familial .", "Defective complement regulation occurs...	[ "Atypical hemolytic uremic syndrome ( aHUS ) is associated with defective complement regulation .", "Disease-associated mutations have been described in the genes encoding the complement regulators complement factor H , membrane cofactor protein , factor B , and factor I .", "In this study , we show in two inde...	[ "Hemolytic uremic syndrome ( HUS ) is a severe kidney disease , which is characterized by hemolytic anemia , thrombocytopenia , and acute renal failure .", "The nondiarrhea-associated form , also known as atypical HUS ( aHUS ) , is rare , sometimes familial , often recurrent , and has a poor outcome .", "Severa...	2007
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "coronary artery disease", "medicine", "public health and epidemiology", "cardiovascular disease epidemiology", "genetic association studies", "epidemiology", "genetics", "biology", "human genetics", "genetics of disease", "genetics and genomics", "genetic epidemiology", "cardiovascular" ]	Large-Scale Gene-Centric Analysis Identifies Novel Variants for Coronary Artery Disease	journal.pgen.1002260	null	[ [ "Coronary artery disease ( CAD ) has a substantial genetic component which is incompletely characterised .", "Genomewide association ( GWA ) studies have recently identified several novel susceptibility loci for CAD [1]–[9] .", "Because GWA studies involve assumption-free surveys of common genetic var...	[ "Coronary artery disease ( CAD ) has a significant genetic contribution that is incompletely characterized .", "To complement genome-wide association ( GWA ) studies , we conducted a large and systematic candidate gene study of CAD susceptibility , including analysis of many uncommon and functional variants .", ...	[ "Coronary artery disease ( CAD ) has a strong genetic basis that remains poorly characterised .", "Using a custom-designed array , we tested the association with CAD of almost 50 , 000 common and low frequency variants in ∼2 , 000 genes of known or suspected cardiovascular relevance .", "We genotyped the array ...	2011
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "physiotherapy", "infectious diseases", "medicine and health sciences", "health care" ]	Persisting Social Participation Restrictions among Former Buruli Ulcer Patients in Ghana and Benin	journal.pntd.0003303	null	[ [ "Buruli ulcer ( BU ) is a skin condition caused by Mycobacterium ulcerans , which is the third most prevalent mycobacterial disease in immuno-competent humans , after the diseases caused by Mycobacterium tuberculosis and Mycobacterium leprae [1] .", "BU presents as a small nodule or a plaque sometimes acc...	[ "Buruli ulcer may induce severe disabilities impacting on a person's well-being and quality of life .", "Information about long-term disabilities and participation restrictions is scanty .", "The objective of this study was to gain insight into participation restrictions among former Buruli ulcer patients in Gh...	[ "Disabilities among Buruli ulcer patients remain a problem .", "Previous studies revealed contractures , deformities and functional limitations in daily life after treatment .", "According to the International Classification of Functioning , Disability and Health , disabilities occur not only at the physical an...	2014
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[]	Venezuelan Equine Encephalitis Viruses (VEEV) in Argentina: Serological Evidence of Human Infection	journal.pntd.0002551	null	[ [ "Venezuelan equine encephalitis ( VEE ) is a reemerging mosquito-borne viral disease that is severely debilitating and sometimes fatal to humans [1] .", "The etiological agent , VEE virus ( VEEV ) , belongs to the VEE complex ( Togaviridae: Alphavirus ) , one of the major alphavirus serogroups found in th...	[ "Venezuelan equine encephalitis viruses ( VEEV ) are responsible for human diseases in the Americas , producing severe or mild illness with symptoms indistinguishable from dengue and other arboviral diseases .", "For this reason , many cases remain without certain diagnosis .", "Seroprevalence studies for VEEV ...	[ "Venezuelan equine encephalitis viruses ( VEEV ) are responsible for human diseases in the Americas .", "They produce severe or mild illnesses with symptoms indistinguishable from dengue and other arboviral diseases; for this reason , many cases remain undiagnosed .", "We detected neutralizing antibodies ( NTAb...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine", "genetics", "biology", "genomics", "neuroscience", "genetics and genomics" ]	Age-Dependent Brain Gene Expression and Copy Number Anomalies in Autism Suggest Distinct Pathological Processes at Young Versus Mature Ages	journal.pgen.1002592	null	[ [ "Clinical and subclinical manifestations of autism begin during the first years of life [1] .", "Neuroimaging studies of living infants and young children with autism have revealed abnormal brain overgrowth in the majority of cases , particularly in prefrontal , temporal and amygdala regions [2]–[13] .", ...	[ "Autism is a highly heritable neurodevelopmental disorder , yet the genetic underpinnings of the disorder are largely unknown .", "Aberrant brain overgrowth is a well-replicated observation in the autism literature; but association , linkage , and expression studies have not identified genetic factors that explai...	[ "Autism is a disorder characterized by aberrant social , communication , and restricted and repetitive behaviors .", "It develops clinically in the first years of life .", "Toddlers and children with autism often exhibit early brain enlargement and excess neuron numbers in the prefrontal cortex .", "Adults wi...	2012
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "medicine", "infectious diseases", "public health and epidemiology", "public health" ]	Predictive Models for the Diagnostic of Human Visceral Leishmaniasis in Brazil	journal.pntd.0001542	null	[ [ "Visceral leishmaniasis ( VL ) is a neglected tropical disease caused by the intracellular protozoan parasite Leishmania infantum ( syn . Leishmania chagasi ) .", "The disease is endemic to 65 countries and 90% of world cases are reported in India , Bangladesh , Nepal , Ethiopia , Brazil , and the Sudan [...	[ "In Brazil , as in many other affected countries , a large proportion of visceral leishmaniasis ( VL ) occurs in remote locations and treatment is often performed on basis of clinical suspicion .", "This study aimed at developing predictive models to help with the clinical management of VL in patients with sugges...	[ "Visceral leishmaniasis ( VL ) is a neglected tropical disease endemic to 65 countries , including Brazil , where the disease frequently occurs in remote locations and treatment is often performed on the basis of clinical suspicion .", "Predictive models based on scoring systems could be a helpful tool for the cl...	2012
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "eye infections", "medicine", "disease mapping", "public health and epidemiology", "survey methods", "epidemiology", "ophthalmology", "trachoma" ]	The Prevalence of Blinding Trachoma in Northern States of Sudan	journal.pntd.0001027	null	[ [ "Trachoma is an eye disease caused by ocular infection with Chlamydia trachomatis , which can result in blindness after cycles of repeated infections .", "The World Health Organization ( WHO ) estimates that trachoma accounts for 2 . 9% of blindness globally [1] .", "Since 1997 , the WHO has advocated...	[ "Despite historical evidence of blinding trachoma , there have been no widespread contemporary surveys of trachoma prevalence in the northern states of Sudan .", "We aimed to conduct district-level surveys in this vast region in order to map the extent of the problem and estimate the need for trachoma control int...	[ "Trachoma is an infectious disease which is caused by a bacterium , Chlamydia trachomatis and is the leading cause of preventable blindness , estimated to be responsible for 2 . 9% of blindness globally .", "The World Health Organization ( WHO ) recommends an integrated strategy for control and elimination of bli...	2011
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "systems biology", "evolutionary modeling", "regulatory networks", "biology", "computational biology", "evolutionary biology", "evolutionary theory" ]	Epigenetics Decouples Mutational from Environmental Robustness. Did It Also Facilitate Multicellularity?	journal.pcbi.1003450	null	[ [ "Understanding the evolution of major transitions in the complexity of organisms remains one of the key challenges in modern biology [1] , [2] .", "In particular , the transition to multicellularity required the evolution of several innovations at the molecular level in order to satisfy three key requirem...	[ "The evolution of ever increasing complex life forms has required innovations at the molecular level in order to overcome existing barriers .", "For example , evolving processes for cell differentiation , such as epigenetic mechanisms , facilitated the transition to multicellularity .", "At the same time , stud...	[ "Understanding the transition to multicellularity remains a key unanswered question in evolutionary biology .", "The transition required three essential cellular features to evolve: adhesion , signaling and differentiation .", "In particular , cell differentiation requires sensitivity to environmental cues to c...	2014
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "medicine and health sciences", "ecology and environmental sciences", "immunology", "geographical locations", "vertebrates", "social sciences", "animals", "mammals", "primates", "preventive medicine", "land use", "vaccination and immunization", "human geography", "public and occupational h...	Geographic patterns and environmental factors associated with human yellow fever presence in the Americas	journal.pntd.0005897	null	[ [ "Yellow fever ( YF ) is a zoonotic disease caused by an arbovirus of the family Flaviviridae , the same family of the dengue and Zika viruses , of which the latter was declared in 2016 a Public Health Emergency of International Concern [1] .", "YF is caused by yellow fever virus ( YFV ) , which is transmi...	[ "In the Americas , yellow fever virus transmission is a latent threat due to the proximity between urban and wild environments .", "Although yellow fever has nearly vanished from North and Central America , there are still 13 countries in the Americas considered endemic by the World Health Organization .", "Hum...	[ "Yellow fever ( YF ) is a zoonotic disease caused by yellow fever virus ( YFV ) , which is transmitted to humans through the bite of an infected mosquito .", "Sylvatic and urban cycles have been present in different periods , but currently most cases result from human exposure to jungle or forested environments ....	2017
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "bacteriology", "genetic mutation", "genome evolution", "microbiology", "mutation types", "emerging infectious diseases", "microbial evolution", "biology", "heredity", "genetics", "gene flow", "genomics", "bacterial evolution", "genetics and genomics" ]	Natural Transformation Facilitates Transfer of Transposons, Integrons and Gene Cassettes between Bacterial Species	journal.ppat.1002837	null	[ [ "The acquisition and dissemination of antibiotic resistance in Gram-negative bacteria is frequently facilitated by integrons [1]–[3] .", "Integrons contain genetic determinants for site-specific recombination and promoters driving the expression of gene cassettes [4]; the integrase ( IntI ) encoded by the...	[ "We have investigated to what extent natural transformation acting on free DNA substrates can facilitate transfer of mobile elements including transposons , integrons and/or gene cassettes between bacterial species .", "Naturally transformable cells of Acinetobacter baylyi were exposed to DNA from integron-carryi...	[ "Genetic elements , such as transposons and integrons , frequently carry antimicrobial resistance determinants and can be found widely disseminated among pathogenic bacteria .", "Their distribution pattern suggests dissemination through horizontal gene transfer .", "The role of natural transformation in horizon...	2012
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "medicine and health sciences", "reproductive system", "pathology and laboratory medicine", "maternal health", "obstetrics and gynecology", "nervous system", "pathogens", "microbiology", "vertebrates", "brain", "animals", "mammals", "primates", "viruses", "developmental biology", "wome...	Zika virus infection at mid-gestation results in fetal cerebral cortical injury and fetal death in the olive baboon	journal.ppat.1007507	null	[ [ "Originally isolated from a febrile sentinel rhesus monkey in the Zika forest in Uganda in 1947 , Zika virus ( ZIKV ) belongs to the Flaviviridae family , genus Flavivirus , which includes dengue ( DENV ) , West Nile ( WNV ) , yellow fever ( YFV ) , and Japanese encephalitis virus ( JEV ) [1 , 2] .", "Zik...	[ "Zika virus ( ZIKV ) infection during pregnancy in humans is associated with an increased incidence of congenital anomalies including microcephaly as well as fetal death and miscarriage and collectively has been referred to as Congenital Zika Syndrome ( CZS ) .", "Animal models for ZIKV infection in pregnancy hav...	[ "Zika virus is endemic in the Americas , primarily spread through mosquitos and sexual contact .", "Zika virus infection during pregnancy in women is associated with a variety of fetal pathologies now referred to as Congenital Zika Syndrome ( CZS ) , with the most severe pathology being fetal microcephaly .", "...	2019
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genetics and genomics/complex traits", "plant biology/plant growth and development", "plant biology/plant genetics and gene expression" ]	A Multiparent Advanced Generation Inter-Cross to Fine-Map Quantitative Traits in Arabidopsis thaliana	journal.pgen.1000551	null	[ [ "Most plant traits of agronomic and economic interest , such as seed dormancy , flowering time , fruit production , disease resistance , etc . , vary quantitatively and have complex genetic inheritance .", "Their phenotypic expression is determined by the combination of many genetic and environmental fact...	[ "Identifying natural allelic variation that underlies quantitative trait variation remains a fundamental problem in genetics .", "Most studies have employed either simple synthetic populations with restricted allelic variation or performed association mapping on a sample of naturally occurring haplotypes .", "B...	[ "Most traits of economic and evolutionary interest vary quantitatively and have multiple genes affecting their expression .", "Dissecting the genetic basis of such traits is crucial for the improvement of crops and management of diseases .", "Here , we develop a new resource to identify genes underlying such qu...	2009
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "phosphorylation", "renal cell carcinoma", "medicine and health sciences", "endocrine tumors", "carcinomas", "cancers and neoplasms", "genitourinary tract tumors", "oncology", "neurological tumors", "mutation", "substitution mutation", "renal diseases", "mutation databases", "research and ...	Genotype-phenotype relations of the von Hippel-Lindau tumor suppressor inferred from a large-scale analysis of disease mutations and interactors	journal.pcbi.1006478	null	[ [ "Familial cancers are rare , accounting for about 5–10% of all cancers [1–3] and generally characterized by inherited inactivation of important tumor suppressors .", "Inherited tumors represent a valuable source of information about the mechanisms driving cancerogenesis .", "These cancers are associat...	[ "Familiar cancers represent a privileged point of view for studying the complex cellular events inducing tumor transformation .", "Von Hippel-Lindau syndrome , a familiar predisposition to develop cancer is a clear example .", "Here , we present our efforts to decipher the role of von Hippel-Lindau tumor suppre...	[ "Cancer is generally caused by a series of mutations accumulating over time in a healthy tissue , which becomes re-programmed to proliferate at the expense of the hosting organism .", "This process is difficult to follow and understand as events in a multitude of different genes can lead to similar outcomes witho...	2019
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "blood cells", "phosphorylation", "nuclear import", "innate immune system", "medicine and health sciences", "immune cells", "immune physiology", "cytokines", "immunology", "cell processes", "parasitic diseases", "developmental biology", "clinical medicine", "molecular development", "stat...	STAT2 Is a Pervasive Cytokine Regulator due to Its Inhibition of STAT1 in Multiple Signaling Pathways	journal.pbio.2000117	null	[ [ "Cytokines are a structurally and functionally diverse group of small proteins that function as extracellular signaling molecules .", "They control all aspects of immune cell biology including development , differentiation , activation , and death and orchestrate the functioning of the entire immune syste...	[ "STAT2 is the quintessential transcription factor for type 1 interferons ( IFNs ) , where it functions as a heterodimer with STAT1 .", "However , the human and murine STAT2-deficient phenotypes suggest important additional and currently unidentified type 1 IFN-independent activities .", "Here , we show that STA...	[ "For more than a quarter century , we have known that STAT1 and STAT2 are essential for the classic host immune defense system against viral infections known as the type 1 interferon response .", "While STAT1 has since been assigned multiple additional roles , STAT2 is thought to function exclusively as the princ...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Structure of a Bimodular Botulinum Neurotoxin Complex Provides Insights into Its Oral Toxicity	journal.ppat.1003690	null	[ [ "The seven botulinum neurotoxin serotypes ( BoNT/A–G ) produced by Clostridium botulinum are the causative agents of the neuroparalytic syndrome of botulism and pose a serious threat for bioterrorism [1] .", "Conversely , BoNT/A is a highly effective therapy for treating neurological disorders [2] .", ...	[ "Botulinum neurotoxins ( BoNTs ) are produced by Clostridium botulinum and cause the fatal disease botulism , a flaccid paralysis of the muscle .", "BoNTs are released together with several auxiliary proteins as progenitor toxin complexes ( PTCs ) to become highly potent oral poisons .", "Here , we report the s...	[ "Food-borne botulinum neurotoxin ( BoNT ) poisoning results in fatal muscle paralysis .", "But how can BoNT–a large protein released by the bacteria clostridia–survive the hostile gastrointestinal ( GI ) tract to gain access to neurons that control muscle contraction ?", "Here , we report the complete structure...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "mathematics/statistics", "computational biology/ecosystem modeling", "infectious diseases/epidemiology and control of infectious diseases" ]	Dynamic Modeling of Vaccinating Behavior as a Function of Individual Beliefs	journal.pcbi.1000425	null	[ [ "In the UK , MMR vaccine uptake started to decline after a controversial study linking MMR vaccine to autism [6] .", "In a decade , vaccine coverage went well below the target herd immunity level of 95% .", "Despite the confidence of researchers and most health professionals on the vaccine safety , th...	[ "Individual perception of vaccine safety is an important factor in determining a person's adherence to a vaccination program and its consequences for disease control .", "This perception , or belief , about the safety of a given vaccine is not a static parameter but a variable subject to environmental influence ....	[ "A frequently made assumption in population models is that individuals make decisions in a standard way , which tends to be fixed and set according to the modeler's view on what is the most likely way individuals should behave .", "In this paper we acknowledge the importance of modeling behavioral changes ( in th...	2009
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "viral evolution", "rna viruses", "emerging infectious diseases", "virology", "viral classification", "emerging viral diseases", "biology", "evolutionary biology", "microbiology", "evolutionary genetics" ]	Vector-Borne Transmission Imposes a Severe Bottleneck on an RNA Virus Population	journal.ppat.1002897	null	[ [ "RNA virus replication is characterized by a high frequency of mutation , which leads to genetically diverse populations .", "This diversity is thought to enable RNA viruses to effectively survive within the host ( i . e . escape or evade immune responses ) , to be transmitted , and to potentially adapt t...	[ "RNA viruses typically occur in genetically diverse populations due to their error-prone genome replication .", "Genetic diversity is thought to be important in allowing RNA viruses to explore sequence space , facilitating adaptation to changing environments and hosts .", "Some arboviruses that infect both a mo...	[ "The ability of arboviruses to perpetuate in nature given that they must infect two disparate hosts ( the mosquito vector and the vertebrate host ) remains a mystery .", "We studied how viral genetic diversity is impacted by the dual host transmission cycle .", "Our studies of an enzootic cycle using Venezuelan...	2012
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "blood cells", "medicine and health sciences", "immune cells", "pathology and laboratory medicine", "engineering and technology", "pathogens", "immunology", "microbiology", "alleles", "telecommunications", "retroviruses", "viruses", "immunodeficiency viruses", "immune receptor signaling", ...	HIV-1 adaptation to NK cell-mediated immune pressure	journal.ppat.1006361	null	[ [ "Natural killer ( NK ) cells mediate anti-viral immunity by lysing infected cells , producing pro-inflammatory cytokines and modulating adaptive immunity .", "NK cells express activating and inhibitory receptors; the balance of signals from these receptors determines the NK cell response .", "Some of ...	[ "The observation , by Alter et al . , of the enrichment of NK cell “escape” variants in individuals carrying certain Killer-cell Immunoglobulin-like Receptor ( KIR ) genes is compelling evidence that natural killer ( NK ) cells exert selection pressure on HIV-1 .", "Alter et al hypothesise that variant peptide , ...	[ "In our opinion , some of the best evidence that natural killer ( NK ) cells contribute to the control of HIV-1 infection is the identification of 22 virus variants , “KIR footprints” , that were hypothesised to escape the NK cell response ( Nature , 2011 ) .", "The authors ( Alter , Heckerman , Schneidewind , Fa...	2017
[ "Introduction", "Results/Discussion", "Materials and Methods" ]	[ "genetics and genomics/genetics of disease", "genetics and genomics/complex traits", "genetics and genomics/genetics of the immune system" ]	IL2RA Genetic Heterogeneity in Multiple Sclerosis and Type 1 Diabetes Susceptibility and Soluble Interleukin-2 Receptor Production	journal.pgen.1000322	null	[ [ "Recent genome wide association ( GWA ) and candidate gene studies across human autoimmune disease revealed a shared genetic architecture [1] .", "These include PTPN22 , associated with systemic lupus erythematosus ( SLE ) , rheumatoid arthritis ( RA ) , T1D , and Graves' Disease ( GD ) [2] , STAT4 , asso...	[ "Multiple sclerosis ( MS ) and type 1 diabetes ( T1D ) are organ-specific autoimmune disorders with significant heritability , part of which is conferred by shared alleles .", "For decades , the Human Leukocyte Antigen ( HLA ) complex was the only known susceptibility locus for both T1D and MS , but loci outside ...	[ "Multiple sclerosis ( MS ) and type 1 diabetes ( T1D ) are common , organ-specific inflammatory disorders that continue to increase in global prevalence .", "The processes leading to both T1D and MS are genetically determined and are thought to involve an autoimmune mechanism .", "After decades of research into...	2009
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "evolutionary biology/evolutionary ecology", "infectious diseases/neglected tropical diseases", "molecular biology/molecular evolution", "infectious diseases/helminth infections", "ecology/population ecology" ]	Distinct Genetic Diversity of Oncomelania hupensis, Intermediate Host of Schistosoma japonicum in Mainland China as Revealed by ITS Sequences	journal.pntd.0000611	null	[ [ "The snail Oncomelania hupensis , the only intermediate host of Schistosoma japonicum , has been found in China , and also in Japan , Philippines and Indonesian island of Sulawesi .", "Over the past a few decades , the taxonomy of O . hupensis has been a dispute due to the variation in morphological chara...	[ "Oncomelania hupensis is the unique intermediate host of Schistosoma japonicum , which causes schistosomiasis endemic in the Far East , and especially in mainland China .", "O . hupensis largely determines the parasite's geographical range .", "How O . hupensis's genetic diversity is distributed geographically ...	[ "The intermediate host of Schistosoma japonicum in Asia is the snail Oncomelania hupensis , which can be separated phenotypically into ribbed- and smooth-shelled morphotypes .", "In China , the typical morphotype is ribbed-shelled , with its distribution restricted to mainland China .", "Smooth-shelled snails w...	2010
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "blood cells", "medicine and health sciences", "immune cells", "pathology and laboratory medicine", "highly-active antiretroviral therapy", "viral transmission and infection", "antiviral therapy", "pathogens", "immunology", "microbiology", "neuroscience", "learning and memory", "retroviruses...	Negative modulation of suppressive HIV-specific regulatory T cells by IL-2 adjuvanted therapeutic vaccine	journal.ppat.1006489	null	[ [ "CD4+ regulatory T cells ( Tregs ) are central in maintaining peripheral tolerance and constitute the most important extrinsic inhibitory mechanism that control T-cell responses ( reviewed in [1] ) .", "Human peripheral thymic-derived naive and effector Tregs are delineated as CD4+CD25hiCD127lowFoxP3+ CD4...	[ "The potential benefit in using IL-2 in immunotherapy for cancer and autoimmunity has been linked to the modulation of immune responses , which partly relies on a direct effect on Tregs populations .", "Here , we revisited the role of IL-2 in HIV infection and investigated whether its use as an adjuvant with ther...	[ "Interleukin-2 ( IL-2 ) has been used in immunotherapy for cancer and autoimmunity and its beneficial effect has been linked to the modulation of immune responses , which partly relies on a direct effect on Tregs populations .", "In this study , we assessed the role of IL-2 in HIV infection and investigated wheth...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "microbiology/plant-biotic interactions" ]	Rac1 Is Required for Pathogenicity and Chm1-Dependent Conidiogenesis in Rice Fungal Pathogen Magnaporthe grisea	journal.ppat.1000202	null	[ [ "Magnaporthe grisea ( M . grisea ) is a good model organism to study plant pathogenic filamentous fungi [1] , [2] .", "In addition , it is closely related to other prominent non-pathogenic model fungi , such as Neurospora crassa and Aspergillus nidulans [3] .", "The fungus infects many cereal crops su...	[ "Rac1 is a small GTPase involved in actin cytoskeleton organization and polarized cell growth in many organisms .", "In this study , we investigate the biological function of MgRac1 , a Rac1 homolog in Magnaporthe grisea .", "The Mgrac1 deletion mutants are defective in conidial production .", "Among the few ...	[ "The fungus Magnaporthe grisea ( M . grisea ) is an important pathogen in plants and has a great impact on agriculture .", "Its infection of rice causes one of the most destructive diseases , the rice blast disease , around the world .", "M . grisea starts infection by producing conidia , which generate infecti...	2008
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "evolutionary biology/human evolution", "microbiology/environmental microbiology", "evolutionary biology/microbial evolution and genomics" ]	Evolutionary Relationships of Wild Hominids Recapitulated by Gut Microbial Communities	journal.pbio.1000546	Although bacteria are continually acquired over the lifetime of an individual, the phylogenetic relationships of great ape species is mirrored in the compositions of their gut microbial communities.	[ [ "The mammalian digestive tract is sterile at birth but is soon colonized by bacteria that typically derive from the mother [1]–[3] .", "In the absence of any subsequent alterations or additional colonizations , strict parental inheritance would result in a pattern in which the constituents and composition...	[ "Multiple factors over the lifetime of an individual , including diet , geography , and physiologic state , will influence the microbial communities within the primate gut .", "To determine the source of variation in the composition of the microbiota within and among species , we investigated the distal gut micro...	[ "The microbial communities that inhabit the gastrointestinal tract of humans and other mammals are complex , dynamic , and critical to both health and disease .", "The composition and constituents of these communities are influenced by multiple factors such as host diet , geography , physiology , and disease stat...	2010
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "developmental biology", "genetics", "biology", "genomics", "molecular cell biology", "genetics and genomics" ]	Asynchronous Replication, Mono-Allelic Expression, and Long Range Cis-Effects of ASAR6	journal.pgen.1003423	null	[ [ "Morphological differences between mitotic chromosomes residing within the same cell were first described in mammalian cells over forty years ago ( reviewed in [1] ) .", "In addition , numerous reports have described an abnormal chromosomal phenotype affecting single or a few chromosomes in mitotic prepar...	[ "Mammalian chromosomes initiate DNA replication at multiple sites along their length during each S phase following a temporal replication program .", "The majority of genes on homologous chromosomes replicate synchronously .", "However , mono-allelically expressed genes such as imprinted genes , allelically exc...	[ "Mammalian chromosomes are duplicated every cell cycle during a precise temporal DNA replication program .", "Thus , every chromosome contains regions that are replicated early and other regions that are replicated late during each S phase .", "Most of the genes , present in two copies on homologous chromosomes...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "phosphorylation", "protein interactions", "chemical compounds", "dna-binding proteins", "threonine", "organic compounds", "dna transcription", "immunoprecipitation", "amino acids", "co-immunoprecipitation", "research and analysis methods", "proteins", "gene expression", "chemistry", "re...	Binding of the Fkh1 Forkhead Associated Domain to a Phosphopeptide within the Mph1 DNA Helicase Regulates Mating-Type Switching in Budding Yeast	journal.pgen.1006094	null	[ [ "The Saccharomyces cerevisiae Fkh1 ( forkhead homolog 1 ) protein is a member of the FOX ( forkhead box ) family of proteins defined by their winged-helix DNA binding domains .", "The FOX family proteins are best known for their transcriptional roles in regulating the cell cycle and differentiation [1] ."...	[ "The Saccharomyces cerevisiae Fkh1 protein has roles in cell-cycle regulated transcription as well as a transcription-independent role in recombination donor preference during mating-type switching .", "The conserved FHA domain of Fkh1 regulates donor preference by juxtaposing two distant regions on chromosome II...	[ "Specific chromosomal interactions between distal regions of the genome allow for DNA transactions necessary for normal cell function , but the protein-protein interfaces that regulate such interactions remain largely unknown .", "The budding yeast Fkh1 protein uses its evolutionarily conserved phosphothreonine-b...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Estrogenic Exposure Alters the Spermatogonial Stem Cells in the Developing Testis, Permanently Reducing Crossover Levels in the Adult	journal.pgen.1004949	null	[ [ "Over the past few decades , there has been increasing concern that sperm counts and quality are declining [1 , 2] .", "In Denmark , for example , sperm counts have declined over time , and more than 40% of young Danish men have sperm counts in the range associated with infertility or decreased fertility ...	[ "Bisphenol A ( BPA ) and other endocrine disrupting chemicals have been reported to induce negative effects on a wide range of physiological processes , including reproduction .", "In the female , BPA exposure increases meiotic errors , resulting in the production of chromosomally abnormal eggs .", "Although nu...	[ "During the past several decades , the incidence of human male reproductive abnormalities such as hypospadias , undescended testicles , testicular cancer , and low sperm counts has increased .", "Environmental factors—and in particular , exposure to environmental estrogens—have been implicated as contributing fac...	2015
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "invertebrates", "innate immune system", "medicine and health sciences", "immune physiology", "cytokines", "gut bacteria", "microbiome", "helminths", "immunology", "microbiology", "parasitic diseases", "animals", "nematode infections", "developmental biology", "molecular development", ...	Rapid environmental effects on gut nematode susceptibility in rewilded mice	journal.pbio.2004108	null	[ [ "Individuals vary tremendously in their susceptibility to infection .", "For example , even with identical exposure rates , some hosts become heavily infected with parasitic worms , while others harbor none [1 , 2] .", "This variation in susceptibility impacts individual health and also shapes pattern...	[ "Genetic and environmental factors shape host susceptibility to infection , but how and how rapidly environmental variation might alter the susceptibility of mammalian genotypes remains unknown .", "Here , we investigate the impacts of seminatural environments upon the nematode susceptibility profiles of inbred C...	[ "The environment in which an individual resides is likely to change how she or he responds to infection .", "However , most of our understanding about host responses to infection arises from experimental studies conducted under uniform environmental conditions in the laboratory .", "We wished to investigate whe...	2018
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "virology/effects of virus infection on host gene expression", "virology" ]	Kaposi's Sarcoma Associated Herpes Virus (KSHV) Induced COX-2: A Key Factor in Latency, Inflammation, Angiogenesis, Cell Survival and Invasion	journal.ppat.1000777	null	[ [ "KSHV , the most recently discovered human tumor virus , is etiologically associated with Kaposi sarcoma ( KS ) , primary effusion lymphoma ( PEL ) and multicentric Castleman's disease ( MCD ) [1] , [2] .", "KS , an AIDS defining condition , is a highly disseminated unusual angiogenic tumor of proliferati...	[ "Kaposi's sarcoma ( KS ) , an enigmatic endothelial cell vascular neoplasm , is characterized by the proliferation of spindle shaped endothelial cells , inflammatory cytokines ( ICs ) , growth factors ( GFs ) and angiogenic factors .", "KSHV is etiologically linked to KS and expresses its latent genes in KS lesio...	[ "Kaposi's sarcoma associated herpes virus ( KSHV ) , with a 160 kb DNA genome , has evolved with two distinct life cycle phases , namely latency and lytic replication .", "KS , a complex angioproliferative disease , is regulated by a balance between pro-angiogenic and anti-angiogenic factors .", "In our previou...	2010
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Condensin II Subunit dCAP-D3 Restricts Retrotransposon Mobilization in Drosophila Somatic Cells	journal.pgen.1003879	null	[ [ "Condensins are complexes which are well known for their roles in ensuring efficient global chromatin condensation during prophase of mitosis [1]–[4] .", "Two Condensin complexes , Condensin I and Condensin II are conserved in multicellular eukaryotes .", "Each complex contains SMC2 and SMC4 proteins ...	[ "Retrotransposon sequences are positioned throughout the genome of almost every eukaryote that has been sequenced .", "As mobilization of these elements can have detrimental effects on the transcriptional regulation and stability of an organism's genome , most organisms have evolved mechanisms to repress their mo...	[ "Condensins are conserved complexes that are well known for their roles in promoting the efficient condensation of chromosomes during early mitosis .", "Previously , we have shown that the Drosophila Condensin II subunit , dCAP-D3 , also functions to regulate transcription in somatic cells during the later stages...	2013
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[]	Mode of Parainfluenza Virus Transmission Determines the Dynamics of Primary Infection and Protection from Reinfection	journal.ppat.1003786	null	[ [ "The Paramyxoviridae family includes a number of important human pathogens that are transmitted by the respiratory route including the human parainfluenza viruses ( HPIVs ) , human respiratory syncytial virus ( HRSV ) , human metapneumovirus ( HMPV ) , measles virus , and mumps virus [1] .", "HRSV , HMPV ...	[ "Little is known about how the mode of respiratory virus transmission determines the dynamics of primary infection and protection from reinfection .", "Using non-invasive imaging of murine parainfluenza virus 1 ( Sendai virus ) in living mice , we determined the frequency , timing , dynamics , and virulence of pr...	[ "Parainfluenza viruses are highly contagious , a leading cause of acute respiratory infection ( ARI ) in children , often reoccurring , and currently controlled by non-pharmaceutical interventions .", "We tracked infection and reinfection of a prototypic murine parainfluenza virus after contact or airborne transm...	2013
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "medicine and health sciences", "nervous system", "astrocytes", "brain", "diet", "neuroscience", "macroglial cells", "nutrition", "nerve fibers", "physical chemistry", "surface chemistry", "lipids", "animal cells", "axons", "chemistry", "corpus callosum", "glial cells", "biochemist...	Oligodendroglial myelination requires astrocyte-derived lipids	journal.pbio.1002605	The formation of myelin membrane by oligodendrocytes in the brain is dependent on extracellular lipids derived from astrocytes and from diet.	[ [ "Myelin membrane integrity is critical for proper functioning of the nervous system .", "Myelin acts as an insulator by increasing the electrical resistance across the cell membrane and by decreasing membrane capacitance , thereby ensuring the fast conduction of action potentials between nodes of Ranvier ...	[ "In the vertebrate nervous system , myelination of axons for rapid impulse propagation requires the synthesis of large amounts of lipids and proteins by oligodendrocytes and Schwann cells .", "Myelin membranes are thought to be cell-autonomously assembled by these axon-associated glial cells .", "Here , we repo...	[ "The myelin membrane is a highly specialized plasma membrane that enwraps axons , acts as an insulator , and is thus important for fast conduction of action potentials .", "It is thereby critical for proper functioning of the nervous system .", "Myelin in the central nervous system is synthesized by oligodendro...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "cell biology/cellular death and stress responses", "cell biology/cell signaling", "genetics and genomics/nuclear structure and function", "biochemistry/replication and repair", "genetics and genomics/gene function", "genetics and genomics/cancer genetics", "molecular biology/dna repair" ]	Human MLH1 Protein Participates in Genomic Damage Checkpoint Signaling in Response to DNA Interstrand Crosslinks, while MSH2 Functions in DNA Repair	journal.pgen.1000189	null	[ [ "A DNA interstrand crosslink ( ICL ) is a type of DNA damage in which both strands of the DNA are covalently linked .", "ICLs present formidable challenges to the cell's essential DNA metabolic processes including replication and transcription .", "DNA crosslinking agents , e . g . , psoralens , mitom...	[ "DNA interstrand crosslinks ( ICLs ) are among the most toxic types of damage to a cell .", "For this reason , many ICL-inducing agents are effective therapeutic agents .", "For example , cisplatin and nitrogen mustards are used for treating cancer and psoralen plus UVA ( PUVA ) is useful for treating psoriasis...	[ "Crosslinks , linking the complementary stands of the DNA double helix , can lead to cell death , because they are so effective at interfering with normal genomic transactions such as DNA replication .", "This property of crosslinking agents has long been utilized in cancer therapy .", "The purpose of our resea...	2008
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "blood cells", "flow cytometry", "innate immune system", "medicine and health sciences", "immune cells", "immune physiology", "cytokines", "pathology and laboratory medicine", "pathogens", "immunology", "immune suppression", "microbiology", "liver diseases", "hepatitis b virus", "organis...	Hepatitis B e antigen induces the expansion of monocytic myeloid-derived suppressor cells to dampen T-cell function in chronic hepatitis B virus infection	journal.ppat.1007690	null	[ [ "Hepatitis B virus ( HBV ) is a blood borne pathogen that chronically infects approximately 350 million people worldwide , and more than 780 , 000 patients die annually due to HBV-related liver diseases , including cirrhosis and hepatocellular carcinoma ( HCC ) [1 , 2] .", "It is well acknowledged that th...	[ "Chronic hepatitis B virus ( HBV ) infection is associated with functionally impaired virus-specific T cell responses .", "Although the myeloid-derived suppressor cells ( MDSCs ) are known to play a critical role in impairing antiviral T cell responses , viral factors responsible for the expansion of MDSCs in chr...	[ "HBeAg is not a structural component of HBV and is not essential for viral DNA replication , however , HBeAg positivity is associated with high levels of viremia in patients .", "HBeAg may represent a viral strategy to establish persistent infection , but the mechanism remains largely ambiguous .", "Growing evi...	2019

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