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headings list	keywords list	title stringlengths 20 281	id stringlengths 20 20	toc stringlengths 57 522 ⌀	sections list	abstract list	summary list	year stringclasses 13 values
[ "Introduction", "Results", "Discussion", "Materials and Methods", "Supporting Information" ]	[ "teleost fishes", "eukaryotes", "vertebrates", "evolutionary biology", "genetics and genomics" ]	Survey Sequencing and Comparative Analysis of the Elephant Shark (Callorhinchus milii) Genome	journal.pbio.0050101	The cartilaginous elephant shark has a basal phylogenetic position useful for understanding jawed vertebrate evolution. Survey sequencing of its genome identified four Hox clusters, suggesting that, unlike for teleost fishes, no additional whole-genome duplication has occurred.	[ [ "Our understanding of the human genome has benefited greatly from comparative studies with other vertebrate genomes .", "Comparison with closely related genomes can identify divergent sequences that may underlie unique phenotypes of human ( e . g . , [1 , 2] ) , while comparison with distantly related gen...	[ "Owing to their phylogenetic position , cartilaginous fishes ( sharks , rays , skates , and chimaeras ) provide a critical reference for our understanding of vertebrate genome evolution .", "The relatively small genome of the elephant shark , Callorhinchus milii , a chimaera , makes it an attractive model cartila...	[ "Cartilaginous fishes ( sharks , rays , skates , and chimaeras ) are the phylogenetically oldest group of living jawed vertebrates .", "They are also an important outgroup for understanding the evolution of bony vertebrates such as human and teleost fishes .", "We performed survey sequencing ( 1 . 4× coverage )...	2007
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "virology/viral replication and gene regulation", "virology" ]	An E2F1-Mediated DNA Damage Response Contributes to the Replication of Human Cytomegalovirus	journal.ppat.1001342	null	[ [ "Cellular DNA is constantly bombarded by insults from both intrinsic sources , such as reactive oxygen species , and extrinsic sources , like genotoxic chemicals .", "DNA damage resulting from these challenge produces a complex protein kinase signaling cascade that promotes repair of the damaged DNA and a...	[ "DNA damage resulting from intrinsic or extrinsic sources activates DNA damage responses ( DDRs ) centered on protein kinase signaling cascades .", "The usual consequences of inducing DDRs include the activation of cell cycle checkpoints together with repair of the damaged DNA or induction of apoptosis .", "Man...	[ "As intracellular parasites , viruses often redirect cellular pathways to facilitate their own replication .", "Infection by DNA viruses often lead to the activation of host DNA damage response pathways , which normally function to repair damage to host chromosomes .", "Some DNA viruses depend on this infection...	2011
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "cell physiology", "medicine and health sciences", "integumentary system", "ears", "neuroscience", "cell polarity", "outer hair cells", "organ of corti", "inner ear", "immunologic techniques", "research and analysis methods", "hair", "animal cells", "head", "inner hair cells", "immunoh...	Disruption of SorCS2 reveals differences in the regulation of stereociliary bundle formation between hair cell types in the inner ear	journal.pgen.1006692	null	[ [ "The sensory “hair” cells of the hearing and balance ( vestibular ) organs in the inner ears of vertebrates convert movements , initiated by sound waves in the cochlea or by translational or rotational motion in the vestibular system , into electrical signals .", "Fundamental to their function is the orga...	[ "Behavioural anomalies suggesting an inner ear disorder were observed in a colony of transgenic mice .", "Affected animals were profoundly deaf .", "Severe hair bundle defects were identified in all outer and inner hair cells ( OHC , IHC ) in the cochlea and in hair cells of vestibular macular organs , but hair...	[ "Sensory “hair” cells in the inner ear derive their name from an organised bundle of mechano-sensory “stereocilia” on their apical surface .", "The finger-like stereocilia are composed of actin filaments and increase in height staircase-like in one direction across the cell surface , a system which provides a def...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Interplay between Active Chromatin Marks and RNA-Directed DNA Methylation in Arabidopsis thaliana	journal.pgen.1003946	null	[ [ "Cytosine DNA methylation is an epigenetic mark that is conserved across all kingdoms of eukaryotes .", "Depending on its location in the genome , DNA methylation can be broadly classified as either genic or non-genic .", "Genic—or gene-body—methylation has been observed in several species of plants a...	[ "DNA methylation is an epigenetic mark that is associated with transcriptional repression of transposable elements and protein-coding genes .", "Conversely , transcriptionally active regulatory regions are strongly correlated with histone 3 lysine 4 di- and trimethylation ( H3K4m2/m3 ) .", "We previously showed...	[ "A number of factors contribute to the organization of eukaryotic genomes and the expression state of the underlying genes .", "For example , cytosine bases can be modified with the addition of a methyl-group .", "In the model plant Arabidopsis thaliana , methylated cytosines are typically associated with trans...	2013
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "medicine and health sciences", "immune physiology", "immunology", "antigenic variation", "parasitic protozoans", "genetic mapping", "protozoans", "genome analysis", "molecular biology techniques", "research and analysis methods", "sequence analysis", "immune system proteins", "genomics", ...	Application of long read sequencing to determine expressed antigen diversity in Trypanosoma brucei infections	journal.pntd.0007262	null	[ [ "Antigenic variation is used by many pathogens as a means of staying one step ahead of the host’s adaptive immune response .", "Trypanosoma brucei has long been a paradigm for the study of antigenic variation , and the protein responsible , the variable surface glycoprotein ( VSG ) has been the focus of m...	[ "Antigenic variation is employed by many pathogens to evade the host immune response , and Trypanosoma brucei has evolved a complex system to achieve this phenotype , involving sequential use of variant surface glycoprotein ( VSG ) genes encoded from a large repertoire of ~2 , 000 genes .", "T . brucei express mu...	[ "Antigenic variation is a system whereby pathogens switch identity of a protein that is exposed to the host adaptive immune response as a way of remaining one step ahead and avoiding being detected .", "African trypanosomes have evolved a spectacularly elaborate system of antigenic variation , with variants being...	2019
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "medicine and health sciences", "pathology and laboratory medicine", "neural networks", "engineering and technology", "pathogens", "signal processing", "bacillus", "signaling networks", "microbiology", "neuroscience", "prokaryotic models", "signal inhibition", "network analysis", "experime...	A neural network model predicts community-level signaling states in a diverse microbial community	journal.pcbi.1007166	null	[ [ "In microbiology , quorum sensing ( QS ) is a process in which bacteria produce and secrete small chemical molecules known as autoinducers .", "Many bacteria regulate gene expression in response to the external concentration of autoinducer , including regulation of processes related to biofilm formation ,...	[ "Signal crosstalk within biological communication networks is common , and such crosstalk can have unexpected consequences for decision making in heterogeneous communities of cells .", "Here we examined crosstalk within a bacterial community composed of five strains of Bacillus subtilis , with each strain produci...	[ "Bacteria can communicate with each other using chemical signals to activate genetic expression in a process known as quorum sensing .", "Quorum sensing in bacteria is known to regulate a number collective behaviors in bacteria such as biofilm formation , antibiotic production and production of virulence factors ...	2019
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "molecular cell biology", "cell biology", "gene expression", "genetics", "plant genetics", "epigenetics", "biology", "dna modification", "plant cell biology", "molecular biology", "genetics and genomics", "histone modification" ]	The SET-Domain Protein SUVR5 Mediates H3K9me2 Deposition and Silencing at Stimulus Response Genes in a DNA Methylation–Independent Manner	journal.pgen.1002995	null	[ [ "In eukaryotes , chromatin structure regulates the access of the transcriptional machinery to genetic elements , playing an important role in the regulation of gene expression .", "The transition between transcriptionally active ( loosely packed ) chromatin and repressed ( tightly packed ) chromatin state...	[ "In eukaryotic cells , environmental and developmental signals alter chromatin structure and modulate gene expression .", "Heterochromatin constitutes the transcriptionally inactive state of the genome and in plants and mammals is generally characterized by DNA methylation and histone modifications such as histon...	[ "The ability of eukaryotic cells to respond to external stimuli depends on the coordinated activation and repression of specific subsets of genes , often relying on chromatin structure modification .", "Here , we have characterized a locus-specific mechanism to repress gene expression by the action of an Arabidop...	2012
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "medicine", "public health and epidemiology", "epidemiology", "environmental epidemiology", "spatial epidemiology", "epidemiological methods" ]	Spatiotemporal Transmission and Determinants of Typhoid and Paratyphoid Fever in Hongta District, Yunnan Province, China	journal.pntd.0002112	null	[ [ "Typhoid and paratyphoid fever are serious infections , particularly in low-income countries , causing about 16 million cases and 600 , 000 deaths annually worldwide [1] .", "These diseases are notorious for their high infection rate , long duration , and heavy health burden .", "In China , typhoid an...	[ "Typhoid and paratyphoid fever are endemic in Hongta District and their prevalence , at 113 per 100 , 000 individuals , remains the highest in China .", "However , the exact sources of the disease and its main epidemiological characteristics have not yet been clearly identified .", "Numbers of typhoid and parat...	[ "Typhoid and paratyphoid epidemics are serious events in low-income countries; these diseases are notorious for their high infection rate , long duration , and heavy health burden .", "In China , typhoid and paratyphoid are considered to be under control , although the situation varies considerably from place to ...	2013
[ "Introduction", "Materials and methods", "Results", "Discussion" ]	[ "medicine and health sciences", "ears", "immunology", "sand flies", "parasitic diseases", "parasitic protozoans", "otology", "ear infections", "protozoans", "leishmania", "insect vectors", "antibody response", "digestive system", "infectious diseases", "exocrine glands", "head", "oto...	DNA plasmid coding for Phlebotomus sergenti salivary protein PsSP9, a member of the SP15 family of proteins, protects against Leishmania tropica	journal.pntd.0007067	null	[ [ "As a vector-borne parasitic and tropical disease , leishmaniasis has been reported in 98 countries ( in 4 continents ) with an annual incidence level of 0 . 9–1 . 6 million individuals , and 350 million individuals are at the risk of this infection [1 , 2] .", "The Leishmania parasite , as the causative ...	[ "The vector-borne disease leishmaniasis is transmitted to humans by infected female sand flies , which transmits Leishmania parasites together with saliva during blood feeding .", "In Iran , cutaneous leishmaniasis ( CL ) is caused by Leishmania ( L . ) major and L . tropica , and their main vectors are Phlebotom...	[ "Leishmaniasis is a vector-borne disease transmitted to humans by an infected sand fly bite , through which Leishmania parasites and saliva are co-delivered into the host skin .", "Despite the numerous studies performed in this area , no vaccine is yet available to control this neglected disease in humans .", "...	2019
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "molecular biology/histone modification", "molecular biology/transcription initiation and activation", "molecular biology/dna methylation", "neurological disorders/developmental and pediatric neurology", "genetics and genomics/epigenetics" ]	SIRT1 Inhibition Alleviates Gene Silencing in Fragile X Mental Retardation Syndrome	journal.pgen.1000017	null	[ [ "The most common cause of Fragile X mental retardation syndrome ( FXS ) is the silencing of the FMR1 gene that occurs when the number of CGG•CCG-repeats in its 5′ untranslated region ( 5′ UTR ) exceeds 200 [1] , [2] .", "The net result is a deficiency in the FMR1 gene product , FMRP , a protein that regul...	[ "Expansion of the CGG•CCG-repeat tract in the 5′ UTR of the FMR1 gene to >200 repeats leads to heterochromatinization of the promoter and gene silencing .", "This results in Fragile X syndrome ( FXS ) , the most common heritable form of mental retardation .", "The mechanism of gene silencing is unknown .", "W...	[ "Fragile X syndrome is the leading cause of heritable intellectual disability .", "The affected gene , FMR1 , encodes FMRP , a protein that regulates the synthesis of a number of important neuronal proteins .", "The causative mutation is an increase in the number of CGG•CCG-repeats found at the beginning of the...	2008
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "bacteriology", "cell physiology", "fluorescence imaging", "medicine and health sciences", "pathology and laboratory medicine", "fungal spore germination", "pathogens", "cell cycle and cell division", "cell processes", "microbiology", "cell polarity", "streptomyces", "mathematics", "statis...	Unique Function of the Bacterial Chromosome Segregation Machinery in Apically Growing Streptomyces - Targeting the Chromosome to New Hyphal Tubes and its Anchorage at the Tips	journal.pgen.1006488	null	[ [ "Chromosome segregation in unicellular bacteria is strictly coordinated with the cell cycle and chromosomes are segregated during their replication and prior to cell division .", "However , the spatial chromosome organization in bacteria , determined by the position of the origin of replication ( oriC ) i...	[ "The coordination of chromosome segregation with cell growth is fundamental to the proliferation of any organism .", "In most unicellular bacteria , chromosome segregation is strictly coordinated with cell division and involves ParA that moves the ParB nucleoprotein complexes bi- or unidirectionally toward the ce...	[ "To proliferate , cells synchronize growth and division with chromosome segregation .", "In unicellular bacteria , chromosomes segregate during replication by active movement of nucleoprotein complexes toward the cell pole ( s ) .", "Here , we asked the question how active chromosome segregation occurs in the a...	2016
[ "Introduction", "Results/Discussion", "Materials and Methods" ]	[ "bacteriology", "biochemistry", "biology", "microbiology", "biophysics", "bacterial pathogens" ]	Structural and Functional Insights into the Pilotin-Secretin Complex of the Type II Secretion System	journal.ppat.1002531	null	[ [ "The secretins are an important group of bacterial membrane proteins whose function is to facilitate the transport of secreted proteins and macromolecular complexes across the outer membrane [1] .", "They are essential components of the type II and type III secretion systems ( T2SS and T3SS respectively )...	[ "Gram-negative bacteria secrete virulence factors and assemble fibre structures on their cell surface using specialized secretion systems .", "Three of these , T2SS , T3SS and T4PS , are characterized by large outer membrane channels formed by proteins called secretins .", "Usually , a cognate lipoprotein pilot...	[ "Pathogenic bacteria deliver toxins and virulence proteins into host cells and tissues using specialised secretion systems such as the type II and type III secretion systems .", "These secretion systems have a pore formed by secretin protein subunits through which the disease causing protein effectors and toxins ...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "neuroscience" ]	Rapid Interhemispheric Switching during Vocal Production in a Songbird	journal.pbio.0060250	Motor dominance across cerebral hemispheres bounces back and forth like a virtual ping-pong ball during song production in zebra finches.	[ [ "Owing to its complexity and high precision , birdsong has provided an important animal model for studies of motor control .", "Adult zebra finch songs are formed by repetitions of a highly stereotyped motif that is composed of two to eight syllables and is acquired from a tutor during a critical sensorim...	[ "To generate complex bilateral motor patterns such as those underlying birdsong , neural activity must be highly coordinated across the two cerebral hemispheres .", "However , it remains largely elusive how this coordination is achieved given that interhemispheric communication between song-control areas in the a...	[ "As for all vertebrates , the songbird cerebrum has two halves ( or hemispheres ) , each of which controls mainly the muscles in one half of the body .", "Many motor behaviors such as singing rely on high coordination of activity in both hemispheres , yet little is known about the neural mechanisms of this coordi...	2008
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "animal models", "model organisms", "reproductive system", "biology", "anatomy and physiology", "mouse" ]	Liver X Receptors Protect from Development of Prostatic Intra-Epithelial Neoplasia in Mice	journal.pgen.1003483	null	[ [ "The Liver X Receptors ( LXRα , encoded by the gene Nr1h3 , and LXRβ , encoded by the gene Nr1h2 ) belong to the nuclear receptor superfamily and bind to naturally occurring oxidized forms of cholesterol , known as oxysterols [1]–[3] .", "These receptors heterodimerize with RXR ( Retinoid X Receptor ) and...	[ "LXR ( Liver X Receptors ) act as “sensor” proteins that regulate cholesterol uptake , storage , and efflux .", "LXR signaling is known to influence proliferation of different cell types including human prostatic carcinoma ( PCa ) cell lines .", "This study shows that deletion of LXR in mouse fed a high-cholest...	[ "Cholesterol is one of the major metabolic molecules required for a broad range of cellular processes .", "Recent advances in prostate cancer research have demonstrated that tumor cells need to increase their supply of cholesterol to sustain membrane building , proliferation , and survival capacities .", "Liver...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "cognitive neuroscience", "cognitive psychology", "neural networks", "biology and life sciences", "vision", "brain electrophysiology", "evoked potentials", "sensory perception", "cognitive science", "neuroscience", "neurophysiology", "attention" ]	Dynamic Changes in Phase-Amplitude Coupling Facilitate Spatial Attention Control in Fronto-Parietal Cortex	journal.pbio.1001936	Electrocorticography reveals how coupling between two frequencies of neuronal oscillation allows the frontal and parietal areas of the cortex to control visual attention from moment to moment in the human brain.	[ [ "Attention , a critical component of perception and goal-directed behavior , allows the brain to allocate its limited resources depending on current task demands .", "A number of areas located in frontal and posterior parietal cortex ( PPC ) , often referred to collectively as the fronto-parietal attentio...	[ "Attention is a core cognitive mechanism that allows the brain to allocate limited resources depending on current task demands .", "A number of frontal and posterior parietal cortical areas , referred to collectively as the fronto-parietal attentional control network , are engaged during attentional allocation in...	[ "The frontal and parietal areas of the cortex control the ability to focus visuospatial attention , and damage to these areas results in profound attentional disturbances .", "Although much research has concentrated on where these areas are located , little is known about how these areas may function in humans ."...	2014
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "species colonization", "medicine and health sciences", "ecology and environmental sciences", "invasive species", "neutral theory", "population genetics", "social sciences", "random variables", "covariance", "mathematics", "tongue", "population biology", "digestive system", "ecological eco...	Novel Covariance-Based Neutrality Test of Time-Series Data Reveals Asymmetries in Ecological and Economic Systems	journal.pcbi.1005124	null	[ [ "Adaptive evolution requires that rivalrous goods are consumed by agents , those agents have heritable variation in how they acquire and consume the rivalrous goods , and the fitness of agents increases with the amount of goods consumed [2] .", "By Lewontin’s listing of the necessary conditions of evoluti...	[ "Systems as diverse as the interacting species in a community , alleles at a genetic locus , and companies in a market are characterized by competition ( over resources , space , capital , etc ) and adaptation .", "Neutral theory , built around the hypothesis that individual performance is independent of group me...	[ "From fisheries and forestries to game parks and gut microbes , managing a community of organisms is much like managing a portfolio .", "Managers care about diversity , and calculations of risk—for extinction or financial ruin—require accurate models of the covariance between the parts of the portfolio .", "To ...	2016
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "antimicrobials", "medicine and health sciences", "pathology and laboratory medicine", "pathogens", "drugs", "tropical diseases", "microbiology", "geographical locations", "treponematoses", "bacterial diseases", "signs and symptoms", "antibiotics", "ulcers", "neglected tropical diseases", ...	A Single Dose Oral Azithromycin versus Intramuscular Benzathine Penicillin for the Treatment of Yaws-A Randomized Non Inferiority Trial in Ghana	journal.pntd.0005154	null	[ [ "Yaws is a relapsing non-venereal treponematosis caused by Treponema pallidum subspecies pertenue .", "The disease mainly affects the skin , but if untreated , can also affect bone , joints and cartilage .", "Yaws may persist for many years as a chronic infection , and late stage disease may lead to c...	[ "Yaws is a treponemal infection that was almost eradicated fifty years ago; however , the disease has re-emerged in a number of countries including Ghana .", "A single-dose of intramuscular benzathine penicillin has been the mainstay of treatment for yaws .", "However , intramuscular injections are painful and ...	[ "Yaws is a tropical infection caused by a bacterium closely related to that which causes syphilis .", "It is transmitted from person to person through skin to skin contact and often causes papillomatous and ulcerative skin lesions , usually in young children .", "Without treatment , it can lead to deformities a...	2017
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "infectious diseases/neglected tropical diseases", "public health and epidemiology/infectious diseases", "pharmacology", "dermatology/skin infections" ]	Is Paromomycin an Effective and Safe Treatment against Cutaneous Leishmaniasis? A Meta-Analysis of 14 Randomized Controlled Trials	journal.pntd.0000381	null	[ [ "More than 12 million people in 88 countries suffer from leishmaniasis , a condition caused by parasites of the genus Leishmania [1] .", "Annually , two million new cases of leishmaniasis are diagnosed , of which about one quarter present as visceral leishmaniasis , a potentially fatal condition .", "...	[ "High cost , poor compliance , and systemic toxicity have limited the use of pentavalent antimony compounds ( SbV ) , the treatment of choice for cutaneous leishmaniasis ( CL ) .", "Paromomycin ( PR ) has been developed as an alternative to SbV , but existing data are conflicting .", "We searched PubMed , Scopu...	[ "Millions of people worldwide are suffering from cutaneous leishmaniasis that is caused by parasites of the genus Leishmania .", "Although pentavalent antimony compounds are the treatment of choice , their use is limited by high cost , poor compliance , and systemic toxicity .", "Paromomycin was developed to ov...	2009
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "dna damage", "biochemistry", "genetics", "biology and life sciences", "dna", "dna repair", "dna recombination" ]	Fission Yeast Pxd1 Promotes Proper DNA Repair by Activating Rad16XPF and Inhibiting Dna2	journal.pbio.1001946	During DNA double-strand break repair, two structure-specific DNA nucleases are controlled by the same regulator Pxd1, but in opposite manners.	[ [ "Structure-specific DNA nucleases contribute to the maintenance of genome stability by processing DNA secondary structures during DNA replication and repair [1] , [2] .", "The activities of these nucleases must be tightly controlled to prevent unintended cleavage; however , the molecular mechanisms underl...	[ "Structure-specific nucleases play crucial roles in many DNA repair pathways .", "They must be precisely controlled to ensure optimal repair outcomes; however , mechanisms of their regulation are not fully understood .", "Here , we report a fission yeast protein , Pxd1 , that binds to and regulates two structur...	[ "Genome stability maintenance relies on DNA repair enzymes , among which are structure-specific nucleases that cleave DNA in a sequence-independent but structure-dependent manner .", "It is important to understand how the activities of such nucleases are controlled , because either insufficient or excessive cleav...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biochemistry", "cell biology", "yeast and fungi", "microbiology", "computational biology", "eukaryotes", "genetics and genomics", "saccharomyces" ]	Cell Size at S Phase Initiation: An Emergent Property of the G1/S Network	journal.pcbi.0030064	null	[ [ "During the life cycle of eukaryotic cells , DNA replication is restricted to a specific time window , called the S phase .", "Several control mechanisms ensure that each DNA sequence is replicated once , and only once , in the period from one cell division to the next .", "Following S phase , replica...	[ "The eukaryotic cell cycle is the repeated sequence of events that enable the division of a cell into two daughter cells .", "It is divided into four phases: G1 , S , G2 , and M . Passage through the cell cycle is strictly regulated by a molecular interaction network , which involves the periodic synthesis and de...	[ "A major property of living cells is their ability to maintain mass homeostasis throughout cell divisions .", "It has been proposed that in order to achieve such homeostasis , some critical event ( s ) in the cell cycle will take place only when the cell has grown beyond a critical cell size .", "In the budding...	2007
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "invertebrates", "medicine and health sciences", "viral transmission and infection", "molecular probe techniques", "enzymes", "immunology", "microbiology", "enzymology", "animals", "developmental biology", "molecular biology techniques", "research and analysis methods", "immune system protei...	Inhibition of melanization by serpin-5 and serpin-9 promotes baculovirus infection in cotton bollworm Helicoverpa armigera	journal.ppat.1006645	null	[ [ "The cotton bollworm , Helicoverpa armigera , is a major pest of cotton and one of the most destructive and polyphagous pest species .", "It is widespread in central and southern Europe , temperate Asia , Africa , Australia and Oceania , and Brazil [1] .", "Moreover , the rapid spread of H . armigera ...	[ "Melanization , an important insect defense mechanism , is mediated by clip-domain serine protease ( cSP ) cascades and is regulated by serpins .", "Here we show that proteolytic activation of prophenoloxidase ( PPO ) and PO-catalyzed melanization kill the baculovirus in vitro .", "Our quantitative proteomics a...	[ "Melanization is one of important modules in insect defense system .", "It consists of a cascade of clip-domain serine proteases ( cSPs ) that converts the zymogen prophenoloxidase ( PPO ) to active phenoloxidase ( PO ) , which is negatively regulated by serpins .", "PO then catalyses the formation of melanin t...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "evolutionary biology", "genetics and genomics/microbial evolution and genomics", "evolutionary biology/microbial evolution and genomics", "evolutionary biology/evolutionary and comparative genetics" ]	Multiple Molecular Mechanisms Cause Reproductive Isolation between Three Yeast Species	journal.pbio.1000432	Incompatibility between nuclear and mitochondrial genomes in yeast species may represent a general mechanism of reproductive isolation during yeast evolution.	[ [ "Reproductive isolation preventing gene flow between diverging populations is crucial for the process of speciation [1] .", "One of the general reproductive isolation mechanisms that lead to hybrid inviability or sterility is genetic incompatibility ( Dobzhansky-Muller incompatibility ) , which is caused ...	[ "Nuclear-mitochondrial conflict ( cytonuclear incompatibility ) is a specific form of Dobzhansky-Muller incompatibility previously shown to cause reproductive isolation in two yeast species .", "Here , we identified two new incompatible genes , MRS1 and AIM22 , through a systematic study of F2 hybrid sterility ca...	[ "Hybrids between species are usually inviable or sterile , possibly due to functional incompatibility between genes from the different species .", "Incompatible genes are hypothesized to encode interacting components that cannot function properly when paired with alleles from another species .", "To understand ...	2010
[ "Introduction", "Results/Discussion", "Materials and Methods" ]	[ "computational biology/macromolecular structure analysis", "computer science/applications", "virology/diagnosis", "virology/immunodeficiency viruses", "molecular biology/bioinformatics", "computational biology/macromolecular sequence analysis", "biophysics", "virology/host invasion and cell entry" ]	Prediction of Co-Receptor Usage of HIV-1 from Genotype	journal.pcbi.1000743	null	[ [ "Specific protein interactions are central to biological processes , and the infection of cells with viruses is no exception there .", "In the case of pathogenic viruses , such protein interactions are potential targets for medical intervention .", "An example of particularly high relevance is Human I...	[ "Human Immunodeficiency Virus 1 uses for entry into host cells a receptor ( CD4 ) and one of two co-receptors ( CCR5 or CXCR4 ) .", "Recently , a new class of antiretroviral drugs has entered clinical practice that specifically bind to the co-receptor CCR5 , and thus inhibit virus entry .", "Accurate prediction...	[ "Human Immunodeficiency Virus is the pathogen causing the disease AIDS .", "A precondition for virus entry into human cells is the contact of its glycoprotein gp120 with two cellular proteins , a receptor and a co-receptor .", "Depending on the viral strain , one specific co-receptor is used .", "The type of ...	2010
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "mathematics/statistics", "oncology/pediatric oncology", "computational biology/systems biology", "hematology/acute lymphoblastic leukemia" ]	Modeling Mechanisms of In Vivo Variability in Methotrexate Accumulation and Folate Pathway Inhibition in Acute Lymphoblastic Leukemia Cells	journal.pcbi.1001019	null	[ [ "Methotrexate ( MTX ) is one of the primary anticancer agents used for the treatment of acute lymphoblastic leukemia ( ALL ) [1]–[3] .", "The ability of cells to accumulate intracellular polyglutamate metabolites of MTX ( MTXPG ) is an important factor in its antileukemic effects [4] .", "Specifically...	[ "Methotrexate ( MTX ) is widely used for the treatment of childhood acute lymphoblastic leukemia ( ALL ) .", "The accumulation of MTX and its active metabolites , methotrexate polyglutamates ( MTXPG ) , in ALL cells is an important determinant of its antileukemic effects .", "We studied 194 of 356 patients enro...	[ "One of the primary agents used in the treatment of childhood acute lymphoblastic leukemia ( ALL ) is methotrexate ( MTX ) .", "By better understanding its intracellular disposition , we are able to better design treatments that circumvent drug resistance and thus help improve ALL cure rates .", "In this study ...	2010
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "blood cells", "medicine and health sciences", "neurochemistry", "immune cells", "pathology and laboratory medicine", "statistics", "pathogens", "immunology", "microbiology", "neuroscience", "staphylococcus aureus", "bacterial diseases", "mathematics", "test statistics", "bacteria", "b...	Human genetic variation in GLS2 is associated with development of complicated Staphylococcus aureus bacteremia	journal.pgen.1007667	null	[ [ "Staphylococcus aureus is a significant human pathogen and leading cause of skin and soft tissue infection ( SSTI ) and bacteremia ( SAB ) in community and healthcare settings .", "Incidence of SAB ranges from 10 to 30 per 100 , 000 person-years in developed countries and may present as an “uncomplicated”...	[ "The role of host genetic variation in the development of complicated Staphylococcus aureus bacteremia ( SAB ) is poorly understood .", "We used whole exome sequencing ( WES ) to examine the cumulative effect of coding variants in each gene on risk of complicated SAB in a discovery sample of 168 SAB cases ( 84 co...	[ "Complications from bloodstream infection with Staphylococcus aureus ( S . aureus ) are important causes of hospitalization , significant illness , and death .", "The causes of these complications are not well understood , but likely involve genetic factors rendering people more susceptible to such infections , d...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "infectious diseases/infectious diseases of the nervous system", "virology/persistence and latency", "molecular biology/translational regulation", "virology/viral replication and gene regulation" ]	Autogenous Translational Regulation of the Borna Disease Virus Negative Control Factor X from Polycistronic mRNA Using Host RNA Helicases	journal.ppat.1000654	null	[ [ "The control of translation initiation on mRNA is one of the most fundamental processes in the regulation of gene expression .", "Most eukaryotic mRNAs initiate translation via the so-called “scanning mechanism” , in which the 40S ribosomal subunit binds to the cap structure at the 5′-terminus of mRNA and...	[ "Borna disease virus ( BDV ) is a nonsegmented , negative-strand RNA virus that employs several unique strategies for gene expression .", "The shortest transcript of BDV , X/P mRNA , encodes at least three open reading frames ( ORFs ) : upstream ORF ( uORF ) , X , and P in the 5′ to 3′ direction .", "The X is a...	[ "All viruses rely on host cell factors to complete their life cycles .", "Therefore , the replication strategies of viruses may provide not only the understanding of virus pathogenesis but also useful models to disentangle the complex machinery of host cells .", "Translation regulation of viral mRNA is a good e...	2009
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "population genetics", "sequence assembly tools", "algorithms", "genome sequencing", "genome analysis tools", "population biology", "mitochondrial diseases", "sequence analysis", "genetic polymorphism", "biology", "computer science", "genetics", "genomics", "computational biology", "gene...	Next-Generation Sequencing of Human Mitochondrial Reference Genomes Uncovers High Heteroplasmy Frequency	journal.pcbi.1002737	null	[ [ "The first complete human ‘genome’ sequenced was that of the mitochondrion in 1981 [1] .", "Since then , over 8 , 250 complete human and 3 , 220 complete non-human vertebrate mitochondrial genomes have been sequenced ( http://www . ncbi . nlm . nih . gov ) .", "These contributions have come from numer...	[ "We describe methods for rapid sequencing of the entire human mitochondrial genome ( mtgenome ) , which involve long-range PCR for specific amplification of the mtgenome , pyrosequencing , quantitative mapping of sequence reads to identify sequence variants and heteroplasmy , as well as de novo sequence assembly ."...	[ "This manuscript details a novel algorithm to evaluate high-throughput DNA sequence data from whole mitochondrial genomes purified from genomic DNA , which also contains multiple fragmented nuclear copies of mtgenomes ( numts ) .", "40 samples were selected from 2 distinct reference ( HapMap ) populations of Afri...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods", "Supporting Information" ]	[ "infectious diseases", "microbiology", "eubacteria" ]	Vaccine Escape Recombinants Emerge after Pneumococcal Vaccination in the United States	journal.ppat.0030168	null	[ [ "Streptococcus pneumoniae ( the “pneumococcus” ) is one of the most important bacterial pathogens worldwide , especially among children .", "Pneumococcal pneumonia , meningitis , and septicemia result in 1 million deaths annually among children <5 y of age [1] .", "PCV7 protects against seven pneumoco...	[ "The heptavalent pneumococcal conjugate vaccine ( PCV7 ) was introduced in the United States ( US ) in 2000 and has significantly reduced invasive pneumococcal disease; however , the incidence of nonvaccine serotype invasive disease , particularly due to serotype 19A , has increased .", "The serotype 19A increase...	[ "The 7-valent pneumococcal conjugate vaccine is a remarkable public health success story .", "It has significantly reduced invasive pneumococcal disease in the United States not only by protecting vaccinated children , but also by protecting unvaccinated older children and adults by herd immunity .", "However ,...	2007
[ "Introduction", "Materials and methods", "Results", "Discussion" ]	[ "cell physiology", "carbohydrate metabolism", "protein metabolism", "biological cultures", "metabolic networks", "enzymology", "cell metabolism", "glucose metabolism", "metabolites", "network analysis", "enzyme metabolism", "cell cultures", "thermodynamics", "enzyme chemistry", "research...	Maximum entropy and population heterogeneity in continuous cell cultures	journal.pcbi.1006823	null	[ [ "Recombinant protein production requires suitable cell hosts and culture conditions [1] .", "For this purpose mammalian cells are often grown in chemostat-like cultures where a continuous flow of incoming fresh media replaces culture liquid containing cells and metabolites .", "Alternative processes s...	[ "Continuous cultures of mammalian cells are complex systems displaying hallmark phenomena of nonlinear dynamics , such as multi-stability , hysteresis , as well as sharp transitions between different metabolic states .", "In this context mathematical models may suggest control strategies to steer the system towar...	[ "While the advantages of continuous culture in the biotechnological industry have been widely advocated in the literature , its adoption over batch or fed-batch modes stalls due to the complexities of these systems .", "In particular , continuous cell cultures display hallmark nonlinear phenomena such as multi-st...	2019
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genetics", "biology", "gene function" ]	CEP-1, the Caenorhabditis elegans p53 Homolog, Mediates Opposing Longevity Outcomes in Mitochondrial Electron Transport Chain Mutants	journal.pgen.1004097	null	[ [ "Mitochondria are major sites of numerous metabolic processes , in particular electron transport and ATP production , and are essential for life .", "Not surprisingly , mitochondria also play central roles in aging and disease [1] .", "In model organisms such as worms , flies , and mice , specific poi...	[ "Caenorhabditis elegans CEP-1 and its mammalian homolog p53 are critical for responding to diverse stress signals .", "In this study , we found that cep-1 inactivation suppressed the prolonged lifespan of electron transport chain ( ETC ) mutants , such as isp-1 and nuo-6 , but rescued the shortened lifespan of ot...	[ "Perturbing different components of the mitochondrial electron transport chain ( ETC ) can affect the lifespan of Caenorhabditis elegans in divergent ways .", "ETC dysfunction can either attenuate or extend C . elegans lifespan .", "Here we demonstrate that the C . elegans homolog of mammalian p53 , CEP-1 , is ...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genetics and genomics/pharmacogenomics", "pharmacology/personalized medicine", "mathematics/statistics" ]	A Genome-Wide Association Study Confirms VKORC1, CYP2C9, and CYP4F2 as Principal Genetic Determinants of Warfarin Dose	journal.pgen.1000433	null	[ [ "Warfarin is the most widely prescribed anticoagulant for reducing thromboembolic events that often give rise to stroke , deep vein thrombosis , pulmonary embolism or serious coronary malfunctions [1] .", "A combination of genetic and non-genetic factors cause Caucasians to exhibit 20-fold interindividual...	[ "We report the first genome-wide association study ( GWAS ) whose sample size ( 1 , 053 Swedish subjects ) is sufficiently powered to detect genome-wide significance ( p<1 . 5×10−7 ) for polymorphisms that modestly alter therapeutic warfarin dose .", "The anticoagulant drug warfarin is widely prescribed for reduc...	[ "Recently , geneticists have begun assaying hundreds of thousands of genetic markers covering the entire human genome to systematically search for and identify genes that cause disease .", "We have extended this “genome-wide association study” ( GWAS ) method by assaying ∼326 , 000 markers in 1 , 053 Swedish pati...	2009
[ "Introduction", "Methods", "Results", "Discussion" ]	[]	Geographic Distribution and Mortality Risk Factors during the Cholera Outbreak in a Rural Region of Haiti, 2010-2011	journal.pntd.0003605	null	[ [ "The cholera epidemic in Haiti , which began in 2010 spread rapidly in both urban and rural areas .", "One month after confirmation of the first case in Mirebalais , in the department of Centre , the whole country had been affected [1 , 2] .", "During the first few days , the focus was on case managem...	[ "In 2010 and 2011 , Haiti was heavily affected by a large cholera outbreak that spread throughout the country .", "Although national health structure-based cholera surveillance was rapidly initiated , a substantial number of community cases might have been missed , particularly in remote areas .", "We conducted...	[ "In October 2010 , a large cholera outbreak was declared in Haiti and rapidly spread throughout the country , quickly overwhelming the existing health system .", "Specialized treatment structures were opened rapidly , generally in cities or large villages , and decentralized treatment units or rehydration points ...	2015
[ "Introduction", "Results", "Discussion", "Methods" ]	[]	The Influence of Synaptic Weight Distribution on Neuronal Population Dynamics	journal.pcbi.1003248	null	[ [ "Experiments analyzing the distribution of synaptic weights impinging onto neurons typically observe low-amplitude peaks with only few , large-amplitude excitatory ( EPSPs ) or inhibitory post-synaptic potentials ( IPSPs ) [1]–[14] .", "These have been fitted by lognormal [1] , truncated Gaussian [10] , [...	[ "The manner in which different distributions of synaptic weights onto cortical neurons shape their spiking activity remains open .", "To characterize a homogeneous neuronal population , we use the master equation for generalized leaky integrate-and-fire neurons with shot-noise synapses .", "We develop fast semi...	[ "Neurons communicate via action potentials .", "Typically , depolarizations caused by presynaptic firing are small , such that many synaptic inputs are necessary to exceed the firing threshold .", "This is the assumption made by standard mathematical approaches such as the Fokker-Planck formalism .", "However...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Leishmania infantum Modulates Host Macrophage Mitochondrial Metabolism by Hijacking the SIRT1-AMPK Axis	journal.ppat.1004684	null	[ [ "Visceral leishmaniasis ( VL ) is a potentially fatal vector-borne disease caused by protozoan Leishmania donovani and L . infantum parasites .", "Infection of the mammalian host is initiated with the inoculation of the flagellated promastigote forms during the sand fly bloodmeal .", "Once inside the ...	[ "Metabolic manipulation of host cells by intracellular pathogens is currently recognized to play an important role in the pathology of infection .", "Nevertheless , little information is available regarding mitochondrial energy metabolism in Leishmania infected macrophages .", "Here , we demonstrate that during...	[ "Leishmania infantum , a causative agent of visceral leishmaniasis , is able to infect host macrophages and modulate a myriad of signalling pathways that contributes to the disease outcome .", "In order to survive , L . infantum must compete with the host for the same metabolic resources , however scarce attentio...	2015
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "learning", "decision making", "applied mathematics", "social sciences", "neuroscience", "habits", "learning and memory", "simulation and modeling", "algorithms", "cognitive psychology", "mathematics", "statistics (mathematics)", "cognition", "discrete mathematics", "combinatorics", "r...	Flexibility to contingency changes distinguishes habitual and goal-directed strategies in humans	journal.pcbi.1005753	null	[ [ "For optimal decision-making , animals must learn to associate the choices they make with the outcomes that arise from them .", "Classical learning theories suggest that this problem is addressed by habitual or goal-directed strategies for reinforcement learning [1 , 2] .", "These strategies differ in...	[ "Decision-making in the real world presents the challenge of requiring flexible yet prompt behavior , a balance that has been characterized in terms of a trade-off between a slower , prospective goal-directed model-based ( MB ) strategy and a fast , retrospective habitual model-free ( MF ) strategy .", "Theory pr...	[ "To make good decisions , we must learn to associate actions with their true outcomes .", "Flexibility to changes in action/outcome relationships , therefore , is essential for optimal decision-making .", "For example , actions can lead to outcomes that change in value – one day , your favorite food is poorly m...	2017
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "rna interference", "brassica", "rna stability", "model organisms", "epigenetics", "plants", "research and analysis methods", "arabidopsis thaliana", "gene expression", "biochemistry", "rna", "plant and algal models", "rna processing", "cell biology", "nucleic acids", "genetics", "bi...	The RNA Helicases AtMTR4 and HEN2 Target Specific Subsets of Nuclear Transcripts for Degradation by the Nuclear Exosome in Arabidopsis thaliana	journal.pgen.1004564	null	[ [ "Efficient processing and degradation of RNA is a key process for the post-transcriptional control of gene expression .", "The main 3′-5′ RNA degradation machine of eukaryotic cells is the exosome , a multi-subunit complex found in both cytoplasm and nuclear compartments [1] , [2] .", "The exosome par...	[ "The RNA exosome is the major 3′-5′ RNA degradation machine of eukaryotic cells and participates in processing , surveillance and turnover of both nuclear and cytoplasmic RNA .", "In both yeast and human , all nuclear functions of the exosome require the RNA helicase MTR4 .", "We show that the Arabidopsis core ...	[ "Cells rely on a number of RNA degradation pathways to ensure correct and timely processing and turnover of both coding and non-coding RNAs .", "Another important function of RNA degradation is the rapid elimination of misprocessed RNA species , maturation by-products , and nonfunctional RNAs that are frequently ...	2014
[ "Introduction", "Materials and methods", "Results and discussion", "Conclusion" ]	[ "phosphorylation", "random variables", "covariance", "protein expression", "mathematics", "tcr signaling cascade", "molecular biology techniques", "cellular structures and organelles", "mapk signaling cascades", "cytoskeleton", "research and analysis methods", "proteins", "gene expression", ...	A knowledge-based T2-statistic to perform pathway analysis for quantitative proteomic data	journal.pcbi.1005601	null	[ [ "Great progress has been made toward the development of high-throughput technologies and their application to biological and clinical research .", "In a quantitative experiment , genes or proteins with significant changes in expression are potential to have important roles in a given phenotype or phenomen...	[ "Approaches to identify significant pathways from high-throughput quantitative data have been developed in recent years .", "Still , the analysis of proteomic data stays difficult because of limited sample size .", "This limitation also leads to the practice of using a competitive null as common approach; which...	[ "Pathway analysis is a common approach to quickly access the pathways being regulated in the experiments .", "There are numerous statistics to perform pathway analysis; most of them assume that the genes or proteins are independent of each other for statistical ease .", "This assumption , however , is unrealist...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine", "infectious diseases", "biology", "microbiology", "molecular cell biology" ]	Leishmania Induces Survival, Proliferation and Elevated Cellular dNTP Levels in Human Monocytes Promoting Acceleration of HIV Co-Infection	journal.ppat.1002635	null	[ [ "Leishmaniasis has recently been recognized to be both one of the world's most neglected and most important parasitic diseases , threatening an estimated 350 million people worldwide [1] , [2] .", "Surveys have estimated that approximately 12 million people are currently infected with 2 million new cases ...	[ "Leishmaniasis is a parasitic disease that is widely prevalent in many tropical and sub-tropical regions of the world .", "Infection with Leishmania has been recognized to induce a striking acceleration of Human Immunodeficiency Virus Type 1 ( HIV-1 ) infection in coinfected individuals through as yet incompletel...	[ "Leishmaniasis is a parasitic disease that infects several human host immune cells , including neutrophils , monocytes , and macrophages .", "Moreover , while HIV-1 infects monocytes and macrophages , only the infected macrophages productively release viral progenies .", "Importantly , patients coinfected with ...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "animal models", "medicine", "oncology", "developmental biology", "model organisms", "genetics", "biology", "genomics", "morphogenesis", "genetics and genomics" ]	Nos2 Inactivation Promotes the Development of Medulloblastoma in Ptch1+/− Mice by Deregulation of Gap43–Dependent Granule Cell Precursor Migration	journal.pgen.1002572	null	[ [ "Medulloblastoma ( MB ) is a highly malignant tumor of the cerebellum that preferentially develops in children and adolescents .", "Although the survival rate for standard risk MB is around 70% [1] surviving patients often suffer from neurodevelopmental and cognitive side effects of the aggressive therapy...	[ "Medulloblastoma is the most common malignant brain tumor in children .", "A subset of medulloblastoma originates from granule cell precursors ( GCPs ) of the developing cerebellum and demonstrates aberrant hedgehog signaling , typically due to inactivating mutations in the receptor PTCH1 , a pathomechanism recap...	[ "Medulloblastoma is a common pediatric brain tumor , a subtype of which is driven by aberrant hedgehog pathway activation in cerebellar granule cell precursors .", "Although this tumor etiology has been intensively investigated in the well-established Ptch1+/− mouse model , knowledge is still lacking about the mo...	2012
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "pestivirus", "medicine and health sciences", "poxviruses", "pathology and laboratory medicine", "enzymes", "pathogens", "microbiology", "enzymology", "viral structure", "viruses", "developmental biology", "rna viruses", "dna viruses", "morphogenesis", "proteins", "medical microbiology...	A positive-strand RNA virus uses alternative protein-protein interactions within a viral protease/cofactor complex to switch between RNA replication and virion morphogenesis	journal.ppat.1006134	null	[ [ "The Flaviviridae family comprises positive-strand RNA viruses and consists of four genera , Flavivirus , Pegivirus , Hepacivirus , and Pestivirus , with the latter three genera showing a significantly higher degree of similarity [1–3] .", "Pestiviruses , like bovine viral diarrhea virus ( BVDV-1 and -2 )...	[ "The viruses of the family Flaviviridae possess a positive-strand RNA genome and express a single polyprotein which is processed into functional proteins .", "Initially , the nonstructural ( NS ) proteins , which are not part of the virions , form complexes capable of genome replication .", "Later on , the NS p...	[ "Many positive-strand RNA viruses replicate without transcribing subgenomic RNAs otherwise often used to temporally coordinate the expression of proteins involved either in genome replication ( early ) or virion formation ( late ) .", "Instead , the RNA genomes of the Flaviviridae are translated into a single pol...	2017
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "population genetics", "ploidy", "microbiology", "parastic protozoans", "dna", "genetic polymorphism", "dna amplification", "biology", "molecular biology", "trypanosoma", "nucleic acids", "genetics", "protozoology", "molecular cell biology", "genetics and genomics" ]	Unequivocal Identification of Subpopulations in Putative Multiclonal Trypanosoma cruzi Strains by FACs Single Cell Sorting and Genotyping	journal.pntd.0001722	null	[ [ "Chagas disease , an American protozoonosis caused by Trypanosoma cruzi , is characterized by various clinical manifestations ranging from asymptomatic to severe cardiac and/or digestive injuries .", "This complex ailment still afflicts 10 million people across Latin America and another 90 million are at ...	[ "Trypanosoma cruzi , the etiological agent of Chagas disease , is a polymorphic species .", "Evidence suggests that the majority of the T . cruzi populations isolated from afflicted humans , reservoir animals , or vectors are multiclonal .", "However , the extent and the complexity of multiclonality remain to b...	[ "Trypanosoma cruzi , the cause of Chagas disease , is responsible for high levels of mortality and morbidity in many countries of Latin America .", "This species is very polymorphic and was recently classified into six discrete typing units ( TcI-VI ) that are associated with different geographical distribution ,...	2012
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "medicine", "infectious diseases", "neglected tropical diseases", "immunology", "biology", "zoology", "parasitic diseases", "immune system" ]	Immunization with L. sigmodontis Microfilariae Reduces Peripheral Microfilaraemia after Challenge Infection by Inhibition of Filarial Embryogenesis	journal.pntd.0001558	null	[ [ "Infections with filarial nematodes are classified among the “neglected tropical diseases” and cause serious public health problems in the tropics and subtropics with more than 150 million people infected and many more at risk .", "Lymphatic filariasis ( LF ) caused by the filarial nematodes Wuchereria ba...	[ "Lymphatic filariasis and onchocerciasis are two chronic diseases mediated by parasitic filarial worms causing long term disability and massive socioeconomic problems .", "Filariae are transmitted by blood-feeding mosquitoes that take up the first stage larvae from an infected host and deliver it after maturation...	[ "Lymphatic filariasis is caused by parasitic filarial worms that are transmitted by mosquitoes , requiring uptake of larvae and distribution into the blood of the host .", "More than 120 million people are infected and about 30% of these individuals suffer from clinical symptoms .", "Reduction in transmission c...	2012
[ "Introduction", "Methods", "Results", "Discussion" ]	[]	Mechanisms of Left-Right Coordination in Mammalian Locomotor Pattern Generation Circuits: A Mathematical Modeling View	journal.pcbi.1004270	null	[ [ "Central Pattern Generators ( CPGs ) are neural networks that can produce organized rhythmic motor activities in the absence of rhythmic inputs and feedbacks from other parts of the nervous system .", "The CPGs that generate basic rhythmic locomotor activities and control locomotion in vertebrates are loc...	[ "The locomotor gait in limbed animals is defined by the left-right leg coordination and locomotor speed .", "Coordination between left and right neural activities in the spinal cord controlling left and right legs is provided by commissural interneurons ( CINs ) .", "Several CIN types have been genetically iden...	[ "Movements of left and right limbs in mammals during locomotion are controlled by distinct rhythm-generating neuronal circuits in the spinal cord .", "Complex interactions between these circuits provide flexible coordination of limb movements in different gaits .", "It was shown that interactions between left a...	2015
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "public and occupational health", "bacterial diseases", "infectious diseases", "buruli ulcer", "medicine and health sciences", "psychology", "disabilities", "behavioral and social aspects of health", "global health", "neglected tropical diseases", "biology and life sciences", "tropical disease...	Good Quality of Life in Former Buruli Ulcer Patients with Small Lesions: Long-Term Follow-up of the BURULICO Trial	journal.pntd.0002964	null	[ [ "Buruli ulcer ( BU ) is listed by the World Health Organization ( WHO ) as a neglected tropical disease , caused by infection with Mycobacterium ulcerans .", "Although the disease has been reported from as many as 30 countries around the world , it is currently most common in West and Central Africa , and...	[ "Buruli Ulcer is a tropical skin disease caused by Mycobacterium ulcerans , which , due to scarring and contractures can lead to stigma and functional limitations .", "However , recent advances in treatment , combined with increased public health efforts have the potential to significantly improve disease outcome...	[ "Buruli ulcer is an infectious skin disease , mainly occurring in West Africa .", "It usually starts with a small nodule that over the course of weeks progresses into an ulcer .", "Effective treatment with antibiotics is available , but patients often report to the hospital late , and there is a serious risk of...	2014
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "geomorphology", "invertebrates", "medicine and health sciences", "landforms", "topography", "vector-borne diseases", "geographical locations", "animals", "tanzania", "molecular biology techniques", "infectious disease control", "insect vectors", "africa", "islands", "research and analys...	Lymphatic filariasis transmission on Mafia Islands, Tanzania: Evidence from xenomonitoring in mosquito vectors	journal.pntd.0005938	null	[ [ "Lymphatic filariasis ( LF ) is a chronic infection with serious physical , mental and socio- economic consequences to the affected individuals , and ranked as one the leading causes of long-term disability in the world [1 , 2] .", "In Sub-Saharan Africa , LF is caused by the filarial nematode Wuchereria ...	[ "Lymphatic filariasis ( LF ) is a chronic nematode infection transmitted by mosquitoes and in sub-Saharan Africa it is caused by Wuchereria bancrofti .", "The disease was targeted for global elimination by 2020 using repeated community-wide mass drug administration ( MDA ) distributed in endemic areas .", "Howe...	[ "Lymphatic filariasis is a chronic human disease caused by parasitic worms and transmitted by mosquitoes .", "The disease is targeted for elimination by 2020 through the treatment of the entire population at risk in endemic areas using a mass drug administration ( MDA ) strategy .", "After several years of MDA ...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "bacterial diseases", "infectious diseases", "mycobacteria", "medicine and health sciences", "medical microbiology", "microbial pathogens", "biology and life sciences", "microbiology", "bacterial pathogens" ]	Adequate Th2-Type Response Associates with Restricted Bacterial Growth in Latent Mycobacterial Infection of Zebrafish	journal.ppat.1004190	null	[ [ "Tuberculosis ( TB ) is a pulmonary disease spread worldwide .", "It is caused by an infection with Mycobacterium tuberculosis .", "Only 5–10% of infected individuals develop a primary active disease while the most common outcome of infection is a latent or subclinical disease with no evident symptoms...	[ "Tuberculosis is still a major health problem worldwide .", "Currently it is not known what kind of immune responses lead to successful control and clearance of Mycobacterium tuberculosis .", "This gap in knowledge is reflected by the inability to develop sufficient diagnostic and therapeutic tools to fight tub...	[ "Tuberculosis is a common and potentially lethal lung disease spread worldwide .", "One third of the world's population is estimated to be infected with Mycobacterium tuberculosis , yet most individuals develop a latent disease which has the potential to reactivate .", "Some are thought to be able to clear the ...	2014
[ "Introduction", "Results", "Materials and methods" ]	[ "herpes simplex virus", "medicine and health sciences", "pathology and laboratory medicine", "pathogens", "microbiology", "nucleocapsids", "viral structure", "viruses", "dna viruses", "herpesviruses", "herpes simplex virus-1", "medical microbiology", "microbial pathogens", "viral packaging...	Structure of the herpes simplex virus portal-vertex	journal.pbio.2006191	null	[ [ "Herpes Simplex Virus 1 and 2 ( HSV-1 and HSV-2 ) are important human pathogens .", "It is estimated that approximately 90% of the world’s population are infected with one or both viruses [1] .", "HSV-1 is the primary cause of cold sores and HSV-2 of genital herpes .", "These conditions are both h...	[ "Herpesviruses include many important human pathogens such as herpes simplex virus , cytomegalovirus , varicella-zoster virus , and the oncogenic Epstein–Barr virus and Kaposi sarcoma–associated herpesvirus .", "Herpes virions contain a large icosahedral capsid that has a portal at a unique 5-fold vertex , simila...	[ "The herpesvirus family includes many important human pathogens such as herpes simplex viruses that cause cold-sores and human cytomegalovirus , a major cause of congenital abnormalities .", "Several herpes viruses are known to cause cancer .", "Herpes viruses assemble enveloped virus particles ( virions ) that...	2018
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[]	Two components of the rhpPC operon coordinately regulate the type III secretion system and bacterial fitness in Pseudomonas savastanoi pv. phaseolicola	journal.ppat.1007673	null	[ [ "Many Gram-negative bacterial pathogens rely on the T3SS for successful infection of their hosts [1] .", "The T3SS is encoded by a cluster of hrp/hrc genes that are essential for the induction of a hypersensitive response ( HR ) in resistant and nonhost plants and pathogenicity in susceptible plants [2] ....	[ "Many plant bacterial pathogens including Pseudomonas species , utilize the type III secretion system ( T3SS ) to deliver effector proteins into plant cells .", "Genes encoding the T3SS and its effectors are repressed in nutrient-rich media but are rapidly induced after the bacteria enter a plant or are transferr...	[ "The induction of the type III secretion system ( T3SS ) is of great importance to the pathogenesis of bacterial pathogens in host plants .", "Pseudomonas savastanoi pv .", "phaseolicola ( Psph ) causes halo blight disease on beans .", "We discovered that the bicistronic genes in the rhpPC locus of Psph act c...	2019
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "medicine and health sciences", "physicians", "medical doctors", "medical personnel", "influenza", "atmospheric science", "spatial epidemiology", "health care", "health care providers", "infectious disease control", "humidity", "public and occupational health", "infectious diseases", "epid...	Deploying digital health data to optimize influenza surveillance at national and local scales	journal.pcbi.1006020	null	[ [ "Seasonal influenza represents an important public health burden worldwide , and even within a single year , there is substantial variation in disease burden across populations [1–3] .", "On the other hand , pandemic influenza , which has the potential to cause millions of fatalities , is characterized by...	[ "The surveillance of influenza activity is critical to early detection of epidemics and pandemics and the design of disease control strategies .", "Case reporting through a voluntary network of sentinel physicians is a commonly used method of passive surveillance for monitoring rates of influenza-like illness ( I...	[ "Influenza contributes substantially to global morbidity and mortality each year , and epidemiological surveillance for influenza is typically conducted by sentinel physicians and health care providers recruited to report cases of influenza-like illness .", "While population coverage and representativeness , and ...	2018
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "medicine and health sciences", "immune physiology", "crystal structure", "pathology and laboratory medicine", "pathogens", "immunology", "condensed matter physics", "microbiology", "viral structure", "retroviruses", "viruses", "immunodeficiency viruses", "monomers (chemistry)", "rna virus...	Lipid interactions and angle of approach to the HIV-1 viral membrane of broadly neutralizing antibody 10E8: Insights for vaccine and therapeutic design	journal.ppat.1006212	null	[ [ "The HIV-1 envelope protein ( Env ) , a hetero-trimer of non-covalently linked gp120 and gp41 subunits , is the target of broadly neutralizing antibodies ( bnAbs ) [1] .", "BnAbs recognize several sites of vulnerability on Env [2] .", "The membrane proximal external region ( MPER ) of Env is one of it...	[ "Among broadly neutralizing antibodies to HIV , 10E8 exhibits greater neutralizing breadth than most .", "Consequently , this antibody is the focus of prophylactic/therapeutic development .", "The 10E8 epitope has been identified as the conserved membrane proximal external region ( MPER ) of gp41 subunit of the...	[ "The trimeric Env glycoprotein located on HIV surface is the target of broadly neutralizing antibodies and is the focus of vaccine and therapeutic approaches to prevent HIV infection .", "Structural studies with HIV Env trimers have shed light on the complete epitopes of several broadly neutralizing antibodies ."...	2017
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "infectious diseases/neglected tropical diseases", "ecology/population ecology", "mathematics/nonlinear dynamics" ]	Estimating Contact Process Saturation in Sylvatic Transmission of Trypanosoma cruzi in the United States	journal.pntd.0000656	null	[ [ "Since the Brazilian physician Carlos Chagas discovered the parasite Trypanosoma cruzi in 1909 , much research has been devoted throughout the Americas to the study of its transmission and control , primarily in the domestic and peridomestic settings in which it is passed to humans , via triatomine insect vec...	[ "Although it has been known for nearly a century that strains of Trypanosoma cruzi , the etiological agent for Chagas' disease , are enzootic in the southern U . S . , much remains unknown about the dynamics of its transmission in the sylvatic cycles that maintain it , including the relative importance of different...	[ "The parasite Trypanosoma cruzi , transmitted by insect vectors , causes Chagas' disease , which affects millions of people throughout the Americas and over 100 other mammalian species .", "In the United States , infection in humans is believed rare , but prevalence is high in hosts like raccoons and opossums in ...	2010
[ "Introduction", "Results", "Discussion", "Material and Methods" ]	[ "animal models", "developmental biology", "zebrafish", "model organisms", "biology", "evolutionary biology", "evolutionary developmental biology" ]	Development and Evolution of the Muscles of the Pelvic Fin	journal.pbio.1001168	null	[ [ "Studies of a number of fossil forms have provided information on the evolution of the appendicular skeleton of the hindlimbs within early tetrapods [1]–9 .", "These analyses have revealed that the tetrapod transition is characterised by the gradual replacement of a relatively gracile , ventrally located ...	[ "Locomotor strategies in terrestrial tetrapods have evolved from the utilisation of sinusoidal contractions of axial musculature , evident in ancestral fish species , to the reliance on powerful and complex limb muscles to provide propulsive force .", "Within tetrapods , a hindlimb-dominant locomotor strategy pre...	[ "The transition of vertebrates from water to land is a fundamental step in the evolution of terrestrial life .", "Innovations that were critical to this transition were the evolution of a weight bearing pelvis , hindlimbs and their associated musculature , and the development of the “rear wheel drive” strategy th...	2011
[ "Introduction", "Materials and methods", "Results", "Discussion" ]	[ "dengue virus", "medicine and health sciences", "enzyme-linked immunoassays", "immune physiology", "pathology and laboratory medicine", "pathogens", "immunology", "microbiology", "viruses", "rna viruses", "antibodies", "immunologic techniques", "cross reactivity", "research and analysis me...	High specificity and sensitivity of Zika EDIII-based ELISA diagnosis highlighted by a large human reference panel	journal.pntd.0007747	null	[ [ "Zika virus ( ZIKV ) was isolated in 1947 in the Zika forest in Uganda [1] and has been responsible for sporadic cases for several decades .", "Epidemics in Yap State , Micronesia ( 2007 ) [2] , French Polynesia ( 2013 ) [3] , and more recently the Americas 2015 [4] , have dramatically changed its status ...	[ "Zika virus ( ZIKV ) and Dengue virus ( DENV ) are often co-endemic .", "The high protein-sequence homology of flaviviruses renders IgG induced by and directed against them highly cross-reactive against their antigen ( s ) , as observed on a large set of sera , leading to poorly reliable sero-diagnosis .", "We ...	[ "The serological detection of Zika virus ( ZIKV ) is a challenge , as ZIKV infection generally leads to an immune response with a high level of cross reactivity against related viruses , such as Dengue virus .", "Although seroneutralization assays are the gold-standard to address specificity , a rapid and cost-ef...	2019
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "immunology/immunomodulation", "virology", "virology/immune evasion", "virology/effects of virus infection on host gene expression" ]	Co-Regulation of NF-κB and Inflammasome-Mediated Inflammatory Responses by Myxoma Virus Pyrin Domain-Containing Protein M013	journal.ppat.1000635	null	[ [ "The nuclear factor κB ( NF-κB ) family comprise a set of related transcription factors that regulate multiple cellular pathways associated with immune responses , inflammation , apoptosis , cell growth and survival [1] , [2] .", "The mammalian NF-κB family members include NF-κB1 ( p105 and p50 ) , NF-κB2...	[ "NF-κB and inflammasomes both play central roles in orchestrating anti-pathogen responses by rapidly inducing a variety of early-response cytokines and chemokines following infection .", "Myxoma virus ( MYXV ) , a pathogenic poxvirus of rabbits , encodes a member of the cellular pyrin domain ( PYD ) superfamily ,...	[ "Myxoma virus ( MYXV ) , a rabbit-specific poxvirus pathogen , encodes diverse immunomodulatory proteins that can collectively overcome essentially all of the host immune defenses .", "MYXV-encoded protein M013 , a member of the cellular PYRIN domain-containing superfamily of proteins , was previously shown to be...	2009
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	The Hippo Pathway Regulates Homeostatic Growth of Stem Cell Niche Precursors in the Drosophila Ovary	journal.pgen.1004962	null	[ [ "The Hippo pathway is a tissue-intrinsic regulator of organ size , and is also implicated in stem cell maintenance and cancer [1 , 2 , 3] .", "An outstanding question in the field is whether the Hippo pathway regulates proliferation of cells comprising stem cell niches during development in order to ensur...	[ "The Hippo pathway regulates organ size , stem cell proliferation and tumorigenesis in adult organs .", "Whether the Hippo pathway influences establishment of stem cell niche size to accommodate changes in organ size , however , has received little attention .", "Here , we ask whether Hippo signaling influences...	[ "During development , organ growth must be carefully regulated to make sure that organs achieve the correct final size needed for organ function .", "In organs that are made of many different types of cells , this growth regulation is likely to be particularly complex , because it is important for organs to have ...	2015
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "medicine and health sciences", "enzyme-linked immunoassays", "immune physiology", "pathology and laboratory medicine", "immunology", "tropical diseases", "geographical locations", "bacterial diseases", "eye diseases", "sexually transmitted diseases", "neglected tropical diseases", "antibodies...	Serological and PCR-based markers of ocular Chlamydia trachomatis transmission in northern Ghana after elimination of trachoma as a public health problem	journal.pntd.0007027	null	[ [ "Trachoma is a disease caused by Chlamydia trachomatis ( Ct ) .", "Repeated ocular infections [1] result in inflammation leading to conjunctival scarring , trichiasis ( in-turned eyelashes which touch the eye ) and ultimately corneal opacity ( CO ) .", "The intervention strategy for trachoma is the Wo...	[ "Validation of elimination of trachoma as a public health problem is based on clinical indicators , using the WHO simplified grading system .", "Chlamydia trachomatis ( Ct ) infection and anti-Ct antibody responses ( anti-Pgp3 ) have both been evaluated as alternative indicators in settings with varying levels of...	[ "Trachoma is a disease caused by Chlamydia trachomatis ( Ct ) .", "Validation of elimination of trachoma as a public health problem is based on clinical indicators .", "Antibody and infection data may provide a better understanding of transmission dynamics in elimination settings .", "Dried blood spots ( DBSs...	2018
[ "Introduction", "Results and Discussion", "Materials and Methods" ]	[ "microbiology" ]	Nongenetic Individuality in the Host–Phage Interaction	journal.pbio.0060120	Mathematical analysis and single-cell observations of bacteria persistent to antibiotic treatments shed new light on the ecology of bacteria and phages.	[ [ "Fifty years ago , studies on the heterogeneity of genetically uniform populations demonstrated the importance of single-cell individuality for understanding a number of phenomena , including enzyme induction and radiation resistance [1–3] .", "The importance of heterogeneity is evident in the response of...	[ "Isogenic bacteria can exhibit a range of phenotypes , even in homogeneous environmental conditions .", "Such nongenetic individuality has been observed in a wide range of biological processes , including differentiation and stress response .", "A striking example is the heterogeneous response of bacteria to an...	[ "Persistence of subpopulations of bacteria to antibiotic treatments is a major problem in recurrent infections .", "Unlike resistance , which is passed on to the next generations , persistence is a transient trait characterized by slow growth or dormancy .", "It has been suggested that the existence of both per...	2008
[ "Introduction", "Results/Discussion", "Materials and Methods", "Supporting Information" ]	[ "infectious diseases", "microbiology", "computational biology", "evolutionary biology", "molecular biology", "genetics and genomics", "eubacteria" ]	Helicobacter pylori Evolution: Lineage- Specific Adaptations in Homologs of Eukaryotic Sel1-Like Genes	journal.pcbi.0030151	null	[ [ "Helicobacter pylori chronically infects billions of people worldwide , typically for decades .", "Most H . pylori reside on gastric epithelial cell surfaces and in the overlying mucin layer , a tissue that turns over rapidly , is infiltrated by inflammatory cells after infection , and is buffeted by gast...	[ "Geographic partitioning is postulated to foster divergence of Helicobacter pylori populations as an adaptive response to local differences in predominant host physiology .", "H . pylori's ability to establish persistent infection despite host inflammatory responses likely involves active management of host defen...	[ "Helicobacter pylori is a genetically diverse bacterial species that infects billions of people worldwide , typically for decades .", "Long-term infection is a major risk factor for stomach ulcers and cancer , although most infections are benign , and the risks of various disease outcomes vary markedly among huma...	2007
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "invertebrates", "medicine and health sciences", "classical mechanics", "geographical locations", "australia", "mechanical stress", "light", "animals", "wolbachia", "electromagnetic radiation", "developmental biology", "infectious disease control", "insect vectors", "bacteria", "infectio...	Loss of cytoplasmic incompatibility in Wolbachia-infected Aedes aegypti under field conditions	journal.pntd.0007357	null	[ [ "Aedes aegypti mosquitoes are the principal vectors of dengue and are widespread in the tropics where they live near humans [1 , 2] .", "Chemical insecticides have historically been used to control Ae .", "aegypti populations during disease outbreaks , but this approach is unlikely to be sustainable a...	[ "Wolbachia bacteria are now being introduced into Aedes aegypti mosquito populations for dengue control .", "When Wolbachia infections are at a high frequency , they influence the local transmission of dengue by direct virus blocking as well as deleterious effects on vector mosquito populations .", "However , t...	[ "Aedes aegypti mosquitoes infected with Wolbachia symbionts are being deployed in the tropics as a way of reducing disease transmission .", "Some Wolbachia strains are vulnerable to high temperatures but these effects have not been evaluated outside of a laboratory setting .", "We reared Ae .", "aegypti infec...	2019
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "cell physiology", "invertebrates", "microtubules", "caenorhabditis", "enzymes", "enzymology", "neuroscience", "animals", "cell polarity", "animal models", "caenorhabditis elegans", "model organisms", "experimental organism systems", "genetic interactions", "cellular structures and organ...	RHO-1 and the Rho GEF RHGF-1 interact with UNC-6/Netrin signaling to regulate growth cone protrusion and microtubule organization in Caenorhabditis elegans	journal.pgen.1007960	null	[ [ "The connectivity of neuronal circuits is established through properly guided axons which form functional synaptic connections .", "The growing axon is guided to its target by the motile , actin-based growth cone at the tip of the growing neurite .", "Growth cone response to extracellular guidance cue...	[ "UNC-6/Netrin is a conserved axon guidance cue that directs growth cone migrations in the dorsal-ventral axis of C . elegans and in the vertebrate spinal cord .", "UNC-6/Netrin is expressed in ventral cells , and growth cones migrate ventrally toward or dorsally away from UNC-6/Netrin .", "Recent studies of gro...	[ "Neural circuits are formed by precise connections between axons .", "During axon formation , the growth cone leads the axon to its proper target in a process called axon guidance .", "Growth cone outgrowth involves asymmetric protrusion driven by extracellular cues that stimulate and inhibit protrusion .", "...	2019
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "cell biology", "virology", "computational biology/systems biology", "computational biology" ]	A Stochastic Model for Microtubule Motors Describes the In Vivo Cytoplasmic Transport of Human Adenovirus	journal.pcbi.1000623	null	[ [ "The small number of motor proteins involved in microtubule transport implies a system where the fluctuations in the behavior of motors and the randomness of molecular reactions are essential characteristics [13] suggesting a stochastic modeling of the governing processes .", "Here we propose a stochastic...	[ "Cytoplasmic transport of organelles , nucleic acids and proteins on microtubules is usually bidirectional with dynein and kinesin motors mediating the delivery of cargoes in the cytoplasm .", "Here we combine live cell microscopy , single virus tracking and trajectory segmentation to systematically identify the ...	[ "Molecular motors , due to their transportation function , are essential to the cell , but they are often hijacked by viruses to reach their replication site .", "Imaging of virus trajectories provides information about the patterns of virus transport in the cytoplasm , leading to improved understanding of the un...	2009
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "invertebrates", "medicine and health sciences", "infectious disease epidemiology", "china", "vector-borne diseases", "geographical locations", "social sciences", "spatial epidemiology", "human mobility", "animals", "infectious disease control", "insect vectors", "human geography", "infect...	Inferring the Spatio-temporal Patterns of Dengue Transmission from Surveillance Data in Guangzhou, China	journal.pntd.0004633	null	[ [ "Dengue is a mosquito-borne disease caused by one of the four dengue virus serotypes ( DENV 1–4 ) , and is primarily transmitted by Aedes aegypti and Aedes albopictus [1 , 2] .", "The virus and its vectors are now widely distributed throughout tropical and subtropical regions , resulting in about half the...	[ "Dengue is a serious vector-borne disease , and incidence rates have significantly increased during the past few years , particularly in 2014 in Guangzhou .", "The current situation is more complicated , due to various factors such as climate warming , urbanization , population increase , and human mobility .", ...	[ "Dengue transmission is a spatio-temporal process with interactions between hosts , vectors , and viruses .", "Its transmission also involves multiple complex or even hidden factors , such as climate , social environment , vector ecology , and host mobility .", "These complexities make the underlying process of...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine", "infectious diseases", "immunology", "biology" ]	Efficient Capture of Infected Neutrophils by Dendritic Cells in the Skin Inhibits the Early Anti-Leishmania Response	journal.ppat.1002536	null	[ [ "Leishmaniasis is a vector-borne disease initiated by the bite of an infected sand fly .", "Based on exhaustive findings in the murine model of cutaneous leishmaniasis due to Leishmania major , the clinical course of disease is thought to depend on the balance of activating cytokines , produced largely by...	[ "Neutrophils and dendritic cells ( DCs ) converge at localized sites of acute inflammation in the skin following pathogen deposition by the bites of arthropod vectors or by needle injection .", "Prior studies in mice have shown that neutrophils are the predominant recruited and infected cells during the earliest ...	[ "Prior studies in mice have shown that the inoculation of Leishmania major into the skin by sand fly bite or by needle provokes a massive recruitment of neutrophils that take up the parasite , and that this response somehow suppresses immunity since neutrophil depletion results in better control of the infection ."...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	YAP1 Exerts Its Transcriptional Control via TEAD-Mediated Activation of Enhancers	journal.pgen.1005465	null	[ [ "YAP1 ( Yes-associated protein 1 ) is a major transcriptional effector of the evolutionary and functionally conserved Hippo pathway , which is a crucial regulator of organ size , proliferation but also tumor growth [1–3] .", "Activation of the Hippo pathway leads to phosphorylation and inactivation of the...	[ "YAP1 is a major effector of the Hippo pathway and a well-established oncogene .", "Elevated YAP1 activity due to mutations in Hippo pathway components or YAP1 amplification is observed in several types of human cancers .", "Here we investigated its genomic binding landscape in YAP1-activated cancer cells , as ...	[ "The YAP1/Hippo signaling pathway is a key regulator of organ size and tissue homeostasis , and its dysregulation is linked to cancer development .", "Elevated activity of YAP1 , a transcriptional coactivator and well-established oncogene has been reported to occur in human cancers .", "Comprehensive identifica...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biochemistry", "rna", "medicine and health sciences", "rna transport", "cell biology", "nucleic acids", "pathology and laboratory medicine", "host-pathogen interactions", "virology", "viruses and cancer", "biology and life sciences", "microbiology", "molecular cell biology", "pathogenesis...	A Novel Mechanism Inducing Genome Instability in Kaposi's Sarcoma-Associated Herpesvirus Infected Cells	journal.ppat.1004098	null	[ [ "Genome instability , an enabling characteristic of the hallmarks of cancer , has long been established as a major contributing factor to cancer formation and progression [1] , [2] .", "However , our understanding of the underlying molecular causes is still in its relative infancy .", "Contributing fa...	[ "Kaposi's sarcoma-associated herpesvirus ( KSHV ) is an oncogenic herpesvirus associated with multiple AIDS-related malignancies .", "Like other herpesviruses , KSHV has a biphasic life cycle and both the lytic and latent phases are required for tumorigenesis .", "Evidence suggests that KSHV lytic replication c...	[ "The hallmarks of cancer comprise the essential elements that permit the formation and development of human tumours .", "Genome instability is an enabling characteristic that allows the progression of tumorigenesis through genetic mutation and therefore , understanding the molecular causes of genome instability i...	2014
[ "Introduction", "Results/Discussion", "Methods" ]	[ "systems biology", "biochemistry", "microbial metabolism", "evolutionary biology", "microbial evolution", "origin of life", "biology", "computational biology", "metabolic networks", "metabolism", "microbiology", "genetics and genomics" ]	The Emergence and Early Evolution of Biological Carbon-Fixation	journal.pcbi.1002455	null	[ [ "Six different autotrophic carbon-fixation pathways have been identified across the tree of life [1]–[3] .", "It has been recognized that some of these pathways share reaction sequences , but a comprehensive framework does not yet exist to interpret the relatedness among all these extant phenotypes , or t...	[ "The fixation of into living matter sustains all life on Earth , and embeds the biosphere within geochemistry .", "The six known chemical pathways used by extant organisms for this function are recognized to have overlaps , but their evolution is incompletely understood .", "Here we reconstruct the complete ear...	[ "The existence of the biosphere today depends on its capacity to fix inorganic into living matter .", "A wide range of evidence also suggests that the earliest life forms on Earth likewise derived their carbon from .", "From these two observations one can assume that the global biological carbon cycle has alway...	2012
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "medicine and health sciences", "physicians", "medical doctors", "pathology and laboratory medicine", "clinical research design", "nervous system", "tropical diseases", "social sciences", "neuroscience", "health care", "research design", "bacterial diseases", "health care providers", "sign...	A Randomized Controlled Double Blind Trial of Ciclosporin versus Prednisolone in the Management of Leprosy Patients with New Type 1 Reaction, in Ethiopia	journal.pntd.0004502	null	[ [ "Leprosy is a chronic granulomatous infection principally affecting the skin and peripheral nerves caused by the obligate intracellular organism Mycobacterium Leprae [1] .", "In 2014 , the WHO reported 213 899 new cases globally [2] .", "Multi-drug therapy ( MDT ) cures the infection by Mycobacterium ...	[ "Leprosy Type 1 ( T1R ) reactions are immune-mediated events leading to nerve damage and preventable disability affecting hands , feet and eyes .", "Type 1 Reactions are treated with oral corticosteroids .", "There is little evidence on alternative treatments for patients who do not respond to steroids or exper...	[ "Leprosy infection is cured with multi-drug therapy ( MDT ) , but patients may develop immune mediated skin and nerve lesions .", "These immunological reactions lead to disability and deformity secondary to neuropathy .", "Prednisolone is the main drug used to treat reactions but is only partially effective and...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine", "infectious diseases", "biology", "genomics", "evolutionary biology", "microbiology", "genetics and genomics" ]	Experimental Evolution of Legionella pneumophila in Mouse Macrophages Leads to Strains with Altered Determinants of Environmental Survival	journal.ppat.1002731	null	[ [ "L . pneumophila is a Gram-negative intracellular pathogen with a broad host range that extends from unicellular protozoa to alveolar macrophages of the human lung [1] .", "L . pneumophila is an accidental pathogen: responsible for severe , sporadic disease in humans [2]–[4] , but ubiquitous in nature [5]...	[ "The Gram-negative bacterium , Legionella pneumophila , is a protozoan parasite and accidental intracellular pathogen of humans .", "We propose a model in which cycling through multiple protozoan hosts in the environment holds L . pneumophila in a state of evolutionary stasis as a broad host-range pathogen .", ...	[ "Legionella pneumophila is an accidental pathogen of humans , responsible for the severe , often-fatal pneumonia known as Legionnaires' disease .", "In the environment , L . pneumophila survives and replicates within protozoa by co-opting the intracellular machinery of these microbial predators .", "These fresh...	2012
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "medicine and health sciences", "pathology and laboratory medicine", "infectious disease epidemiology", "applied mathematics", "pathogens", "immunology", "simulation and modeling", "algorithms", "preventive medicine", "mathematics", "infectious disease control", "vaccination and immunization",...	Control fast or control smart: When should invading pathogens be controlled?	journal.pcbi.1006014	null	[ [ "Effective management of infectious disease remains a significant challenge [1–3] .", "Mathematical modelling is a powerful tool for integrating over uncertainty in predicting the future spread of outbreaks [4 , 5] , and provides a rational methodology for assessing the likely performance of proposed inte...	[ "The intuitive response to an invading pathogen is to start disease management as rapidly as possible , since this would be expected to minimise the future impacts of disease .", "However , since more spread data become available as an outbreak unfolds , processes underpinning pathogen transmission can almost alw...	[ "Infectious disease outbreaks in human , animal and plant populations can have devastating consequences .", "Where and how much control should be deployed are difficult questions to answer .", "However , mathematical modelling is increasingly used by policy-makers to underpin these–sometimes contentious–decisio...	2018
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "children", "medicine and health sciences", "diagnostic radiology", "functional magnetic resonance imaging", "education", "sociology", "brain", "social sciences", "neuroscience", "cerebral hemispheres", "learning and memory", "left hemisphere", "magnetic resonance imaging", "face recogniti...	The emergence of the visual word form: Longitudinal evolution of category-specific ventral visual areas during reading acquisition	journal.pbio.2004103	null	[ [ "In both human and nonhuman primates , the ventral visual cortex comprises multiple specialized subregions that are involved in the visual recognition of image categories such as objects , faces , or places [1–5] .", "What is striking in humans , however , is that this mosaic of specialized regions is par...	[ "How does education affect cortical organization ?", "All literate adults possess a region specialized for letter strings , the visual word form area ( VWFA ) , within the mosaic of ventral regions involved in processing other visual categories such as objects , places , faces , or body parts .", "Therefore , t...	[ "Reading acquisition is a major landmark in child development .", "We examined how it changes the child’s brain .", "Ten young children were scanned repeatedly , once every 2 months , before , during , and after their first year of school .", "In the scanner , they watched images of faces , tools , bodies , h...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biochemistry", "plant biochemistry", "transmembrane proteins", "protein interactions", "plant microbiology", "proteins", "regulatory proteins", "biology", "microbiology", "bacterial pathogens" ]	Fha Interaction with Phosphothreonine of TssL Activates Type VI Secretion in Agrobacterium tumefaciens	journal.ppat.1003991	null	[ [ "The type VI secretion system ( T6SS ) is the most recently described protein secretion system encoded as one or multiple copies in ∼25% of all sequenced Gram-negative bacteria [1] .", "T6SS is highly regulated and exhibits cytotoxicity to eukaryotic or bacterial hosts in a contact-dependent manner [2]–[6...	[ "The type VI secretion system ( T6SS ) is a widespread protein secretion system found in many Gram-negative bacteria .", "T6SSs are highly regulated by various regulatory systems at multiple levels , including post-translational regulation via threonine ( Thr ) phosphorylation .", "The Ser/Thr protein kinase Pp...	[ "The bacterial type VI secretion system ( T6SS ) resembles a contractile phage tail structure and functions to deliver effectors to eukaryotic or prokaryotic target cells for the survival of many pathogenic bacteria .", "T6SS is highly regulated by various regulatory systems at multiple levels in response to envi...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Group Selection and Contribution of Minority Variants during Virus Adaptation Determines Virus Fitness and Phenotype	journal.ppat.1004838	null	[ [ "The extreme mutation rates of RNA viruses and the highly diverse populations they generate in few replication cycles are considered the basis for their rapid adaptation to new environments [1 , 2] .", "Such adaptive steps result in the emergence of new variants capable of escaping immune responses , resi...	[ "Understanding how a pathogen colonizes and adapts to a new host environment is a primary aim in studying emerging infectious diseases .", "Adaptive mutations arise among the thousands of variants generated during RNA virus infection , and identifying these variants will shed light onto how changes in tropism and...	[ "When RNA viruses replicate , they do so with a high rate of error; hence , their populations are not composed of a single genotype , but of a swarm of different , yet related , genomes .", "This mutant spectrum has been described as the viral quasispecies , and its composition has important consequences for evol...	2015
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "cell physiology", "cell fusion", "cellular stress responses", "aspergillus", "cell processes", "fungal molds", "aspergillus nidulans", "developmental biology", "fungi", "model organisms", "experimental organism systems", "morphogenesis", "mapk signaling cascades", "research and analysis m...	Assembly of a heptameric STRIPAK complex is required for coordination of light-dependent multicellular fungal development with secondary metabolism in Aspergillus nidulans	journal.pgen.1008053	null	[ [ "Signaling pathways that regulate morphological and physiological processes in response to stimuli are often highly conserved throughout eukaryotes , signifying their importance .", "Striatin is one of the regulatory proteins proposed to act as a signalling hub for the control of many cellular processes i...	[ "Eukaryotic striatin forms striatin-interacting phosphatase and kinase ( STRIPAK ) complexes that control many cellular processes including development , cellular transport , signal transduction , stem cell differentiation and cardiac functions .", "However , detailed knowledge of complex assembly and its roles i...	[ "The multisubunit STRIPAK complex has been studied from yeast to human and plays a range of roles from cell-cycle arrest , fruit body formation to neuronal functions .", "Molecular assembly of the STRIPAK complex and its roles in stress responses are not well-documented .", "Fungi , with an estimated 1 . 5 mill...	2019
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "plant anatomy", "medicine and health sciences", "yeast infections", "pathology and laboratory medicine", "immunology", "immune suppression", "toxicology", "toxicity", "fungi", "plant science", "rice", "model organisms", "metabolites", "signs and symptoms", "experimental organism systems...	The effector AvrRxo1 phosphorylates NAD in planta	journal.ppat.1006442	null	[ [ "A central theme in gram-negative bacterial pathogenesis is the injection of Type III-secreted effectors ( T3E ) into host cells .", "Plant pathogen effectors may suppress two tiers of innate immunity: PAMP-Triggered Immunity ( PTI ) , triggered by perception of pathogen-associated molecular patterns ( PA...	[ "Gram-negative bacterial pathogens of plants and animals employ type III secreted effectors to suppress innate immunity .", "Most characterized effectors work through modification of host proteins or transcriptional regulators , although a few are known to modify small molecule targets .", "The Xanthomonas type...	[ "Infectious bacteria have many strategies to weaken the defenses of their hosts .", "One common strategy is to inject proteins called effectors into the host cells .", "Many effectors inactivate proteins that transmit defense signals , disabling the alarm systems that alert the plant to defend against the patho...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genetics", "genome-wide association studies", "biology", "animal genetics" ]	Meta-Analysis Identifies Gene-by-Environment Interactions as Demonstrated in a Study of 4,965 Mice	journal.pgen.1004022	null	[ [ "Identifying environmentally specific genetic effects is a key challenge in understanding the structure of complex traits .", "In humans , gene-by-environment ( GxE ) interactions have been widely discussed [1]–[12] yet only a few have been replicated .", "One reason for this discrepancy is the inabil...	[ "Identifying environmentally-specific genetic effects is a key challenge in understanding the structure of complex traits .", "Model organisms play a crucial role in the identification of such gene-by-environment interactions , as a result of the unique ability to observe genetically similar individuals across mu...	[ "Identifying gene-by-environment interactions is important for understand the architecture of a complex trait .", "Discovering gene-by-environment interaction requires the observation of the same phenotype in individuals under different environments .", "Model organism studies are often conducted under differen...	2014
[ "Introduction", "Methods", "Results", "Discussion" ]	[]	Household Socioeconomic and Demographic Correlates of Cryptosporidium Seropositivity in the United States	journal.pntd.0004080	null	[ [ "Cryptosporidium are parasitic protozoa that infect humans , domestic animals , and wildlife globally [1] .", "In humans , cryptosporidiosis is a major cause of global diarrheal illness , and in the United States an estimated 750000 cases occur annually [2] .", "Although direct mortality from Cryptosp...	[ "Cryptosporidium are parasitic protozoa that infect humans , domestic animals , and wildlife globally .", "In the United States , cryptosporidiosis occurs in an estimated 750 , 000 persons annually , and is primarily caused by either of the Cryptosporidium parvum genotypes 1 and 2 , exposure to which occurs throu...	[ "We examined if and how social inequality in the United States influences seropositivity to Cryptosporidium parvum .", "By using nationwide data on parasite seropositivity , demographics , and household metrics of socioeconomic status provided through the National Health and Nutritional Examination Survey , we qu...	2015
[ "Introduction", "Results", "Discussion" ]	[ "medicine and health sciences", "hydrocele", "pathology and laboratory medicine", "education", "sociology", "tropical diseases", "social sciences", "parasitic diseases", "health care", "health services administration and management", "filariasis", "signs and symptoms", "global health", "ne...	A Delphi consultation to assess indicators of readiness to provide quality health facility-based lymphoedema management services	journal.pntd.0006699	null	[ [ "Lymphatic filariasis ( LF ) is a parasitic infection caused by filarial nematodes that are transmitted by mosquitoes .", "Chronic infection with LF can lead to clinical manifestations such as lymphoedema and hydrocele that have significant impacts on the mobility and quality of life of affected individua...	[ "The World Health Organization ( WHO ) in collaboration with partners is developing a toolkit of resources to guide lymphatic filariasis ( LF ) morbidity management and disability prevention ( MMDP ) implementation and evaluation .", "Direct health facility inspection is the preferred method for documenting the r...	[ "Prior to this assessment , there was a need for clearly defined , measurable indicators for global lymphoedema management programmes to use to evaluate their lymphoedema morbidity management and disability prevention services .", "The results presented in this report outline a framework for indicators to assess ...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "virology/animal models of infection", "virology/host invasion and cell entry" ]	Adaptation of Hepatitis C Virus to Mouse CD81 Permits Infection of Mouse Cells in the Absence of Human Entry Factors	journal.ppat.1000978	null	[ [ "HCV is an enveloped virus with a positive sense single stranded RNA genome , belonging to the family of Flaviviridae [1] .", "Based on sequence comparison patient isolates are classified into seven genotypes which differ from each other by ca .", "31–33% at the nucleotide level [2] , [3] .", "Chr...	[ "Hepatitis C virus ( HCV ) naturally infects only humans and chimpanzees .", "The determinants responsible for this narrow species tropism are not well defined .", "Virus cell entry involves human scavenger receptor class B type I ( SR-BI ) , CD81 , claudin-1 and occludin .", "Among these , at least CD81 and ...	[ "The hepatitis C virus ( HCV ) infects only humans and chimpanzees , which has hampered development of suitable animal models .", "The inability of HCV to penetrate non-human cells is primarily due to inefficient usage of non-human CD81 and occludin .", "In this study we adapted HCV to mouse CD81 .", "Efficie...	2010
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biology and life sciences", "immunology", "ecology and environmental sciences" ]	An Immunological Marker of Tolerance to Infection in Wild Rodents	journal.pbio.1001901	A large-scale field study in naturally occurring vole populations identified gene expression changes over time and demonstrates how wild mammals exhibit tolerance to chronic parasite infections.	[ [ "There is increasing recognition that the ability to tolerate a parasite's presence , where the host accepts infection but actively limits the damage caused , may be a crucial host defence strategy [1] , [2] .", "This is distinct from resistance , where the focus is on limiting the infection burden itself...	[ "Hosts are likely to respond to parasitic infections by a combination of resistance ( expulsion of pathogens ) and tolerance ( active mitigation of pathology ) .", "Of these strategies , the basis of tolerance in animal hosts is relatively poorly understood , with especially little known about how tolerance is ma...	[ "Hosts do not always resist parasites .", "And once infection establishes , relatively little is known of how naturally occurring hosts tolerate ( mitigate for ) adverse effects , or what the life history consequences of this tolerance may be .", "In this article we demonstrate a pattern of tolerance to parasit...	2014
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "smell", "medicine and health sciences", "pathology and laboratory medicine", "carcinomas", "tropical diseases", "cancers and neoplasms", "social sciences", "geographical locations", "neuroscience", "oncology", "bacterial diseases", "mathematics", "signs and symptoms", "forecasting", "st...	Improving clinical and epidemiological predictors of Buruli ulcer	journal.pntd.0006713	null	[ [ "Buruli ulcer ( BU ) is a chronic necrotizing infectious disease of the skin caused by Mycobacterium ulcerans .", "After tuberculosis and leprosy , BU is the third most common mycobacterial disease worldwide [1 , 2] .", "BU has been reported in over 30 countries , typically in warm and humid intertrop...	[ "Buruli ulcer ( BU ) is a chronic necrotizing infectious skin disease caused by Mycobacterium ulcerans .", "The treatment with BU-specific antibiotics is initiated after clinical suspicion based on the WHO clinical and epidemiological criteria .", "This study aimed to estimate the predictive values of these cri...	[ "Buruli ulcer ( BU ) is a neglected necrotizing skin disease caused by Mycobacterium ulcerans .", "The treatment with BU-specific antibiotics is initiated after clinical suspicion based on WHO diagnostic criteria .", "In this study we evaluated the WHO diagnostic guidelines for BU and how these criteria could b...	2018
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "reverse transcriptase-polymerase chain reaction", "medicine and health sciences", "enzyme-linked immunoassays", "fluorescence", "pathology and laboratory medicine", "togaviruses", "chikungunya infection", "pathogens", "immunology", "tropical diseases", "microbiology", "rna extraction", "alp...	Development of 2, 7-Diamino-1, 8-Naphthyridine (DANP) Anchored Hairpin Primers for RT-PCR Detection of Chikungunya Virus Infection	journal.pntd.0004887	null	[ [ "Chikungunya virus ( CHIKV ) is an arthropod-borne virus transmitted to humans primarily via the bite of an infected [1] Aedes agypti and Aedes albopictus mosquito .", "[2 , 3] Currently , there are more than 40 countries including Africa , United States , European countries and Southeast Asian countries ...	[ "A molecular diagnostic platform with DANP-anchored hairpin primer was developed and evaluated for the rapid and cost-effective detection of Chikungunya virus ( CHIKV ) with high sensitivity and specificity .", "The molecule 2 , 7-diamino-1 , 8-naphthyridine ( DANP ) binds to a cytosine-bulge and emits fluorescen...	[ "Chikungunya has reemerged as an important mosquito-borne infection with global health significance .", "Rapid diagnosis plays an important role in early clinical management of patients due to lack of a vaccine and effective treatment .", "Laboratory diagnosis is generally accomplished by blood tests to detect ...	2016
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "neuroscience/neurodevelopment" ]	An Integrated Micro- and Macroarchitectural Analysis of the Drosophila Brain by Computer-Assisted Serial Section Electron Microscopy	journal.pbio.1000502	A new software package allows for dense electron microscopy reconstructions of neuronal networks in the fruit fly brain, and reveals specific differences in microcircuits between insects and vertebrates.	[ [ "The brain of all higher animals is formed by a large number of interconnected neurons .", "Typically , neurons are grouped into larger assemblies ( “brain compartments” ) , such as brain stem nuclei or cortical layers in the vertebrate brain , or neural lineages in the insect brain [1] , [2] .", "The...	[ "The analysis of microcircuitry ( the connectivity at the level of individual neuronal processes and synapses ) , which is indispensable for our understanding of brain function , is based on serial transmission electron microscopy ( TEM ) or one of its modern variants .", "Due to technical limitations , most prev...	[ "Brains contain a vast number of connections between neurons , termed synapses .", "The precise patterns of these synaptic contacts form the structural underpinning of electrical microcircuits responsible for animal behavior .", "Due to their small size , synaptic contacts can be conclusively shown using only h...	2010
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biochemistry", "basement membrane", "molecular cell biology", "cell biology", "proteins", "extracellular matrix", "microbial pathogens", "biology", "microbiology", "host-pathogen interaction", "extracellular matrix adhesions", "bacterial pathogens", "pathogenesis" ]	Activation and Proteolytic Activity of the Treponema pallidum Metalloprotease, Pallilysin	journal.ppat.1002822	null	[ [ "The expression of host-interacting proteases has been shown to contribute to the pathogenesis of bacteria of medical interest by promoting host colonization and immune evasion , acquisition of nutrients , tissue invasion and dissemination of infection .", "Several pathogenic bacteria , including Streptoc...	[ "Treponema pallidum is a highly invasive pathogen that undergoes rapid dissemination to establish widespread infection .", "Previous investigations identified the T . pallidum adhesin , pallilysin , as an HEXXH-containing metalloprotease that undergoes autocatalytic cleavage and degrades laminin and fibrinogen ."...	[ "Syphilis , caused by the spirochete Treponema pallidum , is a chronic sexually transmitted disease which infects 12 million people annually .", "Treponema pallidum is highly invasive and undergoes widespread dissemination via the circulatory system .", "Similar to other invasive pathogens , T . pallidum has be...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods", "Supporting Information" ]	[ "oncology", "biochemistry" ]	Assessing Tumor Progression Factors by Somatic Gene Transfer into a Mouse Model: Bcl-xL Promotes Islet Tumor Cell Invasion	journal.pbio.0050276	A new technique using lentivirus to deliver genes into targeted cell types reveals that the tumor progression geneBcl-xL not only promotes cell survival in premalignant cells but also promotes tumor cell invasion.	[ [ "Cancer typically arises by a multi-step process during which cells acquire activating mutations in oncogenes and inactivating mutations in tumor suppressor genes [1] .", "By comparing cancer tissues with their normal counterparts , it is possible to identify many differences in cellular , molecular , and...	[ "Tumors develop through multiple stages , implicating multiple effectors , but the tools to assess how candidate genes contribute to stepwise tumor progression have been limited .", "We have developed a novel system in which progression of phenotypes in a mouse model of pancreatic islet cell tumorigenesis can be ...	[ "Cancer cells accumulate multiple genetic alterations .", "Some of these contribute to tumor development while others are a mere by-product of genomic instability .", "To determine whether a candidate gene can promote tumor development , we have developed a novel experimental system using engineered viruses to ...	2007
[ "Introduction", "Results", "Discussion", "Material and methods" ]	[ "blood cells", "graduates", "innate immune system", "medicine and health sciences", "immune cells", "immune physiology", "cytokines", "pathology and laboratory medicine", "pathogens", "immunology", "microbiology", "alumni", "vaccines", "preventive medicine", "developmental biology", "f...	Ligation of Dectin-2 with a novel microbial ligand promotes adjuvant activity for vaccination	journal.ppat.1006568	null	[ [ "Fungal disease remains a challenging clinical and public health problem .", "Despite medical advances , invasive fungal infections have skyrocketed over the last decade and pose a mounting health threat in immune-competent and -deficient hosts with worldwide mortality rates ranking 7th , even ahead of tu...	[ "The development of vaccines against fungi and other intracellular microbes is impeded in part by a lack of suitable adjuvants .", "While most current vaccines against infectious diseases preferentially induce production of antibodies , cellular immunity is essential for the resolution of fungal infections .", ...	[ "Despite several million new systemic fungal infections annually worldwide , there are no commercial vaccines available .", "The lack of appropriate adjuvants is one major impediment to developing safe and effective vaccines against infections with fungal pathogens .", "Current vaccines against infectious disea...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "virology/virion structure, assembly, and egress", "virology/host invasion and cell entry" ]	Requirements for Receptor Engagement during Infection by Adenovirus Complexed with Blood Coagulation Factor X	journal.ppat.1001142	null	[ [ "Adenoviruses are non-enveloped , icosahedral double-stranded DNA viruses of 70–90nm diameter .", "54 different human serotypes have been identified to date and are classified into species based on their ability to agglutinate human , monkey or rat erythrocytes [1] .", "Adenoviruses cause a range of i...	[ "Human adenoviruses from multiple species bind to coagulation factor X ( FX ) , yet the importance of this interaction in adenovirus dissemination is unknown .", "Upon contact with blood , vectors based on adenovirus serotype 5 ( Ad5 ) binds to FX via the hexon protein with nanomolar affinity , leading to selecti...	[ "Adenoviruses can infect many cell types and cause a range of illnesses in humans , including respiratory , ocular and gastrointestinal disorders .", "These illnesses are rarely fatal; however , in immunocompromised individuals , especially young children , disseminated adenovirus infections can cause serious and...	2010
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "medicine and health sciences", "hela cells", "prions", "biological cultures", "brain", "vertebrates", "animals", "mammals", "cell cultures", "research and analysis methods", "hamsters", "infectious diseases", "specimen preparation and treatment", "staining", "zoonoses", "proteins", ...	Cross-seeding of prions by aggregated α-synuclein leads to transmissible spongiform encephalopathy	journal.ppat.1006563	null	[ [ "Aggregation of misfolded proteins or peptides is a common feature of neurodegenerative diseases including Alzheimer’s , Parkinson’s , Huntington’s , prion and other diseases [1 , 2] .", "According to traditional view , each neurodegenerative disease is characterized by aggregation of one or two disease-s...	[ "Aggregation of misfolded proteins or peptides is a common feature of neurodegenerative diseases including Alzheimer’s , Parkinson’s , Huntington’s , prion and other diseases .", "Recent years have witnessed a growing number of reports of overlap in neuropathological features that were once thought to be unique t...	[ "Aggregation of misfolded proteins or peptides is a common feature of neurodegenerative diseases .", "Recent years have witnessed a growing number of reports of overlap in neuropathological features specific to two or more neurodegenerative diseases in individual patients .", "However , the origin for the overl...	2017
[ "Introduction", "Design and implementation", "Results", "Discussion", "Availability and future directions" ]	[ "fluorescence imaging", "chemical characterization", "diffraction", "digital video imaging microscopy", "medicine and health sciences", "engineering and technology", "light microscopy", "light", "electromagnetic radiation", "simulation and modeling", "adaptive optics", "light scattering", "o...	Biobeam—Multiplexed wave-optical simulations of light-sheet microscopy	journal.pcbi.1006079	null	[ [ "Light-sheet fluorescence microscopy is a popular tool for the volumetric imaging of developing organisms [1–5] .", "As light-sheet microscopes continue to be developed for progressively bigger biological samples [6 , 7] , there is an increasing need for computers to process gigantic sets of imaging data ...	[ "Sample-induced image-degradation remains an intricate wave-optical problem in light-sheet microscopy .", "Here we present biobeam , an open-source software package that enables simulation of operational light-sheet microscopes by combining data from 105–106 multiplexed and GPU-accelerated point-spread-function c...	[ "Modern microscopes permit to acquire high quality images of large fields of view , which is the result of a decade-long development of computer aided optical design .", "However , this high image quality can only be obtained at the very surface of biological specimens: when trying to penetrate deeper into biolog...	2018
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "neuroscience", "neuroscience/theoretical neuroscience", "neuroscience/neurodevelopment", "neuroscience/sensory systems" ]	Maturation of GABAergic Inhibition Promotes Strengthening of Temporally Coherent Inputs among Convergent Pathways	journal.pcbi.1000797	null	[ [ "Association-based Hebbian plasticity is a powerful form of activity-dependent synaptic modification capable of shaping the response properties of neurons during development , and is a proposed substrate for experience-dependent learning [1]–[3] .", "However , associative forms of plasticity by themselves...	[ "Spike-timing-dependent plasticity ( STDP ) , a form of Hebbian plasticity , is inherently stabilizing .", "Whether and how GABAergic inhibition influences STDP is not well understood .", "Using a model neuron driven by converging inputs modifiable by STDP , we determined that a sufficient level of inhibition w...	[ "Evidence suggests that maturation of inhibition is required for the development of plasticity to proceed in the visual cortex .", "However , the mechanisms by which increased inhibition promotes plasticity are not clear .", "Here we characterized the maturation of synaptic and intrinsic ionic properties of par...	2010
[ "Introduction", "Results/Discussion", "Materials and Methods" ]	[ "infectious diseases/protozoal infections", "infectious diseases/epidemiology and control of infectious diseases", "genetics and genomics/population genetics" ]	Self-Mating in the Definitive Host Potentiates Clonal Outbreaks of the Apicomplexan Parasites Sarcocystis neurona and Toxoplasma gondii	journal.pgen.1001261	null	[ [ "Population genetic studies of pathogenic microbes have been paramount to our understanding of disease resulting from emerging and re-emerging infectious organisms [1] .", "Studies performed to determine the relative contributions of drift and recombination in the production of genetic diversity have iden...	[ "Tissue-encysting coccidia , including Toxoplasma gondii and Sarcocystis neurona , are heterogamous parasites with sexual and asexual life stages in definitive and intermediate hosts , respectively .", "During its sexual life stage , T . gondii reproduces either by genetic out-crossing or via clonal amplification...	[ "The parasites Toxoplasma gondii and Sarcocystis neurona have lifecycles that include a sexual stage in a definitive host and an asexual stage in intermediate hosts .", "For T . gondii , laboratory studies have demonstrated that the sexual stage can serve the dual purpose of producing new , virulent genotypes thr...	2010
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	The Candida albicans Histone Acetyltransferase Hat1 Regulates Stress Resistance and Virulence via Distinct Chromatin Assembly Pathways	journal.ppat.1005218	null	[ [ "Eukaryotic chromatin is densely packed with the nucleosome being its basic repeating unit [1] .", "This structure represents a barrier for enzymes reading or modifying genomic DNA .", "Thus , disassembly and reassembly of histones , the core components of nucleosomes , is essential for various biolog...	[ "Human fungal pathogens like Candida albicans respond to host immune surveillance by rapidly adapting their transcriptional programs .", "Chromatin assembly factors are involved in the regulation of stress genes by modulating the histone density at these loci .", "Here , we report a novel role for the chromatin...	[ "Candida albicans is the most prevalent fungal pathogen infecting humans , causing life-threatening infections in immunocompromised individuals .", "Host immune surveillance imposes stress conditions upon C . albicans , to which it has to adapt quickly to escape host killing .", "This can involve regulation of ...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "rna interference", "gene regulation", "rna stability", "animal models", "caenorhabditis elegans", "model organisms", "epigenetics", "molecular genetics", "gene expression", "biology", "molecular biology", "rna", "rna processing", "nucleic acids", "gene identification and analysis", "g...	The Caenorhabditis elegans HEN1 Ortholog, HENN-1, Methylates and Stabilizes Select Subclasses of Germline Small RNAs	journal.pgen.1002617	null	[ [ "Argonautes are an evolutionarily conserved family of proteins implicated in diverse cellular processes .", "They function as effector proteins in the RNA-induced silencing complex ( RISC ) , a gene regulatory complex that binds small , non-coding RNAs to target its silencing effects .", "Small RNAs a...	[ "Small RNAs regulate diverse biological processes by directing effector proteins called Argonautes to silence complementary mRNAs .", "Maturation of some classes of small RNAs involves terminal 2′-O-methylation to prevent degradation .", "This modification is catalyzed by members of the conserved HEN1 RNA methy...	[ "Small RNAs serve as sentinels of the genome , policing activity of selfish genetic elements , modulating chromatin dynamics , and fine-tuning gene expression .", "Nowhere is this more important than in the germline , where endogenous small interfering RNAs ( endo-siRNAs ) and Piwi-interacting RNAs ( piRNAs ) pro...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Collective Dynamics Underlying Allosteric Transitions in Hemoglobin	journal.pcbi.1003232	null	[ [ "Hemoglobin ( Hb ) consists of two and two protein chains that bind oxygen to a heme group for the transport through the blood .", "These binding sites act cooperatively , i . e . the binding affinity for in one site is increased after binding in one of the other sites .", "The remarkable efficiency o...	[ "Hemoglobin is the prototypic allosteric protein .", "Still , its molecular allosteric mechanism is not fully understood .", "To elucidate the mechanism of cooperativity on an atomistic level , we developed a novel computational technique to analyse the coupling of tertiary and quaternary motions .", "From Mo...	[ "Hemoglobin transports oxygen from our lungs to other tissues .", "Its effectiveness in binding and unbinding of oxygen is based on a type of regulation called allostery .", "Thereby , already bound oxygen molecules in either of the four binding sites of hemoglobin increase the likelihood of oxygen binding in t...	2013
[ "Introduction", "Methods", "Results", "Discussion" ]	[]	Infrared Fluorescent Imaging as a Potent Tool for In Vitro, Ex Vivo and In Vivo Models of Visceral Leishmaniasis	journal.pntd.0003666	null	[ [ "Neglected Tropical Diseases ( NTDs ) are severe scourges that affect the less protected layer of the poorest population of low-income countries [1 , 2] .", "Their neglected consideration implies a poor attention by most of the actors involved in their eradication including Pharma Industries , which are m...	[ "Visceral leishmaniasis ( VL ) is hypoendemic in the Mediterranean region , where it is caused by the protozoan Leishmania infantum .", "An effective vaccine for humans is not yet available and the severe side-effects of the drugs in clinical use , linked to the parenteral administration route of most of them , a...	[ "Visceral leishmaniasis ( VL ) , caused by Leishmania infantum or L . donovani , is still one of the most threatening diseases affecting poor people in developing countries , with a fatality rate as high as 100% in two years in infected and untreated people .", "With no vaccine available and ineffective and toxic...	2015
[ "Introduction", "Results/Discussion", "Methods" ]	[ "computational biology/population genetics", "genetics and genomics/comparative genomics", "evolutionary biology/evolutionary and comparative genetics", "evolutionary biology/human evolution", "computational biology/comparative sequence analysis", "computational biology/molecular genetics", "molecular b...	Widespread Genomic Signatures of Natural Selection in Hominid Evolution	journal.pgen.1000471	null	[ [ "The action of natural selection on genome sequences is most directly revealed by a deficit or excess of substitutions relative to the neutral rate , but detecting this requires sequences that have been diverging long enough to experience a high density of mutations [1] .", "An alternative approach , appl...	[ "Selection acting on genomic functional elements can be detected by its indirect effects on population diversity at linked neutral sites .", "To illuminate the selective forces that shaped hominid evolution , we analyzed the genomic distributions of human polymorphisms and sequence differences among five primate ...	[ "Comparisons of the human and chimpanzee genomes have revealed that the frequency of sequence differences between these species varies dramatically across the genome .", "Previously proposed explanations for this variation include a large ancestral population , variable mutation rates , or a complex speciation sc...	2009
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biochemistry", "cell biology", "genetics and genomics" ]	The Nucleosome-Remodeling ATPase ISWI Is Regulated by Poly-ADP-Ribosylation	journal.pbio.0060252	Enzymes that mediate nucleosome remodeling and poly-ADP-ribosylation play essential roles in the eukaryotic cell. A new study suggests a mechanism to explain how two nuclear enzymes can coordinate their activities to regulate chromatin structure and function.	[ [ "Eukaryotic chromatin is packaged in a highly organized hierarchy of structural building blocks , all composed of the basic repeating unit of the nucleosome .", "ATP-dependent nucleosome-remodeling activities as well as covalent modifications of chromatin components underlie the dynamic nature of chromati...	[ "ATP-dependent nucleosome-remodeling enzymes and covalent modifiers of chromatin set the functional state of chromatin .", "However , how these enzymatic activities are coordinated in the nucleus is largely unknown .", "We found that the evolutionary conserved nucleosome-remodeling ATPase ISWI and the poly-ADP-...	[ "The ISWI protein is a highly conserved nucleosome remodeler that plays essential roles in regulating chromosome structure , DNA replication , and gene expression .", "The variety of functions associated with ISWI activity are probably connected to the ability of other cellular factors to regulate its ATP-depende...	2008
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "sequence analysis", "systems biology", "genome expression analysis", "genomics", "functional genomics", "gene expression", "genetics", "molecular genetics", "biology", "computational biology", "genetics and genomics" ]	Positively Charged Residues Are the Major Determinants of Ribosomal Velocity	journal.pbio.1001508	Positively charged amino acid residues in the nascent peptide, not RNA-level features as long thought, slow ribosomes.	[ [ "While it is known that there is great variation in ribosomal velocity along even a single transcript [1] , what determines how fast a transcript ( or part thereof ) is processed is unresolved .", "Resolving this issue is important for understanding causes of disease and for the generation of transgenes ,...	[ "Both for understanding mechanisms of disease and for the design of transgenes , it is important to understand the determinants of ribosome velocity , as changes in the rate of translation are important for protein folding , error attenuation , and localization .", "While there is great variation in ribosomal occ...	[ "Ribosomes do not synthesize protein at a constant rate along transcripts , and changes in translation speed can have knock-on consequences for the expression of that protein , even altering its folding or subcellular localization .", "It has long been thought that RNA-level features modulate translation rates , ...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "molecular neuroscience", "cellular neuroscience", "model organisms", "sensory systems", "biology", "sensory perception", "molecular cell biology", "neuroscience" ]	Ligands for Pheromone-Sensing Neurons Are Not Conformationally Activated Odorant Binding Proteins	journal.pbio.1001546	An in vivo functional analysis of an odorant binding protein in Drosophila challenges the established model of its role in pheromone signaling.	[ [ "Pheromones—“carriers of excitement” in Greek—are chemical signals produced by an individual and recognized by conspecifics to induce a defined behavioral response [1] .", "Because pheromones are the basis of communication controlling diverse social interactions in many organisms ( e . g . , aggregation ,...	[ "Pheromones form an essential chemical language of intraspecific communication in many animals .", "How olfactory systems recognize pheromonal signals with both sensitivity and specificity is not well understood .", "An important in vivo paradigm for this process is the detection mechanism of the sex pheromone ...	[ "Animals produce chemical signals , called pheromones , to communicate with other members of the same species to regulate social behaviors .", "How pheromones are detected is a fundamental question .", "One important model system for pheromone recognition is in Drosophila , where the sex pheromone cis-vaccenyl ...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Intracellular Interferons in Fish: A Unique Means to Combat Viral Infection	journal.ppat.1003736	null	[ [ "Interferons ( IFN ) are a key antiviral defence in jawed vertebrates , with many well characterised IFN-induced genes expressed following their release [1] , [2] , that participate in various ways to try to inhibit virus replication and modulate immune responses [3]–[6] .", "Three types of IFNs are known...	[ "We demonstrate for the first time in vertebrates , that alternative splicing of interferon ( IFN ) genes can lead to a functional intracellular IFN ( iIFN ) .", "Fish IFN genes possess introns and in rainbow trout three alternatively spliced transcripts of the IFN1 gene exist .", "Two of the encoded IFNs are p...	[ "The type I interferon ( IFN ) family consists of multiple members which are encoded by intronless genes in reptiles , birds and mammals but intron-containing genes in amphibians and fish .", "They coordinate antiviral defence by binding to cell surface receptors .", "Here , we demonstrate for the first time in...	2013
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "medicine", "public health and epidemiology", "epidemiology", "infectious disease epidemiology", "genetics", "immunology", "biology", "genomics", "microbiology", "genetics and genomics" ]	The Genetic and Molecular Basis of O-Antigenic Diversity in Burkholderia pseudomallei Lipopolysaccharide	journal.pntd.0001453	null	[ [ "Lipopolysaccharide ( LPS ) is a major component of the outer membrane of Gram-negative bacteria , playing an important role in cell integrity and in signaling host innate immune response [1] .", "Structurally , LPS is composed of three major components: lipid A , the bacterial endotoxin that is embedded ...	[ "Lipopolysaccharide ( LPS ) is one of the most important virulence and antigenic components of Burkholderia pseudomallei , the causative agent of melioidosis .", "LPS diversity in B . pseudomallei has been described as typical , atypical or rough , based upon banding patterns on SDS-PAGE .", "Here , we studied ...	[ "Burkholderia pseudomallei is an environmental Gram-negative bacterium and the cause of melioidosis , an often life-threatening disease affecting people in Southeast Asia and northern Australia .", "Melioidosis is usually contracted by bacterial inoculation , ingestion or inhalation .", "Effective vaccines for ...	2012

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