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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", "New BEAST functionality", "Beyond time trees: Extended phylogenetic structures", "New models", "Model selection and model adequacy", "New simulation tools", "Validation, testing and quality management", "Availability and future directions", "Discussion and conclusion" ]	[]	BEAST 2.5: An advanced software platform for Bayesian evolutionary analysis	journal.pcbi.1006650	null	[ [ "BEAST is a package for conducting Bayesian phylogenetic inference using MCMC .", "At its core are rooted time trees ( or time networks in latest developments ) , which can be inferred from multiple sources of data .", "BEAST supports sequence data for nucleotides , amino acids , codon models , discre...	[ "Elaboration of Bayesian phylogenetic inference methods has continued at pace in recent years with major new advances in nearly all aspects of the joint modelling of evolutionary data .", "It is increasingly appreciated that some evolutionary questions can only be adequately answered by combining evidence from mu...	[ "Bayesian phylogenetic inference methods have undergone considerable development in recent years , and joint modelling of rich evolutionary data , including genomes , phenotypes and fossil occurrences is increasingly common .", "Advanced computational software packages that allow robust development of compatible ...	2019
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Discovery of Drug Synergies in Gastric Cancer Cells Predicted by Logical Modeling	journal.pcbi.1004426	null	[ [ "It has long been envisaged that future anticancer treatment will adopt combinatorial approaches , in which several specific anti-cancer drugs together target multiple robustness features or weaknesses of a specific tumor [1–3] .", "The effectiveness of combinatorial anti-cancer treatments can be further ...	[ "Discovery of efficient anti-cancer drug combinations is a major challenge , since experimental testing of all possible combinations is clearly impossible .", "Recent efforts to computationally predict drug combination responses retain this experimental search space , as model definitions typically rely on extens...	[ "Fighting cancer with combinations of drugs increases success of treatment .", "However , due to the large number of drugs and tumor variants , it remains a tremendous challenge to identify efficient combinations .", "To illustrate this , a set of 150 drugs corresponds to more than 10 . 000 possible pairwise dr...	2015
[ "Introduction", "Materials and methods", "Results", "Discussion" ]	[ "invertebrates", "medicine and health sciences", "pathology and laboratory medicine", "togaviruses", "chikungunya infection", "pathogens", "tropical diseases", "microbiology", "geographical locations", "animals", "alphaviruses", "reproductive physiology", "viruses", "singapore", "chikung...	Peridomestic Aedes malayensis and Aedes albopictus are capable vectors of arboviruses in cities	journal.pntd.0005667	null	[ [ "Globally , dengue virus ( DENV ) is the most commonly transmitted arbovirus and infects an estimated 390 million people per year with greater than half the world’s population at risk of infection [1] .", "Chikungunya virus ( CHIKV ) periodically emerges to cause epidemics in populated areas and is mainta...	[ "Dengue and chikungunya are global re-emerging mosquito-borne diseases .", "In Singapore , sustained vector control coupled with household improvements reduced domestic mosquito populations for the past 45 years , particularly the primary vector Aedes aegypti .", "However , while disease incidence was low for t...	[ "Dengue and chikungunya are mosquito-borne diseases and re-emerging as a global burden of the 21st century .", "Because of the absence of cure and limitations of the current vaccine , vector control remains the sole efficient intervention to mitigate epidemics .", "The highly-populated city of Singapore represe...	2017
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "cell motility", "classical mechanics", "mathematical models", "multivariate analysis", "developmental biology", "systems science", "mathematics", "stem cells", "statistics (mathematics)", "morphogenesis", "research and analysis methods", "random walk", "computer and information sciences", ...	Inferring cell state by quantitative motility analysis reveals a dynamic state system and broken detailed balance	journal.pcbi.1005927	null	[ [ "Within any group of cells , each individual cell is not necessarily like its neighbors .", "These differences often have functional significance , with cells at different points along the phenotypic spectrum exhibiting distinct behavior [1] .", "This has been noted across a broad swath of cell biolog...	[ "Cell populations display heterogeneous and dynamic phenotypic states at multiple scales .", "Similar to molecular features commonly used to explore cell heterogeneity , cell behavior is a rich phenotypic space that may allow for identification of relevant cell states .", "Inference of cell state from cell beha...	[ "Cells in a population are not all alike .", "The differences between cells impact how each cell responds to stimuli , with implications for development and disease .", "How do cells change between these functionally important states over time ?", "This question is difficult to answer using molecular biology ...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Pelle Modulates dFoxO-Mediated Cell Death in Drosophila	journal.pgen.1005589	null	[ [ "Interleukin-1 receptor-associated kinases ( IRAKs ) are evolutionarily conserved Serine/Threonine ( Ser/Thr ) kinases that modulates Toll-like receptors ( TLRs ) and interleukin-1 receptors ( IL-1Rs ) signaling in the immune and inflammation response [1–3] .", "IRAKs transduce TLR/IL-1R signals to regula...	[ "Interleukin-1 receptor-associated kinases ( IRAKs ) are crucial mediators of the IL-1R/TLR signaling pathways that regulate the immune and inflammation response in mammals .", "Recent studies also suggest a critical role of IRAKs in tumor development , though the underlying mechanism remains elusive .", "Pelle...	[ "In the present study we report a Toll pathway independent function of Pll in modulating apoptotic cell death .", "Our major findings include:", "1 ) loss of pll generates Toll pathway-independent wing phenotypes , which are caused by a reduction in cell number but not cell size;", "2 ) depletion of pll up-re...	2015
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "medicine and health sciences", "post-exposure prophylaxis", "membrane potential", "tropical diseases", "immunology", "vertebrates", "electrophysiology", "animals", "mammals", "vaccines", "preventive medicine", "rabies", "neglected tropical diseases", "vaccination and immunization", "fru...	Potential Exposures to Australian Bat Lyssavirus Notified in Queensland, Australia, 2009−2014	journal.pntd.0005227	null	[ [ "Australian bat lyssavirus ( ABLV ) is a member of the Rhabdoviridae virus family , genus Lyssavirus .", "There are 12 recognised species ( genotypes ) within the genus Lyssavirus , including classic rabies virus and other closely related lyssaviruses ( e . g . European bat lyssaviruses ) [1 , 2] .", ...	[ "Australian bat lyssavirus ( ABLV ) belongs to the genus Lyssavirus which also includes classic rabies virus and the European lyssaviruses .", "To date , the only three known human ABLV cases , all fatal , have been reported from Queensland , Australia .", "ABLV is widely distributed in Australian bats , and an...	[ "Australian bat lyssavirus ( ABLV ) , closely related to classic rabies virus , is widely distributed in bats in Australia .", "So far , the only three known human ABLV cases , all fatal , have been reported in Queensland , Australia .", "Any Australian bat-related injury ( bite or scratch ) , or contact of bat...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "systems biology", "biochemistry", "biology", "computational biology", "molecular cell biology", "genetics and genomics" ]	Genome-Wide RNA Polymerase II Profiles and RNA Accumulation Reveal Kinetics of Transcription and Associated Epigenetic Changes During Diurnal Cycles	journal.pbio.1001442	Genome-wide rhythms in RNA polymerase II loading and dynamic chromatin remodeling underlie periodic gene expression during diurnal cycles in the mouse liver.	[ [ "In most mammalian organs , widespread diurnal rhythms in mRNA expression underlie the temporal compartmentalization of cellular and physiological processes [1] .", "In liver , these rhythms reflect the combined effects of regulation by time-varying systemic signals and by the autonomous circadian oscilla...	[ "Interactions of cell-autonomous circadian oscillators with diurnal cycles govern the temporal compartmentalization of cell physiology in mammals .", "To understand the transcriptional and epigenetic basis of diurnal rhythms in mouse liver genome-wide , we generated temporal DNA occupancy profiles by RNA polymera...	[ "In mammalian organs such as the liver , many metabolic and physiological processes occur preferentially at specific times during the 24-hour daily cycle .", "The timing of these rhythmic functions depends on a complex interplay between the endogenous circadian clock and environmental timing cues relayed through ...	2012
[ "Introduction", "Results", "Discussion", "Material and methods" ]	[ "skin", "invertebrates", "medicine and health sciences", "integumentary system", "gene regulation", "population genetics", "animals", "animal models", "developmental biology", "drosophila melanogaster", "model organisms", "pupae", "experimental organism systems", "epidermis", "population...	bric à brac (bab), a central player in the gene regulatory network that mediates thermal plasticity of pigmentation in Drosophila melanogaster	journal.pgen.1007573	null	[ [ "Complex traits such as size or disease susceptibility are typically modulated by both genetic variation and environmental parameters .", "This has major implications in agronomy , animal husbandry and medicine .", "Furthermore , as the phenotype ( and not the genotype ) is the target of natural selec...	[ "Drosophila body pigmentation has emerged as a major Evo-Devo model .", "Using two Drosophila melanogaster lines , Dark and Pale , selected from a natural population , we analyse here the interaction between genetic variation and environmental factors to produce this complex trait .", "Indeed , pigmentation var...	[ "Complex traits such as size or disease susceptibility are typically modulated by both genetic variation and environmental conditions .", "Model organisms such as fruit flies ( Drosophila ) are particularly appropriate to analyse the interactions between genetic variation and environmental factors during the deve...	2018
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "neuroanatomy", "anatomy", "computational neuroscience", "nervous system", "single neuron function", "biology and life sciences", "computational biology", "neuroscience", "artificial neural networks" ]	Linking Macroscopic with Microscopic Neuroanatomy Using Synthetic Neuronal Populations	journal.pcbi.1003921	null	[ [ "Growing evidence for the importance of dendritic structure on neuronal function has inspired the construction of morphologically realistic computational models of single neurons .", "Dendritic morphology has been shown to have a significant impact on neuronal firing properties , both between neurons of d...	[ "Dendritic morphology has been shown to have a dramatic impact on neuronal function .", "However , population features such as the inherent variability in dendritic morphology between cells belonging to the same neuronal type are often overlooked when studying computation in neural networks .", "While detailed ...	[ "Computational models of neurons and neural networks provide a valuable avenue to test our understanding of brain regions and to make predictions to guide future experimentation .", "Each neuron has a unique dendritic tree , features of which can vary depending on the location of the neuron within the particular ...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Genome-Wide Scan Informed by Age-Related Disease Identifies Loci for Exceptional Human Longevity	journal.pgen.1005728	null	[ [ "Aging and disease are closely related as aging is the largest risk factor for multiple chronic diseases .", "A great deal is known about the genetic basis of disease risk from genome-wide-association studies .", "However , little is known about the specific genetic differences that contribute to vary...	[ "We developed a new statistical framework to find genetic variants associated with extreme longevity .", "The method , informed GWAS ( iGWAS ) , takes advantage of knowledge from large studies of age-related disease in order to narrow the search for SNPs associated with longevity .", "To gain support for our ap...	[ "Longevity is a complex phenotype , and few genetic variants that affect lifespan have been identified .", "However , aging and disease are closely related , and a great deal is known about the genetic basis of disease risk .", "Here , we show using genome-wide association studies ( GWAS ) of longevity and dise...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine", "protein interactions", "neurodegenerative diseases", "amyotrophic lateral sclerosis", "molecular genetics", "motor neuron diseases", "proteins", "gene expression", "biology", "proteomics", "systems biology", "biochemistry", "neurological disorders", "neurology", "computation...	Identification of Human Proteins That Modify Misfolding and Proteotoxicity of Pathogenic Ataxin-1	journal.pgen.1002897	null	[ [ "Accumulation of misfolded proteins with pathogenic polyglutamine ( polyQ ) tracts in insoluble aggregates is a hallmark of late-onset neurodegenerative diseases , including Huntington's disease ( HD ) and spinocerebellar ataxias ( SCAs ) [1] , [2] .", "Misfolded proteins in neurons are often deposited in...	[ "Proteins with long , pathogenic polyglutamine ( polyQ ) sequences have an enhanced propensity to spontaneously misfold and self-assemble into insoluble protein aggregates .", "Here , we have identified 21 human proteins that influence polyQ-induced ataxin-1 misfolding and proteotoxicity in cell model systems .",...	[ "Spinocerebellar ataxias ( SCAs ) are a group of inherited neurodegenerative diseases with around 30 subtypes , which are characterized by a progressive loss of cerebellar neurons .", "Neuronal death has been linked to the aggregation of mutated disease-causing proteins , such as ataxin-1 ( ATXN1 ) .", "Pathoge...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "cell biology", "chromosome biology", "genetics", "biology and life sciences", "epigenetics", "chromatin", "histone modification" ]	Histone Methyltransferase MMSET/NSD2 Alters EZH2 Binding and Reprograms the Myeloma Epigenome through Global and Focal Changes in H3K36 and H3K27 Methylation	journal.pgen.1004566	null	[ [ "Epigenetic control of gene expression plays a critical role in many biological processes and aberrant chromatin regulation is the driving factor in a multitude of diseases , including cancer .", "Through studies of chromosomal rearrangements , copy number changes , and more recently , sequencing of cance...	[ "Overexpression of the histone methyltransferase MMSET in t ( 4;14 ) + multiple myeloma patients is believed to be the driving factor in the pathogenesis of this subtype of myeloma .", "MMSET catalyzes dimethylation of lysine 36 on histone H3 ( H3K36me2 ) , and its overexpression causes a global increase in H3K36...	[ "Precise spatial and temporal gene expression is required for normal development , and aberrant regulation of gene expression is a common factor in many diseases , including cancer .", "Histone modifications contribute to the control of gene expression by altering chromatin structure and affecting the recruitment...	2014
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "transfection", "fluorescence imaging", "medicine and health sciences", "luciferase", "enzymes", "enzymology", "green fluorescent protein", "parasitic diseases", "parasitic protozoans", "luminescent proteins", "protozoans", "molecular biology techniques", "research and analysis methods", "...	Expanding the toolbox for Trypanosoma cruzi: A parasite line incorporating a bioluminescence-fluorescence dual reporter and streamlined CRISPR/Cas9 functionality for rapid in vivo localisation and phenotyping	journal.pntd.0006388	null	[ [ "Trypanosoma cruzi is a protist parasite that causes Chagas disease in humans .", "An estimated 5–8 million people are infected , of whom approximately 30–40% will go on to develop severe , disabling and life-threatening pathologies of the heart and/or gastrointestinal system .", "Approximately 99% of...	[ "Infection with Trypanosoma cruzi causes Chagas disease , a major public health problem throughout Latin America .", "There is no vaccine and the only drugs have severe side effects .", "Efforts to generate new therapies are hampered by limitations in our understanding of parasite biology and disease pathogenes...	[ "5–8 million people in Latin America are infected with the single-cell parasite Trypanosoma cruzi , the causative agent of Chagas disease .", "Of these , approximately one-third will develop chronic disease pathology , leading to disability and premature death .", "Only two drugs are available , both of which c...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "phosphorylation", "medicine and health sciences", "liver", "cell cycle and cell division", "cell processes", "vertebrates", "animals", "animal models", "osteichthyes", "developmental biology", "mutation", "substitution mutation", "model organisms", "organism development", "cell nucleus"...	Phosphorylation of Def Regulates Nucleolar p53 Turnover and Cell Cycle Progression through Def Recruitment of Calpain3	journal.pbio.1002555	During organogenesis, cell proliferation is controlled not only by many known regulatory networks but also by the newly identified Def-CAPN3 nucleolar protein degradation pathway.	[ [ "The nucleolus is a subcellular organelle primarily known for the biogenesis of the ribosomal small and large subunits in eukaryotic cells [1 , 2] .", "However , bioinformatic analyses of nucleolar proteomic studies in cultured human HeLa cells [3 , 4] , Arabidopsis [5] , and human T cells [6] have shown ...	[ "Digestive organ expansion factor ( Def ) is a nucleolar protein that plays dual functions: it serves as a component of the ribosomal small subunit processome for the biogenesis of ribosomes and also mediates p53 degradation through the cysteine proteinase calpain-3 ( CAPN3 ) .", "However , nothing is known about...	[ "The nucleolus is primarily known as the subcellular organelle for the biogenesis of the ribosomal small and large subunits in eukaryotic cells .", "However , it is also increasingly evident that many nucleolar proteins also play essential roles in other biological processes .", "Here , we show that Digestive o...	2016
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[]	A Large-Scale Community-Based Outbreak of Paratyphoid Fever Caused by Hospital-Derived Transmission in Southern China	journal.pntd.0003859	null	[ [ "Typhoid and paratyphoid ( enteric ) fever caused by Salmonella enterica serovar Typhi and Paratyphi A remain significant public health problems for developing countries .", "Globally , 13 . 5 million cases are estimated to occur annually and are associated with 190 , 000 deaths in 2010 [1] .", "Befor...	[ "Since the 1990s , paratyphoid fever caused by Salmonella Paratyphi A has emerged in Southeast Asia and China .", "In 2010 , a large-scale outbreak involving 601 cases of paratyphoid fever occurred in the whole of Yuanjiang county in China .", "Epidemiological and laboratory investigations were conducted to det...	[ "Typhoid and paratyphoid fever remain public health concerns for developing countries .", "From May 2010 to June 2011 , a large-scale outbreak involving 601 cases of paratyphoid fever occurred in China .", "Epidemiological and laboratory investigations were conducted to determine the etiology , source and trans...	2015
[ "Introduction", "Materials and methods", "Results", "Discussion" ]	[ "antimicrobials", "urology", "children", "medicine and health sciences", "pathology and laboratory medicine", "drugs", "tropical diseases", "microbiology", "pediatrics", "bacterial diseases", "age groups", "signs and symptoms", "antibiotics", "neglected tropical diseases", "pharmacology"...	The inappropriate use of antibiotics in hospitalized dengue virus-infected children with presumed concurrent bacterial infection in teaching and private hospitals in Bandung, Indonesia	journal.pntd.0007438	null	[ [ "The municipality of Bandung , like many other cities in Indonesia , is endemic for DVI .", "Indonesia belongs to the highest category ( category A ) for the endemicity of Dengue Fever ( DF ) /Dengue Haemorrhagic Fever ( DHF ) [1] .", "The Ministry of Health in 2016 reported [2] , that DVI was found i...	[ "Dengue virus infection ( DVI ) among children is a leading cause of hospitalization in endemic areas .", "Hospitalized patients are at risk of receiving unnecessary antibiotics .", "A retrospective medical review analysis study was conducted to evaluate the prevalence , indication , and choice of antibiotics g...	[ "DVI among children is a leading cause of hospitalization in endemic areas .", "In developing or underdeveloped countries , the antibiotics stewardship policy has not been well implemented yet .", "Thus , the risk of unnecessary antibiotics used in hospitalized patients becomes higher .", "Changing the way me...	2019
[ "Introduction", "Results/Discussion", "Materials and Methods" ]	[ "biology", "evolutionary biology" ]	Duplicate Abalone Egg Coat Proteins Bind Sperm Lysin Similarly, but Evolve Oppositely, Consistent with Molecular Mimicry at Fertilization	journal.pgen.1003287	null	[ [ "Reproductive genes are often identified in genome-wide scans as targets of positive selection , and some are among the most rapidly evolving proteins known [1]–[4] .", "Their rapid adaptive evolution is observed in a broad range of organisms [5] , [6] , which is remarkable given the central importance of...	[ "Sperm and egg proteins constitute a remarkable paradigm in evolutionary biology: despite their fundamental role in mediating fertilization ( suggesting stasis ) , some of these molecules are among the most rapidly evolving ones known , and their divergence can lead to reproductive isolation .", "Because of stron...	[ "Interacting sperm and egg proteins must co-evolve to maintain compatibility at fertilization , so their divergence among species should be correlated—lineages with rapidly evolving sperm proteins should have rapidly evolving egg proteins .", "We use this expectation to target biochemical studies of fertilization...	2013
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "blood cells", "invertebrates", "medicine and health sciences", "immune cells", "pathology and laboratory medicine", "respiratory infections", "immunology", "tropical diseases", "parasitic diseases", "animals", "pulmonology", "developmental biology", "ascaris", "signs and symptoms", "neg...	Multiple Exposures to Ascaris suum Induce Tissue Injury and Mixed Th2/Th17 Immune Response in Mice	journal.pntd.0004382	null	[ [ "New information from the Global Burden of Disease Study 2010 ( GBD 2010 ) indicates that more than 800 million people are infected with Ascaris spp .", "( A . lumbricoides and A . suum ) , which ranks ascariasis as the most common affliction of people living in poverty [1] .", "In the past , A . suum...	[ "Ascaris spp .", "infection affects 800 million people worldwide , and half of the world population is currently at risk of infection .", "Recurrent reinfection in humans is mostly due to the simplicity of the parasite life cycle , but the impact of multiple exposures to the biology of the infection and the con...	[ "Human ascariasis caused by the helminths Ascaris lumbricoides and Ascaris suum , is the most prevalent neglected tropical disease in the world , affecting more than 800 million people and mainly school-aged children .", "The parasite life cycle may be divided in two distinct phases after the initial infection:",...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "systems biology", "microbial metabolism", "theoretical biology", "biology", "computational biology", "metabolic networks", "microbiology", "genetics and genomics" ]	Hydrophobicity and Charge Shape Cellular Metabolite Concentrations	journal.pcbi.1002166	null	[ [ "Living cells exhibit a preference towards certain types of metabolites .", "Many of these tendencies can be explained as consequences of chemical constraints imposed on metabolism .", "For example , the cellular ubiquity of charged metabolites , like those containing phosphoryl or carboxyl groups , i...	[ "What governs the concentrations of metabolites within living cells ?", "Beyond specific metabolic and enzymatic considerations , are there global trends that affect their values ?", "We hypothesize that the physico-chemical properties of metabolites considerably affect their in-vivo concentrations .", "The r...	[ "What governs the identity and concentrations of metabolites within living cells ?", "The first part of this question has received much attention .", "Organisms were found to qualitatively prefer hydrophilic and charged metabolites , a phenomenon that was explained to be a result of constraints imposed by conte...	2011
[ "Introduction", "Methods", "Results", "Discussion" ]	[]	Mitochondrial Genome Analyses Suggest Multiple Trichuris Species in Humans, Baboons, and Pigs from Different Geographical Regions	journal.pntd.0004059	null	[ [ "Neglected tropical diseases , including helminthiases , have a devastating effect on human health .", "It is estimated that about one billion people are infected with soil-transmitted helminths ( STHs ) , including the common roundworm ( Ascaris ) , hookworms ( Necator and Ancylostoma spp . ) , and whipw...	[ "The whipworms Trichuris trichiura and Trichuris suis are two parasitic nematodes of humans and pigs , respectively .", "Although whipworms in human and non-human primates historically have been referred to as T . trichiura , recent reports suggest that several Trichuris spp .", "are found in primates .", "We...	[ "Trichuris trichiura and Trichuris suis are whipworms found in humans and pigs , respectively , causing morbidity in humans and being associated with production losses in pigs .", "Although Trichuris from non-human primates is attributed to T . trichiura , hence considered the same species as the one infecting hu...	2015
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "medicine", "network analysis (management)", "social and behavioral sciences", "theoretical biology", "management engineering", "epidemiology", "social networks", "sociology", "management planning and control", "biology", "spatial epidemiology", "engineering" ]	Epidemic Spread on Weighted Networks	journal.pcbi.1003352	null	[ [ "Contact structure between hosts is known to have a key influence on disease spread [1] .", "A striking result is for instance that the more heterogeneous the contact network is ,", "i . e .", "the higher the variance in the number of contacts per individual , the more rapid the initial disease sp...	[ "The contact structure between hosts shapes disease spread .", "Most network-based models used in epidemiology tend to ignore heterogeneity in the weighting of contacts between two individuals .", "However , this assumption is known to be at odds with the data for many networks ( e . g . sexual contact networks...	[ "Understanding how infectious diseases spread has public health and ecological implications .", "The contact structure between hosts strongly affects this spread .", "However , most studies assume that all types of contacts are identical , when in reality some individuals interact more strongly than others .", ...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genome expression analysis", "gene regulation", "host-pathogen interaction", "microbiology", "rna stability", "developmental biology", "genome analysis tools", "plant science", "molecular cell biology", "molecular development", "plant pathology", "molecular genetics", "microbial growth and ...	Small RNA sX13: A Multifaceted Regulator of Virulence in the Plant Pathogen Xanthomonas	journal.ppat.1003626	null	[ [ "The survival and prosperity of bacteria depends on their ability to adapt to a variety of environmental cues such as nutrient availability , osmolarity and temperature .", "Besides the adaptation to the environment by transcriptional regulation of gene expression bacteria express regulatory RNAs that mod...	[ "Small noncoding RNAs ( sRNAs ) are ubiquitous posttranscriptional regulators of gene expression .", "Using the model plant-pathogenic bacterium Xanthomonas campestris pv .", "vesicatoria ( Xcv ) , we investigated the highly expressed and conserved sRNA sX13 in detail .", "Deletion of sX13 impinged on Xcv vir...	[ "Since the discovery of the first regulatory RNA in 1981 , hundreds of small RNAs ( sRNAs ) have been identified in bacteria .", "Although sRNA-mediated control of virulence was demonstrated for numerous animal- and human-pathogenic bacteria , sRNAs and their functions in plant-pathogenic bacteria have been enigm...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine", "infectious diseases", "neurological disorders", "neurology", "chemistry", "chemical biology" ]	Biochemical Properties of Highly Neuroinvasive Prion Strains	journal.ppat.1002522	null	[ [ "Prion diseases are fatal neurodegenerative disorders that include Creutzfeldt-Jakob disease ( CJD ) in humans , bovine spongiform encephalopathy ( BSE ) in cattle , and chronic wasting disease ( CWD ) in cervids ( reviewed in [1] ) .", "These disorders are caused by misfolding of the cellular prion prote...	[ "Infectious prions propagate from peripheral entry sites into the central nervous system ( CNS ) , where they cause progressive neurodegeneration that ultimately leads to death .", "Yet the pathogenesis of prion disease can vary dramatically depending on the strain , or conformational variant of the aberrantly fo...	[ "Prion diseases are fatal neurodegenerative disorders that are also infectious .", "Prions are composed of a misfolded , aggregated form of a normal cellular protein that is highly expressed in neurons .", "Prion- infected individuals show variability in the clinical signs and brain regions that selectively acc...	2012
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "infectious diseases", "medicine and health sciences", "veterinary diseases", "zoonoses", "parasitic intestinal diseases", "biology and life sciences", "tropical diseases", "parasitic diseases", "veterinary science", "nematode infections" ]	Toxocara Seroprevalence among Clinically Healthy Individuals, Pregnant Women and Psychiatric Patients and Associated Risk Factors in Shandong Province, Eastern China	journal.pntd.0003082	null	[ [ "Toxocarosis , a typical neglected and underestimated human health problem , is caused by the larval stages of Toxocara canis , the intestinal roundworms of dogs , and probably by the roundworm of cats ( Toxocara cati ) as well [1]–[3] .", "T . canis , the major cause of human toxocarosis , can reach a hi...	[ "Toxocarosis is a widespread zoonosis caused by the ascarid nematodes Toxocara canis and Toxocara cati , which primarily infect dogs and cats , respectively .", "Most human infections with Toxocara are asymptomatic; however , some infected individuals may develop a serious illness and even death .", "Neverthele...	[ "Toxocarosis , a typical neglected and underestimated human health problem , is caused by the ascarid nematodes Toxocara canis and Toxocara cati , which primarily infect dogs and cats , respectively .", "Previous studies have reported an increased risk for Toxocara infection in humans worldwide , especially in ch...	2014
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "experimental psychology", "psychology", "social and behavioral sciences", "mathematics", "statistics", "biology", "computational biology", "neuroscience", "probability theory" ]	Optimizing Experimental Design for Comparing Models of Brain Function	journal.pcbi.1002280	null	[ [ "The history of causal modeling of fMRI data in terms of effective connectivity began in the mid-1990's and has unfolded in two major phases ( for reviews , see [1]–[2] ) .", "The first phase addressed the optimization of connectivity estimates .", "This involved optimising methods that exploited the ...	[ "This article presents the first attempt to formalize the optimization of experimental design with the aim of comparing models of brain function based on neuroimaging data .", "We demonstrate our approach in the context of Dynamic Causal Modelling ( DCM ) , which relates experimental manipulations to observed net...	[ "During the past two decades , brain mapping research has undergone a paradigm switch .", "In addition to localizing brain regions that encode specific sensory , motor or cognitive processes , neuroimaging data is nowadays further exploited to ask questions about how information is transmitted through brain netwo...	2011
[ "Introduction", "Materials and Methods", "Results/Discussion" ]	[ "biochemistry", "cancer genetics", "proteins", "protein folding", "protein structure", "genetics", "biology and life sciences", "biophysics" ]	Use of Long Term Molecular Dynamics Simulation in Predicting Cancer Associated SNPs	journal.pcbi.1003318	null	[ [ "Most genetic variations in human were portrayed by single nucleotide polymorphisms ( SNPs ) , and most of them were thought to cause phenotypic differences amid individuals .", "Due to the use of high-throughput sequencing methods , the amount of identified variants in the human genome was rising rapidly...	[ "Computational prediction of cancer associated SNPs from the large pool of SNP dataset is now being used as a tool for detecting the probable oncogenes , which are further examined in the wet lab experiments .", "The lack in prediction accuracy has been a major hurdle in relying on the computational results obtai...	[ "The genetic mutations in human were shown by single nucleotide polymorphisms ( SNPs ) , and several of them were supposed to cause deleterious and disease associated phenotypic effects .", "The ability to differentiate between pathogenic and neutral nsSNPs ( non-synonymous Single Nucleotide Polymorphisms ) using...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "microbiology/environmental microbiology", "molecular biology/recombination", "genetics and genomics/chromosome biology", "molecular biology", "genetics and genomics", "molecular biology/dna repair" ]	RAD50 Is Required for Efficient Initiation of Resection and Recombinational Repair at Random, γ-Induced Double-Strand Break Ends	journal.pgen.1000656	null	[ [ "Double-strand breaks ( DSBs ) in chromosomal DNA are common sources of genetic change that may be deleterious or beneficial to an organism .", "They can arise as direct and processed lesions , errors during replication such as fork collapse , unprotected telomere ends , and they can be integral to progra...	[ "Resection of DNA double-strand break ( DSB ) ends is generally considered a critical determinant in pathways of DSB repair and genome stability .", "Unlike for enzymatically induced site-specific DSBs , little is known about processing of random “dirty-ended” DSBs created by DNA damaging agents such as ionizing ...	[ "Double-strand breaks ( DSBs ) in chromosomal DNA are common sources of genomic change that may be beneficial or deleterious to an organism , from yeast to humans .", "While they can arise through programmed cellular events , DSBs are frequently associated with defective chromosomal replication , and they are ind...	2009
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "acute myeloid leukemia", "leukemias", "medicine and health sciences", "genetic networks", "breast tumors", "myeloid leukemia", "gene regulation", "regulatory proteins", "cancers and neoplasms", "dna-binding proteins", "oncology", "hematologic cancers and related disorders", "regulator genes...	Identifying Network Perturbation in Cancer	journal.pcbi.1004888	null	[ [ "Genes do not act in isolation but instead work as part of complex networks to perform various cellular processes .", "Many human diseases including cancer are caused by dysregulated genes , with underlying DNA or epigenetic mutations within the gene region or its regulatory elements , leading to perturba...	[ "We present a computational framework , called DISCERN ( DIfferential SparsE Regulatory Network ) , to identify informative topological changes in gene-regulator dependence networks inferred on the basis of mRNA expression datasets within distinct biological states .", "DISCERN takes two expression datasets as in...	[ "Certain genes can regulate other genes’ expression and activity levels to perform key biological processes in a cell .", "Understanding how genes affect expression levels among one another is a fundamental goal in molecular biology .", "New statistical techniques that analyze genome-wide mRNA expression data o...	2016
[ "Introduction", "Results" ]	[ "biotechnology", "plant anatomy", "gene regulation", "brassica", "dna-binding proteins", "regulator genes", "plant science", "model organisms", "genetically modified plants", "gene types", "molecular biology techniques", "plants", "flowering plants", "genetic engineering", "arabidopsis t...	NUCLEAR FACTOR Y, Subunit A (NF-YA) Proteins Positively Regulate Flowering and Act Through FLOWERING LOCUS T	journal.pgen.1006496	null	[ [ "Plants undergo numerous developmental phase changes that are both species specific and intimately linked to the environments in which they evolved .", "One of the most important phase changes—as evidenced by the numerous pathways controlling the process—is the transition from vegetative to reproductive g...	[ "Photoperiod dependent flowering is one of several mechanisms used by plants to initiate the developmental transition from vegetative growth to reproductive growth .", "The NUCLEAR FACTOR Y ( NF-Y ) transcription factors are heterotrimeric complexes composed of NF-YA and histone-fold domain ( HFD ) containing NF-...	[ "For plants to have reproductive success , they must time their flowering with the most beneficial biotic and abiotic environmental conditions—after all , reproductive success would likely be low if flowers developed when pollinators were not present or freezing temperatures were on the horizon .", "Proper timing...	2016
[ "Introduction", "Results/Discussion", "Methods" ]	[ "biotechnology", "bioengineering", "biochemistry", "biological systems engineering", "biomedical engineering", "systems biology", "metabolic pathways", "biology", "computational biology", "metabolic networks", "metabolism", "genetics and genomics", "drug discovery" ]	Inferring Metabolic States in Uncharacterized Environments Using Gene-Expression Measurements	journal.pcbi.1002988	null	[ [ "The metabolic state of a cell is defined by the distribution of all its metabolic fluxes .", "It constitutes a significant aspect of cellular phenotype and is of both medical and industrial relevance .", "There are , for instance , striking differences in the metabolic states of healthy and cancer ce...	[ "The large size of metabolic networks entails an overwhelming multiplicity in the possible steady-state flux distributions that are compatible with stoichiometric constraints .", "This space of possibilities is largest in the frequent situation where the nutrients available to the cells are unknown .", "These t...	[ "Metabolic fluxes are steady-state rates of metabolite interconversion within living cells .", "They determine the rates of growth and product formation , and are of biotechnological and medical importance .", "An important and pressing question is how to identify the actual distribution of fluxes in living cel...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	BRCA1 Regulates IFI16 Mediated Nuclear Innate Sensing of Herpes Viral DNA and Subsequent Induction of the Innate Inflammasome and Interferon-β Responses	journal.ppat.1005030	null	[ [ "Sensing of microbial nucleic acids by pattern-recognition receptors ( PRRs ) is a crucial step for an effective innate immune response [1] .", "The best established function of PRRs like NLRPs ( NOD-like receptors with PYRIN ( PYD ) domain ) and ALRs ( absent in melanoma 2 [AIM2]-like receptors ) is thei...	[ "The innate immune system pattern recognition receptors ( PRR ) are the first line of host defenses recognizing the various pathogen- or danger-associated molecular patterns and eliciting defenses by regulating the production of pro-inflammatory cytokines such as IL-1β , IL-18 or interferon β ( IFN-β ) .", "NOD-l...	[ "Invasion of a host cell by pathogens , including viruses , is sensed by pattern-recognition receptors resulting in the elicitation of the host innate defenses such as the formation of multi-protein inflammasome complexes , inflammatory IL-1β and IL-18 cytokine production and interferon-β production via the cytopla...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "infectious diseases", "hiv infections", "evolutionary ecology", "medicine and health sciences", "major histocompatibility complex", "ecology", "clinical immunology", "population modeling", "aids", "biology and life sciences", "immunology", "infectious disease modeling", "computational biolo...	Disentangling Human Tolerance and Resistance Against HIV	journal.pbio.1001951	Title: Human tolerance against HIV An evolutionary ecology perspective on clinical data reveals that human traits can affect how well an individual tolerates HIV infection, and identifies host immunity factors associated with disease tolerance.	[ [ "In response to pressure by pathogens , host populations can evolve in two ways: They can develop either resistance or tolerance to the disease [1]–[8] .", "Resistance mechanisms reduce the pathogen burden .", "Tolerance mechanisms , in contrast , reduce the damage that accompanies infection without a...	[ "In ecology , “disease tolerance” is defined as an evolutionary strategy of hosts against pathogens , characterized by reduced or absent pathogenesis despite high pathogen load .", "To our knowledge , tolerance has to date not been quantified and disentangled from host resistance to disease in any clinically rele...	[ "When confronted with pathogens , hosts can either evolve to fight them or learn to live with them .", "The first of these two strategies is called “resistance” and the second “tolerance” .", "In the context of HIV , many genes conferring resistance have been identified , but no tolerance genes are known .", ...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	In Vivo Analysis of Disease-Associated Point Mutations Unveils Profound Differences in mRNA Splicing of Peripherin-2 in Rod and Cone Photoreceptors	journal.pgen.1005811	null	[ [ "The retina converts light into electrical signals via two highly specialized types of neurons , rod and cone photoreceptors .", "Both types of photoreceptors express in their light-sensitive outer segments ( rod outer segments , ROS and cone outer segments , COS , respectively ) a specific member of the ...	[ "Point mutations in peripherin-2 ( PRPH2 ) are associated with severe retinal degenerative disorders affecting rod and/or cone photoreceptors .", "Various disease-causing mutations have been identified , but the exact contribution of a given mutation to the clinical phenotype remains unclear .", "Exonic point m...	[ "Photoreceptors are the light sensing cells of the retina and consist of dim light and night vision mediating rods and daylight and color vision mediating cones .", "PRPH2 is crucial for the structural and functional integrity of photoreceptors .", "Some point mutations in PRPH2 lead to degeneration of rods , w...	2016
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "molecular biology/bioinformatics", "infectious diseases/neglected tropical diseases", "microbiology/parasitology" ]	Analyses of an Expressed Sequence Tag Library from Taenia solium, Cysticerca	journal.pntd.0000919	null	[ [ "Taenia solium is a parasitic tapeworm infecting approximately 50 million people worldwide [1] .", "Humans are the definitive host whereas pigs are the intermediate .", "Cysticercosis is caused when humans accidentally act as the intermediate host and ingest the eggs from tapeworms .", "The cysts ...	[ "Neurocysticercosis is a disease caused by the oral ingestion of eggs from the human parasitic worm Taenia solium .", "Although drugs are available they are controversial because of the side effects and poor efficiency .", "An expressed sequence tag ( EST ) library is a method used to describe the gene expressi...	[ "A method used to describe expressed genes at a specific stage in an organism is an EST library .", "In this method mRNA from a specific organism is isolated , transcribed into cDNA and sequenced .", "The sequence will derive from the 5′-end of the cDNA .", "The library will not have sequences from all genes ...	2010
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine", "infectious diseases", "immunology", "biology", "computational biology" ]	The Role of Exposure History on HIV Acquisition: Insights from Repeated Low-dose Challenge Studies	journal.pcbi.1002767	null	[ [ "Before being tested clinically , vaccines or preventive treatment strategies against human-immunodeficiency virus ( HIV ) are assessed in non-human primates .", "The paradigm of how vaccine candidates are assessed preclinically has been shifting in recent years .", "A decade ago , vaccine protection ...	[ "To assess the efficacy of HIV vaccine candidates or preventive treatment , many research groups have started to challenge monkeys repeatedly with low doses of the virus .", "Such challenge data provide a unique opportunity to assess the importance of exposure history for the acquisition of the infection .", "I...	[ "Individuals are exposed to Human Immunodeficiency Virus ( HIV ) many times before they contract the virus .", "It is not known what an instance of exposure , which does not result in infection , does to the host .", "Frequent exposures to the virus are hypothesized to immunize an individual , and result in res...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "in vitro", "none", "molecular biology", "computational biology" ]	Mechanochemical Coupling in the Myosin Motor Domain. II. Analysis of Critical Residues	journal.pcbi.0030023	null	[ [ "Large-scale conformational transitions driven by a distant chemical event , such as ligand binding , is the hallmark of many allosteric systems [1] .", "Although allostery is historically defined for multisubunit systems [2 , 3] , many of which have a considerable degree of symmetry [4] , it is increasin...	[ "An important challenge in the analysis of mechanochemical coupling in molecular motors is to identify residues that dictate the tight coupling between the chemical site and distant structural rearrangements .", "In this work , a systematic attempt is made to tackle this issue for the conventional myosin .", "B...	[ "Molecular motors are inherently allosteric in nature because the small structural changes associated with the chemistry in the active site are propagated over a long distance and amplified into much larger conformational transitions .", "A fundamental challenge for understanding such processes concerns the ident...	2007
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "conflict epidemiology", "public health", "medicine", "infectious diseases", "health screening", "social and behavioral sciences", "primary care", "mental health", "behavioral and social aspects of health", "epidemiology", "african trypanosomiasis", "alcohol", "neglected tropical diseases", ...	A Mixed Methods Study of a Health Worker Training Intervention to Increase Syndromic Referral for Gambiense Human African Trypanosomiasis in South Sudan	journal.pntd.0002742	null	[ [ "Found in remote sub-Saharan areas where health systems are often weak and/or destabilised by armed conflict , human African trypanosomiasis ( HAT , or sleeping sickness ) is one of the world's most neglected tropical diseases ( NTDs ) .", "It is caused by infection with trypanosome parasites that are tra...	[ "Active screening by mobile teams is considered the most effective method for detecting gambiense-type human African trypanosomiasis ( HAT ) but constrained funding in many post-conflict countries limits this approach .", "Non-specialist health care workers ( HCWs ) in peripheral health facilities could be traine...	[ "Human African trypanosomiasis ( HAT or sleeping sickness ) is a fatal but treatable disease affecting poor people in sub-Saharan Africa .", "Most HAT diagnostic equipment , infrastructure and expertise is located in hospitals .", "The expense of expanding testing services to remote areas using mobile teams sev...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "parastic protozoans", "systems biology", "biochemistry", "protozoology", "biology", "microbiology", "plasmodium falciparum", "parasitology", "parasite physiology", "pathogenesis" ]	Phosphoenolpyruvate Carboxylase Identified as a Key Enzyme in Erythrocytic Plasmodium falciparum Carbon Metabolism	journal.ppat.1003876	null	[ [ "Plasmodium falciparum is the causative agent of malaria , a disease claiming an estimated 660 , 000 lives annually , primarily among children in Africa [1] .", "The spread of drug resistance and the lack of an efficacious vaccine hinder the control of the disease , and new targets for chemotherapies or v...	[ "Phospoenolpyruvate carboxylase ( PEPC ) is absent from humans but encoded in the Plasmodium falciparum genome , suggesting that PEPC has a parasite-specific function .", "To investigate its importance in P . falciparum , we generated a pepc null mutant ( D10Δpepc ) , which was only achievable when malate , a red...	[ "The genome of the human malaria parasite Plasmodium falciparum encodes a protein called phosphoenolpyruvate carboxylase ( PEPC ) absent from the human host .", "PEPC is known to fix CO2 to generate metabolites used for energy metabolism in plants and bacteria , but its function in malaria parasites remained an e...	2014
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "mathematics/statistics", "immunology/immune response", "computational biology" ]	Explicit Kinetic Heterogeneity: Mathematical Models for Interpretation of Deuterium Labeling of Heterogeneous Cell Populations	journal.pcbi.1000666	null	[ [ "There is little consensus about the expected life spans of lymphocyte populations in health and disease .", "Labeling the DNA of dividing cells with deuterium has proved to be one of the most reliable and feasible ways to study the population dynamics of lymphocytes in healthy human volunteers and in pat...	[ "Estimation of division and death rates of lymphocytes in different conditions is vital for quantitative understanding of the immune system .", "Deuterium , in the form of deuterated glucose or heavy water , can be used to measure rates of proliferation and death of lymphocytes in vivo .", "Inferring these rate...	[ "Understanding of cellular processes is impossible without quantitative estimates of how quickly cells in an organism divide and die .", "The most widely used approach to measure rates of cell turnover in humans is by labeling dividing cells with deuterium given in the form of deuterated glucose or heavy water ."...	2010
[ "Introduction", "Results and Discussion", "Materials and Methods" ]	[ "infectious diseases", "medicine and health sciences", "biology and life sciences", "immunology", "microbiology" ]	Exploitation of Mycobacterium tuberculosis Reporter Strains to Probe the Impact of Vaccination at Sites of Infection	journal.ppat.1004394	null	[ [ "The potential impact that an effective vaccine against Mycobacterium tuberculosis ( Mtb ) would have in tuberculosis-endemic countries is undisputed , yet the route towards the development of such a vaccine has remained elusive .", "Most vaccine development strategies involve the use of recombinant Bacil...	[ "Mycobacterium tuberculosis ( Mtb ) remains a major public health problem , with an effective vaccine continuing to prove elusive .", "Progress in vaccination strategies has been hampered by a lack of appreciation of the bacterium's response to dynamic changes in the host immune environment .", "Here , we utili...	[ "Mycobacterium tuberculosis ( Mtb ) remains a serious challenge to global health , a situation that is exacerbated by emerging drug resistance , the paucity of new antibiotics , and the absence of an effective vaccine .", "Whilst there is no doubt that an anti-tuberculosis vaccine would have an extraordinary impa...	2014
[ "Introduction", "Methods", "Results", "Discussion" ]	[]	Modeling and Validation of Environmental Suitability for Schistosomiasis Transmission Using Remote Sensing	journal.pntd.0004217	null	[ [ "Schistosomiasis is a neglected tropical disease caused by blood flukes of the genus Schistosoma .", "From a public health perspective , schistosomiasis is considered the most important water-based disease .", "Indeed , data from mid-2003 suggest that 779 million people were at risk of schistosomiasis...	[ "Schistosomiasis is the most widespread water-based disease in sub-Saharan Africa .", "Transmission is governed by the spatial distribution of specific freshwater snails that act as intermediate hosts and human water contact patterns .", "Remote sensing data have been utilized for spatially explicit risk profil...	[ "Schistosomiasis is a parasitic worm infection that is widespread in sub-Saharan Africa where people get in contact with open freshwater bodies .", "For many years , the strategy to control schistosomiasis was to prevent morbidity through deworming of school-aged children .", "Recently , transmission control ha...	2015
[ "Introduction", "Results", "Discussion" ]	[ "computational biology/macromolecular sequence analysis", "biophysics/theory and simulation" ]	Trade-off between Positive and Negative Design of Protein Stability: From Lattice Models to Real Proteins	journal.pcbi.1000592	null	[ [ "Protein stabilization can be achieved via two different strategies:", "( i ) ‘positive design’ in which the native state is stabilized; and", "( ii ) ‘negative design’ in which non-native states are destabilized [1]–[3] .", "Positive design can be achieved by introducing favorable pairwise intera...	[ "Two different strategies for stabilizing proteins are", "( i ) positive design in which the native state is stabilized and", "( ii ) negative design in which competing non-native conformations are destabilized .", "Here , the circumstances under which one strategy might be favored over the other are explored...	[ "Most proteins are functional only in their native states .", "The stability of the native state of proteins is , therefore , of paramount importance both in vivo and for many biotechnological applications in vitro .", "Protein stability is determined by the difference between the free energies of the native an...	2009
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genetics and genomics/genome projects", "genetics and genomics/population genetics" ]	A Catalog of Neutral and Deleterious Polymorphism in Yeast	journal.pgen.1000183	null	[ [ "DNA sequence polymorphism makes a major contribution to phenotypic variation and provides a mean by which natural selection can lead to microevolutionary change and divergence between species .", "Since the first methods were developed to systematically survey DNA polymorphism within species and divergen...	[ "The abundance and identity of functional variation segregating in natural populations is paramount to dissecting the molecular basis of quantitative traits as well as human genetic diseases .", "Genome sequencing of multiple organisms of the same species provides an efficient means of cataloging rearrangements ,...	[ "DNA sequence variation makes an important contribution to most traits that vary in natural populations .", "However , mapping mutations that underlie a trait of interest is a significant challenge .", "Genome sequencing of multiple organisms provides a complete list of DNA sequence differences responsible for ...	2008
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "flow cytometry", "medicine", "immune cells", "cytokines", "herpes simplex", "immunologic subspecialties", "immunity to infections", "immunology", "host-pathogen interaction", "microbiology", "anatomy and physiology", "adaptive immunity", "immune defense", "dna", "cytometry", "immunolo...	Local CD4 and CD8 T-Cell Reactivity to HSV-1 Antigens Documents Broad Viral Protein Expression and Immune Competence in Latently Infected Human Trigeminal Ganglia	journal.ppat.1003547	null	[ [ "The neurotropic human alphaherpesvirus herpes simplex virus type 1 ( HSV-1 ) is endemic worldwide .", "It is acquired during early childhood via the orofacial route resulting in a lifelong chronic infection of neurons , also referred to as neuronal HSV-1 latency , in the bilateral trigeminal ganglia ( TG...	[ "Herpes simplex virus type 1 ( HSV-1 ) infection results in lifelong chronic infection of trigeminal ganglion ( TG ) neurons , also referred to as neuronal HSV-1 latency , with periodic reactivation leading to recrudescent herpetic disease in some persons .", "HSV-1 proteins are expressed in a temporally coordina...	[ "HSV-1 is an endemic human herpesvirus worldwide that establishes a lifelong latent infection of neurons in the trigeminal ganglion ( TG ) , allowing intermittent reactivation resulting in recurrent disease in some persons .", "Studies in HSV-1 models suggest a central role of TG-infiltrating virus-specific CD8 T...	2013
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "computational biology/population genetics", "virology/emerging viral diseases", "computational biology/evolutionary modeling", "evolutionary biology", "computational biology/molecular dynamics", "infectious diseases/epidemiology and control of infectious diseases" ]	Evolutionary Dynamics and Emergence of Panzootic H5N1 Influenza Viruses	journal.ppat.1000161	null	[ [ "Outbreaks of highly pathogenic avian influenza ( HPAI ) H5N1 virus were first recorded in Guangdong , China in 1996 [1] .", "Since its emergence , the A/goose/Guangdong/1/96 ( Gs/GD ) virus lineage has become the longest recorded HPAI virus to remain endemic in poultry [2] .", "The ecological success...	[ "The highly pathogenic avian influenza ( HPAI ) H5N1 virus lineage has undergone extensive genetic reassortment with viruses from different sources to produce numerous H5N1 genotypes , and also developed into multiple genetically distinct sublineages in China .", "From there , the virus has spread to over 60 coun...	[ "H5N1 influenza virus has been responsible for poultry outbreaks over the last 12 years—the longest recorded example of highly pathogenic avian influenza ( HPAI ) circulation in poultry .", "The ecological success of this virus in diverse species of both poultry and wild birds with sporadic introduction to humans...	2008
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	A Trichomonas vaginalis Rhomboid Protease and Its Substrate Modulate Parasite Attachment and Cytolysis of Host Cells	journal.ppat.1005294	null	[ [ "Trichomonas vaginalis is an extracellular , eukaryotic parasite that is the causative agent of trichomoniasis , the most common non-viral sexually transmitted infection in the world [1] .", "Approximately 276 million people worldwide become newly infected each year [1] .", "In the United States , an ...	[ "Trichomonas vaginalis is an extracellular eukaryotic parasite that causes the most common , non-viral sexually transmitted infection worldwide .", "Although disease burden is high , molecular mechanisms underlying T . vaginalis pathogenesis are poorly understood .", "Here , we identify a family of putative T ....	[ "Trichomonas vaginalis , a common pathogen with a worldwide distribution , causes a sexually transmitted infection and exacerbates other diseases .", "Estimated to infect over a million people annually in the United States alone , the Center for Disease Control and Prevention categorized trichomoniasis as one of ...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "computational neuroscience", "single neuron function", "biology", "neuroscience" ]	Passive Dendrites Enable Single Neurons to Compute Linearly Non-separable Functions	journal.pcbi.1002867	null	[ [ "We present in this section the binary neuron models we used to address our questions with a numerical and a formal analysis .", "We considered two types of dendritic non-linearities modeled by two families of non-linear activation functions , ( Figure 1B–C and definition in Materials and Methods spiking ...	[ "Local supra-linear summation of excitatory inputs occurring in pyramidal cell dendrites , the so-called dendritic spikes , results in independent spiking dendritic sub-units , which turn pyramidal neurons into two-layer neural networks capable of computing linearly non-separable functions , such as the exclusive O...	[ "Classical views on single neuron computation treat dendrites as mere collectors of inputs , that is forwarded to the soma for linear summation and causes a spike output if it is sufficiently large .", "Such a single neuron model can only compute linearly separable input-output functions , representing a small fr...	2013
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "neuroscience/natural and synthetic vision", "neuroscience/theoretical neuroscience", "neuroscience/sensory systems" ]	Vertical Binocular Disparity is Encoded Implicitly within a Model Neuronal Population Tuned to Horizontal Disparity and Orientation	journal.pcbi.1000754	null	[ [ "It is commonly accepted that in order for a neuronal population to encode the value of a quantity x , it must contain cells tuned to a range of values of x .", "Thus for example the retina can encode information about the wavelength of light because it contains three different types of cones with differe...	[ "Primary visual cortex is often viewed as a “cyclopean retina” , performing the initial encoding of binocular disparities between left and right images .", "Because the eyes are set apart horizontally in the head , binocular disparities are predominantly horizontal .", "Yet , especially in the visual periphery ...	[ "Because our eyes are set apart horizontally in our head , the images they see are mainly offset horizontally .", "However , small vertical disparities also occur , and can have a measurable effect on perception , showing that they must be detected by the visual system .", "The trouble is that encoding a two-di...	2010
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "invertebrates", "cell death", "fluorescence imaging", "medicine and health sciences", "autophagic cell death", "microbiome", "cell processes", "microbiology", "diet", "light microscopy", "animals", "nutrition", "microscopy", "insect vectors", "bacteria", "microbial genomics", "resea...	Polyphenol-Rich Diets Exacerbate AMPK-Mediated Autophagy, Decreasing Proliferation of Mosquito Midgut Microbiota, and Extending Vector Lifespan	journal.pntd.0005034	null	[ [ "Arboviruses are the leading vector-borne diseases worldwide .", "Dengue infections alone affect 50–100 million people .", "The lack of drugs or vaccines offers no hope that this scenario will change in the near future [1 , 2] .", "Reducing vector populations has been the only effective way to con...	[ "Mosquitoes feed on plant-derived fluids such as nectar and sap and are exposed to bioactive molecules found in this dietary source .", "However , the role of such molecules on mosquito vectorial capacity is unknown .", "Weather has been recognized as a major determinant of the spread of dengue , and plants und...	[ "The dramatic climate changes currently occurring on our planet may likely influence the biology and the distribution of mosquitoes .", "Aedes aegypti is a major vector of arboviruses .", "However , females feed on plants for a few days before feeding on blood for the first time .", "Plants are sessile and ca...	2016
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "antimicrobials", "medicine and health sciences", "chemical compounds", "caulobacter", "gene regulation", "drugs", "regulatory proteins", "microbiology", "dna-binding proteins", "organic compounds", "prokaryotic models", "regulator genes", "antibiotics", "experimental organism systems", ...	Regulation of bacterial surface attachment by a network of sensory transduction proteins	journal.pgen.1008022	null	[ [ "In natural ecosystems , bacteria often live in surface attached , multicellular communities known as biofilms [1] .", "Biofilms enhance resistance to toxic compounds , promote sorption of nutrients , and facilitate exchange of genes and gene products [2] .", "In aquatic systems , metabolizable substr...	[ "Bacteria are often attached to surfaces in natural ecosystems .", "A surface-associated lifestyle can have advantages , but shifts in the physiochemical state of the environment may result in conditions in which attachment has a negative fitness impact .", "Therefore , bacteria employ numerous mechanisms to co...	[ "Living on a surface within a community of cells confers a number of advantages to a bacterium .", "However , the transition from a free-living , planktonic state to a surface-attached lifestyle should be tightly regulated to ensure that cells avoid adhering to toxic or resource-limited niches .", "Many bacteri...	2019
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "plant anatomy", "medicine and health sciences", "vesicles", "crystal structure", "molecular dynamics", "pathology and laboratory medicine", "condensed matter physics", "toxicology", "membrane proteins", "toxicity", "plant science", "signs and symptoms", "crystallography", "plants", "cel...	Molecular basis for functional diversity among microbial Nep1-like proteins	journal.ppat.1007951	null	[ [ "Necrosis- and ethylene-inducing peptide 1-like proteins ( NLPs ) have been found in plant-associated prokaryotic ( bacteria ) and eukaryotic ( fungi , oomycetes ) microorganisms and are widely known to induce necrosis and ethylene production in eudicot plants [1–3] .", "NLPs share a conserved necrosis in...	[ "Necrosis and ethylene-inducing peptide 1 ( Nep1 ) -like proteins ( NLPs ) are secreted by several phytopathogenic microorganisms .", "They trigger necrosis in various eudicot plants upon binding to plant sphingolipid glycosylinositol phosphorylceramides ( GIPC ) .", "Interestingly , HaNLP3 from the obligate bi...	[ "The rhizosphere and phyllosphere of terrestrial plants are home to a number of microorganisms , many of which are potentially pathogenic at certain stages during their associations with plants .", "The pathogens use diverse routes to penetrate physical barriers and colonize host plants with different lifestyles ...	2019
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Wolbachia Variants Induce Differential Protection to Viruses in Drosophila melanogaster: A Phenotypic and Phylogenomic Analysis	journal.pgen.1003896	null	[ [ "Many arthropods are infected by bacterial secondary ( facultative ) symbionts [1] .", "These are vertically transmitted bacteria that are not essential for the host to survive or reproduce , but nonetheless can have important effects on their host's biology .", "The fitness of these secondary symbion...	[ "Wolbachia are intracellular bacterial symbionts that are able to protect various insect hosts from viral infections .", "This tripartite interaction was initially described in Drosophila melanogaster carrying wMel , its natural Wolbachia strain .", "wMel has been shown to be genetically polymorphic and there h...	[ "Wolbachia are bacterial symbionts that infect many arthropods and can protect insects from viral infection .", "Here we show that different variants of Wolbachia from Drosophila melanogaster ( wMel ) are phenotypically heterogeneous: they differ in the level of protection they confer and the titres they reach in...	2013
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "biology and life sciences" ]	Slow Noise in the Period of a Biological Oscillator Underlies Gradual Trends and Abrupt Transitions in Phasic Relationships in Hybrid Neural Networks	journal.pcbi.1003622	null	[ [ "Synchronized neural firing is a characteristic activity pattern of neural systems .", "Synchronized neural activity in cortical circuits [1] is thought to underlie many aspects of cognition [2] , [3] , including recognition [4] , recall [5] , perception [6] , [7] , and attention [8] .", "Phase-locked...	[ "In order to study the ability of coupled neural oscillators to synchronize in the presence of intrinsic as opposed to synaptic noise , we constructed hybrid circuits consisting of one biological and one computational model neuron with reciprocal synaptic inhibition using the dynamic clamp .", "Uncoupled , both n...	[ "Many biological phenomena exhibit synchronized oscillations in the presence of noise and heterogeneity .", "These include brain rhythms that underlie cognition and spinal rhythms that underlie rhythmic motor activity like breathing and locomotion .", "A two oscillator system was constructed in which most of th...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Rapid Evolution of Recombinant Saccharomyces cerevisiae for Xylose Fermentation through Formation of Extra-chromosomal Circular DNA	journal.pgen.1005010	null	[ [ "Microbial evolutionary experiments have received considerable attention in recent years for various reasons .", "First they allow in depth understanding of the fundamental process of evolution in a rapid and rigorously controlled way [1] .", "Second , microbial evolution raises great interest in vari...	[ "Circular DNA elements are involved in genome plasticity , particularly of tandem repeats .", "However , amplifications of DNA segments in Saccharomyces cerevisiae reported so far involve pre-existing repetitive sequences such as ribosomal DNA , Ty elements and Long Terminal Repeats ( LTRs ) .", "Here , we repo...	[ "Xylose is an important component of lignocellulose hydrolysates used for the production of bioethanol , but the yeast Saccharomyces cerevisiae is unable to utilize xylose .", "Insertion of a bacterial xylose isomerase gene and improvement of growth on xylose by evolutionary adaptation resulted in amplification o...	2015
[ "Introduction", "Student recruitment and selection", "Structure of the research experience", "Results", "Discussion" ]	[ "learning", "employment", "education", "social sciences", "neuroscience", "learning and memory", "careers", "research design", "scientists", "cognitive psychology", "undergraduates", "educational status", "science and technology workforce", "research and analysis methods", "computer and ...	A cyber-linked undergraduate research experience in computational biomolecular structure prediction and design	journal.pcbi.1005837	null	[ [ "Computational biology is an interdisciplinary field , and many computational biology research projects are performed by distributed international teams of scientists .", "In the coming decade , it will be imperative for computational biologists to collaborate within these virtual communities [1 , 2] .", ...	[ "Computational biology is an interdisciplinary field , and many computational biology research projects involve distributed teams of scientists .", "To accomplish their work , these teams must overcome both disciplinary and geographic barriers .", "Introducing new training paradigms is one way to facilitate res...	[ "Computational biology research is frequently conducted by virtual teams: groups of scientists in different locations that use shared resources and online communication tools to collaborate on a problem .", "It is imperative that the next generation of computational biologists can easily work in these interdiscip...	2017
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "learning", "medicine and health sciences", "engineering and technology", "transportation", "sociology", "geographical locations", "tropical diseases", "social sciences", "ebola hemorrhagic fever", "neuroscience", "learning and memory", "cognitive psychology", "social communication", "negl...	Development of a set of community-informed Ebola messages for Sierra Leone	journal.pntd.0005742	null	[ [ "The West African Ebola outbreak of 2013–2016 was by far the largest outbreak of the disease on record , with a total of 28 , 646 reported cases and 11 , 323 deaths [1] .", "Sierra Leone suffered nearly half of all the reported cases ( 14 , 124 , of whom 3 , 956 died ) ; while Liberia and Guinea had 10 , ...	[ "The West African Ebola epidemic of 2013–2016 was by far the largest outbreak of the disease on record .", "Sierra Leone suffered nearly half of the 28 , 646 reported cases .", "This paper presents a set of culturally contextualized Ebola messages that are based on the findings of qualitative interviews and foc...	[ "The work on which the paper is based was conducted in two Ebola ‘hotspots’ in Sierra Leone ( urban Freetown and rural Bombali district ) between January and April 2015 .", "Numerous misperceptions about Ebola had developed in the community over the course of 2014 , and it was becoming increasingly clear that the...	2017
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "medicine", "bacterial diseases", "infectious diseases", "immunity", "immunology", "biology", "microbiology", "bacterial pathogens" ]	An Encapsulated Yersinia pseudotuberculosis Is a Highly Efficient Vaccine against Pneumonic Plague	journal.pntd.0001528	null	[ [ "Plague , the dreadful infectious disease that caused three major pandemics in history , is still a public health problem .", "Since the 1980s , an increase of cases worldwide has been observed , leading to categorize plague as a re-emerging disease .", "Whereas the most active foci of human plague ar...	[ "Plague is still a public health problem in the world and is re-emerging , but no efficient vaccine is available .", "We previously reported that oral inoculation of a live attenuated Yersinia pseudotuberculosis , the recent ancestor of Yersinia pestis , provided protection against bubonic plague .", "However ,...	[ "Plague , among the most deadly infections of mankind's history , is present in Africa , Asia and America , and is currently re-emerging , recently causing cases in areas from where it had disappeared for decades .", "Pneumonic plague , its most deadly and contagious form , is responsible for human-to-human sprea...	2012
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "mathematics", "neuroscience", "neuroscience/theoretical neuroscience", "computational biology/computational neuroscience" ]	Evaluation of the Oscillatory Interference Model of Grid Cell Firing through Analysis and Measured Period Variance of Some Biological Oscillators	journal.pcbi.1000573	null	[ [ "Grid cells are a type of cells first found in rat medial entorhinal cortex [1]–[3] that are characterized by their spatial firing correlates .", "Each cell has multiple place fields ( locations in the environment where the cell fires at a high rate ) which are located at the vertices of an equilateral tr...	[ "Models of the hexagonally arrayed spatial activity pattern of grid cell firing in the literature generally fall into two main categories: continuous attractor models or oscillatory interference models .", "Burak and Fiete ( 2009 , PLoS Comput Biol ) recently examined noise in two continuous attractor models , bu...	[ "For many animals , including rats , accurate spatial memory over relatively large areas is important in order to find food and shelter .", "Just as unique points in time can be efficiently represented by combinations of repeating elements like hours , days , and months , points in space can be represented as com...	2009
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine", "bacterial and foodborne illness", "immunity", "gastroenterology and hepatology", "innate immunity", "immune defense", "immunology", "immune tolerance", "biology", "immunity to infections", "immunoregulation", "inflammatory bowel disease", "gastrointestinal infections", "immune...	SIGIRR, a Negative Regulator of TLR/IL-1R Signalling Promotes Microbiota Dependent Resistance to Colonization by Enteric Bacterial Pathogens	journal.ppat.1003539	null	[ [ "Citrobacter rodentium is a mouse-specific attaching/effacing ( A/E ) bacterial pathogen related to the clinically important enteropathogenic Escherichia coli ( EPEC ) and enterohemorrhagic E . coli ( EHEC ) .", "C . rodentium has been widely used to define the in vivo virulence strategies employed by A/E...	[ "Enteric bacterial pathogens such as enterohemorrhagic E . coli ( EHEC ) and Salmonella Typhimurium target the intestinal epithelial cells ( IEC ) lining the mammalian gastrointestinal tract .", "Despite expressing innate Toll-like receptors ( TLRs ) , IEC are innately hypo-responsive to most bacterial products ....	[ "Despite being in close contact with billions of commensal bacteria , the epithelial cells that line the intestine develop very weak innate inflammatory responses to bacterial products .", "The goal of this study was to explore why these cells respond so poorly , and how increasing their innate responsiveness wou...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "community ecology", "evolutionary ecology", "adaptation", "coevolution", "ecology", "ecosystems", "evolutionary biology", "ecosystem functioning", "biology", "species interactions", "evolutionary processes" ]	Species Interactions Alter Evolutionary Responses to a Novel Environment	journal.pbio.1001330	Adaptation to a novel environment is altered by the presence of co-occurring species. Species in diverse communities evolved complementary resource use, which altered the functioning of the experimental ecosystems.	[ [ "Understanding how species adapt to novel environments is an important task both for understanding the dynamics of living systems and for predicting biotic responses to anthropogenic changes in the natural environment [1]–[3] .", "However , most studies of evolutionary adaptation consider single species i...	[ "Studies of evolutionary responses to novel environments typically consider single species or perhaps pairs of interacting species .", "However , all organisms co-occur with many other species , resulting in evolutionary dynamics that might not match those predicted using single species approaches .", "Recent t...	[ "Understanding how species adapt to new environments is important both for evolutionary theory and for predicting and managing ecosystem responses to changing environments .", "However , most research into adaptation to new environments has considered species in isolation .", "Whether results from these systems...	2012
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "genetics and genomics", "computational biology/genomics", "computational biology/transcriptional regulation" ]	Calibrating the Performance of SNP Arrays for Whole-Genome Association Studies	journal.pgen.1000109	null	[ [ "It has been estimated that the human genome contains more than 5 million common single nucleotide polymorphisms ( SNPs ) with minor allele frequencies ( MAF ) ≥10% [1]–[3] , and 7 . 5 million common SNPs with MAF ≥5% [4] .", "These SNPs may account for the genetic risk of many common human disorders .", ...	[ "To facilitate whole-genome association studies ( WGAS ) , several high-density SNP genotyping arrays have been developed .", "Genetic coverage and statistical power are the primary benchmark metrics in evaluating the performance of SNP arrays .", "Ideally , such evaluations would be done on a SNP set and a coh...	[ "Advances in SNP genotyping array technologies have made whole-genome association studies ( WGAS ) a readily available approach .", "Genetic coverage and the statistical power are two key properties to evaluate on the arrays .", "In this study , 359 newly sampled individuals were genotyped using Affymetrix 500K...	2008
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "protein chemistry", "genomics", "computational chemistry", "molecular dynamics", "biophysic al simulations", "chemical physics", "gaussian fluctuations", "chemistry", "biology", "computational biology", "biophysics simulations", "biophysics", "physical chemistry" ]	“Fluctuograms” Reveal the Intermittent Intra-Protein Communication in Subtilisin Carlsberg and Correlate Mechanical Coupling with Co-Evolution	journal.pcbi.1002023	null	[ [ "During protein dynamics , the temporal and spatial couplings between amino acids are governed by the atomic details encoded in the sequence and protein's environment .", "A critical outcome is that ligand binding , chemical modification , and changes in solvent conditions not only alter structures and th...	[ "The mechanism of intra-protein communication and allosteric coupling is key to understanding the structure-property relationship of protein function .", "For subtilisin Carlsberg , the Ca2+-binding loop is distal to substrate-binding and active sites , yet the serine protease function depends on Ca2+ binding .",...	[ "A hallmark of protein molecules is their machine-like behaviors while carrying out biological functions .", "At the molecular level , molecular signals such as binding a metal ion at an action site can cause long-range effects and alter protein function .", "Such phenomena are often referred to as intra-protei...	2011
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "cell biology/neuronal and glial cell biology", "neuroscience", "neuroscience/sensory systems", "cell biology/cell signaling", "biophysics/experimental biophysical methods", "biophysics/theory and simulation", "cell biology", "cell biology/neuronal signaling mechanisms", "computational biology/compu...	Encoding of Spatio-Temporal Input Characteristics by a CA1 Pyramidal Neuron Model	journal.pcbi.1001038	null	[ [ "The Cornus Ammonis 1 ( CA1 ) region serves as the output of the hippocampus and has been associated with several memory processes including working memory [1] , [2] , [3] , [4] , acquisition and retrieval of contextual fear conditioning [4] as well as spatial and object novelty detection [5] , [6] , [7] .", ...	[ "The in vivo activity of CA1 pyramidal neurons alternates between regular spiking and bursting , but how these changes affect information processing remains unclear .", "Using a detailed CA1 pyramidal neuron model , we investigate how timing and spatial arrangement variations in synaptic inputs to the distal and ...	[ "Pyramidal neurons in the hippocampus are crucially involved in learning and memory functions , but the ways in which they contribute to the processing of sensory inputs and their internal representation remain mostly unclear .", "The principal neurons of the CA1 region of the hippocampus are surrounded by at lea...	2010
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "plant anatomy", "ecology and environmental sciences", "gene regulation", "regulatory proteins", "brassica", "dna-binding proteins", "plant physiology", "sweet potato", "plant science", "model organisms", "herbivory", "transcription factors", "crops", "transactivation", "dna", "plant e...	The Sweet Potato NAC-Domain Transcription Factor IbNAC1 Is Dynamically Coordinated by the Activator IbbHLH3 and the Repressor IbbHLH4 to Reprogram the Defense Mechanism against Wounding	journal.pgen.1006397	null	[ [ "Wounding from insect herbivory is a common environmental stress that impacts agricultural productivity worldwide .", "Plants have developed sophisticated defense systems to cope with this frequent challenge .", "Among these systems , transcription factors play essential roles by modulating the expres...	[ "IbNAC1 is known to activate the defense system by reprogramming a genetic network against herbivory in sweet potato .", "This regulatory activity elevates plant defense potential but relatively weakens plants by IbNAC1-mediated JA response .", "The mechanism controlling IbNAC1 expression to balance plant vital...	[ "Plants develop sophisticated defense systems against insect attack .", "IbNAC1 is a transcriptional activator , which up-regulates sporamin expression against herbivory in sweet potato .", "However , it simultaneously injures the plant by IbNAC1-induced JA response .", "Thus , dynamic regulatory networks to ...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Regulation of Gene Expression Patterns in Mosquito Reproduction	journal.pgen.1005450	null	[ [ "Numerous studies in model organisms have identified patterns of gene expression correlated with embryogenesis and development [1–9] .", "These studies have eloquently demonstrated the existence of a tight coordination between large gene cohorts and various stages of a developing organism on a spatiotempo...	[ "In multicellular organisms , development , growth and reproduction require coordinated expression of numerous functional and regulatory genes .", "Insects , in addition to being the most speciose animal group with enormous biological and economical significance , represent outstanding model organisms for studyin...	[ "In addition to being vectors of devastating human diseases , mosquitoes represent outstanding model organisms for studying regulatory mechanisms of differential gene expression due to their rapid reproductive cycles .", "About 7500 transcripts are differentially expressed in four sequential waves during the 72-h...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine and health sciences", "neurochemistry", "milk", "body fluids", "vertebrates", "mice", "neuroscience", "animals", "mammals", "hormones", "animal models", "model organisms", "probability distribution", "animal behavior", "mathematics", "zoology", "research and analysis method...	A Novel Mutant Allele of Pw1/Peg3 Does Not Affect Maternal Behavior or Nursing Behavior	journal.pgen.1006053	null	[ [ "Parental imprinting is a form of epigenetic regulation that results in an allele-specific expression of a gene according to its parental origin and is restricted to placental mammals [1–3] .", "Since 1991 , about 100 parentally imprinted genes have been identified and mutant mice have been generated for ...	[ "Parental imprinting is a mammalian-specific form of epigenetic regulation in which one allele of a gene is silenced depending on its parental origin .", "Parentally imprinted genes have been shown to play a role in growth , metabolism , cancer , and behavior .", "Although the molecular mechanisms underlying pa...	[ "Parental genomic imprinting is a mammalian-specific form of epigenetic control that regulates genes differently depending upon whether they are paternally or maternally inherited .", "The selective advantage of genomic imprinting is poorly understood and has been the subject of numerous theories .", "In the la...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "gene function", "developmental biology", "stem cells", "animal cells", "cell biology", "genetics", "biology and life sciences", "cellular types", "cell differentiation", "adult stem cells" ]	Three RNA Binding Proteins Form a Complex to Promote Differentiation of Germline Stem Cell Lineage in Drosophila	journal.pgen.1004797	null	[ [ "Adult stem cells divide to replenish differentiated , dead , or damaged cells in regenerative tissues .", "To produce sufficient number of differentiated progeny for tissue homeostasis and to avoid the accumulation of oncogenic mutations derived from frequent cell divisions , stem cell daughters undergo ...	[ "In regenerative tissues , one of the strategies to protect stem cells from genetic aberrations , potentially caused by frequent cell division , is to transiently expand the stem cell daughters before further differentiation .", "However , failure to exit the transit amplification may lead to overgrowth , and the...	[ "In regenerative tissues , the successive differentiation of stem cell lineage is well controlled and coordinated with proper cell proliferation at each differentiation stage .", "Disruption of the control mechanism can lead to tumor growth or tissue degeneration .", "The germline stem cell lineage of Drosophil...	2014
[ "Introduction", "Results", "Discussion", "Methods" ]	[]	Structure-Based Function Prediction of Uncharacterized Protein Using Binding Sites Comparison	journal.pcbi.1003341	null	[ [ "Experimental determination of protein function is the most reliable way to characterize proteins of unknown activity but it is difficult to prioritize functional experiments amongst the many possible functions a protein could perform .", "To guide experimentalists , a number of computer approaches have b...	[ "A challenge in structural genomics is prediction of the function of uncharacterized proteins .", "When proteins cannot be related to other proteins of known activity , identification of function based on sequence or structural homology is impossible and in such cases it would be useful to assess structurally con...	[ "For a substantial proportion of proteins , their functions are not known since these proteins are not related in sequence to any other known proteins .", "Binding sites are evolutionarily conserved across very distant protein families , and finding similar binding sites between known and unknown proteins can pro...	2013
[ "Introduction", "Models", "Results", "Discussion" ]	[ "invertebrates", "classical mechanics", "fluid mechanics", "condensed matter physics", "anisotropy", "animals", "simulation and modeling", "animal models", "developmental biology", "viscosity", "drosophila melanogaster", "model organisms", "molecular motors", "actin motors", "materials s...	Geometry can provide long-range mechanical guidance for embryogenesis	journal.pcbi.1005443	null	[ [ "The morphogenesis of living organisms involves precise shape changes and displacements of the tissues that constitute the embryo under the control of gene expression [1] .", "These movements result from changes in the mechanical balance , which can be caused by local growth [2] or by local activation of ...	[ "Downstream of gene expression , effectors such as the actomyosin contractile machinery drive embryo morphogenesis .", "During Drosophila embryonic axis extension , actomyosin has a specific planar-polarised organisation , which is responsible for oriented cell intercalation .", "In addition to these cell rearr...	[ "The morphogenesis of living organisms is a facinating process during which a genetic programme controls a sequence of molecular changes which will cause the original embryo to acquire a new shape .", "While we have a growing knowledge of the timing and spatial distribution of key molecules downstream of genetic ...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biochemistry", "cell biology", "biology and life sciences", "microbiology", "molecular biology", "parasitology" ]	A Novel Alpha Kinase EhAK1 Phosphorylates Actin and Regulates Phagocytosis in Entamoeba histolytica	journal.ppat.1004411	null	[ [ "Phagocytosis is an essential process both in unicellular organisms which use this process to obtain their food [1] , and multicellular organisms , where it plays a central role in the innate immune system [2] .", "In the protist pathogen Entamoeba histolytica it is an important process for nutrient uptak...	[ "Phagocytosis plays a key role in nutrient uptake and virulence of the protist parasite Entamoeba histolytica .", "Phagosomes have been characterized by proteomics , and their maturation in the cells has been studied .", "However , there is so far not much understanding about initiation of phagocytosis and form...	[ "Entamoeba histolytica is one of the major causes of morbidity and mortality in developing countries .", "Phagocytosis plays an important role in both survival and virulence , and has been used as one of the virulence markers .", "E . histolytica displays a high rate of phagocytosis and offers a unique system t...	2014
[ "Introduction", "Materials and methods", "Results", "Discussion" ]	[ "protein interactions", "nucleobases", "messenger rna", "nucleotides", "amino acid sequence analysis", "mathematics", "statistics (mathematics)", "research and analysis methods", "sequence analysis", "rna structure", "bioinformatics", "proteins", "mathematical and statistical techniques", ...	mRNA/protein sequence complementarity and its determinants: The impact of affinity scales	journal.pcbi.1005648	null	[ [ "The relationship between mRNAs and the proteins they encode is one of the key defining characteristics of life at the molecular level [1–3] .", "While this relationship has primarily been studied in the context of biological information transfer , less attention has been paid to a potential link between ...	[ "It has recently been demonstrated that the nucleobase-density profiles of mRNA coding sequences are related in a complementary manner to the nucleobase-affinity profiles of their cognate protein sequences .", "Based on this , it has been proposed that cognate mRNA/protein pairs may bind in a co-aligned manner , ...	[ "Messenger RNAs and proteins , two essential types of biopolymers , have recently been shown to exhibit closely related , complementary physicochemical properties .", "Specifically , density profiles of certain groups in messenger RNA sequences directly match the affinity profiles for precisely those groups in pr...	2017
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[]	IRES-Containing VEEV Vaccine Protects Cynomolgus Macaques from IE Venezuelan Equine Encephalitis Virus Aerosol Challenge	journal.pntd.0003797	null	[ [ "Venezuelan equine encephalitis ( VEE ) virus ( VEEV ) , an arbovirus with a wide geographic distribution across North , Central and South America , causes periodic outbreaks in human and equine populations as well as endemic disease following spillover from enzootic transmission cycles [1] .", "There are...	[ "Venezuelan equine encephalitis virus ( VEEV ) is an arbovirus endemic to the Americas that is responsible for severe , sometimes fatal , disease in humans and horses .", "We previously described an IRES-based VEE vaccine candidate based up the IE serotype that offers complete protection against a lethal subtype ...	[ "Venezuelan equine encephalitis virus ( VEEV ) is a mosquito-borne arbovirus endemic to the Americas that affects a wide range of equids and humans .", "Vaccination has been one of the strategies to combat spread of disease in areas with high rates incidence of VEEV , although existing vaccines have proven less t...	2015
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "bacteriology", "antimicrobials", "medicine and health sciences", "pathology and laboratory medicine", "bacteriophages", "pathogens", "drugs", "microbiology", "staphylococcus aureus", "viruses", "antibiotic resistance", "lysogeny", "antibiotics", "bacterial genetics", "pharmacology", "...	Bacteriophages benefit from generalized transduction	journal.ppat.1007888	null	[ [ "Temperate bacteriophages ( phages ) have a dual life cycle .", "They reside in the bacterial chromosome as prophages until induction initiates lytic replication , where phage structural proteins are produced , phage DNA is packaged into virions , and the cell ultimately lyses releasing the phage progeny ...	[ "Temperate phages are bacterial viruses that as part of their life cycle reside in the bacterial genome as prophages .", "They are found in many species including most clinical strains of the human pathogens , Staphylococcus aureus and Salmonella enterica serovar Typhimurium .", "Previously , temperate phages w...	[ "Viruses ( phages ) that only attack bacteria are highly common .", "Some of these phages naturally reside within the bacterial chromosome for extended periods of time .", "Upon release and propagation on phage susceptible cells , new phage particles are made but occasionally bacterial rather than phage DNA is ...	2019
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "microbiology/immunity to infections", "immunology/immune response", "microbiology/innate immunity", "pathology/histopathology", "molecular biology/bioinformatics", "public health and epidemiology/infectious diseases", "infectious diseases/respiratory infections", "infectious diseases/bacterial infect...	Getting to Grips with Strangles: An Effective Multi-Component Recombinant Vaccine for the Protection of Horses from Streptococcus equi Infection	journal.ppat.1000584	null	[ [ "Access to the genome sequence data of bacterial pathogens permitting the identification of surface exposed and secreted proteins has long been anticipated to revolutionize vaccine design , referred to as reverse vaccinology [1] , [2] .", "However , few vaccines have been taken beyond studies in mouse mod...	[ "Streptococcus equi subspecies equi ( S . equi ) is a clonal , equine host-adapted pathogen of global importance that causes a suppurative lymphodendopathy of the head and neck , more commonly known as Strangles .", "The disease is highly prevalent , can be severe and is highly contagious .", "Antibiotic treatm...	[ "Numerous research groups have vaccinated , using recombinant antigens , against streptococcal infections in mouse model systems and shown protection .", "We have here demonstrated efficient protective vaccination of the natural host , the horse , using recombinant antigens .", "Streptococcus equi subspecies eq...	2009
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "connectomics", "medicine and health sciences", "dementia", "neuroanatomy", "anatomy", "mental health and psychiatry", "computational neuroscience", "nervous system", "neurology", "neurodegenerative diseases", "biology and life sciences", "alzheimer disease", "computational biology", "auto...	Epidemic Spreading Model to Characterize Misfolded Proteins Propagation in Aging and Associated Neurodegenerative Disorders	journal.pcbi.1003956	null	[ [ "Misfolded proteins ( MP ) are associated with aging processes and several human neurodegenerative diseases [1]–[3] .", "The prion-like hypothesis explains the neurodegenerative progression by the intercellular transfer of pathogenic proteins [4]–[6] , under the perspective that MP behave like infectious-...	[ "Misfolded proteins ( MP ) are a key component in aging and associated neurodegenerative disorders .", "For example , misfolded Amyloid-ß ( Aß ) and tau proteins are two neuropathogenic hallmarks of Alzheimer's disease .", "Mechanisms underlying intra-brain MP propagation/deposition remain essentially uncharact...	[ "Misfolded proteins ( MP ) mechanisms are a characteristic pathogenic feature of most prevalent human neurodegenerative diseases , such as Alzheimer's disease ( AD ) .", "Characterizing the mechanisms underlying intra-brain MP propagation and deposition still constitutes a major challenge .", "Here , we hypothe...	2014
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "cell biology/microbial physiology and metabolism", "biochemistry/molecular evolution", "genetics and genomics/microbial evolution and genomics", "evolutionary biology/microbial evolution and genomics", "mathematics", "computational biology/evolutionary modeling", "computational biology/metabolic networ...	Evolution under Fluctuating Environments Explains Observed Robustness in Metabolic Networks	journal.pcbi.1000907	null	[ [ "High-throughput single gene deletion studies in several organisms revealed that a large fraction of genes have little or no detectable fitness effects when compromised [1]–[5] .", "These observations raise the question of how biological systems can acquire and maintain such robustness against gene loss ....	[ "A high level of robustness against gene deletion is observed in many organisms .", "However , it is still not clear which biochemical features underline this robustness and how these are acquired during evolution .", "One hypothesis , specific to metabolic networks , is that robustness emerges as a byproduct o...	[ "One of the most surprising recent biological findings is the high level of tolerance organisms show towards loss of single genes .", "This observation suggests that there are certain features of biological systems that give them a high tolerance ( i . e . robustness ) towards gene loss .", "We still lack an ex...	2010
[ "Introduction", "Methods", "Results/Discussion" ]	[ "biochemistry", "signal transduction", "molecular cell biology", "immune cells", "proteins", "t cells", "immunology", "biology", "computational biology", "signaling networks", "molecular biology", "t-cell receptors" ]	Integrating Signals from the T-Cell Receptor and the Interleukin-2 Receptor	journal.pcbi.1002121	null	[ [ "A number of receptor signaling networks have been elucidated beginning with the proximal events at the receptor , initiated by ligand binding , and extending down to the level of transcription factor activation .", "However , this top-down approach to describe pathways usually ignores the potential input...	[ "T cells orchestrate the adaptive immune response , making them targets for immunotherapy .", "Although immunosuppressive therapies prevent disease progression , they also leave patients susceptible to opportunistic infections .", "To identify novel drug targets , we established a logical model describing T-cel...	[ "The cells of the mammalian immune system do not exist in isolation , but rather form an integrated network that is constantly scanning the body for signs of ‘foreign’ invasion .", "Working together , these cells possess the ability to repel invaders and thereby establish protective immunity .", "One central po...	2011
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "evolutionary ecology", "behavioral neuroscience", "animal behavior", "ecology", "parasitology", "biology", "sensory perception", "zoology", "neuroscience", "animal cognition", "behavioral ecology" ]	Fatal Attraction Phenomenon in Humans – Cat Odour Attractiveness Increased for Toxoplasma-Infected Men While Decreased for Infected Women	journal.pntd.0001389	null	[ [ "The protozoan parasite Toxoplasma gondii is well known for changing behaviour of intermediate hosts , for review see [1] , [2] .", "In general , it is believed that specific behavioural changes represent a biological adaptation of the parasite aimed to enhance its transmission from an intermediate host (...	[ "Latent toxoplasmosis , a lifelong infection with the protozoan Toxoplasma gondii , has cumulative effects on the behaviour of hosts , including humans .", "The most impressive effect of toxoplasmosis is the “fatal attraction phenomenon , ” the conversion of innate fear of cat odour into attraction to cat odour i...	[ "Latent toxoplasmosis , a lifelong infection with the protozoan Toxoplasma gondii , has cumulative effects on the behaviour of hosts , including humans .", "The most impressive effect of toxoplasmosis is the so-called “fatal attraction phenomenon , ” the conversion of innate fear of odour of the definitive host ,...	2011
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "animal models", "biochemistry", "developmental biology", "lipids", "signal transduction", "model organisms", "molecular cell biology", "organism development", "molecular development", "biology", "metabolism", "molecular biology" ]	A Novel 3-Hydroxysteroid Dehydrogenase That Regulates Reproductive Development and Longevity	journal.pbio.1001305	A multidisciplinary approach identifies novel biochemical activities involved in the synthesisof C. elegans bile acid-like steroids, which act as hormones that regulate sterol metabolism and longevity.	[ [ "Small molecule metabolites and peptide hormones are well known to regulate various aspects of animal physiology , metabolism , and homeostasis .", "More recently they have emerged as important modulators of life span .", "Notably , a modest reduction in insulin/IGF-1 signaling ( IIS ) has been shown ...	[ "Endogenous small molecule metabolites that regulate animal longevity are emerging as a novel means to influence health and life span .", "In C . elegans , bile acid-like steroids called the dafachronic acids ( DAs ) regulate developmental timing and longevity through the conserved nuclear hormone receptor DAF-12...	[ "Although well known for their role in the absorption of dietary fat , bile acids have emerged as important metabolic signaling molecules that regulate cholesterol , fat , and glucose metabolism .", "Bile acids work through nuclear receptors , a class of transcription factors that bind to fat soluble hormones to ...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "infectious diseases/bacterial infections", "virology/virulence factors and mechanisms", "microbiology/cellular microbiology and pathogenesis", "cell biology/nuclear structure and function" ]	The Enteropathogenic E. coli Effector EspF Targets and Disrupts the Nucleolus by a Process Regulated by Mitochondrial Dysfunction	journal.ppat.1000961	null	[ [ "Central to the pathogenesis of many viral pathogens is the requirement to target the nucleolus [1] , a sub-nuclear structure found in all eukaryotic cells that is the primary site of ribosome biogenesis .", "Although the main function of the nucleolus is the synthesis of ribosomes , it is a highly dynami...	[ "The nucleolus is a multifunctional structure within the nucleus of eukaryotic cells and is the primary site of ribosome biogenesis .", "Almost all viruses target and disrupt the nucleolus—a feature exclusive to this pathogen group .", "Here , using a combination of bio-imaging , genetic and biochemical analyse...	[ "Many of the world's most important diseases are caused by bacterial pathogens that deliver effector proteins into the cells of their host .", "Effector proteins are collectively responsible for causing disease and an important area of research is to define the functions of these proteins and identify how they ar...	2010
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biotechnology", "developmental biology", "genetics", "biology", "genomics", "molecular cell biology", "genetics and genomics" ]	Contribution of Intragenic DNA Methylation in Mouse Gametic DNA Methylomes to Establish Oocyte-Specific Heritable Marks	journal.pgen.1002440	null	[ [ "Throughout mammalian gametogenesis , dynamic DNA methylation changes occur in a sex- and sequence-specific manner .", "These changes result in the establishment of oocyte- and sperm-specific genomic imprints and unique methylation patterns of repetitive elements via DNA methyltransferase activity [1]–[4]...	[ "Genome-wide dynamic changes in DNA methylation are indispensable for germline development and genomic imprinting in mammals .", "Here , we report single-base resolution DNA methylome and transcriptome maps of mouse germ cells , generated using whole-genome shotgun bisulfite sequencing and cDNA sequencing ( mRNA-...	[ "In mammals , germ-cell–specific methylation patterns and genomic imprints are established throughout large-scale de novo DNA methylation in oogenesis and spermatogenesis .", "These steps are required for normal germline differentiation and embryonic development; however , current DNA methylation analyses only pr...	2012
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "developmental biology", "model organisms", "genetics", "biology and life sciences", "genomics", "research and analysis methods" ]	Combinatorial Interactions Are Required for the Efficient Recruitment of Pho Repressive Complex (PhoRC) to Polycomb Response Elements	journal.pgen.1004495	null	[ [ "Polycomb Group ( PcG ) proteins are critical regulators of metazoan development and cell differentiation [1]–[4] .", "Their best understood role is to repress key developmental genes that trigger alternative programs of genome expression in cells where these programs should not be executed [4] .", "P...	[ "Polycomb Group ( PcG ) proteins are epigenetic repressors that control metazoan development and cell differentiation .", "In Drosophila , PcG proteins form five distinct complexes targeted to genes by Polycomb Response Elements ( PREs ) .", "Of all PcG complexes PhoRC is the only one that contains a sequence-s...	[ "Polycomb Group ( PcG ) proteins are epigenetic repressors essential for development and cell differentiation .", "PcG proteins form five complexes targeted to specific genes by Polycomb Response Elements ( PREs ) .", "How PcG complexes are recruited to PREs is poorly understood .", "Here we investigate the r...	2014
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "infectious diseases/helminth infections", "immunology/immunity to infections", "immunology/immune response", "infectious diseases/gastrointestinal infections" ]	Intraspecific Epitopic Variation in a Carbohydrate Antigen Exposed on the Surface of Trichostrongylus colubriformis Infective L3 Larvae	journal.ppat.1000597	null	[ [ "A wide variety of parasitic nematodes are capable of establishing long term chronic infections in mammals , including those that penetrate tissues and those that reside only in the gastrointestinal tract .", "Each of these nematode species must overcome a variety of host immune effector mechanisms withou...	[ "The carbohydrate larval antigen , CarLA , is present on the exposed surface of all strongylid nematode infective L3 larvae tested , and antibodies against CarLA can promote rapid immune rejection of incoming Trichostrongylus colubriformis larvae in sheep .", "A library of ovine recombinant single chain Fv ( scFv...	[ "Strongylid nematode worm parasites currently infect hundreds of millions of people , and most farmed animals , causing enormous morbidity and economic loss .", "These parasites commonly produce chronic gastrointestinal infections that are highly refractory to immune clearance mechanisms .", "Mucosal antibodies...	2009
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "virology/host invasion and cell entry" ]	Dissecting the Cell Entry Pathway of Dengue Virus by Single-Particle Tracking in Living Cells	journal.ppat.1000244	null	[ [ "Dengue virus ( DENV ) is a mosquito-transmitted , enveloped RNA virus that belongs to the family Flaviviridae .", "This family also includes West-Nile virus ( WNV ) and tick-borne encephalitis virus ( TBEV ) .", "DENV causes the most common arthropod-borne infection worldwide with 50–100 million case...	[ "Dengue virus ( DENV ) is an enveloped RNA virus that causes the most common arthropod-borne infection worldwide .", "The mechanism by which DENV infects the host cell remains unclear .", "In this work , we used live-cell imaging and single-virus tracking to investigate the cell entry , endocytic trafficking , ...	[ "Dengue virus ( DENV ) is the most common arthropod-borne infection worldwide with 50–100 million cases annually .", "Despite its high clinical impact , little is known about the infectious cell entry pathway of the virus .", "Previous studies have shown conflicting evidence about whether the virus fuses direct...	2008
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "biomacromolecule-ligand interactions", "biochemistry", "molecular complexes", "biophysics theory", "biology and life sciences", "computational biology", "biophysics", "molecular biology", "biophysical simulations" ]	Evidence of Conformational Selection Driving the Formation of Ligand Binding Sites in Protein-Protein Interfaces	journal.pcbi.1003872	null	[ [ "Many protein-protein interactions ( PPIs ) are involved in disease pathways where therapeutic intervention could bring widespread benefit , and hence are biologically compelling targets for drug discovery [1] , [2] .", "A number of systems are known for which small molecules inhibit the interaction betwe...	[ "Many protein-protein interactions ( PPIs ) are compelling targets for drug discovery , and in a number of cases can be disrupted by small molecules .", "The main goal of this study is to examine the mechanism of binding site formation in the interface region of proteins that are PPI targets by comparing ligand-f...	[ "Many protein-protein interfaces ( PPIs ) are biologically compelling drug targets .", "Disrupting the interaction between two large proteins by a small inhibitor requires forming a high affinity binding site in the interface that generally can bind both peptides and drug-like compounds .", "Here we investigate...	2014
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "taxonomy", "invertebrates", "dengue virus", "animal types", "medicine and health sciences", "body fluids", "immune physiology", "pathology and laboratory medicine", "pathogens", "immunology", "microbiology", "vertebrates", "animals", "mammals", "viruses", "phylogenetics", "data mana...	Neotropical bats that co-habit with humans function as dead-end hosts for dengue virus	journal.pntd.0005537	null	[ [ "Dengue is the most important arthropod-borne viral infection of humans , it is established in the tropics worldwide , and its geographical expansion is expected to increase due to factors such as modern dynamics of climate change , globalization , travel , trade , poverty , unplanned urbanization , and viral...	[ "Several studies have shown Dengue Virus ( DENV ) nucleic acids and/or antibodies present in Neotropical wildlife including bats , suggesting that some bat species may be susceptible to DENV infection .", "Here we aim to elucidate the role of house-roosting bats in the DENV transmission cycle .", "Bats were sam...	[ "Dengue is the most important human vector-borne disease .", "Several studies have shown DENV presence in mammalian wildlife such as bats , thus considering them putative reservoirs or hosts .", "We aimed to elucidate if bats that cohabit in houses in close proximity with humans may be involved in a dengue tran...	2017
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "blood cells", "innate immune system", "medicine and health sciences", "immune cells", "immune physiology", "respiratory infections", "cytokines", "pathology and laboratory medicine", "pathogens", "immunology", "microbiology", "orthomyxoviruses", "pulmonology", "viruses", "developmental ...	Early IL-6 signalling promotes IL-27 dependent maturation of regulatory T cells in the lungs and resolution of viral immunopathology	journal.ppat.1006640	null	[ [ "The prototypic pro-inflammatory cytokine interleukin 6 ( IL-6 ) is upregulated in a wide variety of immunological conditions including autoimmunity , cancer , infection and vaccination ( reviewed in [1] ) .", "IL-6 signalling influences both innate and adaptive immunity by regulating a broad range of pro...	[ "Interleukin-6 is a pleiotropic , pro-inflammatory cytokine that can promote both innate and adaptive immune responses .", "In humans with respiratory virus infections , such as Respiratory Syncytial Virus ( RSV ) , elevated concentrations of IL-6 are associated with more severe disease .", "In contrast the pol...	[ "In clearing a respiratory virus , the host must strike a careful balance between the need to clear the infection and the potential of the immune response to damage the delicate structure of the lungs .", "Here we show that Interleukin-6 , a soluble mediator commonly associated with inflammation and seen in human...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Diverse Heterologous Primary Infections Radically Alter Immunodominance Hierarchies and Clinical Outcomes Following H7N9 Influenza Challenge in Mice	journal.ppat.1004642	null	[ [ "Human infections with a novel , avian-origin H7N9 influenza A virus ( IAV ) were first seen in Southeast China in April 2013[1] , re-emerged through the 2013 winter and spread to other regions [2] .", "Hospitalized cases were characterized by severe morbidity and , to date , around 30% mortality [1 , 3–5...	[ "The recent emergence of a novel H7N9 influenza A virus ( IAV ) causing severe human infections in China raises concerns about a possible pandemic .", "The lack of pre-existing neutralizing antibodies in the broader population highlights the potential protective role of IAV-specific CD8+ cytotoxic T lymphocyte ( ...	[ "The emergence of human infections with a novel strain of avian-origin H7N9 virus in China raises a pandemic concern .", "The introduction of a new subtype in humans makes people at all ages susceptible due to the lack of population-wide neutralizing antibodies .", "However , cross-subtype protection from exist...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Optineurin Regulates the Interferon Response in a Cell Cycle-Dependent Manner	journal.ppat.1004877	null	[ [ "Innate immunity is a host mechanism found in most multicellular organisms that serves as a first line of defense against microbial pathogens .", "The innate immune response results in the production of immune modulatory cytokines and the mobilization of innate immune cells .", "Detection of pathogen ...	[ "Viral invasion into a host is initially recognized by the innate immune system , mainly through activation of the intracellular cytosolic signaling pathway and coordinated activation of interferon regulatory factor 3 ( IRF3 ) and nuclear factor kappa B ( NF-κB ) transcription factors that promote type I interferon...	[ "The innate immune system has evolved to detect and neutralize viral invasion .", "Triggering of this defense mechanism relies on the production and secretion of soluble factors that stimulate an intracellular antiviral defense mechanism .", "The protein Optineurin was shown to negatively regulate this process ...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biochemistry", "rna", "rna viruses", "nucleic acids", "virology", "viral classification", "biology", "microbiology" ]	Monomeric Nucleoprotein of Influenza A Virus	journal.ppat.1003275	null	[ [ "Negative strand RNA viruses have an RNA genome in the opposite sense of that of messenger RNA .", "Therefore , the first viral activity after entering the host cell is transcription by the viral RNA-dependent RNA polymerase .", "The template for transcription is a complex between the viral RNA and th...	[ "Isolated influenza A virus nucleoprotein exists in an equilibrium between monomers and trimers .", "Samples containing only monomers or only trimers can be stabilized by respectively low and high salt .", "The trimers bind RNA with high affinity but remain trimmers , whereas the monomers polymerise onto RNA fo...	[ "The RNAs of negative strand RNA viruses are encapsidated by their specific viral nucleoproteins , forming helical nucleoprotein-RNA structures that are the template for transcription and replication .", "All these nucleoproteins have two activities in common: RNA binding and self-polymerisation , and it is likel...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "ecology and environmental sciences", "engineering and technology", "transportation", "geographical locations", "vertebrates", "biodiversity", "animals", "transportation infrastructure", "roads", "habitats", "civil engineering", "birds", "ecosystems", "conservation science", "people and ...	Getting Road Expansion on the Right Track: A Framework for Smart Infrastructure Planning in the Mekong	journal.pbio.2000266	null	[ [ "The world is undergoing an unprecedented expansion of human infrastructure .", "For example , more than 450 new hydropower dams are planned for the Amazon , Congo , and Mekong basins alone [1] .", "Likewise , a recent report from the International Energy Agency states that by 2050 the world will buil...	[ "The current unprecedented expansion of infrastructure promises to enhance human wellbeing but risks causing substantial harm to natural ecosystems and the benefits they provide for people .", "A framework for systematically and proactively identifying the likely benefits and costs of such developments is badly n...	[ "Proposals for new infrastructure in developing countries are typically muted on its environmental impacts , while environmentalists typically say little about its potential benefits for people .", "This study explores a more conciliatory approach by trying to identify where beneficial infrastructure might be exp...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "developmental biology/aging" ]	Fatty Acid Desaturation Links Germ Cell Loss to Longevity Through NHR-80/HNF4 in C. elegans	journal.pbio.1000599	Lifespan extension induced by germline ablation in C. elegans is regulated by the nuclear hormone receptor NHR-80 in a process that requires the production of oleic acid by activation of the lipid desaturase FAT-6/SCD1.	[ [ "Removing the germ line of Caenorhabditis elegans extends its lifespan by approximately 60% [1] .", "Eliminating germ cells also increases the lifespan of Drosophila , suggesting that a conserved mechanism links the germ line to longevity [2] .", "In C . elegans , removal of the germ line can be achie...	[ "Preventing germline stem cell proliferation extends lifespan in nematodes and flies .", "So far , studies on germline-longevity signaling have focused on daf-16/FOXO and daf-12/VDR .", "Here , we report on NHR-80/HNF4 , a nuclear receptor that specifically mediates longevity induced by depletion of the germ li...	[ "Reproduction and aging are two processes that seem to be closely intertwined .", "Experiments in Caenorhabditis elegans and Drosophila have shown that depletion of the germ line increases lifespan and that this process depends on insulin and lipophilic-hormone signaling .", "Recently , it was demonstrated that...	2011
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "phosphorylation", "medicine and health sciences", "rna interference", "microtubules", "pathology and laboratory medicine", "neurodegenerative diseases", "toxicology", "toxicity", "epigenetics", "tubulins", "alzheimer disease", "cellular structures and organelles", "cytoskeleton", "genetic...	Stabilization of Microtubule-Unbound Tau via Tau Phosphorylation at Ser262/356 by Par-1/MARK Contributes to Augmentation of AD-Related Phosphorylation and Aβ42-Induced Tau Toxicity	journal.pgen.1005917	null	[ [ "Alzheimer’s disease ( AD ) is a progressive neurodegenerative disease characterized by two pathological lesions: deposition of β-amyloid peptides ( Aβ ) as amyloid plaques and the microtubule-associated protein tau in the form of paired helical filaments in neurofibrillary tangles ( NFTs ) [1] .", "Genet...	[ "Abnormal accumulation of the microtubule-interacting protein tau is associated with neurodegenerative diseases including Alzheimer’s disease ( AD ) .", "β-amyloid ( Aβ ) lies upstream of abnormal tau behavior , including detachment from microtubules , phosphorylation at several disease-specific sites , and self-...	[ "Alzheimer’s disease ( AD ) is the most common cause of dementia resulting from progressive neuron loss .", "Two proteins , β-amyloid ( Aβ ) and tau , accumulate in AD brains and are involved in AD pathogenesis .", "In healthy neurons , tau binds to microtubules to regulate its stability; in AD brains , however...	2016
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "medicine and health sciences", "reproductive system", "body fluids", "nervous system", "vertebrates", "neuroscience", "animals", "reproductive physiology", "endocrine physiology", "germ cells", "osteichthyes", "oocytes", "gnrh stimulation test", "pharmacology", "pharmacologic-based diag...	A Computational Model of the Rainbow Trout Hypothalamus-Pituitary-Ovary-Liver Axis	journal.pcbi.1004874	null	[ [ "Fishes , like other vertebrates , have an endocrine signaling network operating between the brain and the gonads controlling reproduction .", "This network spans the hypothalamus , the pituitary , the gonads and , in fishes and other egg-laying vertebrates , the liver , and is referred to in this paper a...	[ "Reproduction in fishes and other vertebrates represents the timely coordination of many endocrine factors that culminate in the production of mature , viable gametes .", "In recent years there has been rapid growth in understanding fish reproductive biology , which has been motivated in part by recognition of th...	[ "Reproduction in fishes and other vertebrates represents the timely coordination of many endocrine factors that culminate in the production of mature , viable gametes .", "Improving the ability to estimate reproductive performance in fish is important , due to the growth of the aquaculture industry and the need t...	2016
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "fish", "medicine and health sciences", "skeletal muscles", "computational biology", "vertebrates", "animals", "animal models", "osteichthyes", "developmental biology", "fungi", "model organisms", "experimental organism systems", "genome analysis", "mitochondria", "bioenergetics", "cel...	Loss of the Mia40a oxidoreductase leads to hepato-pancreatic insufficiency in zebrafish	journal.pgen.1007743	null	[ [ "Mitochondria are important organelles with multiple cellular functions , serving as energy- and biosynthetic centres , participating in Ca2+ signalling and cell stress responses , and executing cell death .", "Thus , compromised mitochondrial activity is associated with numerous human pathologies .", ...	[ "Development and function of tissues and organs are powered by the activity of mitochondria .", "In humans , inherited genetic mutations that lead to progressive mitochondrial pathology often manifest during infancy and can lead to death , reflecting the indispensable nature of mitochondrial biogenesis and functi...	[ "Mitochondrial pathologies which result from mutations in the nuclear DNA remain incurable and often lead to death .", "As mitochondria play various roles in cellular and tissue-specific contexts , the symptoms of mitochondrial pathologies can differ between patients .", "Thus , diagnosis and treatment of mitoc...	2018
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "infectious diseases", "infectious diseases/neglected tropical diseases", "immunology/immune response", "immunology/innate immunity", "critical care and emergency medicine/sepsis and multiple organ failure", "immunology", "infectious diseases/bacterial infections", "infectious diseases/tropical and tr...	Soluble ST2 Levels Are Associated with Bleeding in Patients with Severe Leptospirosis	journal.pntd.0000453	null	[ [ "Leptospirosis is a worldwide occurring zoonosis [1] , reported to be fatal in up to 50% of cases [2] .", "The disease is caused by spirochetes that are spread by the urine of infected animals , for example rats , mice and cattle amongst others .", "Survival of Leptospira is enhanced in a warm and hum...	[ "Severe leptospirosis features bleeding and multi-organ failure , leading to shock and death .", "Currently it is assumed that both exaggerated inflammation and immune suppression contribute to mortality in sepsis .", "Indeed , several proinflammatory cytokines are reported to be induced during leptospirosis ."...	[ "Leptospirosis is a bacterial disease that is mainly spread by rodents and other small mammals .", "Transmission frequently occurs in ( sub- ) tropical countries , where environmental circumstances are most favourable .", "Severe leptospirosis can cause bleeding and vital organ dysfunction .", "An exaggerated...	2009
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "blood cells", "medicine and health sciences", "immune cells", "immune physiology", "pathology and laboratory medicine", "spleen", "pathogens", "animal models of disease", "immunology", "microbiology", "animal models", "bacterial diseases", "model organisms", "cytotoxic t cells", "bacter...	Protective and Pathogenic Roles of CD8+ T Lymphocytes in Murine Orientia tsutsugamushi Infection	journal.pntd.0004991	null	[ [ "Orientia ( O . ) tsutsugamushi , the causative agent of scrub typhus , is an obligate intracellular bacterium of the Rickettsiaceae family .", "The pathogen resides in the cytoplasm of its host cells , which are mainly macrophages , monocytes and dendritic cells ( DCs ) [1 , 2] .", "Furthermore , inf...	[ "T cells are known to contribute to immune protection against scrub typhus , a potentially fatal infection caused by the obligate intracellular bacterium Orientia ( O . ) tsutsugamushi .", "However , the contribution of CD8+ T cells to protection and pathogenesis during O . tsutsugamushi infection is still unknow...	[ "Orientia ( O . ) tsutsugamushi is the causative agent of scrub typhus , a potentially fatal disease that is endemic in South East Asia .", "This bacterium replicates in the cytoplasm of its host cells .", "The obligate intracytoplasmic lifestyle resembles that of many viruses , but among pathogenic bacteria it...	2016
[ "Introduction", "Materials and Methods", "Results", "Discussion", "Conclusion" ]	[ "death rates", "invertebrates", "livestock", "animal types", "medicine and health sciences", "ruminants", "demography", "african trypanosomiasis", "tropical diseases", "vertebrates", "parasitic diseases", "animals", "mammals", "glossina", "simulation and modeling", "systems science", ...	A Multi-Host Agent-Based Model for a Zoonotic, Vector-Borne Disease. A Case Study on Trypanosomiasis in Eastern Province, Zambia	journal.pntd.0005252	null	[ [ "Human African trypanosomiasis ( HAT ) , also known as sleeping sickness , is a parasitic disease which poses a significant disease burden in affected communities living in HAT foci across sub-Saharan Africa [1 , 2] .", "HAT is caused by two sub-species of the protozoan parasite Trypanosoma brucei s . l ....	[ "This paper presents a new agent-based model ( ABM ) for investigating T . b .", "rhodesiense human African trypanosomiasis ( rHAT ) disease dynamics , produced to aid a greater understanding of disease transmission , and essential for development of appropriate mitigation strategies .", "The ABM was developed ...	[ "African trypanosomiasis is a parasitic disease which affects humans and other animals in 36 sub-Saharan African countries .", "The disease is transmitted by the tsetse fly , and the human form of the diseases is known as sleeping sickness .", "Infectious disease transmission has traditionally been modelled usi...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genetic association studies", "genome analysis", "trait locus analysis", "genetics", "biology and life sciences", "epigenomics", "computational biology", "human genetics" ]	Quantitative Genetics of CTCF Binding Reveal Local Sequence Effects and Different Modes of X-Chromosome Association	journal.pgen.1004798	null	[ [ "A major challenge in human genetics is to understand the mechanisms that link variation in genomic sequence to phenotypes of interest , including disease .", "Since 2005 , a growing number of genome-wide association studies ( GWAS ) have associated both disease and normal phenotypes with over 9 , 800 sin...	[ "Associating genetic variation with quantitative measures of gene regulation offers a way to bridge the gap between genotype and complex phenotypes .", "In order to identify quantitative trait loci ( QTLs ) that influence the binding of a transcription factor in humans , we measured binding of the multifunctional...	[ "We have systematically measured the effect of normal genetic variation present in a human population on the binding of a specific chromatin protein ( CTCF ) to DNA by measuring its binding in 51 human cell lines .", "We observed a large number of changes in protein binding that we can confidently attribute to ge...	2014
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "systems biology", "cellular structures", "theoretical biology", "cell biology", "biology", "computational biology", "molecular cell biology", "biophysics", "genetics and genomics" ]	Mitochondrial Variability as a Source of Extrinsic Cellular Noise	journal.pcbi.1002416	null	[ [ "Stochastic influences significantly affect a multitude of processes in cellular biology [1]–[5] .", "Understanding the sources of this randomness within and between cells is a central current challenge in quantitative biology .", "Noise has been found to affect processes including stem cell fate deci...	[ "We present a study investigating the role of mitochondrial variability in generating noise in eukaryotic cells .", "Noise in cellular physiology plays an important role in many fundamental cellular processes , including transcription , translation , stem cell differentiation and response to medication , but the ...	[ "Cellular variability has been found to play a major role in diverse and important phenomena , including stem cell differentiation and drug resistance , but the sources of this variability have yet to be satisfactorily explained .", "We propose a mechanism , supported by a substantial number of recent and new exp...	2012

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