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headings list	keywords list	title stringlengths 20 281	id stringlengths 20 20	toc stringlengths 57 522 ⌀	sections list	abstract list	summary list	year stringclasses 13 values
[ "Introduction", "Results and Discussion", "Materials and Methods" ]	[ "organismal evolution", "physical anthropology", "human evolution", "biology and life sciences", "population genetics", "gene flow", "social sciences", "evolutionary biology", "anthropology" ]	Early Back-to-Africa Migration into the Horn of Africa	journal.pgen.1004393	null	[ [ "The timing and extent of migration and admixture are questions that are central to the entire scope of human evolutionary history from the origin of our species to the present day .", "The most important event underlying human population structure is the origin of anatomically modern humans in Africa and...	[ "Genetic studies have identified substantial non-African admixture in the Horn of Africa ( HOA ) .", "In the most recent genomic studies , this non-African ancestry has been attributed to admixture with Middle Eastern populations during the last few thousand years .", "However , mitochondrial and Y chromosome d...	[ "The Horn of Africa ( HOA ) occupies a central place in our understanding of modern human origins .", "This region is the location of the earliest known modern human fossils , a possible source for the out-of-Africa migration , and one of the most genetically and linguistically diverse regions of the world .", ...	2014
[ "Introduction", "Material and methods", "Results", "Discussion" ]	[ "invertebrates", "medicine and health sciences", "immune physiology", "body fluids", "helminths", "immunology", "tropical diseases", "hookworms", "sorption", "animals", "vaccines", "preventive medicine", "desorption", "neglected tropical diseases", "antibodies", "vaccination and immuni...	Advances in neglected tropical disease vaccines: Developing relative potency and functional assays for the Na-GST-1/Alhydrogel hookworm vaccine	journal.pntd.0005385	null	[ [ "Over the next decade , a new generation of vaccines for the neglected tropical diseases ( NTDs ) , especially those for helminthic parasites such schistosomiasis and hookworm ( Necator americanus ) will advance into clinical trials [1] .", "The Na-GST-1/Alhydrogel Hookworm Vaccine has already entered int...	[ "A new generation of vaccines for the neglected tropical diseases ( NTDs ) have now advanced into clinical development , with the Na-GST-1/Alhydrogel Hookworm Vaccine already being tested in Phase 1 studies in healthy adults .", "The current manuscript focuses on the often overlooked critical aspects of NTD vacci...	[ "As vaccines targeting NTDs advance into clinical trials , product development and vaccine maintenance become critical activities for the success of these vaccines .", "A key activity during this phase of vaccine development is the “relative potency” of a vaccine or the quality of the immune response that the vac...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "molecular cell biology", "cell biology", "biology and life sciences", "molecular biology" ]	Developmental Regulation of the Tetrahymena thermophila Origin Recognition Complex	journal.pgen.1004875	null	[ [ "DNA replication initiates at specific sites in chromosomes , termed origins of replication .", "While the genomic architecture of replication initiation sites varies widely across the eukaryotic lineage , a conserved feature is their association with the six-subunit Origin Recognition Complex ( ORC ) [1]...	[ "The Tetrahymena thermophila DNA replication machinery faces unique demands due to the compartmentalization of two functionally distinct nuclei within a single cytoplasm , and complex developmental program .", "Here we present evidence for programmed changes in ORC and MCM abundance that are not consistent with c...	[ "The Origin Recognition Complex is required for site-specific replication initiation in eukaryotic chromosomes .", "Null mutations are lethal in yeast and metazoa , and hypomorphs induce genome instability , a hallmark of cancer .", "We exploited the unique biology of Tetrahymena to explore ORC's role in conven...	2015
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "genomics", "biology", "computational biology", "genetics and genomics" ]	Joint Analysis of Multiple Metagenomic Samples	journal.pcbi.1002373	null	[ [ "Metagenomic samples are pooled samples of the genomes of multiple microorganisms living in the same environment .", "They can be taken either from the outer environment or from microbial populations colonizing other living organisms .", "Metagenomic studies focus on the taxonomic and functional chara...	[ "The availability of metagenomic sequencing data , generated by sequencing DNA pooled from multiple microbes living jointly , has increased sharply in the last few years with developments in sequencing technology .", "Characterizing the contents of metagenomic samples is a challenging task , which has been extens...	[ "Microorganisms are extremely abundant and diverse , and occupy almost every habitat on earth .", "Most of these habitats contain a complex mixture of many different microorganisms , and the characterization of these metagenomic mixtures , in terms of both taxonomy and function , is of great interest to science a...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine", "biochemistry", "infectious diseases", "chemical biology", "chemistry", "biology", "microbiology", "molecular cell biology" ]	CcpA Regulates Arginine Biosynthesis in Staphylococcus aureus through Repression of Proline Catabolism	journal.ppat.1003033	null	[ [ "Staphylococcus aureus is a common cause of skin and soft tissue infections; however more serious complications such as bacteremia , osteomyelitis , endocarditis , and necrotizing pneumonia can occur [1] .", "During infection , S . aureus must catabolize diverse carbon sources including carbohydrates , pr...	[ "Staphylococcus aureus is a leading cause of community-associated and nosocomial infections .", "Imperative to the success of S . aureus is the ability to adapt and utilize nutrients that are readily available .", "Genomic sequencing suggests that S . aureus has the genes required for synthesis of all twenty am...	[ "Although Staphylococcus aureus encodes the highly conserved arginine biosynthesis pathway via glutamate , arginine is an essential amino acid .", "We found that a mutation in ccpA , a gene encoding a protein facilitating carbon catabolite repression , mediates arginine biosynthesis under in vitro growth conditio...	2012
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "public health and epidemiology/infectious diseases", "genetics and genomics/genetics of the immune system" ]	Fine Pathogen Discrimination within the APL1 Gene Family Protects Anopheles gambiae against Human and Rodent Malaria Species	journal.ppat.1000576	null	[ [ "Malaria remains a major global health problems , with more than 300 million estimated cases and more than one million deaths annually [1] .", "Plasmodium falciparum is the most common human malaria parasite in Africa and is responsible for the majority of mortality due to malaria .", "The vector mosq...	[ "Genetically controlled resistance of Anopheles gambiae mosquitoes to Plasmodium falciparum is a common trait in the natural population , and a cluster of natural resistance loci were mapped to the Plasmodium-Resistance Island ( PRI ) of the A . gambiae genome .", "The APL1 family of leucine-rich repeat ( LRR ) p...	[ "The African malaria vector mosquito Anopheles gambiae possesses immune mechanisms that can protect it against infection with malaria parasites , which kill more than one million people per year .", "Much work studying mosquito response to malaria has used model rodent malaria parasites that do not infect people ...	2009
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "fluorescence imaging", "medicine and health sciences", "diagnostic radiology", "neural networks", "light microscopy", "neuroscience", "in vivo imaging", "microscopy", "cellular structures and organelles", "bacteria", "research and analysis methods", "computer and information sciences", "ima...	Deep Learning Automates the Quantitative Analysis of Individual Cells in Live-Cell Imaging Experiments	journal.pcbi.1005177	null	[ [ "Image segmentation of single cells in microscopy images can be converted into an image classification problem [38] .", "Consider a manually annotated image where each pixel has been identified as either a cell boundary , cellular interior , or background ( non-cell ) pixel , as depicted in Fig 1a .", ...	[ "Live-cell imaging has opened an exciting window into the role cellular heterogeneity plays in dynamic , living systems .", "A major critical challenge for this class of experiments is the problem of image segmentation , or determining which parts of a microscope image correspond to which individual cells .", "...	[ "Dynamic live-cell imaging experiments are a powerful tool to interrogate biological systems with single cell resolution .", "The key barrier to analyzing data generated by these measurements is image segmentation—identifying which parts of an image belong to which individual cells .", "Here we show that deep l...	2016
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "medicine", "bacterial diseases", "infectious diseases", "neglected tropical diseases", "salmonellosis", "salmonella" ]	Antimicrobial Resistance in Invasive Non-typhoid Salmonella from the Democratic Republic of the Congo: Emergence of Decreased Fluoroquinolone Susceptibility and Extended-spectrum Beta Lactamases	journal.pntd.0002103	null	[ [ "Non typhoid Salmonella ( NTS ) are among the leading causes of bacterial bloodstream infections in sub-Saharan Africa [1] , [2] .", "NTS bacteremia mainly affects immune compromised hosts and young children , in whom they are associated with high mortality rates up to 27% [3] .", "Usually , most case...	[ "Co-resistance against the first-line antibiotics ampicillin , chloramphenicol and trimethoprim/sulphamethoxazole or multidrug resistance ( MDR ) is common in non typhoid Salmonella ( NTS ) .", "Use of alternative antibiotics , such as fluoroquinolones or third generation cephalosporins is threatened by increasin...	[ "Invasive non typhoid Salmonella spp .", "( NTS ) are an important cause of bloodstream infection in sub-Saharan Africa and associated with a high mortality .", "Levels of multidrug resistance have become alarmingly high .", "Treatment therefore increasingly relies on the oral fluoroquinolones such as ciprofl...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "systems biology", "developmental biology", "biology", "computational biology", "signaling networks", "pattern formation", "genetics and genomics" ]	Mutual Inactivation of Notch Receptors and Ligands Facilitates Developmental Patterning	journal.pcbi.1002069	null	[ [ "Notch signaling is the canonical metazoan juxtacrine signaling pathway .", "It is involved in many developmental processes in which neighboring cells adopt distinct fates .", "Examples of such processes include the delineation of sharp boundaries during the formation of Drosophila wing veins [1] , [2...	[ "Developmental patterning requires juxtacrine signaling in order to tightly coordinate the fates of neighboring cells .", "Recent work has shown that Notch and Delta , the canonical metazoan juxtacrine signaling receptor and ligand , mutually inactivate each other in the same cell .", "This cis-interaction gene...	[ "Multicellular development requires tightly regulated spatial pattern formation , frequently including the generation of sharp differences over short length scales .", "Classic examples include boundary formation in the Drosophila wing veins and lateral inhibition patterning in the differentiation of sensory cell...	2011
[ "Introduction", "Methods", "Results", "Discussion" ]	[]	Impact of School Cycles and Environmental Forcing on the Timing of Pandemic Influenza Activity in Mexican States, May-December 2009	journal.pcbi.1004337	null	[ [ "There is strong evidence that seasonal influenza activity around the world is modulated by environmental variability [1] .", "Temperate regions are characterized by annual winter epidemics [2 , 3] that may result from seasonal decreases in specific humidity and subsequent increases in virus survival and ...	[ "While a relationship between environmental forcing and influenza transmission has been established in inter-pandemic seasons , the drivers of pandemic influenza remain debated .", "In particular , school effects may predominate in pandemic seasons marked by an atypical concentration of cases among children .", ...	[ "An influenza pandemic virus emerged in North America in 2009 .", "Although the virus spread worldwide within months of its emergence , the timing of peak pandemic activity varied by nearly a year across global populations .", "In fact , the most intense period of pandemic activity occurred earlier in temperate...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "neuroglial development", "biochemistry", "developmental neuroscience", "transmembrane proteins", "proteins", "regulatory proteins", "biology", "dna-binding proteins", "neuroscience" ]	A Bacteriophage Tailspike Domain Promotes Self-Cleavage of a Human Membrane-Bound Transcription Factor, the Myelin Regulatory Factor MYRF	journal.pbio.1001624	null	[ [ "Membrane-bound transcription factors ( MBTFs ) are a remarkable class of transcription factors that are initially generated as integral membrane proteins .", "Upon relevant cues , they undergo proteolytic processing , releasing the transcription factor domain from the membrane and allowing it to transloc...	[ "Myelination of the central nervous system ( CNS ) is critical to vertebrate nervous systems for efficient neural signaling .", "CNS myelination occurs as oligodendrocytes terminally differentiate , a process regulated in part by the myelin regulatory factor , MYRF .", "Using bioinformatics and extensive bioche...	[ "Membrane-bound transcription factors are synthesized as integral membrane proteins , but are proteolytically cleaved in response to relevant cues , untethering their transcription factor domains from the membrane to control gene expression in the nucleus .", "Here , we find that the myelin regulatory factor MYRF...	2013
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "invertebrates", "chemical compounds", "statistics", "animals", "invertebrate genomics", "organic compounds", "animal models", "chi square tests", "drosophila melanogaster", "model organisms", "mathematics", "experimental organism systems", "genome analysis", "evolutionary adaptation", "...	Stress response, behavior, and development are shaped by transposable element-induced mutations in Drosophila	journal.pgen.1007900	null	[ [ "Understanding how organisms adapt to local environmental conditions requires identifying the loci and the phenotypic traits potentially targeted by natural selection , which should also provide critical knowledge for how organisms will respond to environmental change [1–3] .", "Organisms from plants to h...	[ "Most of the current knowledge on the genetic basis of adaptive evolution is based on the analysis of single nucleotide polymorphisms ( SNPs ) .", "Despite increasing evidence for their causal role , the contribution of structural variants to adaptive evolution remains largely unexplored .", "In this work , we ...	[ "Transposable elements are fragments of genomic DNA that have the ability to move around the genome by creating new copies of themselves .", "Although there is evidence suggesting that transposable elements play important roles in genome function and genome evolution , our current understanding is based on the an...	2019
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biotechnology", "plant anatomy", "protein interactions", "hormones", "cereal crops", "plant science", "rice", "model organisms", "plant hormones", "genetically modified plants", "crops", "seedlings", "plants", "genetic engineering", "research and analysis methods", "grasses", "genet...	Rice Dwarf Virus P2 Protein Hijacks Auxin Signaling by Directly Targeting the Rice OsIAA10 Protein, Enhancing Viral Infection and Disease Development	journal.ppat.1005847	null	[ [ "Viral infection causes enormous losses in crop yield and crop quality , posing a constant threat to food security .", "These losses are attributed to virus-induced abnormal growth and development , exhibited as disease symptoms .", "However , The molecular basis of disease symptom development in plan...	[ "The phytohormone auxin plays critical roles in regulating myriads of plant growth and developmental processes .", "Microbe infection can disturb auxin signaling resulting in defects in these processes , but the underlying mechanisms are poorly understood .", "Auxin signaling begins with perception of auxin by ...	[ "Auxin regulates plant growth and development through auxin signaling , which begins with the interaction of an F-box transport inhibitor response 1/auxin signaling F-box ( TIR1/AFB ) protein and an auxin/indole-3-acetic acid ( Aux/IAA ) protein co-receptor .", "Auxin binding to the co-receptor complex triggers u...	2016
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "medicine and health sciences", "chemical characterization", "body fluids", "pathology and laboratory medicine", "pathogens", "microbiology", "social sciences", "viral structure", "signaling networks", "orthomyxoviruses", "neuroscience", "viruses", "wireless sensor networks", "rna viruses"...	Kinetic analysis of the influenza A virus HA/NA balance reveals contribution of NA to virus-receptor binding and NA-dependent rolling on receptor-containing surfaces	journal.ppat.1007233	null	[ [ "Specificity , avidity and dynamics of influenza A virus ( IAV ) -receptor interactions are determining factors in host tropism and pathogenesis .", "Virus attachment to sialic acid ( SIA ) receptors on host cell surfaces and decoy mucins is mediated by hemagglutinin ( HA ) [1–3] , while neuraminidase ( N...	[ "Interactions of influenza A virus ( IAV ) with sialic acid ( SIA ) receptors determine viral fitness and host tropism .", "Binding to mucus decoy receptors and receptors on epithelial host cells is determined by a receptor-binding hemagglutinin ( HA ) , a receptor-destroying neuraminidase ( NA ) and a complex in...	[ "Influenza A virus ( IAV ) tropism is largely determined by the interaction of virus particles with the sialic acid receptor repertoire of the host .", "IAVs encounter a diverse range of sialic acid receptors that can function as decoys ( e . g . in the mucus that covers epithelial cells ) or as entry receptors ....	2018
[ "Introduction", "Results", "Materials and Methods" ]	[ "plant anatomy", "vesicles", "plant growth and development", "plant embryo anatomy", "ovules", "light microscopy", "hormones", "pollen", "developmental biology", "plant science", "confocal laser microscopy", "microscopy", "plant hormones", "confocal microscopy", "cellular structures and ...	HAPLESS13-Mediated Trafficking of STRUBBELIG Is Critical for Ovule Development in Arabidopsis	journal.pgen.1006269	null	[ [ "Tissue or planar polarity that distinguishes multicellular organisms from unicellular ones requires coordinated cell behavior within a tissue or the plane of a tissue layer through intercellular communications and intracellular asymmetry [1 , 2] .", "Ovule development in angiosperms manifests the complex...	[ "Planar morphogenesis , a distinct feature of multicellular organisms , is crucial for the development of ovule , progenitor of seeds .", "Both receptor-like kinases ( RLKs ) such as STRUBBELIG ( SUB ) and auxin gradient mediated by PIN-FORMED1 ( PIN1 ) play instructive roles in this process .", "Fine-tuned int...	[ "Ovules , being the progenitors of seeds , hold an important role in crop production .", "Ovule is a complex organ connecting two generations , i . e . diploid sporophytic cells and haploid female gametophytes ( FG ) .", "Fertilization of female gametes leads to the development of embryo and endosperm while the...	2016
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "developmental biology", "physiology", "diabetes and endocrinology", "genetics and genomics" ]	Brain IGF-1 Receptors Control Mammalian Growth and Lifespan through a Neuroendocrine Mechanism	journal.pbio.0060254	Inactivating IGF receptors in the brain decreased growth hormone and IGF-I, and increased lifespan in healthy mice. Such neuroendocrine longevity could be a physiological response to environment.	[ [ "Growth hormone ( GH ) and insulin-like growth factors ( IGFs ) promote mammalian growth", "[1 , 2] and contribute to metabolic regulation", "[3–5] .", "In contrast , inhibiting the", "actions of GH or IGF extends lifespan: mice constitutively lacking growth hormone receptor", "( GHR knock...	[ "Mutations that decrease insulin-like growth factor ( IGF ) and growth hormone signaling", "limit body size and prolong lifespan in mice .", "In vertebrates , these somatotropic hormones", "are controlled by the neuroendocrine brain .", "Hormone-like regulations discovered in", "nematodes and flies sugges...	[ "Using a mouse model relevant for humans , we showed that lifespan can be significantly", "extended by reducing the signaling selectively of a protein called IGF-I in the central", "nervous system .", "This effect occurred through changes in specific neuroendocrine", "pathways .", "Dissecting the pathophy...	2008
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "mathematical models", "public health and epidemiology", "malaria", "epidemiology" ]	Determination of the Processes Driving the Acquisition of Immunity to Malaria Using a Mathematical Transmission Model	journal.pcbi.0030255	null	[ [ "Plasmodium falciparum malaria continues to be a major cause of human morbidity and mortality , especially in Africa , but varies greatly in endemicity across the continent and elsewhere [1] .", "The consequent variation in levels of acquired immunity and age-specific disease patterns complicates malaria ...	[ "Acquisition of partially protective immunity is a dominant feature of the epidemiology of malaria among exposed individuals .", "The processes that determine the acquisition of immunity to clinical disease and to asymptomatic carriage of malaria parasites are poorly understood , in part because of a lack of vali...	[ "Whilst it is clear that natural immunity to malaria infection develops in those living in malaria-endemic regions of the world , the precise way in which it is acquired and the duration of immune memory are less-well-understood .", "We used a mathematical model that mimics malaria transmission between humans and...	2007
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "neuroscience/motor systems", "neuroscience/neurobiology of disease and regeneration", "neurological disorders/movement disorders", "neuroscience/theoretical neuroscience" ]	Stroke Rehabilitation Reaches a Threshold	journal.pcbi.1000133	null	[ [ "Stroke is the leading cause of disability in the US , and about 65% of stroke survivors experience long-term upper extremity functional limitations [1] .", "Although patients may regain some motor functions in the months following stroke due to spontaneous recovery , stroke often leaves patients with pre...	[ "Motor training with the upper limb affected by stroke partially reverses the loss of cortical representation after lesion and has been proposed to increase spontaneous arm use .", "Moreover , repeated attempts to use the affected hand in daily activities create a form of practice that can potentially lead to fur...	[ "Stroke often leaves patients with predominantly unilateral functional limitations of the arm and hand .", "Although recovery of function after stroke is often achieved by compensatory use of the less affected limb , improving use of the more affected limb has been associated with increased quality of life .", ...	2008
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "medicine and health sciences", "parasite evolution", "drugs", "immunology", "tropical diseases", "microbiology", "parasitic diseases", "parasitic protozoans", "parasitology", "antimalarials", "protozoans", "pharmacology", "cross reactivity", "antimicrobial resistance", "malarial parasit...	Within-host competition can delay evolution of drug resistance in malaria	journal.pbio.2005712	null	[ [ "Drug resistance is a recurring threat to effective treatment and control of P . falciparum malaria .", "Chloroquine—a highly effective synthetic antimalarial—was used to combat malaria on a massive scale in the 1950s; by the 1960s , resistance to chloroquine had developed in Southeast Asia and South Amer...	[ "In the malaria parasite P . falciparum , drug resistance generally evolves first in low-transmission settings , such as Southeast Asia and South America .", "Resistance takes noticeably longer to appear in the high-transmission settings of sub-Saharan Africa , although it may spread rapidly thereafter .", "Her...	[ "The malaria parasite Plasmodium falciparum has evolved resistance to most antimalarial drugs , greatly complicating treatment and control of the disease .", "Curiously , although sub-Saharan Africa accounts for the majority of the global burden of malaria , the evolution of drug resistance in Africa has been mar...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biochemistry", "proteins", "virology", "biology", "microbiology", "biophysics" ]	Characterization of Monomeric Intermediates during VSV Glycoprotein Structural Transition	journal.ppat.1002556	null	[ [ "Entry of enveloped viruses into host cells requires fusion of the viral envelope with the cellular membrane .", "This step is mediated by virally encoded glycoproteins , anchored in the viral membrane by a transmembrane ( TM ) domain , that undergo large structural rearrangements following interaction wi...	[ "Entry of enveloped viruses requires fusion of viral and cellular membranes , driven by conformational changes of viral glycoproteins .", "Crystal structures provide static pictures of pre- and post-fusion conformations of these proteins but the transition pathway remains elusive .", "Here , using several bioph...	[ "Vesicular stomatitis virus ( VSV ) enters cells via endocytosis .", "At low pH , its unique glycoprotein G catalyzes fusion between viral and endosomal membranes by going from a pre-fusion trimeric conformation to a post-fusion trimeric conformation .", "There is a lack of information about G structural interm...	2012
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "medicine and health sciences", "cell cycle and cell division", "cell processes", "simulation and modeling", "multivariate analysis", "probability distribution", "mathematics", "statistics (mathematics)", "algebra", "polynomials", "digestive system", "research and analysis methods", "mathema...	A new dynamic correlation algorithm reveals novel functional aspects in single cell and bulk RNA-seq data	journal.pcbi.1006391	null	[ [ "The biological system involves tens of thousands of genes/proteins that are tightly regulated in a complex network [1–3] .", "Interactions and regulations in the network are highly dynamic .", "They change substantially in different cell types , developmental stages , or in response to environmental ...	[ "Dynamic correlations are pervasive in high-throughput data .", "Large numbers of gene pairs can change their correlation patterns in response to observed/unobserved changes in physiological states .", "Finding changes in correlation patterns can reveal important regulatory mechanisms .", "Currently there is ...	[ "Dynamic correlation is an important area in expression data .", "However it hasn’t received much attention because of the lack of effective methods that can unravel the complex relationship .", "Here we describe a new method that represents a substantial improvement over existing approaches .", "It achieves ...	2018
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "kala-azar", "ecology and environmental sciences", "medicine and health sciences", "parasitic diseases", "parasitology", "zoology", "veterinary science", "veterinary diseases", "zoonoses", "insect pheromones", "protozoan infections", "behavioral ecology", "biochemistry", "ecology", "ento...	Multi-modal Analysis of Courtship Behaviour in the Old World Leishmaniasis Vector Phlebotomus argentipes	journal.pntd.0003316	null	[ [ "Visceral leishmaniasis ( VL ) is a debilitating disease estimated to cause 20 , 000–40 , 000 deaths worldwide each year [1] .", "The Indian subcontinent is one of the areas most affected by VL , with over 140 , 000 cases per year estimated to occur in India alone [1] .", "The etiologic agent in this ...	[ "The sand fly Phlebotomus argentipes is arguably the most important vector of leishmaniasis worldwide .", "As there is no vaccine against the parasites that cause leishmaniasis , disease prevention focuses on control of the insect vector .", "Understanding reproductive behaviour will be essential to controlling...	[ "The sand fly Phlebotomus argentipes transmits Leishmania parasites through female blood-feeding .", "These parasites cause leishmaniasis , a potentially fatal disease for which there is no vaccine .", "Understanding how insect vectors behave can aid in developing strategies to reduce disease transmission .", ...	2014
[ "Introduction", "Results", "Discussion", "Methods and materials" ]	[ "invertebrates", "cell motility", "medicine and health sciences", "rna interference", "gene regulation", "animals", "epithelial cells", "animal models", "developmental biology", "drosophila melanogaster", "model organisms", "parietal cells", "experimental organism systems", "epigenetics", ...	Evolutionary rate covariation analysis of E-cadherin identifies Raskol as a regulator of cell adhesion and actin dynamics in Drosophila	journal.pgen.1007720	null	[ [ "The adherens junction ( AJ ) is a multiprotein complex that is essential for intercellular adhesion in metazoa .", "The core of the AJ is the cadherin-catenin complex .", "Classical cadherins are single-pass transmembrane proteins with an extracellular domain that mediates calcium-dependent homotypic...	[ "The adherens junction couples the actin cytoskeletons of neighboring cells to provide the foundation for multicellular organization .", "The core of the adherens junction is the cadherin-catenin complex that arose early in the evolution of multicellularity to link actin to intercellular adhesions .", "Over tim...	[ "The establishment of intercellular adhesions facilitated the genesis of multicellular organisms .", "The adherens junction , which links the actin cytoskeletons of neighboring cells , arose early in the evolution of multicellularity and selective pressures have shaped its function and molecular composition over ...	2019
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	The Autophagy Receptor TAX1BP1 and the Molecular Motor Myosin VI Are Required for Clearance of Salmonella Typhimurium by Autophagy	journal.ppat.1005174	null	[ [ "Macroautophagy is a catabolic lysosomal degradation pathway utilised by cells to degrade cytosolic aggregated proteins and damaged organelles .", "In addition , it is a homeostatic process that maintains cell survival and growth under conditions of starvation , as well as acting as a cellular defence mec...	[ "Autophagy plays a key role during Salmonella infection , by eliminating these pathogens following escape into the cytosol .", "In this process , selective autophagy receptors , including the myosin VI adaptor proteins optineurin and NDP52 , have been shown to recognize cytosolic pathogens .", "Here , we demons...	[ "One of the most common causes of food poisoning is the pathogen Salmonella enterica serovar Typhimurium .", "This pathogen enters the cells of the body through the intestine and after invasion of these cells it survives and multiplies due to its own ability to evade the immune system , thus causing infection .",...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Natural Variation Identifies ICARUS1, a Universal Gene Required for Cell Proliferation and Growth at High Temperatures in Arabidopsis thaliana	journal.pgen.1005085	null	[ [ "Environmental perturbations can often reveal cryptic phenotypes , which in turn can uncover mechanisms associated with environmental regulation of growth and development [1–5] .", "Light and temperature are the two key environmental factors that have major impacts on plant development .", "The molecu...	[ "Plants are highly sensitive to environmental changes and even small variations in ambient temperature have severe consequences on their growth and development .", "Temperature affects multiple aspects of plant development , but the processes and mechanisms underlying thermo-sensitive growth responses are mostly ...	[ "The increase in average temperatures across the globe has been predicted to have negative impacts on agricultural productivity .", "Therefore , there is a need to understand the molecular mechanisms that underlie plant growth responses to varying temperature regimes .", "At present , very little is known about...	2015
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "medicine", "infectious diseases", "virology", "biology", "microbiology", "viral diseases" ]	Activation of the Innate Immune Response against DENV in Normal Non-Transformed Human Fibroblasts	journal.pntd.0001420	null	[ [ "Dengue virus ( DENV ) has become one of the most important arthropod-borne viral infections of humans , with approximately 100 million cases per year .", "The etiological agent is a positive-sense , single-stranded RNA virus that belongs to the Flaviviridae family , of which there are four antigenically ...	[ "When mosquitoes infected with DENV are feeding , the proboscis must traverse the epidermis several times ( “probing” ) before reaching a blood vessel in the dermis .", "During this process , the salivary glands release the virus , which is likely to interact first with cells of the various epidermal and dermal l...	[ "In this work , we demonstrate that that both human whole skin and freshly isolated skin fibroblasts are productively infected with Dengue virus ( DENV ) .", "In addition , primary skin fibroblast cultures were established and subsequently infected with DENV-2; we showed in these cells the presence of the viral a...	2011
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "invertebrates", "medicine and health sciences", "lysosomes", "caenorhabditis", "animals", "animal models", "muscle components", "muscle proteins", "caenorhabditis elegans", "model organisms", "muscle functions", "cellular structures and organelles", "mapk signaling cascades", "research an...	The MADD-3 LAMMER Kinase Interacts with a p38 MAP Kinase Pathway to Regulate the Display of the EVA-1 Guidance Receptor in Caenorhabditis elegans	journal.pgen.1006010	null	[ [ "The guided migration of cells and their extensions during development is essential to the proper execution of the body plan .", "In nematodes , the body wall muscles extend membrane protrusions called muscle arms to the motor axons where they form a neuromuscular junction ( Fig 1a ) [1] .", "Using th...	[ "The proper display of transmembrane receptors on the leading edge of migrating cells and cell extensions is essential for their response to guidance cues .", "We previously discovered that MADD-4 , which is an ADAMTSL secreted by motor neurons in Caenorhabditis elegans , interacts with an UNC-40/EVA-1 co-recepto...	[ "In most animals , the physical meeting of the pre- and post-synaptic membranes of the neuromuscular junction occurs via axonal extension towards the muscle .", "In nematodes , however , motor axons do not extend towards the muscle and instead form a dorsal and ventral cord with relatively few branches .", "To ...	2016
[ "Introduction", "Materials and methods", "Results", "Discussion" ]	[ "medicine and health sciences", "geographical locations", "tropical diseases", "diet", "vertebrates", "parasitic diseases", "animals", "mammals", "animal products", "probability distribution", "nutrition", "mathematics", "meat", "neglected tropical diseases", "africa", "food", "swine...	Modelling the risk of Taenia solium exposure from pork produced in western Kenya	journal.pntd.0005371	null	[ [ "The zoonotic tapeworm Taenia solium , has a two host life cycle , with humans as the definitive host , and pigs as an intermediate host .", "Humans are infected after consumption of viable cysticerci in under-cooked pork and harbour the adult tapeworm , a condition known as taeniosis .", "Gravid prog...	[ "The tapeworm Taenia solium is the parasite responsible for neurocysticercosis , a neglected tropical disease of public health importance , thought to cause approximately 1/3 of epilepsy cases across endemic regions .", "The consumption of undercooked infected pork perpetuates the parasite’s life-cycle through th...	[ "Taenia solium is a serious zoonotic helminth which is thought to be responsible for approximately 1/3rd of epilepsy cases in the developing world .", "The work presented in this paper aimed to understand what the risk is of acquiring T . solium taeniosis from pork slaughtered and consumed in western Kenya .", ...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "infectious diseases/neglected tropical diseases", "immunology/immune response", "immunology/innate immunity", "infectious diseases/protozoal infections", "immunology/immunity to infections" ]	Critical Role of IRF-5 in the Development of T helper 1 responses to Leishmania donovani infection	journal.ppat.1001246	null	[ [ "The protozoan parasite Leishmania donovani is the causative agent of visceral leishmaniasis ( VL ) , a chronic life threatening disease if untreated .", "In the experimental model of VL , the two main target organs are the liver and the spleen [1] .", "While the spleen stays chronically infected , in...	[ "The transcription factor Interferon Regulatory Factor 5 ( IRF-5 ) has been shown to be involved in the induction of proinflammatory cytokines in response to viral infections and TLR activation and to play an essential role in the innate inflammatory response .", "In this study , we used the experimental model of...	[ "Leishmania donovani is a parasite that currently infects 12 million people around the world .", "In order to better understand why this parasite causes incurable disease we chose to investigate how the immune system sees L . donovani .", "The immune system sees infecting organisms by the recognition of molecul...	2011
[ "Introduction", "Methods", "Results", "Discussion", "Conclusions" ]	[ "medicine and health sciences", "fish", "pathology and laboratory medicine", "engineering and technology", "vertebrates", "animals", "toxicology", "animal models", "osteichthyes", "developmental biology", "toxicity", "model organisms", "oils", "nanoparticles", "experimental organism syst...	Prolonged mosquitocidal activity of Siparuna guianensis essential oil encapsulated in chitosan nanoparticles	journal.pntd.0007624	null	[ [ "The Aedes aegypti Linnaeus , 1762 ( Diptera: Culicidae ) mosquito is a vector for yellow fever , dengue , Zika , and chikungunya viruses , and can be found throughout the American continents [1–3] , in Africa , and Asia [4] .", "Its control is mainly through insecticides; usually , pyrethroids are used a...	[ "The use of synthetic insecticides is one of the most common strategies for controlling disease vectors such as mosquitos .", "However , their overuse can result in serious risks to human health , to the environment , as well as to the selection of insecticidal resistant insect strains .", "The development of e...	[ "Numerous outbreaks of infectious diseases such as dengue , zika , and chikungunya in tropical countries have occurred where the mosquito Aedes aegypti is the transmitting vector .", "In Brazil , these infections are responsible for deaths and severe sequelae .", "Thus , many efforts have been made by governmen...	2019
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biochemistry", "developmental biology", "cell biology", "biology and life sciences", "neuroscience", "molecular biology" ]	Beclin 1 Is Required for Neuron Viability and Regulates Endosome Pathways via the UVRAG-VPS34 Complex	journal.pgen.1004626	null	[ [ "Autophagy is a regulated “self-digestion” pathway in the cytoplasm of cells involving the synthesis , trafficking and delivery of autophagosomes to lysosomes for degradation .", "Beclin 1 was the first described mammalian autophagy protein and a core component of the class III phosphatidylinositol 3-kina...	[ "Deficiency of autophagy protein beclin 1 is implicated in tumorigenesis and neurodegenerative diseases , but the molecular mechanism remains elusive .", "Previous studies showed that Beclin 1 coordinates the assembly of multiple VPS34 complexes whose distinct phosphatidylinositol 3-kinase III ( PI3K-III ) lipid ...	[ "Beclin 1 was not only the first-described mammalian autophagy protein , but is one of the most widely-characterized players in autophagy regulation .", "It is implicated in multiple human disease conditions .", "As a core component of the essential lipid kinase complex ( PI3K-III ) , beclin 1 has largely been ...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "virology/viral replication and gene regulation", "physiology/respiratory physiology", "genetics and genomics/gene therapy", "microbiology/applied microbiology", "respiratory medicine/respiratory pediatrics", "cell biology/gene expression" ]	CFTR Delivery to 25% of Surface Epithelial Cells Restores Normal Rates of Mucus Transport to Human Cystic Fibrosis Airway Epithelium	journal.pbio.1000155	Delivering CFTR to ciliated cells of cystic fibrosis (CF) patients fully restores ion and fluid transport to the lumenal surface of airway epithelium and returns mucus transport rates to those of non-CF airways.	[ [ "Cystic fibrosis ( CF ) is the most common recessive lethal genetic disorder in Caucasian populations and results from a defect in the CFTR gene .", "Although CF affects many organs , the pulmonary manifestations account for over 90% of the morbidity and mortality [1] .", "Dysfunction of CFTR in CF ai...	[ "Dysfunction of CFTR in cystic fibrosis ( CF ) airway epithelium perturbs the normal regulation of ion transport , leading to a reduced volume of airway surface liquid ( ASL ) , mucus dehydration , decreased mucus transport , and mucus plugging of the airways .", "CFTR is normally expressed in ciliated epithelial...	[ "The ciliated epithelium that lines the conducting airways of the lung normally functions to transport hydrated mucus secretions out of the airways to maintain respiratory sterility .", "Cystic fibrosis ( CF ) lung disease results from reduced airway surface hydration leading to decreased mucus clearance that pre...	2009
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Ih Channels Control Feedback Regulation from Amacrine Cells to Photoreceptors	journal.pbio.1002115	A systematic study of the Drosophila visual system clarifies the molecular mechanisms and physiological effects of feedback regulation of photoreceptors by amacrine cells, essential for maintaining light sensitivity.	[ [ "Feedback regulation is common in neural circuit information processing .", "In both vertebrate and invertebrate visual systems , photoreceptor output is feedback-regulated by interneurons , which is an important mechanism for shaping the transmission of light information [1 , 2] .", "In the vertebrat...	[ "In both vertebrates and invertebrates , photoreceptors’ output is regulated by feedback signals from interneurons that contribute to several important visual functions .", "Although synaptic feedback regulation of photoreceptors is known to occur in Drosophila , many questions about the underlying molecular mech...	[ "Feedback regulation is a common feature of neural circuits during the process of acquiring information .", "Therefore , it is important to understand how this phenomenon occurs .", "Using the primary visual system of the fruit fly Drosophila melanogaster as a model , we systematically investigated the molecula...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "cell biology", "genetics and genomics", "microbiology" ]	Asymmetry of Chromosome Replichores Renders the DNA Translocase Activity of FtsK Essential for Cell Division and Cell Shape Maintenance in Escherichia coli	journal.pgen.1000288	null	[ [ "Cell proliferation involves coordination between replication of the genome , segregation of sister chromosomes to daughter cells and cell division .", "In bacteria , these processes are not necessarily sequential but can overlap: segregation begins during the replicative C period ( S phase ) , continues ...	[ "Bacterial chromosomes are organised as two replichores of opposite polarity that coincide with the replication arms from the ori to the ter region .", "Here , we investigated the effects of asymmetry in replichore organisation in Escherichia coli .", "We show that large chromosome inversions from the terminal ...	[ "In most bacteria , chromosomes consist of a single replication unit .", "Replication initiates at a single ori and terminates in the diametrically opposite zone , ter , defining two replication arms .", "These are also called replichores to account for base composition and sequence motif polarity biases from o...	2008
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "cell death", "invertebrates", "medicine and health sciences", "redox signaling", "cell processes", "animals", "animal models", "c-jun n-terminal kinase signaling cascade", "developmental biology", "drosophila melanogaster", "model organisms", "animal anatomy", "experimental organism systems...	Eiger/TNFα-mediated Dilp8 and ROS production coordinate intra-organ growth in Drosophila	journal.pgen.1008133	null	[ [ "Coordinated tissue growth is essential for the generation of functionally integrated organs during animal development , as well as for tissue homeostasis during adult life .", "Although a broad range of genes and pathways regulating growth has been uncovered , the exact mechanisms by which cells within t...	[ "Coordinated intra- and inter-organ growth during animal development is essential to ensure a correctly proportioned individual .", "The Drosophila wing has been a valuable model system to reveal the existence of a stress response mechanism involved in the coordination of growth between adjacent cell populations ...	[ "The coordination of growth between the parts of a given developing organ is an absolute requirement for the generation of functionally integrated structures during animal development .", "Although this question has fascinated biologists for centuries , the molecular mechanisms responsible have remained elusive t...	2019
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "oncology/genitourinary cancers", "computer science/applications", "oncology/sarcomas", "computational biology/genomics" ]	deFuse: An Algorithm for Gene Fusion Discovery in Tumor RNA-Seq Data	journal.pcbi.1001138	null	[ [ "Next generation sequencing of cDNA ( RNA-Seq or whole transcriptome shotgun sequencing ) provides an ideal experimental platform for expressed gene fusion discovery .", "Analogous to genome sequencing , RNA-Seq enables an unbiased and relatively comprehensive view into tumor transcriptomes , and can prov...	[ "Gene fusions created by somatic genomic rearrangements are known to play an important role in the onset and development of some cancers , such as lymphomas and sarcomas .", "RNA-Seq ( whole transcriptome shotgun sequencing ) is proving to be a useful tool for the discovery of novel gene fusions in cancer transcr...	[ "Genome rearrangements and associated gene fusions are known to be important oncogenic events in some cancers .", "We have developed a novel computational method called deFuse for detecting gene fusions in RNA-Seq data and have applied it to the discovery of novel gene fusions in sarcoma and ovarian tumors .", ...	2011
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "blood cells", "medicine and health sciences", "immune cells", "immune physiology", "spleen", "immunology", "microbiology", "viral genome", "mammalian genomics", "molecular biology techniques", "microbial genetics", "microbial genomics", "research and analysis methods", "viral genomics", ...	Conditional mutagenesis in vivo reveals cell type- and infection stage-specific requirements for LANA in chronic MHV68 infection	journal.ppat.1006865	null	[ [ "Gammaherpesviruses ( GHVs ) are large , enveloped , double-strand DNA viruses that include the human pathogens Epstein-Barr virus ( EBV ) and Kaposi sarcoma-associated herpesvirus ( KSHV ) .", "GHVs establish lifelong , chronic infections in their hosts and are responsible for causing lymphoproliferative...	[ "Gammaherpesvirus ( GHV ) pathogenesis is a complex process that involves productive viral replication , dissemination to tissues that harbor lifelong latent infection , and reactivation from latency back into a productive replication cycle .", "Traditional loss-of-function mutagenesis approaches in mice using mu...	[ "Gammaherpesviruses ( GHVs ) , including the human pathogens Epstein-Barr virus and Kaposi sarcoma-associated herpesvirus , establish lifelong infections that can lead to cancer .", "Defining the functions of viral gene products in acute replication and chronic infection is important for understanding how these v...	2018
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "medicine and health sciences", "nuclear staining", "cloning", "notch signaling", "oncology", "c-jun n-terminal kinase signaling cascade", "developmental signaling", "molecular biology techniques", "eyes", "research and analysis methods", "specimen preparation and treatment", "staining", "ge...	Signalling crosstalk during early tumorigenesis in the absence of Polycomb silencing	journal.pgen.1007187	null	[ [ "Tissues are capable of restoring homeostasis after damage or stress through coordinated signalling responses .", "However , cells sometimes deviate from this normal repair path to attain a tumorigenic state , often entailing the usage of similar signalling modules .", "Cancer cells become self-suffic...	[ "In response to stress and injury a coordinated activation of conserved signalling modules , such as JNK and JAK/STAT , is critical to trigger regenerative tissue restoration .", "While these pathways rebuild homeostasis and promote faithful organ recovery , it is intriguing that they also become activated in var...	[ "Signalling pathways modulate cellular responses in developmental and regenerative processes but can also be misused by cancer cells to promote tissue invasion and growth .", "How signalling outputs are integrated to direct a variety of responses ranging from organ repair to tumour onset remains elusive .", "Lo...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "public and occupational health", "infectious diseases", "plant science", "medicine and health sciences", "disease ecology", "population modeling", "infectious disease epidemiology", "epidemiology", "plant pathology", "biology and life sciences", "infectious disease modeling", "computational b...	Environmental Drivers of the Spatiotemporal Dynamics of Respiratory Syncytial Virus in the United States	journal.ppat.1004591	null	[ [ "Respiratory syncytial virus ( RSV ) is a major cause of severe lower respiratory tract infections , including bronchiolitis and pneumonia .", "Most children experience their first infection by age 2 years , but immunity is imperfect and infections continue to occur throughout life , although subsequent i...	[ "Epidemics of respiratory syncytial virus ( RSV ) are known to occur in wintertime in temperate countries including the United States , but there is a limited understanding of the importance of climatic drivers in determining the seasonality of RSV .", "In the United States , RSV activity is highly spatially stru...	[ "Respiratory syncytial virus ( RSV ) causes annual outbreaks of respiratory disease every winter in temperate climates , which can be severe particularly among infants .", "In the United States , RSV activity begins each autumn in Florida and appears to spread from the southeast to the northwest .", "Using data...	2015
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "genetics and genomics/genetics of disease", "genetics and genomics/gene therapy", "genetics and genomics/bioinformatics", "computational biology/genomics" ]	Retroviral Integration Process in the Human Genome: Is It Really Non-Random? A New Statistical Approach	journal.pcbi.1000144	null	[ [ "The transfer of a therapeutic gene into somatic cells ( gene therapy ) is a promising medical approach for the management of many inherited and acquired diseases .", "Among several systems developed for gene delivery , replication-defective viral vectors derived from retroviruses are the most widely used...	[ "Retroviral vectors are widely used in gene therapy to introduce therapeutic genes into patients' cells , since , once delivered to the nucleus , the genes of interest are stably inserted ( integrated ) into the target cell genome .", "There is now compelling evidence that integration of retroviral vectors follow...	[ "Understanding how retroviral vectors ( such as Moloney Leukemia Virus–based vectors ) integrate in the human genome became a major safety issue in the field of gene therapy , since a concrete risk of developing tumors associated with the integration process was assessed in the clinical setting .", "Moloney Leuke...	2008
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	The Evolutionarily Conserved LIM Homeodomain Protein LIM-4/LHX6 Specifies the Terminal Identity of a Cholinergic and Peptidergic C. elegans Sensory/Inter/Motor Neuron-Type	journal.pgen.1005480	null	[ [ "The proper generation and maintenance of cells in the nervous system is essential for multi-cellular organisms .", "Each neuron achieves its identity by the acquisition of many distinct features , including appropriate synaptic contacts and expression of distinct sets of neurotransmitters .", "Fate d...	[ "The expression of specific transcription factors determines the differentiated features of postmitotic neurons .", "However , the mechanism by which specific molecules determine neuronal cell fate and the extent to which the functions of transcription factors are conserved in evolution are not fully understood ....	[ "The correct generation and maintenance of the nervous system is critical for the animal’s life .", "Dysregulation of these processes leads to multiple neurodevelopmental disorders .", "It has been a daunting challenge not only to identify the developmental mechanisms that determine neuronal cell fate , but als...	2015
[ "Introduction", "Materials and methods", "Results", "Discussion" ]	[ "medicine and health sciences", "gut bacteria", "microbiome", "chemical compounds", "pathology and laboratory medicine", "clostridium", "pathogens", "microbiology", "diet", "carbohydrates", "organic compounds", "nutrition", "metabolites", "enterococcus", "bacteria", "bacterial pathogen...	SteadyCom: Predicting microbial abundances while ensuring community stability	journal.pcbi.1005539	null	[ [ "Metagenomics has brought forth the opportunity for non-culture-based sampling of microorganisms in various environments .", "It has revolutionized our understanding of microbial communities and their impact on diverse ecosystems and human health .", "For example , marine microbes have been estimated ...	[ "Genome-scale metabolic modeling has become widespread for analyzing microbial metabolism .", "Extending this established paradigm to more complex microbial communities is emerging as a promising way to unravel the interactions and biochemical repertoire of these omnipresent systems .", "While several modeling ...	[ "The microbes residing in the human gut , collectively known as the gut microbiota , have an intimate and complicated relationship with human health .", "In this study , we aim to enhance the understanding of the relationship between the gut microbiota composition , the metabolite production , the diet , and the ...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "auditory system", "developmental biology", "growth control", "cell fate determination", "organism development", "organogenesis", "sensory systems", "biology", "morphogenesis", "neuroscience", "pattern formation", "cell differentiation" ]	The Candidate Splicing Factor Sfswap Regulates Growth and Patterning of Inner Ear Sensory Organs	journal.pgen.1004055	null	[ [ "The organ of Corti is an excellent system to study mechanisms of cell patterning due to its highly organized array of sensory cells .", "It contains one row of inner hair cells , three rows of outer hair cells and several classes of specialized supporting cells , including pillar and Deiters' cells .", ...	[ "The Notch signaling pathway is thought to regulate multiple stages of inner ear development .", "Mutations in the Notch signaling pathway cause disruptions in the number and arrangement of hair cells and supporting cells in sensory regions of the ear .", "In this study we identify an insertional mutation in th...	[ "The organ of Corti is a sensory structure in the cochlea that mediates our sense of hearing .", "It consists of one row of inner hair cells and three rows of outer hair cells , together with an array of neighboring supporting cells .", "The precise arrangement of these different cell types is regulated very ti...	2014
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "medicine and health sciences", "dendritic structure", "nervous system", "statistics", "electrophysiology", "neuroscience", "mathematics", "ganglion cells", "brain mapping", "neuronal dendrites", "research and analysis methods", "statistical distributions", "animal cells", "mathematical an...	A regularity index for dendrites - local statistics of a neuron's input space	journal.pcbi.1006593	null	[ [ "The primary function of dendritic trees is to collect inputs from other neurons in the nervous tissue [1 , 2] .", "Different cell types play distinct roles in wiring up the brain and are typically visually identifiable by the particular shape of their dendrites [3] .", "However , so far no branching ...	[ "Neurons collect their inputs from other neurons by sending out arborized dendritic structures .", "However , the relationship between the shape of dendrites and the precise organization of synaptic inputs in the neural tissue remains unclear .", "Inputs could be distributed in tight clusters , entirely randoml...	[ "Dendritic tree structures of nerve cells are built to optimally collect inputs from other cells in the circuit .", "By looking at how regularly the branch and termination points of dendrites are distributed , we find characteristic differences between cell types that correlate little with other traditional branc...	2018
[ "Introduction", "Materials and Methods", "Results and Discussion" ]	[ "microbiology/medical microbiology" ]	Comparative Transcriptional and Translational Analysis of Leptospiral Outer Membrane Protein Expression in Response to Temperature	journal.pntd.0000560	null	[ [ "Leptospirosis is a widespread zoonotic disease caused by spirochetes of the genus Leptospira , which can persist for prolonged periods in the environment and cause human infection via contact with infected animals or contaminated soil/water [1] .", "The organism has a broad host range and maintenance hos...	[ "Leptospirosis is a global zoonosis affecting millions of people annually .", "Transcriptional changes in response to temperature were previously investigated using microarrays to identify genes potentially expressed upon host entry .", "Past studies found that various leptospiral outer membrane proteins are di...	[ "Leptospirosis , caused by Leptospira spp .", ", is a disease of worldwide significance affecting millions of people annually .", "Bacteria of this species are spread by various carrier animals , including rodents and domestic livestock , which shed the leptospires via their urine into the environment .", "Hu...	2009
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "acoustics", "medicine and health sciences", "engineering and technology", "scalp", "signal processing", "brain electrophysiology", "social sciences", "electrophysiology", "neuroscience", "signal filtering", "autocorrelation", "analysis of variance", "cognitive psychology", "mathematics", ...	Neural mechanisms of rhythm-based temporal prediction: Delta phase-locking reflects temporal predictability but not rhythmic entrainment	journal.pbio.2001665	null	[ [ "Information processing is optimized by predicting not only the location or identity of upcoming events but also their timing and allocating resources accordingly [1–6] .", "Understanding the mechanisms of temporal prediction is thus central for models of cognitive and neural processing .", "One ubiqu...	[ "Predicting the timing of upcoming events enables efficient resource allocation and action preparation .", "Rhythmic streams , such as music , speech , and biological motion , constitute a pervasive source for temporal predictions .", "Widely accepted entrainment theories postulate that rhythm-based predictions...	[ "Making predictions is a major adaptive brain function .", "Predicting the timing of upcoming events enables the brain to prepare for them .", "However , it is unclear how this is achieved .", "It is believed that in rhythmic environmental context , such as in music and speech , temporal predictions are achie...	2017
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "medicine", "infectious disease epidemiology", "microbiology", "rift valley fever", "emerging infectious diseases", "neglected tropical diseases", "infectious disease control", "veterinary science", "oropouche fever", "japanese encephalitis", "sequence analysis", "infectious diseases", "vete...	Multi-Gene Detection and Identification of Mosquito-Borne RNA Viruses Using an Oligonucleotide Microarray	journal.pntd.0002349	null	[ [ "Arthropod-borne viruses ( arboviruses ) are important human and veterinary pathogens that are biologically transmitted to vertebrates by hematophagous ( blood feeding ) arthropod vectors , such as female mosquitoes .", "The diverse group of mosquito-borne RNA viruses primarily includes flaviviruses ( Fla...	[ "Arthropod-borne viruses are important emerging pathogens world-wide .", "Viruses transmitted by mosquitoes , such as dengue , yellow fever , and Japanese encephalitis viruses , infect hundreds of millions of people and animals each year .", "Global surveillance of these viruses in mosquito vectors using molecu...	[ "Approximately half of the world's population is at risk of viral , mosquito-borne illness such as dengue , yellow fever , Japanese encephalitis , Rift Valley fever , and chikungunya .", "In the past , these viruses have been regarded as pathogens of the tropics; however , they are emerging as global causes of il...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "cell biology/neuronal and glial cell biology", "virology/virion structure, assembly, and egress", "biochemistry/cell signaling and trafficking structures", "biochemistry/biomacromolecule-ligand interactions", "biochemistry/macromolecular assemblies and machines", "virology/host invasion and cell entry", ...	Plus- and Minus-End Directed Microtubule Motors Bind Simultaneously to Herpes Simplex Virus Capsids Using Different Inner Tegument Structures	journal.ppat.1000991	null	[ [ "To reach their destined subcellular location , viruses utilize motor proteins that move unidirectional along microtubules ( MT ) or actin filaments [1] , [2] , [3] , [4] , [5] .", "Digital time-lapse microscopy experiments in living cells have provided fundamental insights into the dynamics of intracellu...	[ "Many viruses depend on host microtubule motors to reach their destined intracellular location .", "Viral particles of neurotropic alphaherpesviruses such as herpes simplex virus 1 ( HSV1 ) show bidirectional transport towards the cell center as well as the periphery , indicating that they utilize microtubule mot...	[ "Many viruses , particularly neurotropic alphaherpesviruses such as herpes simplex virus ( HSV ) , require an intact microtubule network for efficient replication and pathogenesis .", "In living cells , host and viral cargo show rapid reversals in transport direction , suggesting that they can recruit motors of o...	2010
[ "Introduction", "Materials and methods", "Results", "Discussion", "Conclusion" ]	[ "invertebrates", "medicine and health sciences", "plagues", "body fluids", "vertebrates", "sand flies", "animals", "mammals", "diptera", "bacterial diseases", "fleas", "infectious disease control", "insect vectors", "infectious diseases", "agrochemicals", "phlebotomus", "disease vect...	Field evaluation of a 0.005% fipronil bait, orally administered to Rhombomys opimus, for control of fleas (Siphonaptera: Pulicidae) and phlebotomine sand flies (Diptera: Psychodidae) in the Central Asian Republic of Kazakhstan	journal.pntd.0006630	null	[ [ "Plague is a fatal , rodent-associated , flea-borne pathogen found throughout Asia , Africa and the Americas .", "Between 2010–2015 , 584 plague-related deaths were reported globally [6] .", "While plague-induced mortality is far less common than during the pandemics of previous centuries [7] , the di...	[ "Plague ( Yersinia pestis ) and zoonotic cutaneous leishmaniasis ( Leishmania major ) are two rodent-associated diseases which are vectored by fleas and phlebotomine sand flies , respectively .", "In Central Asia , the great gerbil ( Rhombomys opimus ) serves as the primary reservoir for both diseases in most nat...	[ "Plague and cutaneous leishmaniasis are two diseases transmissible to humans vectored by fleas and sand flies , respectively .", "Although the diseases are vectored by two different insect types , the primary reservoir host for both diseases in desert foci in Central Asia is the great gerbil .", "Therefore , a ...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	The Contribution of Alu Elements to Mutagenic DNA Double-Strand Break Repair	journal.pgen.1005016	null	[ [ "DNA double-strand breaks ( DSBs ) are the most dangerous type of DNA damage due to their tendency to lead to chromosomal rearrangements , a hallmark of tumorigenesis , when they are repaired [1] .", "One way in which chromosomal rearrangements occur in DSB repair is the use of non-allelic recombination b...	[ "Alu elements make up the largest family of human mobile elements , numbering 1 . 1 million copies and comprising 11% of the human genome .", "As a consequence of evolution and genetic drift , Alu elements of various sequence divergence exist throughout the human genome .", "Alu/Alu recombination has been shown...	[ "DNA double-strand breaks ( DSBs ) are a highly mutagenic form of DNA damage that can be repaired through one of several pathways with varied degrees of sequence preservation .", "Faithful repair of DSBs often occurs through gene conversion in which a sister chromatid is used as a repair template .", "Unfaithfu...	2015
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "phosphorylation", "medicine and health sciences", "nucleic acid synthesis", "enzyme-linked immunoassays", "pathology and laboratory medicine", "pathogens", "microbiology", "viral structure", "retroviruses", "viruses", "immunodeficiency viruses", "analysis of variance", "mathematics", "rna...	Phosphorylation of the HIV-1 capsid by MELK triggers uncoating to promote viral cDNA synthesis	journal.ppat.1006441	null	[ [ "During the course of human immunodeficiency virus type 1 ( HIV-1 ) infection , the virus encounters numerous bottlenecks constituted by a variety of host cell proteins essential for or inhibitory to HIV-1 replication [1] .", "HIV-1 particles must attach to and fuse with the plasma membrane of target cell...	[ "Regulation of capsid disassembly is crucial for efficient HIV-1 cDNA synthesis after entry , yet host factors involved in this process remain largely unknown .", "Here , we employ genetic screening of human T-cells to identify maternal embryonic leucine zipper kinase ( MELK ) as a host factor required for optima...	[ "Phosphorylation of the HIV-1 capsid has long been known to regulate viral uncoating and cDNA synthesis processes , but the cellular kinases responsible for this have remained unidentified .", "Here , we report that a host cell kinase MELK dictates optimal capsid disassembly through phosphorylation of Ser-149 in ...	2017
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "invertebrates", "chemical compounds", "dna-binding proteins", "organic compounds", "animals", "alleles", "animal models", "drosophila melanogaster", "model organisms", "experimental organism systems", "basic amino acids", "amino acids", "epigenetics", "chromatin", "drosophila", "resea...	Lysine 27 of replication-independent histone H3.3 is required for Polycomb target gene silencing but not for gene activation	journal.pgen.1007932	null	[ [ "Inside the nucleus , DNA is wrapped around histone proteins to form nucleosomes , the basic building block of chromatin .", "In addition to compacting the genome within the confines of a small nuclear space , histone proteins also serve as substrates for regulating genome activity .", "In particular ...	[ "Proper determination of cell fates depends on epigenetic information that is used to preserve memory of decisions made earlier in development .", "Post-translational modification of histone residues is thought to be a central means by which epigenetic information is propagated .", "In particular , modification...	[ "During development , naïve precursor cells acquire distinct identities through differential regulation of gene expression .", "The process of cell fate specification is progressive and depends on memory of prior developmental decisions .", "Maintaining cell identities over time is not dependent on changes in g...	2019
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine", "chemistry", "biology" ]	Protease-Sensitive Conformers in Broad Spectrum of Distinct PrPSc Structures in Sporadic Creutzfeldt-Jakob Disease Are Indicator of Progression Rate	journal.ppat.1002242	null	[ [ "Prions cause a group of fatal and rapidly progressing neurodegenerative diseases , originally described as transmissible spongiform encephalopathies ( TSEs ) [1] , [2] .", "The most common of these diseases is sporadic Creutzfeldt-Jakob disease ( sCJD ) , which accounts for ∼85% of all CJD cases worldwid...	[ "The origin , range , and structure of prions causing the most common human prion disease , sporadic Creutzfeldt-Jakob disease ( sCJD ) , are largely unknown .", "To investigate the molecular mechanism responsible for the broad phenotypic variability of sCJD , we analyzed the conformational characteristics of pro...	[ "Sporadic Creutzfeldt-Jakob disease ( sCJD ) is the most common human prion disease worldwide .", "This neurodegenerative disease , which is transmissible and invariably fatal , is characterized by the accumulation of an abnormally folded isoform ( PrPSc ) of a host-encoded protein ( PrPC ) , predominantly in the...	2011
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "biophysics", "in vitro", "computational biology" ]	Control of Membrane Fusion Mechanism by Lipid Composition: Predictions from Ensemble Molecular Dynamics	journal.pcbi.0030220	null	[ [ "Membrane fusion plays a key role in cellular function , allowing processes as diverse as neurotransmitter release , secretion of peptide hormones , and infection by enveloped viruses .", "Fusion is also critical in allowing intracellular transport .", "The cellular membranes participating in these fu...	[ "Membrane fusion is critical to biological processes such as viral infection , endocrine hormone secretion , and neurotransmission , yet the precise mechanistic details of the fusion process remain unknown .", "Current experimental and computational model systems approximate the complex physiological membrane env...	[ "Membrane fusion is the transport process used for neurotransmitter release , insulin secretion , and infection by enveloped viruses .", "The precise mechanism of fusion is not yet understood , nor is the means by which membrane properties such as composition and curvature affect the fusion process .", "Here , ...	2007
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "medicine and health sciences", "diagnostic radiology", "elderly", "decision making", "nervous system", "prefrontal cortex", "brain", "social sciences", "neuroscience", "magnetic resonance imaging", "age groups", "brain morphometry", "cognitive psychology", "morphometry", "cognition", ...	Sequential inference as a mode of cognition and its correlates in fronto-parietal and hippocampal brain regions	journal.pcbi.1005418	null	[ [ "Model-based approaches to cognition posit that agents continually perform online inference about the current state of the world , based on incoming sensory information .", "Typically , these approaches assume that the agent optimises beliefs about the current state of the world , referred to as Bayesian ...	[ "Normative models of human cognition often appeal to Bayesian filtering , which provides optimal online estimates of unknown or hidden states of the world , based on previous observations .", "However , in many cases it is necessary to optimise beliefs about sequences of states rather than just the current state ...	[ "When studying human cognition , it is often assumed that agents form and update beliefs only about the current state of the world , an approach known as Bayesian filtering .", "However , in many situations there are advantages to making inferences about the most likely sequence of states that have occurred , whi...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Utilizing CMP-Sialic Acid Analogs to Unravel Neisseria gonorrhoeae Lipooligosaccharide-Mediated Complement Resistance and Design Novel Therapeutics	journal.ppat.1005290	null	[ [ "Sialic acids ( Sias ) are a family of 9-carbon sugars ( nonoses , or nonulosonates ( NulOs ) ) expressed in the tissues of every vertebrate and some “higher” invertebrates [1] .", "Sias serve a wide variety of biological roles , including modulation of several aspects of immune function [2] .", "For ...	[ "Neisseria gonorrhoeae deploys a novel immune evasion strategy wherein the lacto-N-neotetraose ( LNnT ) structure of lipooligosaccharide ( LOS ) is capped by the bacterial sialyltransferase , using host cytidine-5’-monophosphate ( CMP ) -activated forms of the nine-carbon nonulosonate ( NulO ) sugar N-acetyl-neuram...	[ "Neisseria gonorrhoeae , the causative agent of the sexually transmitted infection gonorrhea , has developed widespread resistance to almost every conventional antibiotic currently in clinical use .", "Novel therapeutics are urgently needed against this pathogen .", "Gonococci have the capacity to scavenge CMP-...	2015
[ "Introduction", "Results and discussion", "Materials and methods" ]	[ "chemical compounds", "metabolic networks", "enzymology", "fungi", "model organisms", "metabolites", "network analysis", "experimental organism systems", "enzyme metabolism", "enzyme chemistry", "saccharomyces", "research and analysis methods", "computer and information sciences", "metabol...	lumpGEM: Systematic generation of subnetworks and elementally balanced lumped reactions for the biosynthesis of target metabolites	journal.pcbi.1005513	null	[ [ "Stoichiometric models have been extensively used since 1980s [1–3] and prediction capabilities of these networks have been proven to be very useful .", "The size and structure of these models varied among different studies .", "One of the pioneering studies on E . coli through a small stoichiometric ...	[ "In the post-genomic era , Genome-scale metabolic networks ( GEMs ) have emerged as invaluable tools to understand metabolic capabilities of organisms .", "Different parts of these metabolic networks are defined as subsystems/pathways , which are sets of functional roles to implement a specific biological process...	[ "Stoichiometric models have been used in the area of metabolic engineering and systems biology for many decades .", "The early examples of these models include simplified ad hoc built metabolic pathways , and biomass compositions .", "The development of genome scale models ( GEMs ) brought a standard to metabol...	2017
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "medicinal chemistry", "biophysic al simulations", "chemical biology", "protein structure", "chemistry", "biology", "computational biology", "macromolecular structure analysis" ]	Druggable Protein Interaction Sites Are More Predisposed to Surface Pocket Formation than the Rest of the Protein Surface	journal.pcbi.1002951	null	[ [ "Manipulating the interactions between proteins represents a promising avenue for therapeutic intervention in a variety of settings .", "Given the ubiquitous nature of protein interactions , selectively manipulating such interactions could serve as a means to treat conditions including viral and bacterial...	[ "Despite intense interest and considerable effort via high-throughput screening , there are few examples of small molecules that directly inhibit protein-protein interactions .", "This suggests that many protein interaction surfaces may not be intrinsically “druggable” by small molecules , and elevates in importa...	[ "Identifying small-molecule inhibitors of protein interactions has traditionally presented a challenge for modern screening methods , despite interest stemming from the fact that such interactions comprise the underlying mechanisms for cell proliferation , differentiation , and survival .", "This suggests that ma...	2013
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "cognitive neurology", "medicine and health sciences", "brain", "vertebrates", "mice", "neuroscience", "animals", "mammals", "learning and memory", "animal models", "cognitive neuroscience", "model organisms", "animal behavior", "ganglion cells", "cognition", "experimental organism sys...	Control of recollection by slow gamma dominating mid-frequency gamma in hippocampus CA1	journal.pbio.2003354	null	[ [ "The hippocampus is crucial for both learning and remembering information , especially about space [1] , and because the same place-representing neurons participate in both processes [2–7] , it is unknown what neural events control whether hippocampal neurons are encoding current experience or recollecting in...	[ "Behavior is used to assess memory and cognitive deficits in animals like Fmr1-null mice that model Fragile X Syndrome , but behavior is a proxy for unknown neural events that define cognitive variables like recollection .", "We identified an electrophysiological signature of recollection in mouse dorsal Cornu Am...	[ "Behavior is often used as proxy to study memory and cognitive deficits in animals like Fmr1-KO mice that model Fragile X Syndrome , the most prevalent single-gene cause of intellectual disability and autism .", "However , it is unclear what neural events define cognitive variables like recollection of memory and...	2018
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "genetics and genomics/genomics", "evolutionary biology/genomics", "evolutionary biology/bioinformatics", "evolutionary biology", "genetics and genomics/population genetics" ]	Fine-Scale Phylogenetic Discordance across the House Mouse Genome	journal.pgen.1000729	null	[ [ "With the advent of new sequencing technologies , the reconstruction of phylogenetic histories on the genomic scale has become feasible .", "Genomic data offer the potential to resolve phylogenies that have been difficult to reconstruct from a small number of genes [1]–[5] .", "Although highly resolve...	[ "Population genetic theory predicts discordance in the true phylogeny of different genomic regions when studying recently diverged species .", "Despite this expectation , genome-wide discordance in young species groups has rarely been statistically quantified .", "The house mouse subspecies group provides a mod...	[ "The phylogenetic history of individual genes can differ strongly from the species history if taxa are recently derived , making inferences of a species history from only a handful of genes especially difficult in these cases .", "Genome-scale data sets now allow phylogenetic histories to be reconstructed from a ...	2009
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genetics and genomics/microbial evolution and genomics", "evolutionary biology/microbial evolution and genomics", "genetics and genomics/gene expression", "microbiology/microbial evolution and genomics", "evolutionary biology/genomics", "microbiology/microbial physiology and metabolism" ]	The Repertoire and Dynamics of Evolutionary Adaptations to Controlled Nutrient-Limited Environments in Yeast	journal.pgen.1000303	null	[ [ "The study of organismal evolution at the molecular level is a potent means of understanding how genomes evolve in response to selective pressures .", "Most kinds of evolutionary analysis are necessarily retrospective: individuals are sampled from a population in the present , genetic variation is assesse...	[ "The experimental evolution of laboratory populations of microbes provides an opportunity to observe the evolutionary dynamics of adaptation in real time .", "Until very recently , however , such studies have been limited by our inability to systematically find mutations in evolved organisms .", "We overcome th...	[ "Adaptive evolution is a central biological process that underlies diverse phenomena from the acquisition of antibiotic resistance by microbes to the evolution of niche specialization .", "Two unresolved questions regarding adaptive evolution are what types of genomic variation are associated with adaptation and ...	2008
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "flow cytometry", "innate immune system", "medicine and health sciences", "immune physiology", "cytokines", "pathology and laboratory medicine", "engineering and technology", "pathogens", "signal processing", "immunology", "microbiology", "green fluorescent protein", "light microscopy", "r...	Nonlatching positive feedback enables robust bimodality by decoupling expression noise from the mean	journal.pbio.2000841	null	[ [ "Bimodality is a recurring feature in many biological fate-selection programs [1] , such as the HIV active-versus-latent decision ( Fig 1A ) .", "Bimodal expression is a population-wide distribution pattern comprises 2 gene-expression modes , each corresponding to a specific fate path [2] .", "The mec...	[ "Fundamental to biological decision-making is the ability to generate bimodal expression patterns where 2 alternate expression states simultaneously exist .", "Here , we use a combination of single-cell analysis and mathematical modeling to examine the sources of bimodality in the transcriptional program controll...	[ "A central and recurring feature of cell-fate regulating circuits is their ability to generate bimodal expression—2 alternate expression states that exist simultaneously—with each state corresponding to a different cell fate .", "To understand the mechanisms enabling bimodality in a natural decision-making circui...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "immunology/immunomodulation", "infectious diseases/protozoal infections" ]	Plasmodium falciparum–Mediated Induction of Human CD25hiFoxp3hi CD4 T Cells Is Independent of Direct TCR Stimulation and Requires IL-2, IL-10 and TGFβ	journal.ppat.1000543	null	[ [ "Malaria is one of the most important infectious diseases in humans , affecting 300–600 million people annually with more than a million fatal cases per year [1] .", "Infection with the Plasmodium parasite occurs hand in hand with a disturbance of immune homeostasis .", "While malaria is associated wi...	[ "CD4+CD25+Foxp3+ regulatory T cells ( Tregs ) regulate disease-associated immunity and excessive inflammatory responses , and numbers of CD4+CD25+Foxp3+ Tregs are increased during malaria infection .", "The mechanisms governing their generation , however , remain to be elucidated .", "In this study we investiga...	[ "Infection with the malaria parasite Plasmodium falciparum affects 300–600 million people each year .", "Regulatory T cells ( Tregs ) expressing the transcription factor Foxp3 , which drives genes involved in immunosuppression , are specialized immune cells that can inhibit both protective and harmful inflammator...	2009
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "inflammatory diseases", "medicine and health sciences", "body fluids", "nervous system", "blood-brain barrier", "permeability", "pediatrics", "physiological parameters", "materials science", "cardiovascular analysis", "bioassays and physiological analysis", "pharmacology", "research and ana...	Development of a physiologically-based pharmacokinetic pediatric brain model for prediction of cerebrospinal fluid drug concentrations and the influence of meningitis	journal.pcbi.1007117	null	[ [ "Growth and development significantly impact handling of drugs in children across the pediatric age range .", "Simple linear bodyweight-based extrapolations from adult to pediatric doses have resulted in toxicity or therapy failure [1] .", "Taking developmental changes of the processes involved in dru...	[ "Different pediatric physiologically-based pharmacokinetic ( PBPK ) models have been described incorporating developmental changes that influence plasma drug concentrations .", "Drug disposition into cerebrospinal fluid ( CSF ) is also subject to age-related variation and can be further influenced by brain diseas...	[ "Developmental processes in children affect pharmacokinetics and should ideally be taken into account when establishing drug dosing regimens .", "One way to incorporate developmental differences is by making use of physiologically-based pharmacokinetic ( PBPK ) models in which kinetic equations are used to descri...	2019
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "dengue virus", "innate immune system", "medicine and health sciences", "immune physiology", "cytokines", "pathology and laboratory medicine", "togaviruses", "chikungunya infection", "pathogens", "immunology", "tropical diseases", "microbiology", "alphaviruses", "viruses", "developmental...	Suppression of chikungunya virus replication and differential innate responses of human peripheral blood mononuclear cells during co-infection with dengue virus	journal.pntd.0005712	null	[ [ "Dengue virus ( DENV ) currently causes the most prevalent arthropod-borne human disease .", "Chikungunya virus ( CHIKV ) re-emerged in 2005–2006 with large outbreaks afflicting millions of people in the Indian Ocean areas and has spread into many ( sub ) tropical regions that have long been endemic for D...	[ "Dengue and chikungunya are viral diseases transmitted to humans by infected Aedes spp .", "mosquitoes .", "With an estimated 390 million infected people per year dengue virus ( DENV ) currently causes the most prevalent arboviral disease .", "During the last decade chikungunya virus ( CHIKV ) has caused larg...	[ "Dengue virus ( DENV ) currently causes the most important arthropod-borne viral disease in humans .", "Chikungunya virus ( CHIKV ) re-emerged explosively in 2005–2006 afflicting millions of people in the Indian Ocean area and ever since continues its spread .", "The increasing co-circulation of these mosquito-...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine", "biology" ]	Epstein - Barr Virus Transforming Protein LMP-1 Alters B Cells Gene Expression by Promoting Accumulation of the Oncoprotein ΔNp73α	journal.ppat.1003186	null	[ [ "Epstein-Barr virus , also known as human herpesvirus 4 ( HHV4 ) , belongs to the gammaherpesvirus family and is largely spread as it can be detected in 90% of the worldwide population .", "EBV infects B cells and , in most cases , does not lead to any clinical manifestations .", "However , when EBV i...	[ "Many studies have proved that oncogenic viruses develop redundant mechanisms to alter the functions of the tumor suppressor p53 .", "Here we show that Epstein-Barr virus ( EBV ) , via the oncoprotein LMP-1 , induces the expression of ΔNp73α , a strong antagonist of p53 .", "This phenomenon is mediated by the L...	[ "Approximately 20% of worldwide human cancers have been associated with viral infections .", "Many oncogenic viruses exert their transforming properties by inactivating the products of tumour suppressor genes .", "One of the best characterized events induced by ongocenic viruses is the inactivation of the trans...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Transcriptional Regulation of Culex pipiens Mosquitoes by Wolbachia Influences Cytoplasmic Incompatibility	journal.ppat.1003647	null	[ [ "The intracellular maternally inherited bacterium Wolbachia pipientis , a widespread endosymbiont of invertebrates [1] , can influence reproduction in arthropods .", "The most common manipulation is cytoplasmic incompatibility ( CI ) .", "Sperm from Wolbachia-infected males are modified during maturat...	[ "Cytoplasmic incompatibility ( CI ) induced by the endosymbiont Wolbachia pipientis causes complex patterns of crossing sterility between populations of the Culex pipiens group of mosquitoes .", "The molecular basis of the phenotype is yet to be defined .", "In order to investigate what host changes may underli...	[ "Wolbachia are maternally inherited bacteria that manipulate invertebrate reproduction .", "Cytoplasmic incompatibility is embryo death that occurs when males carrying Wolbachia mate with females that do not , or that carry a different Wolbachia variant; its mechanism is poorly understood .", "In Culex mosquito...	2013
[ "Introduction", "Results/Discussion", "Materials and Methods" ]	[ "computer science", "chemistry", "biology" ]	Chemical Basis of Metabolic Network Organization	journal.pcbi.1002214	null	[ [ "One of the most intriguing findings in systems biology is that despite the varied constituents and metabolic pathways of three domains of life , their metabolic networks exhibit the same scale-free organization .", "That is , a small part of metabolites participate in a large number of reactions ( which ...	[ "Although the metabolic networks of the three domains of life consist of different constituents and metabolic pathways , they exhibit the same scale-free organization .", "This phenomenon has been hypothetically explained by preferential attachment principle that the new-recruited metabolites attach preferentiall...	[ "The metabolic networks of the three domains of life exhibit the same scale-free organization , which has been hypothetically explained in terms of preferential attachment principle .", "Here we reveal that the scale-free organization of metabolic networks may have a chemical basis .", "Through a chemoinformati...	2011
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "lipolysis", "cell death", "medicine and health sciences", "body fluids", "cardiovascular anatomy", "cell processes", "lipid analysis", "cardiology", "lipids", "biological tissue", "chemistry", "heart failure", "molecular biology", "blood plasma", "biochemistry", "hydrolysis", "blood...	Adipose tissue ATGL modifies the cardiac lipidome in pressure-overload-induced left ventricular failure	journal.pgen.1007171	null	[ [ "The development of chronic systolic heart failure is marked by a continuous incline in adrenergic activity that results in the typical clinical signs of this disease , including tachycardia and increased peripheral vascular resistance [1 , 2] .", "In addition to these cardiovascular effects , chronic sym...	[ "Adipose tissue lipolysis occurs during the development of heart failure as a consequence of chronic adrenergic stimulation .", "However , the impact of enhanced adipose triacylglycerol hydrolysis mediated by adipose triglyceride lipase ( ATGL ) on cardiac function is unclear .", "To investigate the role of adi...	[ "Chronic heart failure ( CHF ) is still one of the leading causes of morbidity and mortality worldwide , and new therapeutic approaches are required .", "Here we show that perturbation of adipose tissue lipolysis by tissue-specific deletion of the lypolytic enzyme ATGL ( adipose trigylceride lipase ) protects aga...	2018
[ "Introduction", "Results", "Discussion", "Methods" ]	[]	Hydrodynamic Radii of Intrinsically Disordered Proteins Determined from Experimental Polyproline II Propensities	journal.pcbi.1004686	null	[ [ "Many proteins , and protein domains , that perform critical biological tasks have disordered structures under normal solution conditions [1–3] .", "These proteins are referred to as intrinsically disordered [4] and , accordingly , molecular models of disordered protein structures are needed to understand...	[ "The properties of disordered proteins are thought to depend on intrinsic conformational propensities for polyproline II ( PPII ) structure .", "While intrinsic PPII propensities have been measured for the common biological amino acids in short peptides , the ability of these experimentally determined propensitie...	[ "Molecular models of disordered protein structures are needed to elucidate the functional mechanisms of intrinsically disordered proteins , a class of proteins implicated in many disease pathologies and human health issues .", "Several studies have measured intrinsic conformational propensities for polyproline II...	2016
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "eye infections", "medicine", "bacterial diseases", "infectious diseases", "disease ecology", "clinical research design", "global health", "clinical trials", "ophthalmology", "neglected tropical diseases", "infectious disease control", "trachoma", "public health" ]	Mass Treatment with Azithromycin for Trachoma: When Is One Round Enough? Results from the PRET Trial in The Gambia	journal.pntd.0002115	null	[ [ "The trial aimed to compare the prevalence of TF and ocular Ct infection in 0–5 year olds three years post-baseline between", "1 ) communities randomized to “standard” coverage versus communities randomised to “enhanced” coverage and", "2 ) communities randomized to a laboratory-based strategy to disc...	[ "The World Health Organization has recommended three rounds of mass drug administration ( MDA ) with antibiotics in districts where the prevalence of follicular trachoma ( TF ) is ≥10% in children aged 1–9 years , with treatment coverage of at least 80% .", "For districts at 5–10% TF prevalence it was recommended...	[ "Trachoma , which results from infection with a bacterium Chlamydia trachomatis ( Ct ) , is a leading cause of preventable blindness in the world .", "One of the currently used control methods is mass drug administration ( MDA ) with azithromycin , which is initiated according to rates of follicular trachoma ( TF...	2013
[ "Introduction", "Results", "Discussion" ]	[ "death rates", "invertebrates", "medicine and health sciences", "demography", "population dynamics", "geographical locations", "animals", "glossina", "developmental biology", "mathematics", "pupae", "tsetse fly", "population biology", "insect vectors", "africa", "infectious diseases", ...	Host-seeking efficiency can explain population dynamics of the tsetse fly Glossina morsitans morsitans in response to host density decline	journal.pntd.0005730	null	[ [ "For any blood-feeding arthropod vector , the process of finding and feeding on a host is essential for reproduction .", "Both male and female tsetse flies ( Diptera: Glossinidae ) , vectors of the trypanosomes which cause human and animal African trypanosomiasis , rely exclusively on blood for water and ...	[ "Females of all blood-feeding arthropod vectors must find and feed on a host in order to produce offspring .", "For tsetse—vectors of the trypanosomes that cause human and animal African trypanosomiasis—the problem is more extreme , since both sexes feed solely on blood .", "Host location is thus essential both...	[ "Tsetse flies are the vectors of human and animal African trypanosomiasis .", "The flies rely solely on vertebrate blood for food and water and changes in vertebrate host density may therefore influence tsetse survival .", "We develop models including starvation-dependent mortality to explain changes in numbers...	2017
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[]	Bacillus anthracis Diversity and Geographic Potential across Nigeria, Cameroon and Chad: Further Support of a Novel West African Lineage	journal.pntd.0003931	null	[ [ "Zoonoses , diseases affecting both human and animal populations , can exert tremendous pressures on human and veterinary health systems [1] .", "At the same time , many zoonoses cross the livestock/wildlife interface and have environmental reservoirs making it challenging to define at-risk areas [1] , pa...	[ "Zoonoses , diseases affecting both humans and animals , can exert tremendous pressures on human and veterinary health systems , particularly in resource limited countries .", "Anthrax is one such zoonosis of concern and is a disease requiring greater public health attention in Nigeria .", "Here we describe the...	[ "Anthrax , caused by the soil-borne bacterium Bacillus anthracis , is a disease with important public health and national security implications globally .", "Understanding the global genetic diversity of the pathogen is important for epidemiological and forensic investigations of anthrax events .", "Toward this...	2015
[ "Introduction", "Results/Discussion", "Materials and Methods" ]	[ "genetics and genomics/gene discovery", "genetics and genomics/functional genomics", "dermatology/psoriasis and other inflammatory diseases", "genetics and genomics/genetics of the immune system", "genetics and genomics/disease models", "genetics and genomics/genetics of disease", "immunology/genetics o...	A Genome-Wide Association Study of Psoriasis and Psoriatic Arthritis Identifies New Disease Loci	journal.pgen.1000041	null	[ [ "Psoriasis ( PS ) is a chronic inflammatory disease of the skin affecting 2–3% of the population [1] .", "Approximately 25% of patients also develop psoriatic arthritis ( PSA ) , a common , debilitating auto-immune disease belonging to the family of spondyloarthritides [2] , [3] .", "The recurrence ri...	[ "A genome-wide association study was performed to identify genetic factors involved in susceptibility to psoriasis ( PS ) and psoriatic arthritis ( PSA ) , inflammatory diseases of the skin and joints in humans .", "223 PS cases ( including 91 with PSA ) were genotyped with 311 , 398 single nucleotide polymorphis...	[ "Psoriasis ( PS ) and psoriatic arthritis ( PSA ) are common inflammatory diseases of humans affecting the skin and joints .", "Approximately 2% of Europeans are affected with PS , and ∼10–30% of patients develop PSA .", "Genetic variation in the MHC ( multiple histocompatibility locus antigen cluster ) increas...	2008
[ "Introduction", "Results", "Discussion", "Model" ]	[ "ellipses", "geometry", "membrane proteins", "probability distribution", "mathematics", "stem cells", "cellular structures and organelles", "research and analysis methods", "cell potency", "animal cells", "embryonic stem cells", "biological databases", "proteomics", "pluripotency", "cell...	A Bayesian mixture modelling approach for spatial proteomics	journal.pcbi.1006516	null	[ [ "Spatial proteomics is an interdisciplinary field studying the localisation of proteins on a large-scale .", "Where a protein is localised in a cell is a fundamental question , since a protein must be localised to its required sub-cellular compartment to interact with its binding partners ( for example , ...	[ "Analysis of the spatial sub-cellular distribution of proteins is of vital importance to fully understand context specific protein function .", "Some proteins can be found with a single location within a cell , but up to half of proteins may reside in multiple locations , can dynamically re-localise , or reside w...	[ "Sub-cellular localisation of proteins provides insights into sub-cellular biological processes .", "For a protein to carry out its intended function it must be localised to the correct sub-cellular environment , whether that be organelles , vesicles or any sub-cellular niche .", "Correct sub-cellular localisat...	2018
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "cell death", "invertebrates", "innate immune system", "medicine and health sciences", "rna interference", "immune physiology", "cytokines", "cell processes", "immunology", "animals", "animal models", "dna damage", "physiological processes", "developmental biology", "drosophila melanogas...	A virus-acquired host cytokine controls systemic aging by antagonizing apoptosis	journal.pbio.2005796	null	[ [ "In most metazoans , aging is characterized by a drastic decline in cellular and tissue function .", "This ultimate decline in function is driven by a multitude of complex , age-related cellular changes .", "The cellular and tissue changes that promote aging can be defined by", "( i ) primary caus...	[ "Aging is characterized by degeneration of unique tissues .", "However , dissecting the interconnectedness of tissue aging remains a challenge .", "Here , we employ a muscle-specific DNA damage model in Drosophila to reveal secreted factors that influence systemic aging in distal tissues .", "Utilizing this m...	[ "Aging in multicellular organisms is characterized by a progressive decline in the proper function of organs .", "This deterioration of organ function is a risk factor for many diseases .", "However , it is unlikely that organs age in isolation , as damage in one organ can presumably impact aging of other organ...	2018
[ "Introduction", "Materials and Methods", "Discussion" ]	[]	Antimony to Cure Visceral Leishmaniasis Unresponsive to Liposomal Amphotericin B	journal.pntd.0004304	null	[ [ "Untreated visceral leishmaniasis ( VL ) is generally fatal .", "Although pentavalent antimony is still used in endemic areas [1] , liposomal amphotericin B ( L-AmB ) has become the reference treatment in Europe and the US [2] .", "L-AmB is highly effective , generally better tolerated than pentavalen...	[ "We report on 4 patients ( 1 immunocompetent , 3 immunosuppressed ) in whom visceral leishmaniasis had become unresponsive to ( or had relapsed after ) treatment with appropriate doses of liposomal amphotericin B . Under close follow-up , full courses of pentavalent antimony were administered without life-threateni...	[ "Visceral leishmaniasis causes fever , enlargement of internal organs like the liver and the spleen , and leads to death if no treatment is given .", "It is caused by a microbe called Leishmania and affects children and adults in warm and temperate regions of the world .", "Antimony in different forms has been ...	2016
[ "Introduction", "Methods", "Results", "Discussion" ]	[]	A Recombinant Vesicular Stomatitis Virus-Based Lassa Fever Vaccine Protects Guinea Pigs and Macaques against Challenge with Geographically and Genetically Distinct Lassa Viruses	journal.pntd.0003736	null	[ [ "Lassa virus ( LASV , family Arenaviridae , genus Arenavirus ) is one of the most prominent etiological agents of viral hemorrhagic fever with an estimated 300 , 000–500 , 000 infections diagnosed annually in West Africa [1 , 2] .", "Humans are most commonly infected with LASV through contact with infecte...	[ "Lassa virus ( LASV ) is endemic in several West African countries and is the etiological agent of Lassa fever .", "Despite the high annual incidence and significant morbidity and mortality rates , currently there are no approved vaccines to prevent infection or disease in humans .", "Genetically , LASV demonst...	[ "Lassa fever ( LF ) is an acute viral infection which is often associated with hemorrhagic manifestations and multi-organ failure in humans .", "The etiological agent responsible for LF is Lassa virus ( LASV ) , a rodent-borne Arenavirus which is endemic in several West African countries .", "Up to 500 , 000 ca...	2015
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "chemical bonding", "animal diseases", "medicine and health sciences", "molecular dynamics", "monomers", "electron cryo-microscopy", "simulation and modeling", "animal prion diseases", "microscopy", "protein structure", "zoology", "hydrogen bonding", "research and analysis methods", "physi...	Full atomistic model of prion structure and conversion	journal.ppat.1007864	null	[ [ "Prion diseases are infectious neurodegenerative disorders characterized by an invariably lethal outcome caused by a proteinaceous infectious agent named “prion” [1] .", "The central event in these pathologies is the conversion of PrPC , a GPI-anchored protein of unknown function , into a misfolded isofor...	[ "Prions are unusual protein assemblies that propagate their conformationally-encoded information in absence of nucleic acids .", "The first prion identified , the scrapie isoform ( PrPSc ) of the cellular prion protein ( PrPC ) , caused epidemic and epizootic episodes [1] .", "Most aggregates of other misfoldin...	[ "Prions are unusual infectious pathogens that do not contain any nucleic acid .", "They consist of assemblies of misfolded proteins .", "The scrapie isoform of the mammalian prion protein , PrPSc , is the most notorious prion , and is responsible for deadly neurodegenerative diseases affecting humans , like Cre...	2019
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "allosteric regulation", "protein interactions", "chemical compounds", "crystal structure", "particle physics", "condensed matter physics", "enzymology", "deuterium", "amides", "organic compounds", "atoms", "crystallography", "composite particles", "chemical dissociation", "enzyme chemis...	Predicting Allosteric Effects from Orthosteric Binding in Hsp90-Ligand Interactions: Implications for Fragment-Based Drug Design	journal.pcbi.1004840	null	[ [ "Ligands mediate specific interactions with proteins and alter their conformational dynamics thereby modulating their function , making them important regulators of biological processes [1] .", "Protein-ligand interaction strengths range from weak ( Dissociation constants , KD μM~mM ) to strong affinities...	[ "A key question in mapping dynamics of protein-ligand interactions is to distinguish changes at binding sites from those associated with long range conformational changes upon binding at distal sites .", "This assumes a greater challenge when considering the interactions of low affinity ligands ( dissociation con...	[ "Ligand interactions with proteins result in broad changes that are propagated throughout the target proteins , across space and time .", "These changes can be broadly classified into: orthosteric effects at the ligand binding site and allosteric changes at distal sites .", "These allosteric changes are difficu...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "cellular stress responses", "cell biology", "biology", "molecular cell biology" ]	Specific SKN-1/Nrf Stress Responses to Perturbations in Translation Elongation and Proteasome Activity	journal.pgen.1002119	null	[ [ "Maintenance of protein homeostasis is critical for organismal health , and protection against environmental challenges .", "Protein homeostasis depends upon the balance among the processes of protein synthesis , folding , and degradation .", "Disruptions in this balance result in accumulation of abno...	[ "SKN-1 , the Caenorhabditis elegans Nrf1/2/3 ortholog , promotes both oxidative stress resistance and longevity .", "SKN-1 responds to oxidative stress by upregulating genes that detoxify and defend against free radicals and other reactive molecules , a SKN-1/Nrf function that is both well-known and conserved .",...	[ "The mechanisms through which organisms defend against environmental stresses are critical during diverse disease processes and are likely to be important for longevity .", "The nematode C . elegans is advantageous for genetic analysis of how stress defenses function and contribute to survival .", "The evolutio...	2011
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "fish", "vertebrates", "nucleotides", "animals", "alleles", "animal models", "organisms", "osteichthyes", "developmental biology", "model organisms", "experimental organism systems", "sequence motif analysis", "molecular biology techniques", "embryos", "research and analysis methods", ...	Conditional mutagenesis by oligonucleotide-mediated integration of loxP sites in zebrafish	journal.pgen.1007754	null	[ [ "Model system genetics is undergoing a major shift from forward to reverse genetics , driven by a combination of two key factors .", "The first is the increasing robustness of genomic and proteomic tools , which enable rapid identification of candidate genes with potential roles in biological processes of...	[ "Many eukaryotic genes play essential roles in multiple biological processes in several different tissues .", "Conditional mutants are needed to analyze genes with such pleiotropic functions .", "In vertebrates , conditional gene inactivation has only been feasible in the mouse , leaving other model systems to ...	[ "Some genes are expressed and function in a single tissue , and the effect of their loss on that tissue can be readily determined .", "Frequently , however , genes that are necessary for the development or maintenance of one tissue are also important for other tissues or cell types .", "Genes of the latter type...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "blood cells", "flow cytometry", "medicine and health sciences", "immune cells", "pathology and laboratory medicine", "pathogens", "immunology", "microbiology", "cloning", "retroviruses", "organisms", "viruses", "clinical medicine", "rna viruses", "molecular biology techniques", "cytot...	T Cell Receptor Vβ Staining Identifies the Malignant Clone in Adult T cell Leukemia and Reveals Killing of Leukemia Cells by Autologous CD8+ T cells	journal.ppat.1006030	null	[ [ "Adult T cell leukemia/lymphoma is a mature T cell malignancy caused by the retrovirus human T lymphotropic virus-1 ( HTLV-1 ) .", "Four clinical subtypes exist: acute , lymphoma , chronic and smouldering , which range from highly aggressive to indolent in their clinical course [1 , 2] .", "Advances i...	[ "There is growing evidence that CD8+ cytotoxic T lymphocyte ( CTL ) responses can contribute to long-term remission of many malignancies .", "The etiological agent of adult T-cell leukemia/lymphoma ( ATL ) , human T lymphotropic virus type-1 ( HTLV-1 ) , contains highly immunogenic CTL epitopes , but ATL patients...	[ "Human T lymphotropic virus-1 infects T cells , causing them to multiply .", "In some people , cellular replication is unchecked , resulting in an aggressive blood cancer called adult T-cell leukemia/lymphoma .", "The virus proteins are efficiently recognised as ‘foreign’ by the immune system in most infected i...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Cognitive Impairment Induced by Delta9-tetrahydrocannabinol Occurs through Heteromers between Cannabinoid CB1 and Serotonin 5-HT2A Receptors	journal.pbio.1002194	Specific subtypes of cannabinoid and serotonin receptors interact to form heterodimers that mediate the cognitive deficits—but not the analgesic effects—induced by tetrahydrocannabinol, the major psychoactive constituent in Cannabis sativa.	[ [ "The administration of delta-9-tetrahydrocannabinol ( THC ) , the main psychoactive compound in Cannabis sativa , induces numerous behavioral responses related to undesirable effects , including memory impairments [1 , 2] , anxiogenic effects [3] , and dependence [4 , 5] .", "However , other effects of TH...	[ "Activation of cannabinoid CB1 receptors ( CB1R ) by delta9-tetrahydrocannabinol ( THC ) produces a variety of negative effects with major consequences in cannabis users that constitute important drawbacks for the use of cannabinoids as therapeutic agents .", "For this reason , there is a tremendous medical inter...	[ "Delta-9-tetrahydrocannabinol ( THC ) , the main psychoactive compound of marijuana , induces numerous undesirable effects , including memory impairments , anxiety , and dependence .", "Conversely , THC also has potentially therapeutic effects , including analgesia , muscle relaxation , and neuroprotection .", ...	2015
[ "Introduction", "Results", "Discussion", "Methods and materials" ]	[ "brain development", "children", "deletion mutation", "medicine and health sciences", "maternal health", "obstetrics and gynecology", "computational biology", "preterm birth", "age groups", "mutation", "developmental biology", "women's health", "organism development", "pregnancy", "infan...	Fetal de novo mutations and preterm birth	journal.pgen.1006689	null	[ [ "Preterm birth ( PTB , delivery at less than 37 weeks of gestation ) affects ~10–12% of newborns in the US[1 , 2] , and is the leading cause for neonatal morbidity and mortality[3 , 4] .", "In addition to environmental factors , e . g . smoking during pregnancy[5 , 6] , there is evidence for a genetic com...	[ "Preterm birth ( PTB ) affects ~12% of pregnancies in the US .", "Despite its high mortality and morbidity , the molecular etiology underlying PTB has been unclear .", "Numerous studies have been devoted to identifying genetic factors in maternal and fetal genomes , but so far few genomic loci have been associa...	[ "Preterm birth is a prevalent pregnancy condition and leads to substantial morbidity and mortality .", "Its genetic association has been well observed , but the underlying etiology remains unclear .", "Current research has been focused on identifying risk factors in maternal genomes .", "In this study , we te...	2017
[ "Introduction", "Methods and Materials", "Results", "Discussion" ]	[ "aging", "population metrics", "infectious disease epidemiology", "epidemiology", "population modeling", "gene expression", "death rate", "population biology", "biology", "population ecology", "molecular cell biology", "dna transcription" ]	Adult Survivorship of the Dengue Mosquito Aedes aegypti Varies Seasonally in Central Vietnam	journal.pntd.0002669	null	[ [ "How long mosquitoes live has been a question asked by tropical disease researchers for over a century [1] .", "Mosquito longevity is a limiting factor for the transmission of mosquito-borne pathogens , particularly as the pathogens require a period of time to penetrate the midgut lining from an infectiou...	[ "The survival characteristics of the mosquito Aedes aegypti affect transmission rates of dengue because transmission requires infected mosquitoes to survive long enough for the virus to infect the salivary glands .", "Mosquito survival is assumed to be high in tropical , dengue endemic , countries like Vietnam ."...	[ "Prolonged survival of adult mosquitoes is critical to dengue transmission cycles , particularly because it takes time for the dengue viruses to infect the mosquito midgut , replicate and infect the salivary glands before transmission can occur .", "Reducing mosquito lifespan is one avenue to fight dengue , and m...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "bacteriology", "insertion mutation", "microbiology", "mutation", "substitution mutation", "genetic elements", "bacterial genetics", "dna", "microbial genetics", "microbial genomics", "bacterial genomics", "repeated sequences", "biochemistry", "nucleic acids", "gene identification and an...	Anaerobically Grown Escherichia coli Has an Enhanced Mutation Rate and Distinct Mutational Spectra	journal.pgen.1006570	null	[ [ "Mutations are the ultimate source of genetic variation and play a central role in the tempo of evolution .", "Spontaneous mutation rates [1] vary considerably among different organisms [2–4] and grown in different environments [5] .", "Facultative anaerobes are metabolically versatile , being able to...	[ "Oxidative stress is a major cause of mutation but little is known about how growth in the absence of oxygen impacts the rate and spectrum of mutations .", "We employed long-term mutation accumulation experiments to directly measure the rates and spectra of spontaneous mutation events in Escherichia coli populati...	[ "When organisms are exposed to different environments , the rates and types of mutations that spontaneously arise in each environment can vary due to differing mutagenic pressures imposed by each environment , and these can potentially influence the evolution of the organism .", "Little is known about the types o...	2017
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "deletion mutation", "medicine and health sciences", "anemia", "fibroblasts", "dna damage", "mutation", "immunoprecipitation", "connective tissue cells", "dna", "research and analysis methods", "animal cells", "chromosome biology", "connective tissue", "biological tissue", "hematology", ...	A Hypomorphic PALB2 Allele Gives Rise to an Unusual Form of FA-N Associated with Lymphoid Tumour Development	journal.pgen.1005945	null	[ [ "BRCA2 , PALB2 , BRCA1 , Rad51 and the Rad51 paralogs form the principal constituents of the homologous recombination ( HR ) machinery utilised by the cell not only to repair deleterious DNA lesions , such as DNA double strand breaks ( DSBs ) in an error-free manner , but also to stabilise , protect and resta...	[ "Patients with biallelic truncating mutations in PALB2 have a severe form of Fanconi anaemia ( FA-N ) , with a predisposition for developing embryonal-type tumours in infancy .", "Here we describe two unusual patients from a single family , carrying biallelic PALB2 mutations , one truncating , c . 1676_1677delAAi...	[ "PALB2 is a protein that creates a molecular bridge that promotes the recruitment of Homologous Recombination Repair ( HRR ) proteins BRCA1 , BRCA2 and Rad51 to sites of DNA damage .", "Cells with functional loss of PALB2 show a defect in HRR and are characterized by an increased number of spontaneous chromosome ...	2016
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "deletion mutation", "genome evolution", "population genetics", "computational biology", "ploidy", "cloning", "mutation", "fungal evolution", "nonsense mutation", "molecular biology techniques", "population biology", "evolutionary adaptation", "frameshift mutation", "research and analysis ...	Adaptive genome duplication affects patterns of molecular evolution in Saccharomyces cerevisiae	journal.pgen.1007396	null	[ [ "The natural life cycle of budding yeast alternates between haploid and diploid phases .", "Both ploidies can be stably propagated asexually through mitotic division .", "Both theory and experimental work show that haploids adapt faster than diploids , likely due to recessive beneficial mutations [1 ,...	[ "Genome duplications are important evolutionary events that impact the rate and spectrum of beneficial mutations and thus the rate of adaptation .", "Laboratory evolution experiments initiated with haploid Saccharomyces cerevisiae cultures repeatedly experience whole-genome duplication ( WGD ) .", "We report re...	[ "Whole genome duplications—the simultaneous doubling of each chromosome—can have a profound influence on evolution .", "Evidence of ancient whole genome duplications can be seen in most modern genomes .", "Experimental evolution , the long-term propagation of organisms under well-controlled laboratory condition...	2018
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "transfection", "rna extraction", "nucleotides", "mutation", "sequence motif analysis", "molecular biology techniques", "extraction techniques", "research and analysis methods", "sequence analysis", "genome complexity", "artificial gene amplification and extension", "bioinformatics", "molecu...	Intronic PAH gene mutations cause a splicing defect by a novel mechanism involving U1snRNP binding downstream of the 5’ splice site	journal.pgen.1007360	null	[ [ "The significant contribution of splicing defects to human disease is to date well established .", "Pathogenic splicing mutations include both genomic variants located in consensus splicing sequences ( 5’ splice site , 3’ splice site , branch point , and polypyrimidine tract ) , as well as other variants ...	[ "Phenylketonuria ( PKU ) , one of the most common inherited diseases of amino acid metabolism , is caused by mutations in the phenylalanine hydroxylase ( PAH ) gene .", "Recently , PAH exon 11 was identified as a vulnerable exon due to a weak 3’ splice site , with different exonic mutations affecting exon 11 spli...	[ "Splicing defects constitute a major cause of human disease .", "Mutations affecting conserved splicing sequences at exon-intron junctions are easily recognized as possibly pathogenic , whereas variants in exonic or intronic regions are difficult to classify without functional evidence provided by transcript anal...	2018
[ "Introduction", "Results/Discussion", "Materials and Methods" ]	[ "biotechnology", "systems biology", "plant science", "model organisms", "plant biology", "biology", "genomics", "genetics and genomics" ]	Genome, Functional Gene Annotation, and Nuclear Transformation of the Heterokont Oleaginous Alga Nannochloropsis oceanica CCMP1779	journal.pgen.1003064	null	[ [ "The search for sustainable sources of liquid transportation fuels has led to renewed interest in microalgae as potential feedstocks and rising research activity focused on the basic biology of algae .", "Microalgae can accumulate large quantities of oils ( triacylglycerols ) and carbohydrates , particula...	[ "Unicellular marine algae have promise for providing sustainable and scalable biofuel feedstocks , although no single species has emerged as a preferred organism .", "Moreover , adequate molecular and genetic resources prerequisite for the rational engineering of marine algal feedstocks are lacking for most candi...	[ "Algae are a highly diverse group of organisms that have become the focus of renewed interest due to their potential for producing biofuel feedstocks , nutraceuticals , and biomaterials .", "Their high photosynthetic yields and ability to grow in areas unsuitable for agriculture provide a potential sustainable al...	2012
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "invertebrates", "medicine and health sciences", "rna interference", "gene regulation", "cancer risk factors", "chromatids", "animals", "oncology", "animal models", "drosophila melanogaster", "model organisms", "dna replication", "experimental organism systems", "dna", "epigenetics", "...	Brca2, Pds5 and Wapl differentially control cohesin chromosome association and function	journal.pgen.1007225	null	[ [ "The cohesin complex mediates sister chromatid cohesion , which ensures accurate chromosome segregation upon cell division .", "Cohesin consists of the Smc1 ( Flybase FBgn0040283 ) , Smc3 ( FBgn0015615 ) , Rad21 ( Vtd , FBgn0260987 ) and SA ( FBgn0020616 ) proteins [1–4] .", "Smc1 , Smc3 and Rad21 for...	[ "The cohesin complex topologically encircles chromosomes and mediates sister chromatid cohesion to ensure accurate chromosome segregation upon cell division .", "Cohesin also participates in DNA repair and gene transcription .", "The Nipped-B–Mau2 protein complex loads cohesin onto chromosomes and the Pds5—Wapl...	[ "The cohesin protein complex has multiple functions in eukaryotic cells .", "It ensures that when a cell divides , the two daughter cells receive the correct number of chromosomes .", "It does this by holding together the sister chromatids that are formed when chromosomes are duplicated by DNA replication .", ...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "virology/virion structure, assembly, and egress", "virology/host invasion and cell entry" ]	A Lipid Receptor Sorts Polyomavirus from the Endolysosome to the Endoplasmic Reticulum to Cause Infection	journal.ppat.1000465	null	[ [ "Viruses must navigate through the complex endocytic machineries of the host cell to successfully cause infection .", "Although some viruses evade or escape degradative compartments such as the endolysosome to infect cells , others rely on this organelle to facilitate infection [1] .", "How these proc...	[ "The mechanisms by which receptors guide intracellular virus transport are poorly characterized .", "The murine polyomavirus ( Py ) binds to the lipid receptor ganglioside GD1a and traffics to the endoplasmic reticulum ( ER ) where it enters the cytosol and then the nucleus to initiate infection .", "How Py rea...	[ "To cause infection , viruses must reach appropriate compartments within the cell where they undergo a programmed series of conformational changes that enable the viral genome to be exposed and released .", "The mechanisms that target viruses to these compartments are often not clear .", "Here we study the infe...	2009
[ "Introduction", "Methods", "Results", "Discussion", "Conclusion" ]	[ "medicine and health sciences", "enzyme-linked immunoassays", "molecular probe techniques", "tropical diseases", "immunoblotting", "parasitic diseases", "biochemical analysis", "enzyme assays", "veterinary diagnostics", "neglected tropical diseases", "bioassays and physiological analysis", "mo...	Development of the multi-epitope chimeric antigen rqTSA-25 from Taenia saginata for serological diagnosis of bovine cysticercosis	journal.pntd.0006371	null	[ [ "Bovine cysticercosis is one of the major public and animal health problems worldwide , and particularly in Brazil where it causes economic losses for slaughterhouses and farmers [1] .", "The human being is the definitive host of the bovine cysticercosis agent , Taenia saginata [2] , while the cattle act ...	[ "Bovine cysticercosis is a worldwide distributed zoonosis caused by the larval form of Taenia saginata present in bovine muscles .", "The diagnosis is based on the postmortem inspection at slaughterhouses and consists of the macroscopic visualization of lesions caused by cysticercosis in muscle sites .", "Howev...	[ "Taenia saginata cysticercosis occurs worldwide .", "The prevalence related is higher mainly in developing countries , causing damage to public health and economic losses .", "Through our study , a new antigen with high diagnostic potential was developed for use in laboratory serological tests , aiming at the d...	2018
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[]	Asymptomatic Helminth Infection in Active Tuberculosis Is Associated with Increased Regulatory and Th-2 Responses and a Lower Sputum Smear Positivity	journal.pntd.0003994	null	[ [ "The high prevalence of chronic infectious diseases such as HIV , tuberculosis ( TB ) and helminth infection has a significant impact on public health in Africa [1] .", "The majority of TB cases and TB related deaths occur in resource poor countries [2] where TB is the most common life-threatening opportu...	[ "The impact of intestinal helminth infection on the clinical presentation and immune response during active tuberculosis ( TB ) infection is not well characterized .", "Our aim was to investigate whether asymptomatic intestinal helminth infection alters the clinical signs and symptoms as well as the cell mediated...	[ "The effects of helminth infection on chronic infectious diseases such as tuberculosis ( TB ) merit further characterization .", "There is limited data regarding the impact of helminth co-infection on clinical and immunological outcomes of TB from clinical field studies in high endemic areas .", "We tried to ad...	2015
[ "Introduction", "Results", "Discussion", "Conclusion", "Methods" ]	[ "learning", "ellipses", "decision making", "statistics", "social sciences", "geometry", "neuroscience", "learning and memory", "cognitive psychology", "mathematics", "probability distribution", "cognition", "research and analysis methods", "behavior", "human learning", "mathematical an...	Human online adaptation to changes in prior probability	journal.pcbi.1006681	null	[ [ "Sensory decision-making involves making decisions under uncertainty .", "Furthermore , optimal sensory decision-making requires the combination of uncertain sensory signals with prior expectations .", "Perceptual models of decision-making often incorporate prior expectations to describe human behavio...	[ "Optimal sensory decision-making requires the combination of uncertain sensory signals with prior expectations .", "The effect of prior probability is often described as a shift in the decision criterion .", "Can observers track sudden changes in probability ?", "To answer this question , we used a change-poi...	[ "We demonstrate how people learn and adapt to changes to the probability of occurrence of one of two categories on decision-making under uncertainty .", "The study combined psychophysical behavioral tasks with computational modeling .", "We used two behavioral tasks: a typical forced-choice categorization task ...	2019
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biology and life sciences", "cell differentiation", "developmental biology", "neuronal differentiation" ]	In Vitro Generation of Neuromesodermal Progenitors Reveals Distinct Roles for Wnt Signalling in the Specification of Spinal Cord and Paraxial Mesoderm Identity	journal.pbio.1001937	Timed pulses of WNT and FGF signaling convert human and mouse pluripotent stem cells into neuromesodermal progenitors that can be directed to differentiate into spinal cord and paraxial mesoderm cells	[ [ "The differentiation of embryonic stem cells ( ESCs ) to specific cell types offers insight into developmental mechanisms and has potential therapeutic applications .", "For example the differentiation of neural progenitors ( NPCs ) from monolayers of ESCs seeded in serum free conditions is a model of neu...	[ "Cells of the spinal cord and somites arise from shared , dual-fated precursors , located towards the posterior of the elongating embryo .", "Here we show that these neuromesodermal progenitors ( NMPs ) can readily be generated in vitro from mouse and human pluripotent stem cells by activating Wnt and Fgf signall...	[ "Stem cells are providing insight into embryo development and offering new approaches to clinical and therapeutic research .", "In part this progress arises from “directed differentiation” – artificially controlling the types of cells produced from stem cells .", "Here we describe the directed differentiation o...	2014
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "blood cells", "medicine and health sciences", "immune cells", "pathology and laboratory medicine", "gene regulation", "metabolic processes", "pathogens", "immunology", "microbiology", "glycolysis", "viruses", "oncology", "micrornas", "dna viruses", "hypoxia", "herpesviruses", "lipid...	Hypoxia-inducible factor-1 alpha as a therapeutic target for primary effusion lymphoma	journal.ppat.1006628	null	[ [ "Primary effusion lymphoma ( PEL ) is an aggressive B-cell non-Hodgkin’s lymphoma caused by an oncogenic human herpesvirus , Kaposi’s sarcoma-associated herpesvirus ( KSHV ) , also called human herpesvirus-8 ( HHV-8 ) .", "KSHV is also the causative agent of Kaposi sarcoma ( KS ) , a form of multicentric ...	[ "Primary effusion lymphoma ( PEL ) is an aggressive B-cell lymphoma with poor prognosis caused by Kaposi’s sarcoma-associated herpesvirus ( KSHV ) .", "Previous studies have revealed that HIF-1α , which mediates much of the cellular response to hypoxia , plays an important role in life cycle of KSHV .", "KSHV i...	[ "Kaposi’s sarcoma-associated herpesvirus ( KSHV ) is an oncogenic herpesvirus that causes several malignancies including primary effusion lymphoma ( PEL ) .", "PEL is an aggressive B-cell lymphoma that usually develops in a hypoxic environment .", "There is no standard treatment for PEL and it carries a poor pr...	2017
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "protein interactions", "hela cells", "gene regulation", "biological cultures", "dna-binding proteins", "light microscopy", "dna transcription", "microscopy", "cell cultures", "research and analysis methods", "transcriptional control", "protein-protein interactions", "proteins", "gene expr...	Single-molecule dynamics and genome-wide transcriptomics reveal that NF-kB (p65)-DNA binding times can be decoupled from transcriptional activation	journal.pgen.1007891	null	[ [ "Transcription factors ( TFs ) are fundamental regulatory components of transcription in both prokaryotes and eukaryotes , which can activate or repress the expression of specific genes .", "The NF-κB family of TFs , universal among nearly all animal cell types , is involved in many signaling pathways and...	[ "Transcription factors ( TFs ) regulate gene expression in both prokaryotes and eukaryotes by recognizing and binding to specific DNA promoter sequences .", "In higher eukaryotes , it remains unclear how the duration of TF binding to DNA relates to downstream transcriptional output .", "Here , we address this q...	[ "To control the rate of transcription of genes , both eukaryotes and prokaryotes express specialized proteins , transcription factors ( TF ) , that bind promoter sequences to mark them for the transcriptional machinery including DNA polymerase II .", "TFs are often multi-subunit proteins containing a DNA-binding ...	2019
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "immunology", "microbiology", "animals", "genetics and genomics", "eubacteria" ]	Distinct TLR- and NLR-Mediated Transcriptional Responses to an Intracellular Pathogen	journal.ppat.0040006	null	[ [ "As sentinels of the immune system , macrophages must be able to determine the nature and scope of microbial threats to mount appropriate transcriptional responses [1 , 2] .", "Macrophages need to discriminate not only viral from bacterial infection , but also extracellular and possibly killed microbes fr...	[ "How the innate immune system tailors specific responses to diverse microbial infections is not well understood .", "Cells use a limited number of host receptors and signaling pathways to both discriminate among extracellular and intracellular microbes , and also to generate responses commensurate to each threat ...	[ "Macrophages are critical cells of the innate immune system , contributing to immediate and robust defense against microbial infections .", "Macrophages detect pathogens using host receptors located on the cell surface , in phagosomal vacuoles , and in the cytosol .", "While fundamental to innate immunity , it ...	2008

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