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headings list	keywords list	title stringlengths 20 281	id stringlengths 20 20	toc stringlengths 57 522 ⌀	sections list	abstract list	summary list	year stringclasses 13 values
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "developmental biology", "danio (zebrafish)", "vertebrates", "teleost fishes", "nephrology" ]	The cdx Genes and Retinoic Acid Control the Positioning and Segmentation of the Zebrafish Pronephros	journal.pgen.0030189	null	[ [ "The kidney eliminates metabolic waste in the body using highly specialized structures called nephrons .", "Individual nephrons are composed of a blood filter ( renal corpuscle ) , a tubule that recovers or secretes solutes , and a collecting duct [1] .", "The renal corpuscle contains epithelial cells...	[ "Kidney function depends on the nephron , which comprises a blood filter , a tubule that is subdivided into functionally distinct segments , and a collecting duct .", "How these regions arise during development is poorly understood .", "The zebrafish pronephros consists of two linear nephrons that develop from ...	[ "In the kidney , structures known as nephrons are responsible for collecting metabolic waste .", "Nephrons are composed of a blood filter ( glomerulus ) followed by a series of specialized tubule regions , or segments , which recover solutes such as salts , and finally terminate with a collecting duct .", "The ...	2007
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "sequencing techniques", "fungal spores", "vertebrates", "animals", "mammals", "fungi", "phylogenetic analysis", "rna isolation", "molecular biology techniques", "rna sequencing", "fungal reproduction", "research and analysis methods", "sequence analysis", "mycology", "rna sequence analy...	Using a Novel Partitivirus in Pseudogymnoascus destructans to Understand the Epidemiology of White-Nose Syndrome	journal.ppat.1006076	null	[ [ "Pseudogymnoascus destructans ( Pd; previously named Geomyces destructans ) is an emerging fungal pathogen responsible for a fatal disease , white-nose syndrome ( WNS ) in hibernating bats in North America [1–3] .", "Experts estimate over 5 millions bats died from WNS in North America since the disease wa...	[ "White-nose syndrome is one of the most lethal wildlife diseases , killing over 5 million North American bats since it was first reported in 2006 .", "The causal agent of the disease is a psychrophilic filamentous fungus , Pseudogymnoascus destructans .", "The fungus is widely distributed in North America and E...	[ "Many species of bats in North America have been severely impacted by a fungal disease , white-nose syndrome , that has killed over 5 million bats since it was first identified in 2006 .", "The fungus is believed to have been introduced into a cave in New York where bats hibernate , and has now spread to 29 state...	2016
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "invertebrates", "medicine and health sciences", "behavioral and social aspects of health", "tropical diseases", "social sciences", "ponds", "neuroscience", "animals", "health care", "developmental biology", "cognitive psychology", "bodies of water", "neglected tropical diseases", "insect ...	The Shan people’s health beliefs, knowledge and perceptions of dengue in Eastern Shan Special Region IV, Myanmar	journal.pntd.0007498	null	[ [ "Dengue fever ( DF ) is a mosquito-borne disease caused by the dengue virus .", "It has become a substantially increasing threat to public health and represents a challenge to health services and a burden to economies .", "It was recently estimated that there are 390 million dengue infections every ye...	[ "Sustainable dengue intervention requires the participation of communities .", "Therefore , understanding the health beliefs , knowledge and perceptions of dengue among the local people can help to design locally appropriate strategies for effective interventions .", "A combination of qualitative semi-structure...	[ "The burden of dengue has been increasing over the last five decades , and dengue fever ( DF ) has become one of the most rapidly spreading mosquito-borne diseases .", "DF has become another disease that threatens public health after malaria has become successfully controlled along the China-Myanmar border .", ...	2019
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "oncology/breast cancer", "oncology/gynecological cancers", "genetics and genomics/genetics of disease", "genetics and genomics/cancer genetics", "genetics and genomics/population genetics" ]	Multi-Variant Pathway Association Analysis Reveals the Importance of Genetic Determinants of Estrogen Metabolism in Breast and Endometrial Cancer Susceptibility	journal.pgen.1001012	null	[ [ "Estrogen exposure is critical for the development of both breast and endometrial cancers and represents the most well-established risk factors for both diseases .", "Estrogen is a metabolic product whose circulating level is determined by de novo synthesis , conversion from other steroid hormones , and m...	[ "Despite the central role of estrogen exposure in breast and endometrial cancer development and numerous studies of genes in the estrogen metabolic pathway , polymorphisms within the pathway have not been consistently associated with these cancers .", "We posit that this is due to the complexity of multiple weak ...	[ "Estrogen exposure is the most important risk factor for breast and endometrial cancers .", "Genetic variation of the genes involved in estrogen metabolism has , however , not been consistently associated with these two cancers .", "We posited that the genetic risk associated with the estrogen metabolic genes i...	2010
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "immunology/cellular microbiology and pathogenesis", "respiratory medicine/respiratory infections", "infectious diseases/neglected tropical diseases", "microbiology/innate immunity", "pathology/histopathology", "immunology/innate immunity", "critical care and emergency medicine/sepsis and multiple organ...	Expression and Function of Macrophage Migration Inhibitory Factor (MIF) in Melioidosis	journal.pntd.0000605	null	[ [ "Macrophage migration inhibitory factor ( MIF ) was one of the first cytokines to be discovered almost half a century ago [1]–[4] .", "Since then MIF has emerged as a pivotal mediator of innate immunity in various inflammatory diseases such as rheumatoid arthritis and atherosclerosis [5] , [6] and is cons...	[ "Macrophage migration inhibitory factor ( MIF ) has emerged as a pivotal mediator of innate immunity and has been shown to be an important effector molecule in severe sepsis .", "Melioidosis , caused by Burkholderia pseudomallei , is an important cause of community-acquired sepsis in Southeast-Asia .", "We aime...	[ "Melioidosis is a severe tropical infection caused by the bacterium Burkholderia pseudomallei .", "B . pseudomallei is the major cause of community-acquired septicemia in northeast Thailand with a mortality rate in severe cases of around 40% Little is known , however , about the mechanisms of the host defense to ...	2010
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "medicine", "infectious diseases", "test evaluation", "diagnostic medicine", "african trypanosomiasis", "neglected tropical diseases", "parasitic diseases" ]	Identification of Mimotopes with Diagnostic Potential for Trypanosoma brucei gambiense Variant Surface Glycoproteins Using Human Antibody Fractions	journal.pntd.0001682	null	[ [ "The chronic form of sleeping sickness or human African trypanosomiasis ( HAT ) in West and Central Africa is caused by the protozoan parasite Trypanosoma brucei ( T . b . ) gambiense while T . b . rhodesiense causes a more fulminant , acute form in East and Southern Africa .", "Both subspecies of T . bru...	[ "At present , screening of the population at risk for gambiense human African trypanosomiasis ( HAT ) is based on detection of antibodies against native variant surface glycoproteins ( VSGs ) of Trypanosoma brucei ( T . b . ) gambiense .", "Drawbacks of these native VSGs include culture of infective T . b . gambi...	[ "Control of the chronic form of sleeping sickness or gambiense human African trypanosomiasis ( HAT ) consists of accurate diagnosis followed by treatment .", "We aim to replace the native variant surface glycoprotein ( VSG ) parasite antigens that are presently used in most antibody detection tests with peptides ...	2012
[ "Introduction", "Materials and methods", "Results", "Discussion" ]	[ "medicine and health sciences", "statistics", "influenza", "geographical regions", "atmospheric science", "temperate regions", "simulation and modeling", "seasons", "mathematics", "forecasting", "regional geography", "humidity", "research and analysis methods", "public and occupational hea...	Development and validation of influenza forecasting for 64 temperate and tropical countries	journal.pcbi.1006742	null	[ [ "Forecasting is an important tool in a number of fields , including weather and climate [1–3] , agriculture [4 , 5] , air quality [6 , 7] , and consumer activity [8–10] .", "When operationalized for use in real time , predictions from probabilistic forecasts can be used in decision-making to inform , for ...	[ "Accurate forecasts of influenza incidence can be used to inform medical and public health decision-making and response efforts .", "However , forecasting systems are uncommon in most countries , with a few notable exceptions .", "Here we use publicly available data from the World Health Organization to generat...	[ "Influenza is responsible for an estimated 3–5 million cases and 300–650 , 000 deaths each year worldwide .", "If produced early enough , accurate forecasts of influenza activity could guide public health practitioners and medical professionals in preparing for an outbreak , reducing the subsequent morbidity and ...	2019
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine", "infectious diseases", "model organisms", "immunology", "biology", "microbiology", "molecular cell biology" ]	Wall Teichoic Acids of Staphylococcus aureus Limit Recognition by the Drosophila Peptidoglycan Recognition Protein-SA to Promote Pathogenicity	journal.ppat.1002421	null	[ [ "The complex cell surface of bacteria has been directly or indirectly associated with different strategies that bacterial pathogens use to interact with the host .", "These include acquisition of specific adhesion factors , formation of biofilms , adaptation to an intracellular environment , production of...	[ "The cell wall of Gram-positive bacteria is a complex network of surface proteins , capsular polysaccharides and wall teichoic acids ( WTA ) covalently linked to Peptidoglycan ( PG ) .", "The absence of WTA has been associated with a reduced pathogenicity of Staphylococcus aureus ( S . aureus ) .", "Here , we a...	[ "Gram-positive bacteria such as the opportunistic pathogen Staphylococcus aureus have their cell wall exposed to the environment found within a host .", "Following an infection these bacteria need to find ways to evade or reduce recognition by the host in order to survive and potentially proliferate .", "The ce...	2011
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "cell physiology", "classical mechanics", "fluid mechanics", "condensed matter physics", "anisotropy", "surface tension", "geometry", "aspect ratio", "simulation and modeling", "cell polarity", "developmental biology", "mathematics", "materials science", "damage mechanics", "embryos", ...	Filopodial-Tension Model of Convergent-Extension of Tissues	journal.pcbi.1004952	null	[ [ "Embryonic development requires numerous changes in tissue morphology .", "Convergent-extension ( CE ) is a basic tissue shape change [1–9] , during which cells in an epithelial sheet rearrange to narrow ( converge ) the tissue along one planar axis while lengthening ( extending ) it along the perpendicul...	[ "In convergent-extension ( CE ) , a planar-polarized epithelial tissue elongates ( extends ) in-plane in one direction while shortening ( converging ) in the perpendicular in-plane direction , with the cells both elongating and intercalating along the converging axis .", "CE occurs during the development of most ...	[ "The development of an embryo from a fertilized egg to an adult organism requires not only cell proliferation and differentiation , but also numerous types of tissue restructuring .", "The development of a relatively round initial embryo into one elongated along its rostral-caudal axis involves coordinated tissue...	2016
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "united states", "invertebrates", "dengue virus", "medicine and health sciences", "pathology and laboratory medicine", "pathogens", "variant genotypes", "geographical locations", "microbiology", "animals", "genetic mapping", "north america", "viruses", "rna viruses", "infectious disease ...	Quantification of permethrin resistance and kdr alleles in Florida strains of Aedes aegypti (L.) and Aedes albopictus (Skuse)	journal.pntd.0006544	null	[ [ "Local vector control programs play a part in public health .", "In many countries , these programs serve as the primary defense against the spread of several mosquito-borne diseases .", "Effective Integrated Vector Management ( IVM ) programs rely on surveillance information coupled with multiple vec...	[ "Recent outbreaks of locally transmitted dengue and Zika viruses in Florida have placed more emphasis on integrated vector management plans for Aedes aegypti ( L . ) and Aedes albopictus Skuse .", "Adulticiding , primarily with pyrethroids , is often employed for the immediate control of potentially arbovirus-inf...	[ "Aedes aegypti ( Yellow-fever mosquito ) and Aedes albopictus ( Asian Tiger mosquito ) can vector a variety of arboviruses that cause diseases and are thus a public health concern .", "Pyrethroid insecticide resistance is common in Ae .", "aegypti in many locations worldwide and can adversely affect vector cont...	2018
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "medicine and health sciences", "body fluids", "pathology and laboratory medicine", "infectious disease epidemiology", "geographical locations", "signs and symptoms", "infectious disease control", "africa", "infectious diseases", "geography", "epidemiology", "people and places", "nausea", ...	Contact tracing performance during the Ebola epidemic in Liberia, 2014-2015	journal.pntd.0006762	null	[ [ "In March 2014 , Liberia detected its first cases of Ebola virus disease ( EVD ) in Lofa , a northern county bordering Guinea and Sierra Leone [1] .", "The Liberian Ministry of Health ( MOH ) ( formerly Ministry of Health and Social Welfare ) established a national task force and initiated control efforts...	[ "During the Ebola virus disease ( EVD ) epidemic in Liberia , contact tracing was implemented to rapidly detect new cases and prevent further transmission .", "We describe the scope and characteristics of contact tracing in Liberia and assess its performance during the 2014–2015 EVD epidemic .", "We performed a...	[ "Contact tracing is comprised of three main steps: identifying , listing , and monitoring persons who have been exposed to infected individuals , with the goal of rapidly diagnosing and treating new cases and preventing further spread of infection .", "This approach has been used to control transmission of infect...	2018
[ "Introduction" ]	[ "death rates", "invertebrates", "medicine and health sciences", "geographical locations", "animals", "developmental biology", "molecular biology techniques", "population biology", "insect vectors", "africa", "research and analysis methods", "infectious diseases", "cameroon", "agrochemicals...	Culex species diversity, susceptibility to insecticides and role as potential vector of Lymphatic filariasis in the city of Yaoundé, Cameroon	journal.pntd.0007229	null	[ [ "Study site- The study was conducted in Yaoundé ( 03°52’N; 11°31’E ) , the capital city of Cameroon from March to December 2017 .", "The city has a population estimated at 2 . 8 million inhabitants .", "Yaoundé belongs to Guinean subequatorial climate type , characterized by four distinct seasons: the...	[ "Culex species are widespread across Cameroon and responsible for high burden of nuisance in most urban settings .", "However , despite their high nuisance , they remain less studied compared to anophelines .", "The present study aimed to assess Culex species distribution , susceptibility to insecticide , biono...	[ "Culex species are highly prevalent in both urban and rural settings in Cameroon and are responsible for high nuisance and transmission of pathogens such as Wuchereria bancrofti and arbovirus .", "Despite the important epidemiological role , that Culex could play , they are still less studied .", "The current s...	2019
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "b vitamins", "carbohydrate metabolism", "genome-wide association studies", "medicine and health sciences", "body fluids", "chemical compounds", "carbohydrates", "glucose metabolism", "organic compounds", "glucose", "glycobiology", "genome analysis", "lipids", "genomics", "chemistry", ...	Organic cation transporter 1 (OCT1) modulates multiple cardiometabolic traits through effects on hepatic thiamine content	journal.pbio.2002907	null	[ [ "Hepatic energy metabolism is a major determinant of systemic glucose and lipid levels as well as total body adiposity , which in turn are key risk factors for cardiovascular and metabolic diseases [1 , 2] .", "Genome-wide association studies ( GWAS ) have provided a wealth of information on the genes and...	[ "A constellation of metabolic disorders , including obesity , dysregulated lipids , and elevations in blood glucose levels , has been associated with cardiovascular disease and diabetes .", "Analysis of data from recently published genome-wide association studies ( GWAS ) demonstrated that reduced-function polymo...	[ "The liver is the major organ for glucose and lipid metabolism; impairment in liver energy metabolism is often found in metabolic disorders .", "Traditionally , excesses in macronutrients ( fat and glucose ) are linked to the development of metabolic disorders .", "Our study provides evidence that imbalances in...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "sequence analysis", "major histocompatibility complex", "immunology", "biology", "computational biology" ]	Proteome Sampling by the HLA Class I Antigen Processing Pathway	journal.pcbi.1002517	null	[ [ "Major histocompatibility complex ( MHC ) class I molecules play a crucial role in the adaptive immune response of higher vertebrates .", "These molecules , in humans referred to as human leukocyte antigen ( HLA ) class I molecules , bind peptides derived from endogenous proteins of host or , in the case ...	[ "The peptide repertoire that is presented by the set of HLA class I molecules of an individual is formed by the different players of the antigen processing pathway and the stringent binding environment of the HLA class I molecules .", "Peptide elution studies have shown that only a subset of the human proteome is...	[ "HLA class I molecules are expressed on the cell surface of almost all cells of the human body in complex with short fragments ( peptides ) of cytosolic proteins , thereby providing a snapshot of the intracellular state of a cell to circulating CD8+ T cells .", "Several processes are involved in shaping the pepti...	2012
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "biophysics", "biophysics/theory and simulation", "biophysics/biomacromolecule-ligand interactions" ]	Predicting Important Residues and Interaction Pathways in Proteins Using Gaussian Network Model: Binding and Stability of HLA Proteins	journal.pcbi.1000845	null	[ [ "Transfer of information between two points in a protein is a fundamental problem relating to function [1] , [2] .", "Fluctuations of residues in the native protein are the essential determinants of information transfer .", "The three dimensional native conformation or the topology of a protein determ...	[ "A statistical thermodynamics approach is proposed to determine structurally and functionally important residues in native proteins that are involved in energy exchange with a ligand and other residues along an interaction pathway .", "The structure-function relationships , ligand binding and allosteric activitie...	[ "We propose a statistical thermodynamics model for determining structurally and functionally important residues in ligand-protein interactions .", "Our method identifies the path that the protein uses in transferring information from one point to the other .", "We show that a few energetically active residues a...	2010
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "animal models", "mutagenesis", "developmental biology", "zebrafish", "animal genetics", "genetic mutation", "organism development", "model organisms", "genetic screens", "genetics", "biology", "anatomy and physiology", "electrophysiology", "morphogenesis", "pattern formation", "limb d...	Bioelectric Signaling Regulates Size in Zebrafish Fins	journal.pgen.1004080	null	[ [ "Organ growth is a complex process that requires attaining not only a certain shape but also an appropriate size .", "The maintenance of proper proportions between organs is tightly regulated [1] .", "The growth of a structure at a different rate with respect to the rest of the body results in changes...	[ "The scaling relationship between the size of an appendage or organ and that of the body as a whole is tightly regulated during animal development .", "If a structure grows at a different rate than the rest of the body , this process is termed allometric growth .", "The zebrafish another longfin ( alf ) mutant ...	[ "The proportions of an animal can change during its lifetime .", "This often occurs through the phenomenon of relative growth , or allometry .", "In humans , for example , the head grows at a lower rate than the body resulting in a change in proportion between children and adults .", "The regulation of size a...	2014
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[]	Eco-Bio-Social Determinants for House Infestation by Non-domiciliated Triatoma dimidiata in the Yucatan Peninsula, Mexico	journal.pntd.0002466	null	[ [ "Chagas disease is a vector-borne disease of major importance in the Americas where it is endemic .", "It affects an estimated 8–10 million people , and nearly 25 millions are at risk of infection [1] .", "In terms of disability-adjusted life years ( DALYs ) , and with a burden of 0 . 7 million DALYs ...	[ "Chagas disease is a vector-borne disease of major importance in the Americas .", "Disease prevention is mostly limited to vector control .", "Integrated interventions targeting ecological , biological and social determinants of vector-borne diseases are increasingly used for improved control .", "We investig...	[ "Chagas disease is a parasitic disease of major importance in the Americas , transmitted by triatomine insects .", "Integrated control interventions targeting a combination of factors associated with the presence of the insect vectors are increasingly investigated for improved control .", "Here we identified th...	2013
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "systems biology", "visual system", "computer science", "theoretical biology", "computational neuroscience", "single neuron function", "biology", "computational biology", "sensory systems", "neuroscience", "genetics and genomics" ]	A Multi-Compartment Model for Interneurons in the Dorsal Lateral Geniculate Nucleus	journal.pcbi.1002160	null	[ [ "The dorsal lateral geniculate nucleus ( dLGN ) receives input from retinal ganglion cells and transmits processed information to visual cortex .", "About 75–80% of the neurons in the dLGN are thalamocortical ( TC ) neurons , also called relay neurons , as they relay information from the retina to the cor...	[ "GABAergic interneurons ( INs ) in the dorsal lateral geniculate nucleus ( dLGN ) shape the information flow from retina to cortex , presumably by controlling the number of visually evoked spikes in geniculate thalamocortical ( TC ) neurons , and refining their receptive field .", "The INs exhibit a rich variety ...	[ "The dorsal lateral geniculate nucleus ( dLGN ) is a part of the visual thalamus .", "This region contains two types of neurons: thalamocortical neurons and local interneurons .", "Thalamocortical neurons receive information from the retina and transmit information to visual cortex .", "The interneurons regul...	2011
[ "Introduction", "Results and discussion", "Materials and methods" ]	[ "medicine and health sciences", "body fluids", "gut bacteria", "microbiome", "quantitative trait loci", "population genetics", "bile", "microbiology", "genetic mapping", "population biology", "microbial genetics", "bacteria", "microbial genomics", "genetic polymorphism", "medical microbi...	Genetic determinants of gut microbiota composition and bile acid profiles in mice	journal.pgen.1008073	null	[ [ "The intestinal microbiota has profound effects on host physiology and health [1–3] .", "The composition of the gut microbiota is governed by a combination of environmental factors , including diet , drugs , maternal seeding , cohabitation , and host genetics [4–7] .", "Together , these factors cause ...	[ "The microbial communities that inhabit the distal gut of humans and other mammals exhibit large inter-individual variation .", "While host genetics is a known factor that influences gut microbiota composition , the mechanisms underlying this variation remain largely unknown .", "Bile acids ( BAs ) are hormones...	[ "Inter-individual variation in the composition of the intestinal microbiota can in part be attributed to host genetics .", "However , the specific genes and genetic variants underlying differences in the microbiota remain largely unknown .", "To address this , we profiled the fecal microbiota composition of 400...	2019
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine", "cell death", "infectious diseases", "molecular cell biology", "cell biology", "biology", "microbiology", "host-pathogen interaction" ]	Monocytes Regulate the Mechanism of T-cell Death by Inducing Fas-Mediated Apoptosis during Bacterial Infection	journal.ppat.1002814	null	[ [ "Innate immunity is critical for the rapid recognition and response to pathogenic micro-organisms [1] .", "A complex relationship exists between innate immune responses and T-cells .", "Innate immune responses recruit and activate T-cells at sites of infection but T-cells in turn regulate phagocyte fu...	[ "Monocytes and T-cells are critical to the host response to acute bacterial infection but monocytes are primarily viewed as amplifying the inflammatory signal .", "The mechanisms of cell death regulating T-cell numbers at sites of infection are incompletely characterized .", "T-cell death in cultures of periphe...	[ "T-cells are important contributors to the early host response to pneumonia , but their numbers must be tightly regulated to limit inflammatory lung injury .", "Cell death regulates T-cell numbers but the mechanism of execution influences the inflammatory cost with apoptosis viewed as predominantly anti-inflammat...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "virology/emerging viral diseases", "cell biology/membranes and sorting", "virology", "microbiology", "microbiology/cellular microbiology and pathogenesis", "virology/host invasion and cell entry" ]	Cellular Entry of Ebola Virus Involves Uptake by a Macropinocytosis-Like Mechanism and Subsequent Trafficking through Early and Late Endosomes	journal.ppat.1001110	null	[ [ "Zaire ebolavirus ( ZEBOV , Genbank:AF086833 ) , a member of the family Filoviridae , genus Filovirus , causes a highly fatal hemorrhagic fever in humans and non-human primates .", "Over the past three decades numerous human outbreaks have occurred in Central Africa involving hundreds of cases with fatali...	[ "Zaire ebolavirus ( ZEBOV ) , a highly pathogenic zoonotic virus , poses serious public health , ecological and potential bioterrorism threats .", "Currently no specific therapy or vaccine is available .", "Virus entry is an attractive target for therapeutic intervention .", "However , current knowledge of th...	[ "Filoviruses , including Zaire ebolavirus ( ZEBOV ) , are among the most pathogenic viruses known .", "Our understanding of how these viruses enter into host cells is very limited .", "A deeper understanding of this process would enable the design of better targeted antiviral therapies .", "This study defines...	2010
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Translation Enhancing ACA Motifs and Their Silencing by a Bacterial Small Regulatory RNA	journal.pgen.1004026	null	[ [ "A relevant chapter in the expanding field of RNA-mediated gene regulation is devoted to the activities of multi-target trans-encoded small RNAs in bacteria .", "Acting in concert with chaperon protein Hfq , these RNA regulators function by base-pairing with short , often imperfectly complementary sequenc...	[ "GcvB is an archetypal multi-target small RNA regulator of genes involved in amino acid uptake or metabolism in enteric bacteria .", "Included in the GcvB regulon is the yifK locus , encoding a conserved putative amino acid transporter .", "GcvB inhibits yifK mRNA translation by pairing with a sequence immediat...	[ "The majority of small RNA ( sRNA ) regulators in bacteria act by inhibiting translation initiation in target messenger RNAs .", "The study of this regulatory mechanism not only allows a better understanding of sRNA function but it can also provide new insight into aspects of the translation initiation process th...	2014
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "medicine and health sciences", "immune physiology", "body fluids", "immunology", "autoantibodies", "alternative splicing", "protein expression", "bioassays and physiological analysis", "molecular biology techniques", "antibodies", "research and analysis methods", "immune system proteins", "...	Identification of a Sjögren's syndrome susceptibility locus at OAS1 that influences isoform switching, protein expression, and responsiveness to type I interferons	journal.pgen.1006820	null	[ [ "Sjögren’s syndrome ( SS ) is a common systemic autoimmune disease with a prevalence rate ( ~0 . 7% of European Americans ) second only to rheumatoid arthritis ( RA ) [1] .", "SS is distinguished by immune cell infiltration , functional destruction , and irreversible dysfunction of exocrine glands , most ...	[ "Sjögren’s syndrome ( SS ) is a common , autoimmune exocrinopathy distinguished by keratoconjunctivitis sicca and xerostomia .", "Patients frequently develop serious complications including lymphoma , pulmonary dysfunction , neuropathy , vasculitis , and debilitating fatigue .", "Dysregulation of type I interfe...	[ "Sjögren’s syndrome ( SS ) is a common autoimmune condition where immune cells infiltrate moisture-producing glands , leading to dryness typically in the eyes and mouth .", "SS patients also manifest debilitating fatigue as well as other diseases in liver , lung , kidney , and skin .", "The cause of this comple...	2017
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "medicine and health sciences", "crystal structure", "protein interactions", "pathology and laboratory medicine", "pathogens", "condensed matter physics", "microbiology", "viruses", "rna viruses", "crystallography", "physical chemistry", "chemical properties", "infectious diseases", "solid...	Convergent evolution in the mechanisms of ACBD3 recruitment to picornavirus replication sites	journal.ppat.1007962	null	[ [ "Enteroviruses are small RNA viruses that belong to the Enterovirus genus of the Picornaviridae family .", "They are non-enveloped positive-sense single-stranded RNA viruses with icosahedral capsids , currently consisting of 15 species .", "Seven enterovirus species ( Enterovirus A-D and Rhinovirus A-...	[ "Enteroviruses , members of the family of picornaviruses , are the most common viral infectious agents in humans causing a broad spectrum of diseases ranging from mild respiratory illnesses to life-threatening infections .", "To efficiently replicate within the host cell , enteroviruses hijack several host factor...	[ "Enteroviruses are the most common viruses infecting humans .", "They cause a broad spectrum of diseases ranging from common cold to life-threatening diseases , such as poliomyelitis .", "To date , no effective antiviral therapy for enteroviruses has been approved yet .", "To ensure efficient replication , en...	2019
[ "Introduction", "Methods", "Discussion" ]	[ "biophysics/theory and simulation", "biochemistry/theory and simulation" ]	Polarizable Water Model for the Coarse-Grained MARTINI Force Field	journal.pcbi.1000810	null	[ [ "Since the first introduction of physics-based coarse-grained ( CG ) models in computational biology [1] , CG models have become increasingly popular in the simulation of complex biological systems [2] .", "They significantly reduce the computational complexity in comparison to all-atom ( AA ) models and ...	[ "Coarse-grained ( CG ) simulations have become an essential tool to study a large variety of biomolecular processes , exploring temporal and spatial scales inaccessible to traditional models of atomistic resolution .", "One of the major simplifications of CG models is the representation of the solvent , which is ...	[ "Many biomolecular processes involve charged species moving between regions of high polarity , such as the water phase , and regions of lower polarity , such as the lipid membrane .", "Due to the change in electrostatic screening between these two environments , the strength of the interactions between the moving...	2010
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "medicine", "biochemistry", "infectious diseases", "nucleic acids", "neglected tropical diseases", "dna", "biology" ]	Sensitive and Specific Target Sequences Selected from Retrotransposons of Schistosoma japonicum for the Diagnosis of Schistosomiasis	journal.pntd.0001579	null	[ [ "Schistosomiasis is caused by Schistosoma haematobium , S . mansoni , S . japonicum , and less frequently , S . mekongi and S . intercalatum .", "It occurs in the tropics and subtropics and it is among the most important parasitic diseases worldwide , with a significant socio-economic impact [1] .", "...	[ "Schistosomiasis japonica is a serious debilitating and sometimes fatal disease .", "Accurate diagnostic tests play a key role in patient management and control of the disease .", "However , currently available diagnostic methods are not ideal , and the detection of the parasite DNA in blood samples has turned ...	[ "Schistosomiasis remains a serious parasitic disease worldwide .", "Adequate case-finding is important and crucial for the effective control programs as schistosomiasis control programs are chiefly based on treatment of infected populations .", "However , the currently available diagnostic assays are not ideal ...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "model organisms", "cell biology", "genetics", "biology and life sciences", "organisms", "research and analysis methods" ]	It's All in Your Mind: Determining Germ Cell Fate by Neuronal IRE-1 in C. elegans	journal.pgen.1004747	null	[ [ "Apoptosis , also known as programed cell death ( PCD ) , is a highly conserved fundamental cellular process that provides a self-elimination mechanism for the removal of unwanted cells .", "PCD is critical for organ development , tissue remodeling , cellular homeostasis and elimination of abnormal and da...	[ "The C . elegans germline is pluripotent and mitotic , similar to self-renewing mammalian tissues .", "Apoptosis is triggered as part of the normal oogenesis program , and is increased in response to various stresses .", "Here , we examined the effect of endoplasmic reticulum ( ER ) stress on apoptosis in the C...	[ "Cells in the C . elegans germline undergo programmed cell death as part of the normal developmental program and in response to various stresses .", "Here , we discovered that more germ cells undergo programmed cell death under stress conditions associated with the accumulation of misfolded proteins in the endopl...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "immunology/immunomodulation", "immunology/immune response", "immunology/innate immunity", "surgery/transplantation", "immunology", "evolutionary biology", "neuroscience/neurobiology of disease and regeneration", "immunology/autoimmunity", "immunology/leukocyte activation" ]	Neo-Lymphoid Aggregates in the Adult Liver Can Initiate Potent Cell-Mediated Immunity	journal.pbio.1000109	Are lymph nodes really essential for successful immunizations? We found that the liver can compensate for missing lymphoid structures in initiating cellular, but not antibody-mediated, immunity.	[ [ "Secondary lymphoid tissues ( SLTs ) are highly organized structures with defined compartments consisting of B and T cell areas .", "These distinct locations support the rapid circulation and concentration of Ag and the interaction of Ag-presenting cells ( APCs ) with lymphocytes .", "Prevailing dogma...	[ "Subcutaneous immunization delivers antigen ( Ag ) to local Ag-presenting cells that subsequently migrate into draining lymph nodes ( LNs ) .", "There , they initiate the activation and expansion of lymphocytes specific for their cognate Ag .", "In mammals , the structural environment of secondary lymphoid tiss...	[ "Lymph nodes ( LNs ) are believed to be the most important tissues initiating immune responses by facilitating the activation of T and B lymphocytes .", "Mice lacking such LNs ( called alymphoplastic ) are severely immune compromised and resistant to immunizations .", "We discovered that the immune-deficiency o...	2009
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "theoretical biology", "biology" ]	Complex Spatial Dynamics of Oncolytic Viruses In Vitro: Mathematical and Experimental Approaches	journal.pcbi.1002547	null	[ [ "Oncolytic viruses replicate selectively in tumor cells and have been explored as a targeted treatment approach against cancers [1] , [2] , [3] , [4] , [5] , [6] , [7] , [8] , [9] , [10] , [11] , [12] , [13] , [14] , [15] .", "In principle an oncolytic virus will spread though the tumor cell population an...	[ "Oncolytic viruses replicate selectively in tumor cells and can serve as targeted treatment agents .", "While promising results have been observed in clinical trials , consistent success of therapy remains elusive .", "The dynamics of virus spread through tumor cell populations has been studied both experimenta...	[ "Traditional chemotherapy of cancers is characterized by strong side effects , while showing a low success rate in the long term control of tumors .", "Besides small molecule inhibitors , which have shown great promise , oncolytic viruses present an emerging specific treatment approach .", "They are engineered ...	2012
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "medicine and health sciences", "biological cultures", "brassica", "optimization", "model organisms", "systems science", "mathematics", "pharmacology", "plants", "drug metabolism", "mapk signaling cascades", "research and analysis methods", "arabidopsis thaliana", "computer and information...	Structural Identifiability of Dynamic Systems Biology Models	journal.pcbi.1005153	null	[ [ "Mathematical modelling has become a fundamental tool in present day biology [1] , and system identification is one of the key tasks of this process [2] .", "Building a dynamic model usually requires establishing the values of some unknown parameters , which raises the issue of parameter identifiability [...	[ "A powerful way of gaining insight into biological systems is by creating a nonlinear differential equation model , which usually contains many unknown parameters .", "Such a model is called structurally identifiable if it is possible to determine the values of its parameters from measurements of the model output...	[ "Advances in computing power have facilitated the development of increasingly larger dynamic models of biological processes , which usually have many unknown parameters .", "Often times , such models contain parameters that are structurally unidentifiable , i . e . , they cannot be uniquely determined from experi...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods", "Supporting Information" ]	[ "diabetes and endocrinology", "computational biology", "genetics and genomics", "cardiovascular disorders" ]	Mapping the Genetic Architecture of Gene Expression in Human Liver	journal.pbio.0060107	Identifying changes in DNA that associate with changes in gene expression in human tissues elucidates the genetic architecture of gene expression in human populations and enables the direct identification of functionally supported candidate susceptibility genes in genomic regions associated with disease.	[ [ "Recent large-scale , genome-wide association studies have now delivered a number of novel findings across a diversity of diseases , including age-related macular degeneration [1–3] , heart disease [4 , 5] , host control of HIV-1 [6] , type I and II diabetes [7 , 8] , and obesity [9] .", "However , despit...	[ "Genetic variants that are associated with common human diseases do not lead directly to disease , but instead act on intermediate , molecular phenotypes that in turn induce changes in higher-order disease traits .", "Therefore , identifying the molecular phenotypes that vary in response to changes in DNA and tha...	[ "Genome-wide association studies seek to identify regions of the genome in which changes in DNA in a given population are correlated with disease , drug response , or other phenotypes of interest .", "However , changes in DNA that associate with traits like common human diseases do not lead directly to disease , ...	2008
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "acoustics", "medicine and health sciences", "engineering and technology", "audio signal processing", "visual signals", "signal processing", "brain electrophysiology", "social sciences", "electrophysiology", "neuroscience", "clinical medicine", "brain mapping", "bioassays and physiological a...	To integrate or not to integrate: Temporal dynamics of hierarchical Bayesian causal inference	journal.pbio.3000210	This electroencephalography-based study temporally resolves how the human brain uses Bayesian Causal Inference in perception, unravelling how the brain arbitrates between information integration and segregation by dynamically encoding multiple perceptual estimates.	[ [ "In our natural environment , our senses are exposed to a barrage of sensory signals: the sight of a rapidly approaching truck , its looming motor noise , the smell of traffic fumes .", "How the brain effortlessly merges these signals into a seamless percept of the environment remains unclear .", "The...	[ "To form a percept of the environment , the brain needs to solve the binding problem—inferring whether signals come from a common cause and are integrated or come from independent causes and are segregated .", "Behaviourally , humans solve this problem near-optimally as predicted by Bayesian causal inference; but...	[ "The ability to tell whether various sensory signals come from the same or different sources is essential for forming a coherent percept of the environment .", "For example , when crossing a busy road at dusk , seeing and hearing an approaching car helps us estimate its location better , but only if its visual im...	2019
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "in vitro", "none", "molecular biology", "computational biology" ]	Mechanochemical Coupling in the Myosin Motor Domain. I. Insights from Equilibrium Active-Site Simulations	journal.pcbi.0030021	null	[ [ "Coupling between chemical events and conformational transitions is crucial for the function of many biomolecules [1] .", "Notable examples include molecular motors [2–4] , signaling proteins [5] , and membrane transporters [6] , in which large-scale conformational transitions are often coupled to the bin...	[ "Although the major structural transitions in molecular motors are often argued to couple to the binding of Adenosine triphosphate ( ATP ) , the recovery stroke in the conventional myosin has been shown to be dependent on the hydrolysis of ATP .", "To obtain a clearer mechanistic picture for such “mechanochemical...	[ "The hydrolysis of Adenosine triphosphate ( ATP ) provides the energy for most life processes , including the motility of molecular motors .", "How the chemical energy of hydrolysis is converted into mechanical work in these fascinating “nanomachines” is a central question that has only been answered in an outlin...	2007
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "bacteriology", "gram negative bacteria", "medicine and health sciences", "pathology and laboratory medicine", "host-pathogen interactions", "medical microbiology", "microbial pathogens", "biology and life sciences", "microbiology", "pathogenesis", "bacterial pathogens" ]	Cytolethal Distending Toxins Require Components of the ER-Associated Degradation Pathway for Host Cell Entry	journal.ppat.1004295	null	[ [ "Cytolethal distending toxins ( CDTs ) are produced by a variety of Gram-negative pathogens including the oral pathogen Aggregatibacter actinomycetemcomitans , the sexually transmitted pathogen Haemophilus ducreyi , and the gastrointestinal pathogens , Escherichia coli and Campylobacter jejuni .", "These ...	[ "Intracellular acting protein exotoxins produced by bacteria and plants are important molecular determinants that drive numerous human diseases .", "A subset of these toxins , the cytolethal distending toxins ( CDTs ) , are encoded by several Gram-negative pathogens and have been proposed to enhance virulence by ...	[ "Cytolethal distending toxins ( CDTs ) are produced by several bacterial pathogens and increase the ability of these bacteria to cause disease .", "After being taken up by host cells , CDTs are trafficked to the endoplasmic reticulum ( ER ) where they must translocate across the ER membrane to gain access to thei...	2014
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "genetics and genomics/genetics of disease", "genetics and genomics/complex traits", "genetics and genomics", "genetics and genomics/population genetics" ]	Application of a New Method for GWAS in a Related Case/Control Sample with Known Pedigree Structure: Identification of New Loci for Nephrolithiasis	journal.pgen.1001281	null	[ [ "Nephrolithiasis is a multifactorial disorder of complex etiology characterized by the presence of stones in the urinary tract .", "Kidney stones are a common disorder , with a prevalence of urinary calculi between 4% and 10% in the adult population , with an increasing incidence in Western societies [1] ...	[ "In contrast to large GWA studies based on thousands of individuals and large meta-analyses combining GWAS results , we analyzed a small case/control sample for uric acid nephrolithiasis .", "Our cohort of closely related individuals is derived from a small , genetically isolated village in Sardinia , with well-c...	[ "There are a number of factors that contribute to renal stone formation , including diet and obesity , specific drugs , other diseases , climate changes , metabolic disorders , and genetic predisposition .", "In this article , we focus on identifying genomic regions that may be involved with nephrolithiasis assoc...	2011
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[]	Ecological and Sociodemographic Determinants of House Infestation by Triatoma infestans in Indigenous Communities of the Argentine Chaco	journal.pntd.0003614	null	[ [ "The strong association between neglected tropical diseases ( NTDs ) , poverty and particular combinations of ecological , social , political and economic determinants explains the occurrence of global hotspots of NTDs [1] .", "One of such hotspots occurs in the Gran Chaco ecoregion in South America , whe...	[ "The Gran Chaco ecoregion , a hotspot for Chagas and other neglected tropical diseases , is home to >20 indigenous peoples .", "Our objective was to identify the main ecological and sociodemographic determinants of house infestation and abundance of Triatoma infestans in traditional Qom populations including a Cr...	[ "Indigenous peoples are especially affected by Chagas and other neglected tropical diseases .", "One of the most numerous ethnic groups in the Gran Chaco region of South America is the Qom ( Toba ) people .", "The living conditions of Qom households most likely differ substantially from those of Creoles , and t...	2015
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "medicine", "public health and epidemiology", "microbiology", "bacterial diseases", "emerging infectious diseases", "infectious disease control", "applied microbiology", "infectious diseases", "disease ecology", "environmental epidemiology", "epidemiology", "biology", "public health", "lep...	Rodent Abundance Dynamics and Leptospirosis Carriage in an Area of Hyper-Endemicity in New Caledonia	journal.pntd.0001361	null	[ [ "Leptospirosis is an endemic bacterial disease in many tropical and sub-tropical areas .", "Various Leptospira strains , maintained in different animal species , are excreted in the urine of asymptomatic chronically infected individuals [1]–[3] .", "Humans get infected when abraded skin or mucous memb...	[ "Widespread but particularly incident in the tropics , leptospirosis is transmitted to humans directly or indirectly by virtually any Mammal species .", "However , rodents are recognized as the most important reservoir .", "In endemic regions , seasonal outbreaks are observed during hot rainy periods .", "In ...	[ "In this study , we surveyed rodents and their Leptospira carriage in an area where human leptospirosis is hyper-endemic .", "We evidenced the well-known associations between specific rodent species and particular leptospires in both mice and rats .", "Overall , the observed Leptospira prevalence was in the ran...	2011
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "gene regulation", "enzymes", "regulatory proteins", "dna-binding proteins", "enzymology", "phosphatases", "dna transcription", "regulator genes", "transcription factors", "gene types", "molecular biology techniques", "mutagenesis and gene deletion techniques", "genetic interactions", "res...	The ability of transcription factors to differentially regulate gene expression is a crucial component of the mechanism underlying inversion, a frequently observed genetic interaction pattern	journal.pcbi.1007061	null	[ [ "Understanding the relationship between genotype and phenotype of an organism is a major challenge [1 , 2] .", "One of the difficulties for unravelling genotype-phenotype relationship has been genetic interactions , when combinations of mutations lead to phenotypic effects that are unexpected based on the...	[ "Genetic interactions , a phenomenon whereby combinations of mutations lead to unexpected effects , reflect how cellular processes are wired and play an important role in complex genetic diseases .", "Understanding the molecular basis of genetic interactions is crucial for deciphering pathway organization as well...	[ "The relationship between genotype and phenotype is one of the major challenges in biology .", "While many previous studies have identified genes involved in complex genetic diseases , there is still a gap between genotype and phenotype .", "One of the difficulties in filling this gap has been attributed to gen...	2019
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "evolutionary biology", "molecular biology", "genetics and genomics" ]	High Rate of Recent Transposable Element–Induced Adaptation in Drosophila melanogaster	journal.pbio.0060251	Transposable elements contributed substantially to the adaptation ofD. melanogaster to the out-of-Africa environments. The majority of these adaptive insertions are likely to be involved in regulatory changes.	[ [ "The recent years have seen a burst in studies searching for signatures of genetic adaptation in a variety of organisms , including natural populations and domesticated plants and animals [1–12] .", "These studies suggest that adaptation is a pervasive force in evolution .", "However , many fundamenta...	[ "Although transposable elements ( TEs ) are known to be potent sources of mutation , their contribution to the generation of recent adaptive changes has never been systematically assessed .", "In this work , we conduct a genome-wide screen for adaptive TE insertions in Drosophila melanogaster that have taken plac...	[ "Transposable elements ( TEs ) are present in virtually all species and often contribute a substantial fraction of the genome size .", "Understanding the functional roles , evolution , and population dynamics of TEs is essential to understanding genome evolution and function .", "Much of our knowledge about TE ...	2008
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "dermatology", "ecology and environmental sciences", "medicine and health sciences", "rivers", "pathology and laboratory medicine", "tropical diseases", "geographical locations", "bacterial diseases", "signs and symptoms", "aquatic environments", "bodies of water", "neglected tropical diseases...	Burden and Historical Trend of Buruli Ulcer Prevalence in Selected Communities along the Offin River of Ghana	journal.pntd.0004603	null	[ [ "Buruli ulcer ( BU ) is a necrotizing skin disease caused by Mycobacterium ulcerans [1] .", "The disease has been reported in over 30 countries worldwide , mainly in the tropics , but the brunt of it seems to be mainly experienced in West Africa with Côte d’Ivoire , Ghana , Benin and Cameroon reporting mo...	[ "Buruli ulcer ( BU ) is a neglected tropical skin disease caused by Mycobacterium ulcerans with more than two thirds of the global cases reported in West Africa .", "A nationwide active BU case search conducted in 1999 identified two health districts along the Offin River as two of the three most endemic district...	[ "Buruli ulcer ( BU ) is a tropical skin disease caused by Mycobacterium ulcerans and more than two thirds of the global cases reported in West Africa .", "The Offin has been considered the most endemic river valley in Ghana following a nationwide active case search conducted in 1999 .", "Here , we present findi...	2016
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "biology", "microbiology" ]	Administration of E2 and NS1 siRNAs Inhibit Chikungunya Virus Replication In Vitro and Protects Mice Infected with the Virus	journal.pntd.0002405	null	[ [ "Chikungunya virus ( CHIKV ) is a mosquito-transmitted alphavirus belonging to the family Togaviridae .", "CHIKV is responsible for an acute infection , characterized by high fever , arthralgia , myalgia , headache , and rash [1] , [2] , [3] .", "Although having immense medical importance , effective ...	[ "Chikungunya virus ( CHIKV ) has reemerged as a life threatening pathogen and caused large epidemics in several countries .", "So far , no licensed vaccine or effective antivirals are available and the treatment remains symptomatic .", "In this context , development of effective and safe prophylactics and thera...	[ "Despite having immense medical importance , still vaccine , chemoprophylactic , or effective therapeutic measures are not commercially available for chikungunya .", "Only strict attention to good infection control practices may prevent CHIKV infection .", "The pathogenic properties of CHIKV necessitate the dev...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "virology/virus evolution and symbiosis", "virology/animal models of infection", "virology/emerging viral diseases" ]	Genetic Compatibility and Virulence of Reassortants Derived from Contemporary Avian H5N1 and Human H3N2 Influenza A Viruses	journal.ppat.1000072	null	[ [ "The emergence of an influenza virus that will cause a pandemic is inevitable and therefore preparedness is mandatory .", "The new pandemic influenza virus is likely to carry a hemagglutinin ( HA ) gene other than the currently circulating H1 and H3 lineages in order to escape immunity in the human popula...	[ "The segmented structure of the influenza virus genome plays a pivotal role in its adaptation to new hosts and the emergence of pandemics .", "Despite concerns about the pandemic threat posed by highly pathogenic avian influenza H5N1 viruses , little is known about the biological properties of H5N1 viruses that m...	[ "The influenza pandemics of 1957 and 1968 were caused by hybrid viruses consisting of a mixture of human and avian influenza genes .", "The introduction of avian genes resulted in a sudden change of the virus surface antigens , allowing its worldwide spread due to lack of immunity in the population .", "The hig...	2008
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genetics of disease", "genome expression analysis", "medicine", "genome analysis tools", "infectious diseases", "bacterial diseases", "gene expression", "gene regulation", "genetics", "molecular genetics", "leprosy", "biology", "genomics", "neglected tropical diseases", "gene networks",...	Gene Set Signature of Reversal Reaction Type I in Leprosy Patients	journal.pgen.1003624	null	[ [ "Leprosy is a chronic human infectious disease caused by Mycobacterium leprae .", "If left untreated the disease results in pronounced skin deformities and nerve disabilities due to preferential invasion of macrophages and Schwann cells by M . leprae .", "Efforts by the World Health Organisation ( WHO...	[ "Leprosy reversal reactions type 1 ( T1R ) are acute immune episodes that affect a subset of leprosy patients and remain a major cause of nerve damage .", "Little is known about the relative importance of innate versus environmental factors in the pathogenesis of T1R .", "In a retrospective design , we evaluate...	[ "Leprosy type 1 reversal reactions ( T1R ) are an important cause of nerve damage in leprosy patients and accurate prediction of patients at increased risk of T1R is a major challenge of current leprosy control .", "The incidence of T1R differs widely from 6% to 67% of leprosy patients in different leprosy endemi...	2013
[ "Introduction", "Results/Discussion", "Materials and Methods" ]	[ "viruses", "homo (human)", "infectious diseases", "eukaryotes" ]	In Vitro Derived Dendritic Cells trans-Infect CD4 T Cells Primarily with Surface-Bound HIV-1 Virions	journal.ppat.0030004	null	[ [ "To ensure their survival , microbial pathogens have evolved strategies to subvert the action of cellular components of the host immune system , including dendritic cells ( DCs ) .", "DCs patrol peripheral mucosal sites , capturing and processing potential pathogens into antigenic peptides for presentatio...	[ "In the prevailing model of HIV-1 trans-infection , dendritic cells ( DCs ) capture and internalize intact virions and transfer these virions to interacting T cells at the virological synapse .", "Here , we show that HIV-1 virions transmitted in trans from in vitro derived DCs to T cells principally originate fro...	[ "Dendritic cells ( DCs ) patrol peripheral mucosal sites , capturing and processing potential pathogens into antigenic peptides for presentation to T cells of lymphoid organs , and thereby initiating an immune response .", "HIV-1 had been proposed to use DCs as “Trojan horses , ” hiding inside the DCs and survivi...	2007
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine and health sciences", "chemical compounds", "immunology", "biological cultures", "carbohydrates", "galactose", "organic compounds", "surgical and invasive medical procedures", "dna damage", "clinical medicine", "cell cultures", "dna", "hypersensitivity", "research and analysis me...	Tel1 and Rif2 Regulate MRX Functions in End-Tethering and Repair of DNA Double-Strand Breaks	journal.pbio.1002387	This study reveals novel roles for the checkpoint kinase Tel1/ATM and Rif2 in regulating the function of the MRX complex during repair of DNA double-strand breaks by nonhomologous end joining and homologous recombination.	[ [ "DNA double-strand breaks ( DSBs ) are among the most cytotoxic DNA lesions , because failure to repair them can lead to genome instability .", "DSBs can be repaired by either nonhomologous end joining ( NHEJ ) or homologous recombination ( HR ) .", "While NHEJ directly ligates the DNA ends , HR requi...	[ "The cellular response to DNA double-strand breaks ( DSBs ) is initiated by the MRX/MRN complex ( Mre11-Rad50-Xrs2 in yeast; Mre11-Rad50-Nbs1 in mammals ) , which recruits the checkpoint kinase Tel1/ATM to DSBs .", "In Saccharomyces cerevisiae , the role of Tel1 at DSBs remains enigmatic , as tel1Δ cells do not s...	[ "Many tumors contain mutations that confer defects in repairing DNA double-strand breaks ( DSBs ) .", "In both yeast and mammals , the MRX/MRN complex ( Mre11-Rad50-Xrs2 in yeast; Mre11-Rad50-Nbs1 in mammals ) plays critical functions in repairing a DSB by either nonhomologous end joining ( NHEJ ) or homologous r...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "oncology", "medicine", "cancer genetics", "breast tumors", "heredity", "genetics", "molecular genetics", "biology", "haploinsufficiency", "genetic testing", "cancers and neoplasms", "genetics and genomics", "human genetics" ]	Genetic Anticipation Is Associated with Telomere Shortening in Hereditary Breast Cancer	journal.pgen.1002182	null	[ [ "Genetic anticipation is the observation of progressively earlier age of onset or an increase of severity of clinical features of a genetic disorder as it is passed on to the next generation .", "The molecular mechanisms underlying anticipation are largely unknown , but it has been typically associated to...	[ "There is increasing evidence suggesting that short telomeres and subsequent genomic instability contribute to malignant transformation .", "Telomere shortening has been described as a mechanism to explain genetic anticipation in dyskeratosis congenita and Li-Fraumeni syndrome .", "Since genetic anticipation ha...	[ "The fact that accelerated telomere shortening accompanies different premature aging syndromes and seems to be associated with increased risk of cancer development prompted us to analyze the role of telomere length in hereditary breast cancer .", "In this study we found that telomeres of peripheral blood cells fr...	2011
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "blood cells", "flow cytometry", "innate immune system", "medicine and health sciences", "immune physiology", "cytokines", "immune cells", "pathology and laboratory medicine", "pathogens", "immunology", "microbiology", "salmonellosis", "epithelial cells", "bacterial diseases", "developme...	Crosstalk between leukocytes triggers differential immune responses against Salmonella enterica serovars Typhi and Paratyphi	journal.pntd.0007650	null	[ [ "Typhoid and paratyphoid fevers are known as enteric fevers and are caused by the intracellular Gram-negative bacteria Salmonella enterica serovars Typhi ( ST ) , Paratyphi A ( PA ) and Paratyphi B ( PB ) [1–4] .", "Enteric fevers are rare in industrialized countries with most infections occurring in mili...	[ "Enteric fevers , caused by the Salmonella enterica serovars Typhi ( ST ) , Paratyphi A ( PA ) and Paratyphi B ( PB ) , are life-threatening illnesses exhibiting very similar clinical symptoms but with distinct epidemiologies , geographical distributions and susceptibilities to antimicrobial treatment .", "Nevert...	[ "Enteric fevers are acute illnesses caused mainly by the Salmonella enterica serovars Typhi ( ST ) , Paratyphi A ( PA ) and Paratyphi B ( PB ) .", "The incidence of enteric fevers is very low in industrialized countries , with most infections occurring in military personnel and individuals traveling to endemic ar...	2019
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biomacromolecule-ligand interactions", "biophysic al simulations", "protein folding", "biophysics theory", "biology", "computational biology", "biophysics simulations", "biophysics" ]	Importance of Electrostatic Interactions in the Association of Intrinsically Disordered Histone Chaperone Chz1 and Histone H2A.Z-H2B	journal.pcbi.1002608	null	[ [ "Nucleosome , the fundamental repeating structural unit of chromatin , is comprised of two superhelical turns of DNA ( base pairs ) wound times around an octamer of histone proteins ( H2A , H2B , H3 , H4 ) or their variants [1]–[4] .", "Histone chaperones prevent histones from aggregating on DNA by blocki...	[ "Histone chaperones facilitate assembly and disassembly of nucleosomes .", "Understanding the process of how histone chaperones associate and dissociate from the histones can help clarify their roles in chromosome metabolism .", "Some histone chaperones are intrinsically disordered proteins ( IDPs ) .", "Rece...	[ "Histone chaperones facilitate the assembly and disassembly of nucleosome by interacting with the corresponding histones or histone variants .", "As the biomolecules in nucleosome are highly charged , electrostatic interactions are particularly important in these processes .", "The experiments have explored tha...	2012
[ "Introduction", "Materials and methods", "Results", "Discussion" ]	[ "invertebrates", "medicine and health sciences", "ecology and environmental sciences", "engineering and technology", "transportation", "china", "infectious disease epidemiology", "spatial epidemiology", "geographical locations", "animals", "transportation infrastructure", "roads", "urban env...	Urban villages as transfer stations for dengue fever epidemic: A case study in the Guangzhou, China	journal.pntd.0007350	null	[ [ "Dengue fever ( DF ) is a febrile illness caused by the dengue virus , which is further classified into four serotypes ( Dengue virus 1–4 ) , and transmitted by Aedes aegypti and Aedes albopictus mosquitoes [1] .", "Dengue is the most prevalent mosquito-borne viral infection of humans in the tropical and ...	[ "Numerous urban villages ( UVs ) and frequent infectious disease outbreaks are major environmental and public health concerns in highly urbanized regions , especially in developing countries .", "However , the spatial and quantitative associations between UVs and infections remain little understood on a fine scal...	[ "Due to the rapid urbanization of China , many villages in the urban fringe are enveloped by ever-expanding cities and become so-called urban villages ( UVs ) .", "UVs are widely distributed in not only the Guangzhou core areas but also the other cities in the highly urbanized region of China ( e . g . , Shenzhen...	2019
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "chemical compounds", "focal adhesions", "organic compounds", "mutation", "developmental biology", "molecular development", "amino acids", "cellular structures and organelles", "cytoskeleton", "cysteine", "proteins", "adhesion molecules", "structural proteins", "chemistry", "biophysics",...	Mechanical unfolding reveals stable 3-helix intermediates in talin and α-catenin	journal.pcbi.1006126	null	[ [ "Protein activity can be modulated by mechanical cues in addition to chemical stimuli and ligand binding .", "Mechanical forces can induce conformational changes in the protein structure , that leads to either a switch between the functional states of the protein , or allows for multiple functions[1 , 2] ...	[ "Mechanical stability is a key feature in the regulation of structural scaffolding proteins and their functions .", "Despite the abundance of α-helical structures among the human proteome and their undisputed importance in health and disease , the fundamental principles of their behavior under mechanical load are...	[ "In order to migrate and survive , most cells need to be attached to their environment .", "Cells anchor to the extracellular matrix via transmembrane integrin , connecting it to contractile the cytoskeleton .", "Similarly , cell-cell contacts are formed via transmembrane cadherin , which also connects to the c...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "infectious diseases", "biology and life sciences", "immunology", "medicine and health sciences" ]	Neutrophil Crawling in Capillaries; A Novel Immune Response to Staphylococcus aureus	journal.ppat.1004379	null	[ [ "Staphylococcus aureus is a Gram-positive , facultatively anaerobic bacterium that poses considerable challenges to human health as a re-emerging pathogen in both hospital and community settings .", "As a commensal bacterium , approximately 50% of the general population carry S . aureus in the anterior na...	[ "Methicillin-resistant Staphylococcus aureus ( MRSA ) , particularly the USA300 strain , is a highly virulent pathogen responsible for an increasing number of skin and soft tissue infections globally .", "Furthermore , MRSA-induced soft tissue infections can rapidly progress into life-threatening conditions , suc...	[ "Methicillin-resistant Staphylococcus aureus ( MRSA ) is a highly virulent pathogen responsible for a significant portion of skin and soft tissue infections throughout the world .", "We investigated the role of neutrophils in soft tissue infections , as these immune cells have been shown to be both essential for ...	2014
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "innate immune system", "medicine and health sciences", "immune physiology", "periodontal diseases", "cytokines", "microbiome", "pathology and laboratory medicine", "pathogens", "immunology", "microbiology", "genomic databases", "developmental biology", "genome analysis", "molecular develo...	Potassium is a key signal in host-microbiome dysbiosis in periodontitis	journal.ppat.1006457	null	[ [ "Dysbiosis , or the imbalance in the structural and/or functional properties of the microbiome , leads to the breakdown of host-microbe homeostasis , and has been associated with the pathogenesis of several important inflammatory diseases mediated by the activity of the microbial community , such as inflammat...	[ "Dysbiosis , or the imbalance in the structural and/or functional properties of the microbiome , is at the origin of important infectious inflammatory diseases such as inflammatory bowel disease ( IBD ) and periodontal disease .", "Periodontitis is a polymicrobial inflammatory disease that affects a large proport...	[ "Homeostasis of the human microbiome plays a key role in maintaining the healthy status of the human body .", "Changes in composition and function of the human microbiome ( dysbiosis ) are at the origin of important infectious inflammatory diseases such as inflammatory bowel disease ( IBD ) and periodontal diseas...	2017
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "biology", "computational biology" ]	OptCom: A Multi-Level Optimization Framework for the Metabolic Modeling and Analysis of Microbial Communities	journal.pcbi.1002363	null	[ [ "Solitary species are rarely found in natural environments as most microorganisms tend to function in concert in integrative and interactive units , ( i . e . , communities ) .", "Natural microbial ecosystems drive global biogeochemical cycling of energy and carbon [1] and are involved in applications ran...	[ "Microorganisms rarely live isolated in their natural environments but rather function in consolidated and socializing communities .", "Despite the growing availability of high-throughput sequencing and metagenomic data , we still know very little about the metabolic contributions of individual microbial players ...	[ "Microorganisms rarely live isolated in their natural environments but rather function in consolidated and socializing communities .", "Despite the growing availability of experimental data , we still know very little about the metabolic contributions of individual species within an ecological niche and the exten...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "systems biology", "biochemical simulations", "control theory", "mathematics", "biophysic al simulations", "applied mathematics", "regulatory networks", "biology", "computational biology", "metabolic networks", "signaling networks" ]	Potassium Starvation in Yeast: Mechanisms of Homeostasis Revealed by Mathematical Modeling	journal.pcbi.1002548	null	[ [ "Potassium is an essential cation required for many cellular processes including the regulation of cell volume , intracellular pH , protein synthesis , activation of enzymes , and maintenance of the plasma membrane potential [1]–[4] .", "In their natural environment , most cell types have to accumulate in...	[ "The intrinsic ability of cells to adapt to a wide range of environmental conditions is a fundamental process required for survival .", "Potassium is the most abundant cation in living cells and is required for essential cellular processes , including the regulation of cell volume , pH and protein synthesis .", ...	[ "Without potassium , all living cells will die; it has to be present in sufficient amounts for the proper function of most cell types .", "Disturbances in potassium levels in animal cells result in potentially fatal conditions and it is also an essential nutrient for plants and fungi .", "Cells have developed e...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "gram negative", "chromosome biology", "biology", "microbiology", "molecular cell biology", "bacterial pathogens" ]	Chromosomal Organization and Segregation in Pseudomonas aeruginosa	journal.pgen.1003492	null	[ [ "Members of the genus Pseudomonas ( γ-proteobacteria ) show remarkable metabolic and physiological diversity and versatility , enabling colonization of diverse terrestrial and aquatic habitats .", "These species are of great interest because of their importance in plant and human diseases and their growin...	[ "The study of chromosomal organization and segregation in a handful of bacteria has revealed surprising variety in the mechanisms mediating such fundamental processes .", "In this study , we further emphasized this diversity by revealing an original organization of the Pseudomonas aeruginosa chromosome .", "We ...	[ "The processes of chromosomal disposition , replication , and segregation in bacteria have been characterized only in a handful of species , yet there is remarkable diversity in the ways such fundamental processes are managed .", "In this study , we analyzed the subcellular chromosomal organization of Pseudomonas...	2013
[ "Introduction", "Materials and methods", "Results", "Discussion" ]	[ "fluorescence imaging", "invertebrates", "medicine and health sciences", "cestodes", "helminths", "depolarization", "membrane potential", "tropical diseases", "electrophysiology", "parasitic diseases", "animals", "pharmaceutics", "neglected tropical diseases", "mitochondria", "bioenerget...	Anthelminthic activity of glibenclamide on secondary cystic echinococcosis in mice	journal.pntd.0006111	null	[ [ "Cystic echinococcosis ( CE ) is among the most serious and life-threatening helminth infections in humans worldwide [1] .", "This disease is caused by the larval stage of the dog-tapeworm Echinococcus granulosus .", "Not only it does affect approximately 2–3 million people around the world but it cau...	[ "Cystic echinococcosis ( CE ) is a worldwide parasitic zoonosis caused by the larval stage of Echinococcus granulosus .", "Current chemotherapy against this disease is based on the administration of benzimidazoles ( BZMs ) .", "However , BZM treatment has a low cure rate and causes several side effects .", "T...	[ "In this work we demonstrated the in vitro and in vivo efficacy of Glb against the larval stage of Echinococcus granulosus .", "At the cellular level , the drug triggered mitochondrial membrane depolarization and increased intracellular Ca2+ levels , thus affecting ATP generation in the parasite .", "In additio...	2017
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "animal models", "genome expression analysis", "embryology", "developmental biology", "model organisms", "genome evolution", "molecular development", "gene expression", "genetics", "comparative genomics", "biology", "genomics", "evolutionary biology", "genomic evolution", "evolutionary g...	Sex-Specific Embryonic Gene Expression in Species with Newly Evolved Sex Chromosomes	journal.pgen.1004159	null	[ [ "Differing dosage of sex chromosomes is one of the most significant forms of natural genetic variation that animals with genetic sex determination face .", "In Drosophila , like humans , females have two X chromosomes , while males have one X and one Y chromosome .", "Thus , roughly half of the popula...	[ "Sex chromosome dosage differences between females and males are a significant form of natural genetic variation in many species .", "Like many species with chromosomal sex determination , Drosophila females have two X chromosomes , while males have one X and one Y . Fusions of sex chromosomes with autosomes have...	[ "Many animals have sex-specific combinations of chromosomes .", "In humans , for example , females have two X chromosomes while males have one X and one Y . In most species with XX:XY systems , the Y chromosome is degenerate and gene-poor while the X encodes a large number of functional genes .", "A variety of ...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genetics and genomics/microbial evolution and genomics", "evolutionary biology/microbial evolution and genomics", "evolutionary biology/evolutionary and comparative genetics" ]	Initial Mutations Direct Alternative Pathways of Protein Evolution	journal.pgen.1001321	null	[ [ "Understanding the factors that determine the outcome of evolution is a long-term goal of evolutionary biology .", "Epistasis ( i . e . non-additive interactions between mutations that affect fitness ) is one such determinant .", "Epistasis can affect the type and order of mutations that can be fixed ...	[ "Whether evolution is erratic due to random historical details , or is repeatedly directed along similar paths by certain constraints , remains unclear .", "Epistasis ( i . e . non-additive interaction between mutations that affect fitness ) is a mechanism that can contribute to both scenarios .", "Epistasis ca...	[ "A long-term goal of evolutionary biology is to understand the factors that govern the outcome of evolution .", "Epistasis ( i . e . the situation in which the fitness effect of a mutation depends on its genetic background ) is one such factor .", "Epistasis not only affects the dynamics of evolution , it may a...	2011
[ "Introduction", "Material and Methods", "Results", "Discussion" ]	[ "invertebrates", "medicine and health sciences", "pathology and laboratory medicine", "pathogens", "microbiology", "parasitic diseases", "parasitic protozoans", "animals", "developmental biology", "fungi", "nymphs", "protozoans", "fungal diseases", "insect vectors", "fungal pathogens", ...	Screening of Fungi for Biological Control of a Triatomine Vector of Chagas Disease: Temperature and Trypanosome Infection as Factors	journal.pntd.0005128	null	[ [ "Insects of the subfamily Triatominae ( Hemiptera: Reduviidae ) are vectors of the protozoan parasite Trypanosoma cruzi , that is the causal agent of Chagas disease in Central and South America .", "This disease has a considerable medical and socioeconomic impact [1] with an estimated 7 to 8 million peopl...	[ "Entomopathogenic fungi have been investigated as an alternative tool for controlling various insects , including triatomine vectors of the protozoan Trypanosoma cruzi , the etiological agent of Chagas disease .", "Here we tested the pathogenicity and virulence of ten isolates of the fungi Metarhizium spp .", "...	[ "Entomopathogenic fungi have potential for use in biopesticides for control of vectors of medical importance .", "As they are biological agents , however , a range of factors may affect their efficacy for this purpose , including temperature and interactions with the vectored parasite .", "Little is known about...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genome-wide association studies", "invertebrates", "population genetics", "quantitative traits", "animals", "animal models", "developmental biology", "drosophila melanogaster", "model organisms", "organism development", "genome analysis", "epigenetics", "drosophila", "chromatin", "resea...	Intrapopulation Genome Size Variation in D. melanogaster Reflects Life History Variation and Plasticity	journal.pgen.1004522	null	[ [ "Genome size evolution is extensive and ubiquitous .", "However , the mechanisms by which this occurs are poorly understood and hotly debated , despite a wealth of information connecting genome size shifts to numerous phenotypes , lineages , and abiotic environments [1]–[16] .", "One critical componen...	[ "We determined female genome sizes using flow cytometry for 211 Drosophila melanogaster sequenced inbred strains from the Drosophila Genetic Reference Panel , and found significant conspecific and intrapopulation variation in genome size .", "We also compared several life history traits for 25 lines with large an...	[ "Genome size evolution is ubiquitous , and–even after decades of research–mysterious .", "There are two major classes of hypotheses regarding genome size evolution , those that attribute its causes to evolutionarily neutral processes and those that suggest a role for selection .", "Numerous correlations between...	2014
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "medicine and health sciences", "toxins", "pathology and laboratory medicine", "toxic agents", "toxicology", "membrane proteins", "materials science", "surfactants", "cellular structures and organelles", "lipids", "geography", "detergents", "materials by attribute", "cartography", "isoth...	The potent effect of mycolactone on lipid membranes	journal.ppat.1006814	null	[ [ "Buruli ulcer ( BU ) is the third most common human mycobacterial infection in the world , after tuberculosis and leprosy [1 , 2] .", "BU is a neglected tropical disease of the skin and subcutaneous tissue caused by an environmental pathogen , Mycobacterium ulcerans ( M . ulcerans ) .", "This disease ...	[ "Mycolactone is a lipid-like endotoxin synthesized by an environmental human pathogen , Mycobacterium ulcerans , the causal agent of Buruli ulcer disease .", "Mycolactone has pleiotropic effects on fundamental cellular processes ( cell adhesion , cell death and inflammation ) .", "Various cellular targets of my...	[ "Buruli ulcer is a necrotizing skin disease caused by an environmental mycobacterial pathogen .", "The pathogenesis of this neglected tropical disease involves the production of a toxin , mycolactone , which spreads through the tissues , away from the infecting organisms .", "Mycolactone has pleiotropic effects...	2018
[ "Introduction", "Results", "Discussion", "Methods and materials" ]	[ "learning", "decision making", "statistics", "sociology", "social sciences", "vertebrates", "neuroscience", "learning and memory", "animals", "mammals", "simulation and modeling", "animal models", "regression analysis", "model organisms", "cognitive psychology", "mathematics", "cogni...	Learning the structure of the world: The adaptive nature of state-space and action representations in multi-stage decision-making	journal.pcbi.1007334	null	[ [ "In sequential decision-making tasks , an agent makes a series of choices and passes through several states before earning rewards .", "Making choices requires knowing the structure of the environment such as the available actions , the number of states of the environment and how they map on to external c...	[ "State-space and action representations form the building blocks of decision-making processes in the brain; states map external cues to the current situation of the agent whereas actions provide the set of motor commands from which the agent can choose to achieve specific goals .", "Although these factors differ ...	[ "Everyday decision-making tasks typically require taking multiple actions and passing through multiple states before reaching desired goals .", "Such states constitute the state-space of the task .", "Here we show that , contrary to current assumptions , the state-space is not static but rather expands during t...	2019
[ "Introduction", "Materials and methods", "Results", "Discussion" ]	[ "invertebrates", "medicine and health sciences", "stereoisomers", "chemical compounds", "cestodes", "helminths", "enzymes", "enzymology", "parasitic diseases", "animals", "drug screening", "isomerism", "nematode infections", "pharmaceutics", "microscopy", "pharmacology", "pepsins", ...	Development of a movement-based in vitro screening assay for the identification of new anti-cestodal compounds	journal.pntd.0005618	null	[ [ "Helminths are separated into the two major phyla of nematodes ( roundworms ) and platyhelminths ( flatworms ) , including trematodes and cestodes , and they are important causes of disease in humans as well as animals .", "An estimated one billion people are infected with at least one helminth in develop...	[ "Intestinal cestodes are infecting millions of people and livestock worldwide , but treatment is mainly based on one drug: praziquantel .", "The identification of new anti-cestodal compounds is hampered by the lack of suitable screening assays .", "It is difficult , or even impossible , to evaluate drugs agains...	[ "Tapeworms ( cestodes ) are a medically important group of helminths that infect humans and animals all around the globe .", "The clinical signs caused by intestinal infection with adult cestodes are mostly mild , in contrast to the more severe disease symptoms inflicted by infection with the tissue-dwelling larv...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biochemistry/cell signaling and trafficking structures", "cell biology/cell signaling" ]	Identification of Positive Regulators of the Yeast Fps1 Glycerol Channel	journal.pgen.1000738	null	[ [ "Under conditions of high osmolarity stress , many fungal species , including Saccharomyces cerevisiae , maintain osmotic equilibrium by producing and retaining high concentrations of glycerol as a compatible solute [1] , [2] .", "Intracellular glycerol concentration is regulated in S . cerevisiae in part...	[ "The yeast Fps1 protein is an aquaglyceroporin that functions as the major facilitator of glycerol transport in response to changes in extracellular osmolarity .", "Although the High Osmolarity Glycerol pathway is thought to have a function in at least basal control of Fps1 activity , its mode of regulation is no...	[ "When challenged by changes in extracellular osmolarity , many fungal species regulate their intracellular glycerol concentration to modulate their internal osmotic pressure .", "Maintenance of osmotic homeostasis prevents either cellular collapse under hyper-osmotic stress or cell rupture under hypo-osmotic stre...	2009
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	HDAC4 Reduction: A Novel Therapeutic Strategy to Target Cytoplasmic Huntingtin and Ameliorate Neurodegeneration	journal.pbio.1001717	HDAC4 histone deacetylase is found to associate with huntingtin in a polyQ-length dependent manner. Reduction of HDAC4 levels in mouse models of Huntington's disease (HD) delays cytoplasmic aggregation in the brain and improves the molecular pathology of HD, providing a potential new therapeutic target.	[ [ "Huntington's disease ( HD ) is a progressive , inherited neurological disorder characterized by severe motor , cognitive , behavioural , and physiological dysfunction for which there is no effective disease-modifying treatment [1] .", "The disease is caused by the expansion of a CAG repeat to more than 3...	[ "Histone deacetylase ( HDAC ) 4 is a transcriptional repressor that contains a glutamine-rich domain .", "We hypothesised that it may be involved in the molecular pathogenesis of Huntington's disease ( HD ) , a protein-folding neurodegenerative disorder caused by an aggregation-prone polyglutamine expansion in th...	[ "Huntington's disease ( HD ) is a late-onset neurodegenerative disorder caused by protein-folding defects in the huntingtin protein .", "Mutations in huntingtin can result in extra-long tracts of the amino acid glutamine , resulting in aberrant interactions with other proteins and also causing huntingtin proteins...	2013
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "viral attachment", "viral entry", "viral transmission and infection", "virology", "biology", "microbiology" ]	TIM-family Proteins Promote Infection of Multiple Enveloped Viruses through Virion-associated Phosphatidylserine	journal.ppat.1003232	null	[ [ "The entry of enveloped viruses is a multi-stage process .", "Following attachment , some viruses fuse to cells at the plasma membrane , whereas others are internalized through various endocytic routes and , primed by low pH or compartment-resident factors , fuse at the endo/lysosomal membranes .", "V...	[ "Human T-cell Immunoglobulin and Mucin-domain containing proteins ( TIM1 , 3 , and 4 ) specifically bind phosphatidylserine ( PS ) .", "TIM1 has been proposed to serve as a cellular receptor for hepatitis A virus and Ebola virus and as an entry factor for dengue virus .", "Here we show that TIM1 promotes infect...	[ "To infect cells , enveloped viruses typically utilize cellular receptors , which mediate specific , high-affinity interactions with the viral entry protein and prime the entry protein for subsequent steps in the viral entry process .", "Viral entry is also enhanced by attachment factors .", "Although less spec...	2013
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "biology" ]	DRAM Triggers Lysosomal Membrane Permeabilization and Cell Death in CD4+ T Cells Infected with HIV	journal.ppat.1003328	null	[ [ "Several proteolytic processes are involved in programmed cell death .", "Lysosomal membrane permeabilization ( LMP ) and mitochondrial outer membrane permeabilization ( MOMP ) have been identified as major events triggering programmed cell death .", "Thus , in a number of models , lysosomal destabili...	[ "Productive HIV infection of CD4+ T cells leads to a caspase-independent cell death pathway associated with lysosomal membrane permeabilization ( LMP ) and cathepsin release , resulting in mitochondrial outer membrane permeabilization ( MOMP ) .", "Herein , we demonstrate that HIV infection induces damage-regulat...	[ "Lysosomes are acidic organelles capable of digesting macromolecules and regulating autophagy .", "In the context of host-pathogen interactions , productive viral infections are associated with lysosome membrane permeabilization ( LMP ) and programmed cell death ( PCD ) .", "At a molecular level , the tumor sup...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	The Compass-like Locus, Exclusive to the Ambulacrarians, Encodes a Chromatin Insulator Binding Protein in the Sea Urchin Embryo	journal.pgen.1003847	null	[ [ "Chromatin insulators are specialized DNA elements that upon binding of specific proteins display barrier and/or directional enhancer-blocking activity .", "The analysis of the genome-wide localization of insulator binding proteins ( IBPs ) in vertebrates and Drosophila suggests that insulators partition ...	[ "Chromatin insulators are eukaryotic genome elements that upon binding of specific proteins display barrier and/or enhancer-blocking activity .", "Although several insulators have been described throughout various metazoans , much less is known about proteins that mediate their functions .", "This article deals...	[ "Mounting evidence in several model organisms collectively demonstrates a role for the DNA-protein complexes known as chromatin insulators in orchestrating the functional domain organization of the eukaryotic genome .", "Several DNA elements displaying features of insulators , viz barrier and/or directional enhan...	2013
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "antimicrobials", "medicine and health sciences", "methods and resources", "hela cells", "dose prediction methods", "drugs", "biological cultures", "microbiology", "drug screening", "pharmaceutics", "antibiotics", "cell cultures", "pharmacology", "research and analysis methods", "cell li...	Prediction of drug cocktail effects when the number of measurements is limited	journal.pbio.2002518	null	[ [ "Cancer and antibiotic treatments face the problem of drug resistance .", "Cancer drugs also face problems of efficacy at the low doses needed to tolerate side effects [1–5] .", "One strategy to overcome these challenges is cocktails of several drugs [5–9] .", "Cocktails overcame the challenges of...	[ "Cocktails of drugs can be more effective than single drugs , because they can potentially work at lower doses and avoid resistance .", "However , it is impossible to test all drug cocktails drawn from a large set of drugs because of the huge number of combinations .", "To overcome this combinatorial explosion ...	[ "Drug cocktails are a promising strategy for diseases such as cancer and infections , because cocktails can be more effective than individual drugs and can overcome problems of drug resistance .", "However , finding the best cocktail comprising a given set of drugs is challenging because the number of experiments...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "homo (human)", "genetics and genomics" ]	Identification and Characterization of Cell Type–Specific and Ubiquitous Chromatin Regulatory Structures in the Human Genome	journal.pgen.0030136	null	[ [ "Biological processes such as proliferation , apoptosis , differentiation , development , and aging require carefully orchestrated spatial and temporal gene expression [1 , 2] .", "To understand the molecular mechanisms that underlie global transcriptional regulation , it is essential to identify all the ...	[ "The identification of regulatory elements from different cell types is necessary for understanding the mechanisms controlling cell type–specific and housekeeping gene expression .", "Mapping DNaseI hypersensitive ( HS ) sites is an accurate method for identifying the location of functional regulatory elements ."...	[ "There are many different types of gene regulatory elements that control gene expression .", "Identifying the location of these regulatory elements in the genome , as well as understanding how exactly they control gene expression in different cell types , has been a major challenge .", "Here , we use a relative...	2007
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "medicine", "infectious diseases", "neglected tropical diseases", "infectious disease modeling", "parasitic diseases", "veterinary science" ]	Non-Invasive In Vivo Study of the Trypanosoma vivax Infectious Process Consolidates the Brain Commitment in Late Infections	journal.pntd.0001976	null	[ [ "Animal African trypanosomosis ( AAT ) is a major protozoan disease due to trypanosomes .", "The disease which is endemic in Africa is mainly caused by Trypanosoma vivax , T . congolense and T . b .", "brucei .", "T . vivax accounts for up to half of all AAT prevalence in West Africa where it is c...	[ "Trypanosoma vivax , one of the leading parasites responsible for Animal African Trypanosomosis ( Nagana ) , is generally cyclically transmitted by Glossina spp .", "but in areas devoid of the tsetse flies in Africa or in Latin American countries is mechanically transmitted across vertebrate hosts by other haemat...	[ "Very little work has been performed on Trypanosoma vivax for decades , but the recent development of murine infection models and axenic cultures has enabled the genetic manipulation of this parasite and has opened the door to a more in-depth understanding of its biology and the infectious process that leads to ani...	2013
[ "Introduction", "Results", "Discussion", "Material and methods" ]	[ "blood cells", "medicine and health sciences", "immune cells", "pathology and laboratory medicine", "viral transmission and infection", "hela cells", "pathogens", "biological cultures", "immunology", "microbiology", "light microscopy", "microscopy", "yersinia", "cell cultures", "cellular...	Visualization of translocons in Yersinia type III protein secretion machines during host cell infection	journal.ppat.1007527	null	[ [ "Bacterial type III secretion systems ( T3SSs ) are molecular machines also termed injectisomes that translocate proteins of bacterial origin ( i . e . effectors ) into host cells .", "T3SSs are essential virulence factors of numerous human , animal and plant pathogens including Chlamydia , Pseudomonas , ...	[ "Type III secretion systems ( T3SSs ) are essential virulence factors of numerous bacterial pathogens .", "Upon host cell contact the T3SS machinery—also named injectisome—assembles a pore complex/translocon within host cell membranes that serves as an entry gate for the bacterial effectors .", "Whether and how...	[ "Many human , animal and plant pathogenic bacteria employ a molecular machine termed injectisome to inject their toxins into host cells .", "Because injectisomes are crucial for these bacteria’s infectious potential they have been considered as targets for antiinfective drugs .", "Injectisomes are highly simila...	2018
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "medicine and health sciences", "pathology and laboratory medicine", "togaviruses", "chikungunya infection", "respiratory infections", "pathogens", "tropical diseases", "microbiology", "alphaviruses", "pulmonology", "viruses", "chikungunya virus", "rna viruses", "signs and symptoms", "ne...	Molecular Virologic and Clinical Characteristics of a Chikungunya Fever Outbreak in La Romana, Dominican Republic, 2014	journal.pntd.0005189	null	[ [ "Chikungunya virus ( CHIKV ) , a mosquito-borne virus in the family Togaviridae , genus Alphavirus , was first isolated in 1952 from a patient on the Makonde plateau that is now part of Tanzania .", "It derives its name from the Makonde term kungunyala , meaning roughly , “that which bends up” [1] .", ...	[ "Since emerging in Saint Martin in 2013 , chikungunya virus ( CHIKV ) , an alphavirus transmitted by the Aedes aegypti mosquito , has infected approximately two million individuals in the Americas , with over 500 , 000 reported cases in the Dominican Republic ( DR ) .", "CHIKV-infected patients typically present ...	[ "Chikungunya virus ( CHIKV ) is known for its ability to cause explosive outbreaks of flu-like illness followed by severe joint pain and swelling , which can persist for months to several years .", "We tested patient serum of both suspected and unsuspected chikungunya fever ( CHIKF ) cases collected at an emergen...	2016
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "computer and information sciences", "medicine and health sciences", "machine learning", "drug-drug interactions", "drug research and development", "artificial intelligence", "gene identification and analysis", "genetics", "adverse reactions", "pharmacology", "biology and life sciences", "gene...	Leveraging genetic interactions for adverse drug-drug interaction prediction	journal.pcbi.1007068	null	[ [ "Drug-drug interactions ( DDIs ) refer to the unexpected pharmacologic or clinical responses due to the co-administration of two or more drugs [1] .", "With the simultaneous use of multiple drugs becoming increasingly prevalent , DDIs have emerged as a severe patient safety concern over recent years [2] ....	[ "In light of increased co-prescription of multiple drugs , the ability to discern and predict drug-drug interactions ( DDI ) has become crucial to guarantee the safety of patients undergoing treatment with multiple drugs .", "However , information on DDI profiles is incomplete and the experimental determination o...	[ "Adverse drug-drug interactions are adverse side effects caused by taking two or more drugs together .", "As co-prescription of multiple drugs becomes an increasingly prevalent practice , affecting 42 . 2% of Americans over 65 years old , adverse drug-drug interactions have become a serious safety concern , accou...	2019
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "physics", "computer science", "mathematics", "biology" ]	Optimal Properties of Analog Perceptrons with Excitatory Weights	journal.pcbi.1002919	null	[ [ "Purkinje cells ( PCs ) are the only outputs of the cerebellar cortex , a brain structure involved in motor learning .", "They receive a very large number ( 150 , 000 ) of excitatory synaptic inputs from Granule Cells ( GCs ) through parallel fibers ( PFs ) , and a single very strong input from the inferi...	[ "The cerebellum is a brain structure which has been traditionally devoted to supervised learning .", "According to this theory , plasticity at the Parallel Fiber ( PF ) to Purkinje Cell ( PC ) synapses is guided by the Climbing fibers ( CF ) , which encode an ‘error signal’ .", "Purkinje cells have thus been mo...	[ "Learning properties of neuronal networks have been extensively studied using methods from statistical physics .", "However , most of these studies ignore a fundamental constraint in networks of real neurons: synapses are either excitatory or inhibitory , and cannot change sign during learning .", "Here , we ch...	2013
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "social and behavioral sciences", "veterinary science" ]	Socio-Economic and Cultural Determinants of Human African Trypanosomiasis at the Kenya – Uganda Transboundary	journal.pntd.0002186	null	[ [ "Human African Trypanosomiasis ( HAT ) or Sleeping sickness caused by Trypanosma brucei protozoa and transmitted by tsetse fly ( Glossina spp ) vector is found only in Sub-Saharan Africa , within 36 countries lying between latitudes 14° North and to 29° South .", "An annual incidence ranging from 50 , 000...	[ "Kenya and Uganda have reported different Human African Trypanosomiasis incidences in the past more than three decades , with the latter recording more cases .", "This cross-sectional study assessed the demographic characteristics , tsetse and trypanosomiasis control practices , socio-economic and cultural risk f...	[ "The prevention and control of Human African Trypanosomiasis depends on application of knowledge and appropriate technologies to modify tsetse ecology by community members and relevant stakeholders .", "In our study Ugandan districts reported more T . b . r . than the neighboring districts in Kenya in the past 30...	2013
[ "Introduction", "Results" ]	[ "cancer genomics", "medicine and health sciences", "carcinomas", "cancer risk factors", "cancers and neoplasms", "basic cancer research", "endometrial carcinoma", "gastrointestinal tumors", "liver diseases", "oncology", "gastroenterology and hepatology", "genome analysis", "head and neck tum...	New functionalities in the TCGAbiolinks package for the study and integration of cancer data from GDC and GTEx	journal.pcbi.1006701	null	[ [ "Cancer is among the leading causes of mortality worldwide .", "It is a complex disease where multiple different mechanisms are at play all at once .", "This complexity also arises from the fact that cancer is extremely heterogeneous and can exist in distinct forms where each cancer type or subtype ca...	[ "The advent of Next-Generation Sequencing ( NGS ) technologies has opened new perspectives in deciphering the genetic mechanisms underlying complex diseases .", "Nowadays , the amount of genomic data is massive and substantial efforts and new tools are required to unveil the information hidden in the data .", "...	[ "The advent of Next-Generation Sequencing ( NGS ) technologies has been generating a massive amount of data which require continuous efforts in developing and maintain computational tool for data analyses .", "The Genomic Data Commons ( GDC ) Data Portal is a platform that contains different cancer genomic studie...	2019
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Widespread Reassortment Shapes the Evolution and Epidemiology of Bluetongue Virus following European Invasion	journal.ppat.1005056	null	[ [ "Reassortment is an important evolutionary process in segmented RNA viruses that can occur when two viruses ( of the same species ) co-infect a single host cell [1] .", "This provides an opportunity for their genome segments to be exchanged and packaged together into progeny viruses that are therefore gen...	[ "Genetic exchange by a process of genome-segment ‘reassortment’ represents an important mechanism for evolutionary change in all viruses with segmented genomes , yet in many cases a detailed understanding of its frequency and biological consequences is lacking .", "We provide a comprehensive assessment of reassor...	[ "Segmented viruses have genomes that are separated into multiple segments , comparable to chromosomes in higher organisms .", "When two segmented viruses of the same species infect the same cell , their progeny may incorporate segments picked up from the “parental” viruses .", "This process is called “reassortm...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biochemistry/molecular evolution", "computational biology/macromolecular structure analysis", "molecular biology/molecular evolution", "biochemistry/protein chemistry", "biochemistry/bioinformatics", "biochemistry/biomacromolecule-ligand interactions", "biotechnology/bioengineering", "computational b...	Interrogating and Predicting Tolerated Sequence Diversity in Protein Folds: Application to E. elaterium Trypsin Inhibitor-II Cystine-Knot Miniprotein	journal.pcbi.1000499	null	[ [ "Protein-protein interactions govern many biological processes in the cell , often with high affinity and specificity .", "Such interactions are typically mediated by a relatively small portion of the protein , while the remainder of the molecule serves as a framework to ensure the proper presentation of ...	[ "Cystine-knot miniproteins ( knottins ) are promising molecular scaffolds for protein engineering applications .", "Members of the knottin family have multiple loops capable of displaying conformationally constrained polypeptides for molecular recognition .", "While previous studies have illustrated the potenti...	[ "The use of engineered proteins in medicine and biotechnology has surged in recent years .", "An emerging approach for developing novel proteins is to use a naturally-occurring protein as a molecular framework , or scaffold , wherein amino acid mutations are introduced to elicit new properties , such as the abili...	2009
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "materials science", "biology", "engineering" ]	Calcium Wave Propagation in Networks of Endothelial Cells: Model-based Theoretical and Experimental Study	journal.pcbi.1002847	null	[ [ "Multi-level organization and dynamics is a hallmark of most biological systems .", "This is particularly true in tissues in which single cells are organized into multicellular structures , which are further assembled into complex tissue and organs .", "For example , endothelial cells are assembled in...	[ "In this paper , we present a combined theoretical and experimental study of the propagation of calcium signals in multicellular structures composed of human endothelial cells .", "We consider multicellular structures composed of a single chain of cells as well as a chain of cells with a side branch , namely a “T...	[ "Calcium wave signal has been found in a wide variety of cell types .", "Over the last years , a large number of calcium experiments have shown that calcium signal is not only an intracellular regulator but is also able to be transmitted to surrounding cells as intercellular signal .", "This paper focuses on th...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "veterinary pathology", "pathology", "pest control", "biology", "zoology", "veterinary science", "parasitology", "agriculture" ]	Synergistic Parasite-Pathogen Interactions Mediated by Host Immunity Can Drive the Collapse of Honeybee Colonies	journal.ppat.1002735	null	[ [ "In the last few years , large-scale losses of honeybees ( Apis mellifera L . ) have been recorded all over the world [1] .", "A poorly understood syndrome , called Colony Collapse Disorder ( CCD ) , reported in the United States of America since 2006 [2] , has attracted the attention of both the scientif...	[ "The health of the honeybee and , indirectly , global crop production are threatened by several biotic and abiotic factors , which play a poorly defined role in the induction of widespread colony losses .", "Recent descriptive studies suggest that colony losses are often related to the interaction between pathoge...	[ "Honeybees are of capital importance for humans since crop production significantly depends upon pollination by these insects .", "In recent years , widespread collapses of honeybee colonies have been reported throughout the world; unfortunately , despite intense research efforts , the causal agents of such losse...	2012
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "medicine", "immune cells", "histoplasmosis", "immunology", "microbiology", "adaptive immunity", "immune defense", "fungal diseases", "immunizations", "infectious diseases", "mycology", "mycosis infections", "blastomycosis", "t cells", "biology", "yeast", "immunity", "systemic myco...	Tc17 Cells Mediate Vaccine Immunity against Lethal Fungal Pneumonia in Immune Deficient Hosts Lacking CD4+ T Cells	journal.ppat.1002771	null	[ [ "The incidence of invasive fungal infections in immune-compromised hosts has skyrocketed .", "These patients often have diminished or dysfunctional CD4+ T cells rendering them susceptible to fungal infections caused by Candida , Aspergillus , Cryptococcus , Histoplasma and Pneumocystis [1] .", "Thus ,...	[ "Vaccines may help reduce the growing incidence of fungal infections in immune-suppressed patients .", "We have found that , even in the absence of CD4+ T-cell help , vaccine-induced CD8+ T cells persist and confer resistance against Blastomyces dermatitidis and Histoplasma capsulatum .", "Type 1 cytokines cont...	[ "Systemic fungal infections have emerged as a public health problem , especially for patients with suppressed immunity .", "At present , there are no vaccines against fungi , partly because it is hard to elicit strong immunity in immune suppressed patients .", "We have found however that residual elements of T ...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "microbiology/cellular microbiology and pathogenesis", "microbiology/medical microbiology" ]	Gain of Function Mutations in CgPDR1 of Candida glabrata Not Only Mediate Antifungal Resistance but Also Enhance Virulence	journal.ppat.1000268	null	[ [ "Candida glabrata has recently emerged as the second most common cause of invasive candidiasis , and there are increasing numbers of reports showing its important role in mucosal or bloodstream infections [1] , [2] .", "Systemic infections due to C . glabrata are characterized by a high mortality rate , a...	[ "CgPdr1p is a Candida glabrata Zn ( 2 ) -Cys ( 6 ) transcription factor involved in the regulation of the ABC-transporter genes CgCDR1 , CgCDR2 , and CgSNQ2 , which are mediators of azole resistance .", "Single-point mutations in CgPDR1 are known to increase the expression of at least CgCDR1 and CgCDR2 and thus t...	[ "Candida glabrata is a yeast causing several diseases in humans and especially in immuno-compromised people .", "C . glabrata infections are treated with antifungal agents , however the use of some agents , for example azoles , is associated with the development of resistance .", "In this yeast species , azole ...	2009
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "g1 phase", "gene regulation", "cell cycle and cell division", "regulatory proteins", "cell processes", "dna-binding proteins", "dna transcription", "regulator genes", "dna replication", "transcription factors", "gene types", "dna", "synthesis phase", "proteins", "gene expression", "bi...	Msa1 and Msa2 Modulate G1-Specific Transcription to Promote G1 Arrest and the Transition to Quiescence in Budding Yeast	journal.pgen.1006088	null	[ [ "The need to stop proliferation and remain in a protected quiescent state is universally conserved and is just as important to yeast as it is to human cells .", "Failure to enter , or unscheduled exit from quiescence results in uncontrolled proliferation and cancer in humans , and death in unicellular org...	[ "Yeast that naturally exhaust their glucose source can enter a quiescent state that is characterized by reduced cell size , and high cell density , stress tolerance and longevity .", "The transition to quiescence involves highly asymmetric cell divisions , dramatic reprogramming of transcription and global change...	[ "In spite of the many differences between yeast and humans , the basic strategies that regulate the cell division cycle are fundamentally conserved .", "In this study , we extend these parallels to include a common strategy by which cells transition from proliferation to quiescence .", "The decision to divide i...	2016
[ "Introduction", "Results/Discussion", "Materials and Methods" ]	[ "biotechnology", "ecology and environmental sciences", "genetics", "synthetic biology", "biology and life sciences", "soil science", "microbiology", "evolutionary biology", "agriculture" ]	Examination of Prokaryotic Multipartite Genome Evolution through Experimental Genome Reduction	journal.pgen.1004742	null	[ [ "While most bacterial genomes have only a single chromosome , many are more complex and consist of two or more large replicons .", "Depending on their characteristics , these replicons are classified as a chromosome ( largest replicon containing most of the core genes ) , megaplasmid ( laterally acquired ...	[ "Many bacteria carry two or more chromosome-like replicons .", "This occurs in pathogens such as Vibrio cholerea and Brucella abortis as well as in many N2-fixing plant symbionts including all isolates of the alfalfa root-nodule bacteria Sinorhizobium meliloti .", "Understanding the evolution and role of this m...	[ "Rhizobia are free-living bacteria of agricultural and environmental importance that form root-nodules on leguminous plants and provide these plants with fixed nitrogen .", "Many of the rhizobia have a multipartite genome , as do several plant and animal pathogens .", "All isolates of the alfalfa symbiont , Sin...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "immunodeficiency viruses", "virology", "immunology", "biology", "microbiology", "host-pathogen interaction", "immune response", "immunoglobulins" ]	Structure-guided Alterations of the gp41-directed HIV-1 Broadly Neutralizing Antibody 2F5 Reveal New Properties Regarding its Neutralizing Function	journal.ppat.1002806	null	[ [ "The membrane proximal external region ( MPER ) of the HIV-1 envelope transmembrane glycoprotein , gp41 , is the target of the two broadly neutralizing monoclonal antibodies ( Mabs ) 2F5 and 4E10 [1] , [2] ( Figure 1A ) .", "Although the exact mechanism of neutralization of these two antibodies is not yet...	[ "The broadly neutralizing HIV-1 antibody 2F5 recognizes an epitope in the gp41 membrane proximal external region ( MPER ) .", "The MPER adopts a helical conformation as free peptide , as post-fusogenic forms of gp41 , and when bound to the 4E10 monoclonal antibody ( Mab ) .", "However , when bound to 2F5 , the ...	[ "Host antibodies raised in response to acute viral infection are often protective to second exposure .", "However , in the less frequent examples of chronic infection , in which the virus actively replicates for prolonged periods , host immunity can impact on viral characteristics by applying selective pressures ...	2012
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "neuronal differentiation", "dna-binding proteins", "cell differentiation", "developmental biology", "dna replication", "sequence motif analysis", "epigenetics", "dna", "mammalian genomics", "dna methylation", "chromatin", "research and analysis methods", "sequence analysis", "genomic sign...	Binding of high mobility group A proteins to the mammalian genome occurs as a function of AT-content	journal.pgen.1007102	null	[ [ "With the advent of genomics techniques , the understanding of the many roles of histone proteins and their modifications has increased rapidly [1 , 2] .", "However , comparably little attention has been given to the second most abundant class of nuclear proteins after histones [3] , the high mobility gro...	[ "Genomic location can inform on potential function and recruitment signals for chromatin-associated proteins .", "High mobility group ( Hmg ) proteins are of similar size as histones with Hmga1 and Hmga2 being particularly abundant in replicating normal tissues and in cancerous cells .", "While several roles fo...	[ "We investigated the chromosomal location of a group of highly abundant nuclear proteins .", "Our genome-wide results for Hmga1 and Hmga2 reveal a unique binding modality indicating preference for DNA rich in A or T bases in vivo .", "Importantly this preferential binding to AT-rich sequences occurs throughout ...	2017
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "ophthalmology", "medicine", "trachoma", "global health" ]	The Outcome of Trachomatous Trichiasis Surgery in Ethiopia: Risk Factors for Recurrence	journal.pntd.0002392	null	[ [ "Blindness from trachoma is the end result of progressive scarring of the conjunctiva driven by Chlamydia trachomatis .", "The major risk factor of blinding corneal opacification ( CO ) is trichiasis ( TT ) , the in turning of the eyelashes .", "TT traumatises the delicate epithelium of the cornea , r...	[ "Over 1 . 2 million people are blind from trachomatous trichiasis ( TT ) .", "Lid rotation surgery is the mainstay of treatment , but recurrence rates can be high .", "We investigated the outcomes ( recurrence rates and other complications ) of posterior lamellar tarsal rotation ( PLTR ) surgery , one of the tw...	[ "Trachoma is the most common infectious cause of blindness worldwide .", "It causes trichiasis ( inturning of the eyelashes to touch the eye ) , which can cause visual loss .", "Trachomatous trichiasis ( TT ) affects over eight million people , 1 . 2 of whom live in Ethiopia – the most affected country worldwid...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biochemistry", "protein interactions", "molecular dynamics", "proteins", "chemistry", "biology", "computational chemistry" ]	Ubiquitin Dynamics in Complexes Reveal Molecular Recognition Mechanisms Beyond Induced Fit and Conformational Selection	journal.pcbi.1002704	null	[ [ "Protein-protein interactions are crucial in most biological processes , yet the principles governing the conformational effects of these interactions are still poorly understood .", "X-ray structures of protein complexes provide a wealth of high resolution structural information but reflect a static snap...	[ "Protein-protein interactions play an important role in all biological processes .", "However , the principles underlying these interactions are only beginning to be understood .", "Ubiquitin is a small signalling protein that is covalently attached to different proteins to mark them for degradation , regulate ...	[ "Due to their importance in biological processes , the investigation of protein-protein interactions is of great interest .", "Experimental structures of protein complexes provide a wealth of information but are limited to a static picture of bound proteins .", "Ubiquitin is a signalling protein that interacts ...	2012
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "biogeography", "ecology and environmental sciences", "population genetics", "geographical locations", "argentina", "genetic mapping", "population biology", "haplogroups", "research and analysis methods", "sequence analysis", "ecological metrics", "geography", "south america", "bioinformat...	Genetic diversity, phylogeography and molecular clock of the Lutzomyia longipalpis complex (Diptera: Psychodidae)	journal.pntd.0006614	null	[ [ "Visceral leishmaniasis ( VL ) is a parasitic disease caused in the American continent , by Leishmania infantum ( syn . Le . chagasi ) .", "VL has an estimated global incidence of 500 , 000 cases and 59 , 000 deaths per year [1] .", "Human cases of VL in Latin America are reported in 12 countries , wh...	[ "The Lutzomyia longipalpis complex has a wide but discontinuous distribution in Latin America , extending throughout the Neotropical realm between Mexico and northern Argentina and Uruguay .", "In the Americas , this sandfly is the main vector of Leishmania infantum , the parasite responsible for Visceral Leishma...	[ "The Lutzomyia longipalpis complex has a wide but discontinuous distribution in Latin America , extending throughout the Neotropical realm between Mexico and northern Argentina and Uruguay .", "In the Americas , this sandfly is the main vector of Leishmania infantum , the parasite responsible for Visceral Leishma...	2018
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "skin", "cell physiology", "medicine and health sciences", "sweat glands", "integumentary system", "membrane staining", "ions", "junctional complexes", "permeability", "tight junctions", "membrane proteins", "materials science", "kidneys", "cations", "cellular structures and organelles",...	Altered paracellular cation permeability due to a rare CLDN10B variant causes anhidrosis and kidney damage	journal.pgen.1006897	null	[ [ "Epithelial and endothelial cells constitute sheets that divide organs into functional compartments .", "Homeostasis of different organ and body compartments are dependent on epithelial cells and their paracellular barrier that prevents solutes and water from leaking between the cells .", "The tissue ...	[ "Claudins constitute the major component of tight junctions and regulate paracellular permeability of epithelia .", "Claudin-10 occurs in two major isoforms that form paracellular channels with ion selectivity .", "We report on two families segregating an autosomal recessive disorder characterized by generalize...	[ "Claudins are tight junction proteins forming paracellular barriers that are critical for normal development and homeostasis .", "The tissue specific paracellular barrier properties are determined by the protein composition of tight junctions that regulates the permeability of solutes and water between different ...	2017
[ "Introduction", "Results", "Materials and Methods", "Discussion" ]	[ "mathematics", "computational biology/synthetic biology", "computational biology/systems biology" ]	Global Entrainment of Transcriptional Systems to Periodic Inputs	journal.pcbi.1000739	null	[ [ "We consider in this paper systems of ordinary differential equations , generally time-dependent: ( 1 ) defined for and , where is a subset of .", "It will be assumed that is differentiable on , and that , as well as the Jacobian of with respect to , denoted as , are both continuous in .", "In applica...	[ "This paper addresses the problem of providing mathematical conditions that allow one to ensure that biological networks , such as transcriptional systems , can be globally entrained to external periodic inputs .", "Despite appearing obvious at first , this is by no means a generic property of nonlinear dynamical...	[ "The activities of living organisms are governed by complex sets of biochemical reactions .", "Often , entrainment to certain external signals helps control the timing and sequencing of reactions .", "An important open problem is to understand the onset of entrainment and under what conditions it can be ensured...	2010
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine", "immunopathology", "infectious diseases", "clinical immunology", "immunology", "respiratory medicine", "critical care and emergency medicine", "pulmonology", "immune response" ]	Macrophage-expressed IFN-β Contributes to Apoptotic Alveolar Epithelial Cell Injury in Severe Influenza Virus Pneumonia	journal.ppat.1003188	null	[ [ "Influenza viruses ( IV ) can cause primary viral pneumonia in humans with rapid progression to lung failure and fatal outcome [1] .", "Histopathologic and clinical features of IV-induced lung injury in humans resemble those of other forms of ARDS ( acute respiratory distress syndrome ) , characterized by...	[ "Influenza viruses ( IV ) cause pneumonia in humans with progression to lung failure and fatal outcome .", "Dysregulated release of cytokines including type I interferons ( IFNs ) has been attributed a crucial role in immune-mediated pulmonary injury during severe IV infection .", "Using ex vivo and in vivo IV ...	[ "Acute lung injury induced by influenza virus ( IV ) infection has been linked to an unbalanced release of pro-inflammatory cytokines including type I interferons ( IFN ) causing immune-mediated organ damage .", "Using ex vivo and in vivo IV infection models , we demonstrate that alveolar macrophage-expressed IFN...	2013
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "medicine", "biology" ]	TNFα-Mediated Liver Destruction by Kupffer Cells and Ly6Chi Monocytes during Entamoeba histolytica Infection	journal.ppat.1003096	null	[ [ "Entamoeba histolytica ( E . histolytica ) is a protozoan parasite that colonizes the human gut .", "Infection is typically asymptomatic; however , in about 10% of cases , E . histolytica trophozoites penetrate into the gut tissue and cause hemorrhagic colitis or spread to the liver and induce amebic live...	[ "Amebic liver abscess ( ALA ) is a focal destruction of liver tissue due to infection by the protozoan parasite Entamoeba histolytica ( E . histolytica ) .", "Host tissue damage is attributed mainly to parasite pathogenicity factors , but massive early accumulation of mononuclear cells , including neutrophils , i...	[ "Amebic liver abscess ( ALA ) , an infectious disease caused by the protozoan parasite Entamoeba histolytica is characterized by severe focal liver damages .", "According to its name giving activity , destruction of liver tissue by E . histolytica has been attributed to parasite-specific effector molecules .", ...	2013
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "blood cells", "flow cytometry", "phosphorylation", "medicine and health sciences", "immune cells", "immunology", "cell processes", "immune receptor signaling", "membrane receptor signaling", "research and analysis methods", "contractile proteins", "specimen preparation and treatment", "acti...	Rictor positively regulates B cell receptor signaling by modulating actin reorganization via ezrin	journal.pbio.2001750	null	[ [ "B cell receptor ( BCR ) signaling is vital for B cell development and function .", "When BCRs are cross-linked by antigens , it induces the conformational changes of signaling subunits immunoglobulin α chain ( Igα ) and immunoglobulin β chain ( Igβ ) .", "The conformational changes of Igα and Igβ lea...	[ "As the central hub of the metabolism machinery , the mammalian target of rapamycin complex 2 ( mTORC2 ) has been well studied in lymphocytes .", "As an obligatory component of mTORC2 , the role of Rictor in T cells is well established .", "However , the role of Rictor in B cells still remains elusive .", "Ri...	[ "As the central hub of cell metabolism , the mammalian target of rapamycin complex ( mTORC ) integrates immune signals and metabolic cues for the maintenance and activation of these systems .", "Rictor is the core component of the mammalian target of rapamycin complex 2 ( mTORC2 ) , and loss of this protein leads...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "infectious diseases/bacterial infections", "cell biology" ]	Wolbachia-Mediated Cytoplasmic Incompatibility Is Associated with Impaired Histone Deposition in the Male Pronucleus	journal.ppat.1000343	null	[ [ "Wolbachia are intracellular bacteria that infect some 65% of all insect species [1] .", "Their success is in large part due to their efficient maternal transmission and their ability to alter host reproduction such that infected females produce more offspring than uninfected females [2] .", "The most...	[ "Wolbachia is a bacteria endosymbiont that rapidly infects insect populations through a mechanism known as cytoplasmic incompatibility ( CI ) .", "In CI , crosses between Wolbachia-infected males and uninfected females produce severe cell cycle defects in the male pronucleus resulting in early embryonic lethality...	[ "Wolbachia are among the most successful of all intracellular bacteria , infecting an estimated 65% of insect species .", "Wolbachia are also present in filarial nematodes and are the cause of African river blindness .", "Wolbachia's success is due in part to its ability to induce a conditional form of sterilit...	2009
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "neuroscience/neuronal signaling mechanisms", "neuroscience/neurobiology of disease and regeneration" ]	Pro-Survival Role for Parkinson's Associated Gene DJ-1 Revealed in Trophically Impaired Dopaminergic Neurons	journal.pbio.1000349	A mouse genetic study reveals a novel cell-survival role for the Parkinson's disease-associated gene DJ-1 in dopaminergic neurons that have reduced support from endogenous survival factors.	[ [ "Specific and progressive loss of substantia nigra ( SN ) neurons is the central pathogenic event in Parkinson disease ( PD ) , the most common movement neurodegenerative disorder , characterized by tremor , rigidity , and bradykinesia .", "A second pathological feature of PD is the presence of aggregated...	[ "The mechanisms underlying the selective death of substantia nigra ( SN ) neurons in Parkinson disease ( PD ) remain elusive .", "While inactivation of DJ-1 , an oxidative stress suppressor , causes PD , animal models lacking DJ-1 show no overt dopaminergic ( DA ) neuron degeneration in the SN .", "Here , we sh...	[ "The major pathological event in Parkinson disease is the loss of dopaminergic neurons in a midbrain structure , the substantia nigra .", "The study of familial Parkinson disease has uncovered several disease-associated genes , including DJ-1 .", "Subsequent studies have suggested that the DJ-1 protein is a sup...	2010
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "biology" ]	Identification of Genetic Determinants and Enzymes Involved with the Amidation of Glutamic Acid Residues in the Peptidoglycan of Staphylococcus aureus	journal.ppat.1002508	null	[ [ "Peptidoglycan forms an essential stress-bearing and shape-maintaining layer in the bacterial cell envelope .", "Its biosynthetic pathway is the target of important classes of antimicrobials such as beta-lactams and glycopeptides , and the polymerized cell wall is targeted by antimicrobial enzymes like ly...	[ "The glutamic acid residues of the peptidoglycan of Staphylococcus aureus and many other bacteria become amidated by an as yet unknown mechanism .", "In this communication we describe the identification , in the genome of S . aureus strain COL , of two co-transcribed genes , murT and gatD , which are responsible ...	[ "Genetic determinants and enzymes that catalyze the multiple steps in the assembly of bacterial cell wall peptidoglycan have been known for some time .", "On the other hand , the mechanism by which glutamic acid residues of this structure undergo modification to glutamine has remained unknown .", "In this commu...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biochemistry/transcription and translation", "cell biology/cellular death and stress responses", "biochemistry/cell signaling and trafficking structures", "cell biology/cell signaling" ]	HSP72 Protects Cells from ER Stress-induced Apoptosis via Enhancement of IRE1α-XBP1 Signaling through a Physical Interaction	journal.pbio.1000410	The cytosolic chaperone Hsp72 directly modulates stress sensing in response to the accumulation of unfolded proteins in the endoplasmic reticulum and promotes cell survival.	[ [ "The human Hsp70 family consists of at least 12 members [1] , [2] .", "Of these , the two best studied members are the constitutive or cognate Hsp70 ( Hsc70 ) and a stress inducible form of cytosolic Hsp70 ( Hsp72 ) .", "Hsc70 is constitutively and ubiquitously expressed in tissues and has a basic and...	[ "Endoplasmic reticulum ( ER ) stress is a feature of secretory cells and of many diseases including cancer , neurodegeneration , and diabetes .", "Adaptation to ER stress depends on the activation of a signal transduction pathway known as the unfolded protein response ( UPR ) .", "Enhanced expression of Hsp72 h...	[ "The endoplasmic reticulum ( ER ) is responsible for production and folding of secreted proteins .", "When the protein folding machinery cannot keep up with demand , misfolded proteins accumulate , leading to a state of ER stress that contributes to diseases such as cancer , neurodegeneration , diabetes , and myo...	2010
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Histone Methylation Restrains the Expression of Subtype-Specific Genes during Terminal Neuronal Differentiation in Caenorhabditis elegans	journal.pgen.1004017	null	[ [ "Epigenetic regulation of gene expression , e . g . , through histone modification , is essential to silence key developmental genes , prevent neural differentiation , and maintain the pluripotency of embryonic stem cells ( ESCs ) [1] .", "For example , methylation on the lysine 27 of histone 3 ( H3K27 ) ...	[ "Although epigenetic control of stem cell fate choice is well established , little is known about epigenetic regulation of terminal neuronal differentiation .", "We found that some differences among the subtypes of Caenorhabditis elegans VC neurons , particularly the expression of the transcription factor gene un...	[ "As neurons differentiate they express specific genes that give them their distinctive shapes , activities , and functions .", "Much of this differentiation is controlled by the expression of transcription factors , proteins that turn on the expression of other genes .", "We find , however , that another aspect...	2013

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