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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", "Methods" ]	[ "transfection", "cell death", "autophagic cell death", "gene regulation", "cell processes", "messenger rna", "polyribosomes", "micrornas", "genome analysis", "bioassays and physiological analysis", "molecular biology techniques", "cellular structures and organelles", "bacteria", "research ...	Mycobacterium tuberculosis-induced miR-155 subverts autophagy by targeting ATG3 in human dendritic cells	journal.ppat.1006790	null	[ [ "As estimated by the 2016 global WHO report , Mycobacterium tuberculosis ( Mtb ) , the causative agent of tuberculosis ( TB ) in humans , infects approximately 10 million people each year , making TB the second leading cause of death from an infectious disease worldwide [1] .", "The success of Mtb princip...	[ "Autophagy is a primordial eukaryotic pathway , which provides the immune system with multiple mechanisms for the elimination of invading pathogens including Mycobacterium tuberculosis ( Mtb ) .", "As a consequence , Mtb has evolved different strategies to hijack the autophagy process .", "Given the crucial rol...	[ "Mycobacterium tuberculosis ( Mtb ) is one of the most successful pathogens in human history and remains the second leading cause of death from an infectious agent worldwide .", "The major reason of Mtb success relies on its ability to evade host immunity .", "Autophagy , a cellular mechanism involved in intrac...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "public health and epidemiology/epidemiology", "genetics and genomics" ]	A Genome-Wide Association Study Identifies Novel Alleles Associated with Hair Color and Skin Pigmentation	journal.pgen.1000074	null	[ [ "There is substantial variation in human pigmentation within and across populations .", "Ultraviolet radiation ( UV ) exposure is the most important environmental factor influencing evolutionary selection pressure on pigmentation .", "In addition to UV-induced DNA damage , UVA can break down folic aci...	[ "We conducted a multi-stage genome-wide association study of natural hair color in more than 10 , 000 men and women of European ancestry from the United States and Australia .", "An initial analysis of 528 , 173 single nucleotide polymorphisms ( SNPs ) genotyped on 2 , 287 women identified IRF4 and SLC24A4 as loc...	[ "It has been a longstanding hypothesis that human pigmentation is tightly regulated by genetic variation .", "However , very few genes have been identified that contain common genetic variants associated with human pigmentation .", "We scanned the genome for genetic variants associated with natural hair color a...	2008
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "immune cells", "antigen-presenting cells", "immunity to infections", "immunology", "microbiology", "host-pathogen interaction", "emerging infectious diseases", "inflammation", "microbial pathogens", "biology", "pathogenesis", "monocytes", "immunity", "innate immunity" ]	Humanized TLR4/MD-2 Mice Reveal LPS Recognition Differentially Impacts Susceptibility to Yersinia pestis and Salmonella enterica	journal.ppat.1002963	null	[ [ "The activation of host defense against Gram-negative bacterial pathogens is initiated after recognition of the bioactive component of lipopolysaccharide ( LPS ) , lipid A , through Toll-like receptor ( TLR ) 4 and its coreceptor MD-2 [1]–[4] .", "Variations in lipid A structure exist among diverse bacter...	[ "Although lipopolysaccharide ( LPS ) stimulation through the Toll-like receptor ( TLR ) -4/MD-2 receptor complex activates host defense against Gram-negative bacterial pathogens , how species-specific differences in LPS recognition impact host defense remains undefined .", "Herein , we establish how temperature d...	[ "The outer leaflet of the outer membrane of Gram-negative bacteria is mainly composed of lipopolysaccharide ( LPS , endotoxin ) .", "The structure of the bioactive component of LPS , lipid A , varies between bacteria and even within the same species grown under different environmental conditions .", "Yersinia p...	2012
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "medicine and health sciences", "decision making", "geographical locations", "tropical diseases", "neuroscience", "ethnicities", "mathematics", "forecasting", "statistics (mathematics)", "cognition", "neglected tropical diseases", "infectious disease control", "research and analysis methods"...	Challenges in Real-Time Prediction of Infectious Disease: A Case Study of Dengue in Thailand	journal.pntd.0004761	null	[ [ "Producing accurate and actionable forecasts of infectious disease incidence at short and long time scales will improve public health response to outbreaks .", "Real-time forecasts of infectious disease outbreaks can facilitate targeted intervention and prevention strategies , such as increased healthcare...	[ "Epidemics of communicable diseases place a huge burden on public health infrastructures across the world .", "Producing accurate and actionable forecasts of infectious disease incidence at short and long time scales will improve public health response to outbreaks .", "However , scientists and public health of...	[ "Predicting the course of infectious disease outbreaks in real-time is a challenging task .", "It requires knowledge of the particular disease system as well as a pipeline that can turn raw data from a public health surveillance system into calibrated predictions of disease incidence .", "Dengue is a mosquito-b...	2016
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "medicine and health sciences", "engineering and technology", "anesthesiology", "information processing", "prefrontal cortex", "signal processing", "brain", "vertebrates", "animals", "mammals", "signal filtering", "mathematics", "pharmaceutics", "anesthesia", "information technology", ...	Breakdown of local information processing may underlie isoflurane anesthesia effects	journal.pcbi.1005511	null	[ [ "To this day it is an open question in anesthesia research how general anesthesia leads to loss of consciousness ( LOC ) .", "Several recent theories agree in proposing that anesthesia-induced LOC may be caused by the disruption of long range inter-areal information transfer in cortex [1–5]—a hypothesis s...	[ "The disruption of coupling between brain areas has been suggested as the mechanism underlying loss of consciousness in anesthesia .", "This hypothesis has been tested previously by measuring the information transfer between brain areas , and by taking reduced information transfer as a proxy for decoupling .", ...	[ "Currently we do not understand how anesthesia leads to loss of consciousness ( LOC ) .", "One popular idea is that we loose consciousness when brain areas lose their ability to communicate with each other–as anesthetics might interrupt transmission on nerve fibers coupling them .", "This idea has been tested b...	2017
[ "Introduction", "Results/Discussion", "Methods" ]	[]	The Hydrophobic Temperature Dependence of Amino Acids Directly Calculated from Protein Structures	journal.pcbi.1004277	null	[ [ "When a protein folds , hydrophobic amino acids get buried inside the protein to form a hydrophobic core .", "Inside this core the hydrophobic side chains are shielded from the water .", "The tendency of hydrophobic groups to cluster together when they are put into water—or the hydrophobic effect—is t...	[ "The hydrophobic effect is the main driving force in protein folding .", "One can estimate the relative strength of this hydrophobic effect for each amino acid by mining a large set of experimentally determined protein structures .", "However , the hydrophobic force is known to be strongly temperature dependent...	[ "In general , proteins become functional once they fold into a specific globular structure .", "On folding , hydrophobic amino acids get buried inside the protein such that they are shielded from the water; this hydrophobic effect makes a protein fold stable .", "However , the strength of the hydrophobicity is ...	2015
[ "Introduction", "Results/Discussion", "Materials and Methods" ]	[ "computational biology/transcriptional regulation", "computational biology/molecular genetics", "genetics and genomics/nuclear structure and function", "genetics and genomics/epigenetics", "genetics and genomics/plant genetics and gene expression" ]	Effects of Aneuploidy on Genome Structure, Expression, and Interphase Organization in Arabidopsis thaliana	journal.pgen.1000226	null	[ [ "Changes in the number of chromosomes from the normal diploid set can be grouped into", "two types: polyploidy and aneuploidy .", "Polyploidy refers to whole genome duplications", "whereas aneuploidy refers to unbalanced losses and/or gains of individual", "chromosomes , or parts of chromosome...	[ "Aneuploidy refers to losses and/or gains of individual chromosomes from the", "normal chromosome set .", "The resulting gene dosage imbalance has a noticeable", "affect on the phenotype , as illustrated by aneuploid syndromes , including Down", "syndrome in humans , and by human solid tumor cells , which a...	[ "Most plants and animals have two copies of each chromosome in the normal", "chromosome set .", "Unbalanced numerical changes resulting from gains or losses of", "individual chromosomes ( aneuploidy ) usually have deleterious consequences .", "For", "example , Down syndrome in humans is caused by an extra...	2008
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "medicine and health sciences", "vesicles", "cell viability testing", "pathology and laboratory medicine", "tropical diseases", "parasitic diseases", "toxicology", "animal models", "toxicity", "model organisms", "pharmaceutics", "oils", "neglected tropical diseases", "bioassays and physiol...	Screening of the Open Source Malaria Box Reveals an Early Lead Compound for the Treatment of Alveolar Echinococcosis	journal.pntd.0004535	null	[ [ "The metacestode stages of the two cestode species Echinococcus granulosus sensu lato and E . multilocularis cause cystic echinococcosis ( CE ) and alveolar echinococcosis ( AE ) , respectively .", "Worldwide , CE is more abundant and accounts for more than 1 million DALYs ( disability-adjusted life years...	[ "The metacestode ( larval ) stage of the tapeworm Echinococcus multilocularis causes alveolar echinococcosis ( AE ) , a very severe and in many cases incurable disease .", "To date , benzimidazoles such as albendazole and mebendazole are the only approved chemotherapeutical treatment options .", "Benzimidazoles...	[ "The fox tapeworm Echinococcus multilocularis causes a deadly disease in humans that is characterized by cancer-like parasite growth in the liver of patients .", "Hence E . multilocularis is ideally removed by radical resection .", "However , as this is not always possible , patients are treated by chemotherapy...	2016
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "neuroscience/motor systems", "neuroscience/sensory systems" ]	Slower Visuomotor Corrections with Unchanged Latency are Consistent with Optimal Adaptation to Increased Endogenous Noise in the Elderly	journal.pcbi.1000708	null	[ [ "We used a computational model to improve the precision of the response latency estimates and to investigate quantitatively the slowing of the post-onset response .", "The structure of this continuous linear feedback control task is suited to modeling using concepts from Linear Quadratic Gaussian ( LQG ) ...	[ "We analyzed age-related changes in motor response in a visuomotor compensatory tracking task .", "Subjects used a manipulandum to attempt to keep a displayed cursor at the center of a screen despite random perturbations to its location .", "Cross-correlation analysis of the perturbation and the subject respons...	[ "In a hand-eye coordination task that requires continuous movement to correct for a disturbance , it turns out that signs of response to the disturbance appear no later in the elderly than in the young .", "The elderly motion is noisy and less efficient , however , and once movements in response to a disturbance ...	2010
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "gene function", "mycology", "model organisms", "genome evolution", "genetics", "biology and life sciences", "yeast and fungal models", "microbiology", "computational biology", "evolutionary biology", "research and analysis methods" ]	Genes That Bias Mendelian Segregation	journal.pgen.1004387	null	[ [ "In many organisms , genetic factors , called Meiotic Drive Elements ( MDs ) , have found ways to break Mendel's laws of heredity .", "MDs skew the expected 1∶1 ratio in their favor and are thus overrepresented in the progeny after meiosis .", "They have been observed in metazoans , plants and fungi [...	[ "Mendel laws of inheritance can be cheated by Meiotic Drive Elements ( MDs ) , complex nuclear genetic loci found in various eukaryotic genomes and distorting segregation in their favor .", "Here , we identify and characterize in the model fungus Podospora anserina Spok1 and Spok2 , two MDs known as Spore Killers...	[ "Chromosome segregation during meiosis ensures that paternal and maternal chromosomes are equally transmitted to the progeny .", "Meiotic Drive Elements ( MDs ) are known to distort this 1∶1 ratio in many animal , plant , and fungal species by killing the gametes not carrying them .", "Most of the known MDs are...	2014
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "taxonomy", "medicine and health sciences", "ecology and environmental sciences", "surface water", "water resources", "giardiasis", "giardia", "demography", "geographical locations", "tropical diseases", "social sciences", "anthropology", "parasitic diseases", "parasitic protozoans", "ph...	Giardiasis as a neglected disease in Brazil: Systematic review of 20 years of publications	journal.pntd.0006005	null	[ [ "Giardia duodenalis is a non-invasive protozoan that attaches to the mucosa of the small intestine in infected hosts leading to giardiasis—a disease that is characterized by a range of clinical symptoms ( mild , moderate , or severe ) or even asymptomatic infection in many cases .", "Giardiasis affects mo...	[ "Giardiasis is an intestinal infection that affects more than two hundred million people annually worldwide; it is caused by the flagellated protozoan Giardia duodenalis .", "In tropical countries and in low or middle-income settings , like Brazil , its prevalence can be high .", "There is currently no systemat...	[ "Giardiasis is an intestinal disease that affect millions of people worldwide , including children .", "Its main route of transmission is by ingestion of food or water contaminated with the protozoan G . duodenalis .", "Transmission does not require an animal host , although transmission from animals to human (...	2017
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "taxonomy", "medicine and health sciences", "canada", "pathology and laboratory medicine", "pathogens", "population dynamics", "geographical locations", "microbiology", "vertebrates", "animals", "mammals", "viruses", "north america", "phylogenetics", "data management", "rna viruses", ...	The phylogeography of Myotis bat-associated rabies viruses across Canada	journal.pntd.0005541	null	[ [ "With the emergence of several recently identified viruses , including Hendra , Nipah and SARS viruses , members of the order Chiroptera have assumed significant importance as the presumptive reservoirs of many zoonotic diseases [1] .", "Most of the 14 recognised species of the Lyssavirus genus , the etio...	[ "As rabies in carnivores is increasingly controlled throughout much of the Americas , bats are emerging as a significant source of rabies virus infection of humans and domestic animals .", "Knowledge of the bat species that maintain rabies is a crucial first step in reducing this public health problem .", "In N...	[ "Reducing the public health burden of rabies is most effectively achieved by elimination of the disease from its hosts .", "While the role of dogs and many wild carnivore species in maintaining and transmitting rabies virus is well established , our understanding of the role of many bat species in this regard is ...	2017
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "somatosensory system", "hiv infections", "medicine and health sciences", "pathology and laboratory medicine", "highly-active antiretroviral therapy", "nervous system", "antiviral therapy", "pathogens", "immunology", "tropical diseases", "microbiology", "neuroscience", "retroviruses", "vir...	Peripheral nerve abnormality in HIV leprosy patients	journal.pntd.0006633	null	[ [ "Leprosy and human immunodeficiency virus ( HIV ) infection are two diseases of public health importance in the world .", "The increasing geographical overlap of these endemic and pandemic diseases may increase the number of individuals with both diseases in the world .", "In 2016 , Brazil had an over...	[ "The geographical overlap of HIV ( human immunodeficiency virus ) and leprosy infection has become increasingly frequent and worrying , bringing many clinical issues .", "Peripheral neuropathy is very frequent in leprosy because of the predilection of its etiologic agent by Schwann cells of the peripheral nervous...	[ "Coinfections of leprosy and HIV are a challenge for clinical management , particularly concerning peripheral neuropathy , which is common in leprosy and is also present in HIV infection .", "We conducted a clinical follow-up of leprosy patients coinfected with HIV and compared them to patients with leprosy alone...	2018
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "computational neuroscience", "single neuron function", "biology", "sensory systems", "neuroscience", "coding mechanisms" ]	Temporal Encoding in a Nervous System	journal.pcbi.1002041	null	[ [ "A considerable amount of research has been focused on determining the information coding schemes used within nervous systems .", "This is due not only to the intrinsic interest in the nature of the neural code , but to the necessity of understanding the coding scheme implemented within any particular sys...	[ "We examined the extent to which temporal encoding may be implemented by single neurons in the cercal sensory system of the house cricket Acheta domesticus .", "We found that these neurons exhibit a greater-than-expected coding capacity , due in part to an increased precision in brief patterns of action potential...	[ "The information coding schemes used within nervous systems have been the focus of an entire field within neuroscience .", "An unresolved issue within the general coding problem is the determination of the neural “symbols” with which information is encoded in neural spike trains , analogous to the determination o...	2011
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine and health sciences", "rna interference", "chemical compounds", "disaccharides", "gene regulation", "appetite", "carbohydrates", "neuroscience", "organic compounds", "physiological processes", "micrornas", "eating", "epigenetics", "molecular biology techniques", "research and a...	A fat-derived metabolite regulates a peptidergic feeding circuit in Drosophila	journal.pbio.2000532	null	[ [ "Animals must balance food intake with energy expenditure to maintain optimal health .", "In choosing what and how much to eat , animals integrate external cues like tastes and smells with internal motivational states like hunger and satiety .", "Powerful homeostatic mechanisms tie these motivational ...	[ "Here , we show that the enzymatic cofactor tetrahydrobiopterin ( BH4 ) inhibits feeding in Drosophila .", "BH4 biosynthesis requires the sequential action of the conserved enzymes Punch , Purple , and Sepiapterin Reductase ( Sptr ) .", "Although we observe increased feeding upon loss of Punch and Purple in the...	[ "As the primary site of energy storage , adipose tissue must somehow monitor energy reserves and communicate this information to the brain .", "The brain must then modulate feeding behavior to maintain energy balance; however , the mechanisms underlying this communication between fat cells and the brain remain po...	2017
[ "Introduction", "Methods", "Results", "Discussion" ]	[]	Airborne Transmission of Melioidosis to Humans from Environmental Aerosols Contaminated with B. pseudomallei	journal.pntd.0003834	null	[ [ "The emerging infectious disease melioidosis is caused by Burkholderia pseudomallei , which is commonly isolated from soil and water in endemic areas such as Southeast Asia and northern Australia [1–5] .", "Melioidosis cases usually cluster during the rainy season , particularly after the appearance of a ...	[ "Melioidosis results from an infection with the soil-borne pathogen Burkholderia pseudomallei , and cases of melioidosis usually cluster after rains or a typhoon .", "In an endemic area of Taiwan , B . pseudomallei is primarily geographically distributed in cropped fields in the northwest of this area , whereas m...	[ "Cases of melioidosis , an emerging disease , are usually clustered after rains or typhoons .", "In Taiwan , the endemic area includes rural cropped fields contaminated with B . pseudomallei in the northwest and a densely populated district in the southeast , where melioidosis-cluster is distributed .", "We hyp...	2015
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "medicine", "infectious diseases", "clinical research design", "giardiasis", "systematic reviews", "parasitic diseases" ]	Efficacy of 5-Nitroimidazoles for the Treatment of Giardiasis: A Systematic Review of Randomized Controlled Trials	journal.pntd.0002733	null	[ [ "Giardiasis is an intestinal illness caused by a flagellated protozoan parasite , Giardia lamblia ( syn . G . intestinalis and G . duodenalis ) .", "The World Health Organization ( WHO ) estimates that 3 billion people reside in places with giardiasis prevalence of around 30% , and suggests that there are...	[ "Giardiasis is one of the most common causes of diarrheal disease worldwide and 5-nitroimidazoles ( 5-NI ) are the most commonly prescribed drugs for the treatment of giardiasis .", "We evaluated the efficacy of 5-nitroimidazoles ( 5-NI ) in the treatment of giardiasis in a systematic review of randomized control...	[ "Giardiasis is a major diarrheal disease with worldwide distribution .", "5-nitroimidazoles , which include metronidazole and tinidazole , are the most commonly used drugs in the treatment of giardiasis .", "In recent years , many other drugs with variable efficacies and adverse effects have been proposed for t...	2014
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "medicine and health sciences", "luciferase", "vesicular stomatitis virus", "pathology and laboratory medicine", "293t cells", "pathogens", "enzymes", "biological cultures", "immunology", "microbiology", "enzymology", "gene regulation", "viruses", "rna viruses", "immunoprecipitation", ...	DHX29 functions as an RNA co-sensor for MDA5-mediated EMCV-specific antiviral immunity	journal.ppat.1006886	null	[ [ "RIG-I-like receptors , Toll-like receptors ( TLRs ) , Nod-like receptors , and DNA sensors are germline-encoded pattern-recognition receptors ( PRRs ) that serve as the first line of defense against invading pathogens , including bacteria and viruses [1 , 2] .", "PRRs possess the abilities to recognize p...	[ "Melanoma differentiation-associated gene-5 ( MDA5 ) recognizes distinct subsets of viruses including Encephalomyocarditis virus ( EMCV ) of picornavirus family , but the molecular mechanisms underlying the specificity of the viral recognition of MDA5 in immune cells remain obscure .", "DHX29 is an RNA helicase r...	[ "Cytosolic sensor melanoma differentiation-associated gene-5 ( MDA5 ) specifically detects long-duplex RNAs in the genome of double-stranded ( ds ) RNA viruses such as Encephalomyocarditis virus ( EMCV ) whereas retinoic acid-inducible gene-I ( RIG-I ) preferentially recognizes vesicular stomatitis virus ( VSV ) to...	2018
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "blood cells", "medicine and health sciences", "immune cells", "pathology and laboratory medicine", "pathogens", "immunology", "microbiology", "vertebrates", "viral structure", "animals", "mammals", "retroviruses", "viruses", "immunodeficiency viruses", "primates", "colobus", "rna vi...	SIVcol Nef counteracts SERINC5 by promoting its proteasomal degradation but does not efficiently enhance HIV-1 replication in human CD4+ T cells and lymphoid tissue	journal.ppat.1007269	null	[ [ "The accessory nef gene is present in the genomes of all primate lentiviruses that infect at least forty different African monkey species as well as great apes and humans .", "Nef performs a striking number of activities [1 , 2] and is required for efficient viral replication and pathogenicity of HIV-1 an...	[ "SERINC5 is a host restriction factor that impairs infectivity of HIV-1 and other primate lentiviruses and is counteracted by the viral accessory protein Nef .", "However , the importance of SERINC5 antagonism for viral replication and cytopathicity remained unclear .", "Here , we show that the Nef protein of t...	[ "The accessory protein Nef promotes primate lentiviral replication and enhances the pathogenicity of HIV-1 by mechanisms of immune evasion and enhancing viral infectivity and replication .", "Here , we show that the evolutionarily most isolated primate lentivirus SIVcol lacks several otherwise conserved Nef funct...	2018
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "viral vaccines", "medicine and health sciences", "immune physiology", "immunology", "microbiology", "vaccines", "preventive medicine", "phase iii clinical investigation", "age groups", "clinical medicine", "pharmacology", "vaccination and immunization", "research and analysis methods", "p...	Safety Overview of a Recombinant Live-Attenuated Tetravalent Dengue Vaccine: Pooled Analysis of Data from 18 Clinical Trials	journal.pntd.0004821	null	[ [ "Dengue is a viral infection found in tropical and subtropical regions of the world that causes flu-like illness and can , in severe cases , result in death [1] .", "The disease is caused by four serotypes of dengue virus ( Flaviviridae ) , DENV1-4 which are transmitted by Aedes mosquitoes .", "The in...	[ "A recombinant live attenuated tetravalent dengue vaccine ( CYD-TDV ) has been shown to be efficacious in preventing virologically-confirmed dengue disease , severe dengue disease and dengue hospitalization in children aged 2–16 years in Asia and Latin America .", "We analyzed pooled safety data from 18 phase I ,...	[ "Dengue is a mosquito-borne viral infection in tropical and subtropical regions of the world that causes flu-like illness and , in severe cases , death .", "Every year , 390 million dengue infections occur worldwide , and over 3 . 9 billion people are now at risk from the disease .", "Although mosquito control ...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genetics and genomics/gene function", "biochemistry/transcription and translation", "molecular biology", "cell biology/gene expression" ]	Evolutionary Conserved Regulation of HIF-1β by NF-κB	journal.pgen.1001285	null	[ [ "Hypoxia Inducible Factor-1 ( HIF-1 ) is a transcription factor which is part of a stress response mechanism that is initiated in the presence of low oxygen tensions .", "Moreover , HIF has been demonstrated to play key roles in development , physiological processes and pathological conditions as its pres...	[ "Hypoxia Inducible Factor-1 ( HIF-1 ) is essential for mammalian development and is the principal transcription factor activated by low oxygen tensions .", "HIF-α subunit quantities and their associated activity are regulated in a post-translational manner , through the concerted action of a class of enzymes call...	[ "The mechanisms by which cells and organisms respond to oxygen are of extreme importance for development and also for certain pathologies such as cancer , ageing , and ischemia .", "These are mediated by a family of transcription factors called hypoxia inducible factor ( HIF ) , a factor that coordinates expressi...	2011
[ "Introduction", "Results/Discussion", "Methods" ]	[ "genetics and genomics/complex traits", "diabetes and endocrinology/obesity", "diabetes and endocrinology", "genetics and genomics", "diabetes and endocrinology/type 2 diabetes" ]	Genome-Wide Association Scan Meta-Analysis Identifies Three Loci Influencing Adiposity and Fat Distribution	journal.pgen.1000508	null	[ [ "The accumulation of abnormal amounts of intra-abdominal fat ( central adiposity ) is associated with serious adverse metabolic and cardiovascular outcomes , including type 2 diabetes ( T2D ) and atherosclerotic heart disease [1] .", "Indeed , because the medical consequences of increasing fat mass are di...	[ "To identify genetic loci influencing central obesity and fat distribution , we performed a meta-analysis of 16 genome-wide association studies ( GWAS , N = 38 , 580 ) informative for adult waist circumference ( WC ) and waist–hip ratio ( WHR ) .", "We selected 26 SNPs for follow-up , for which the evidence of as...	[ "Here , we describe a meta-analysis of genome-wide association data from 38 , 580 individuals , followed by large-scale replication ( in up to 70 , 689 individuals ) designed to uncover variants influencing anthropometric measures of central obesity and fat distribution , namely waist circumference ( WC ) and waist...	2009
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "neural networks", "computational neuroscience", "biology", "neuroscience" ]	External Drive to Inhibitory Cells Induces Alternating Episodes of High- and Low-Amplitude Oscillations	journal.pcbi.1002666	null	[ [ "Oscillations in electrical activity are a characteristic feature of many brain networks , including the hippocampus [1] , [2] , prefrontal cortex [3] , visual cortex [4] , [5] and auditory cortex [6] , and arise as a result of interacting excitatory and inhibitory populations of cells [7] , [8] , [9] .", ...	[ "Electrical oscillations in neuronal network activity are ubiquitous in the brain and have been associated with cognition and behavior .", "Intriguingly , the amplitude of ongoing oscillations , such as measured in EEG recordings , fluctuates irregularly , with episodes of high amplitude alternating with episodes...	[ "Rhythmic changes in electrical activity are observed throughout the brain , and arise as a result of reciprocal interactions between excitatory and inhibitory neurons .", "Synchronized activity of a large number of neurons gives rise to macroscopic oscillations in electrical activity , which can be measured in E...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "blood cells", "medicine and health sciences", "body fluids", "immune cells", "pathology and laboratory medicine", "immunology", "tropical diseases", "parasitic diseases", "animal models", "bone marrow cells", "model organisms", "signs and symptoms", "research and analysis methods", "white...	STING-Licensed Macrophages Prime Type I IFN Production by Plasmacytoid Dendritic Cells in the Bone Marrow during Severe Plasmodium yoelii Malaria	journal.ppat.1005975	null	[ [ "Malaria still remains a significant global health problem worldwide with 214 million people infected ( range 149–303 million , WHO 2015 ) , and half a million deaths each year [1 , 2] .", "Death occurs as a result of severe malaria , a multi-systemic disorder resulting from blood stage Plasmodium infecti...	[ "Malaria remains a global health burden causing significant morbidity , yet the mechanisms underlying disease outcomes and protection are poorly understood .", "Herein , we analyzed the peripheral blood of a unique cohort of Malawian children with severe malaria , and performed a comprehensive overview of blood l...	[ "The Plasmodium parasite is the number one killer among human parasitic diseases worldwide .", "Protection is associated with length of exposure for people living in endemic areas , with severe disease primarily affecting young children .", "Inflammation is a key component in the pathophysiology in malaria , an...	2016
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "cell binding", "cell physiology", "medicine and health sciences", "gene regulation", "regulatory proteins", "carcinomas", "dna-binding proteins", "cancers and neoplasms", "oncology", "transcription factors", "adenocarcinomas", "bioassays and physiological analysis", "epigenetics", "chroma...	Open chromatin profiling identifies AP1 as a transcriptional regulator in oesophageal adenocarcinoma	journal.pgen.1006879	null	[ [ "The incidence of oesophageal adenocarcinoma ( OAC ) in the Western world is increasing and five and ten year survival rates remain low [1 , 2] .", "In comparison to many other cancers , there is a general lack of knowledge about biomarkers and potential therapeutic targets , contributing to the poor prog...	[ "Oesophageal adenocarcinoma ( OAC ) is one of the ten most prevalent forms of cancer and is showing a rapid increase in incidence and yet exhibits poor survival rates .", "Compared to many other common cancers , the molecular changes that occur in this disease are relatively poorly understood .", "However , gen...	[ "Oesophageal adenocarcinoma is one of the ten most prevalent forms of cancer and is showing a rapid increase in incidence and yet exhibits poor survival rates .", "Understanding the molecular causes of this type of cancer will enable us develop more effective treatment strategies which will improve survival rates...	2017
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "parasitic diseases", "infectious diseases", "medicine and health sciences", "protozoan infections" ]	Sarcocystis nesbitti Causes Acute, Relapsing Febrile Myositis with a High Attack Rate: Description of a Large Outbreak of Muscular Sarcocystosis in Pangkor Island, Malaysia, 2012	journal.pntd.0002876	null	[ [ "Sarcocystis spp .", "are intracellular protozoan parasites which may involve humans either as definitive or intermediate hosts .", "Humans are definitive hosts for Sarcocystis hominis and Sarcocystis suihominis , acquired by consuming undercooked sarcocyst-containing beef or pork , respectively .", ...	[ "From the 17th to 19th January 2012 , a group of 92 college students and teachers attended a retreat in a hotel located on Pangkor Island , off the west coast of Peninsular Malaysia .", "Following the onset of symptoms in many participants who presented to our institute , an investigation was undertaken which ult...	[ "Sarcocystis species are protozoan organisms that have been associated with disease in animals but less frequently so in humans .", "Following a retreat on Pangkor Island off Peninsular Malaysia , a number of persons presented to our hospital with prolonged fever and muscle pain that was initially difficult to at...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "developmental biology", "genetic mutation", "gene expression", "genetics", "molecular genetics", "biology", "genetics and genomics" ]	Akirin Links Twist-Regulated Transcription with the Brahma Chromatin Remodeling Complex during Embryogenesis	journal.pgen.1002547	null	[ [ "A fundamental question in embryonic development is how diverse cell lineages are specified , patterned and organized from a single common progenitor .", "These processes are governed by distinct gene expression programs administered by tightly regulated transcription factor activities during embryonic de...	[ "The activities of developmentally critical transcription factors are regulated via interactions with cofactors .", "Such interactions influence transcription factor activity either directly through protein–protein interactions or indirectly by altering the local chromatin environment .", "Using a yeast double-...	[ "The proper development of the diverse array of cell types in an organism depends upon the induction and repression of specific genes at particular times and places .", "This gene regulation requires both the activity of tissue-specific transcriptional regulators and the modulation of the chromatin environment ."...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "bacteriology", "mutation", "microbial mutation", "streptococci", "microbial evolution", "population genetics", "biology", "microbiology", "population biology", "bacterial evolution", "genetics and genomics", "bacterial pathogens" ]	Frequent Beneficial Mutations during Single-Colony Serial Transfer of Streptococcus pneumoniae	journal.pgen.1002232	null	[ [ "Spontaneous mutations provide the underlying variability on which selection acts to drive evolution .", "Among newly-arising mutations that impact fitness , the balance between those that are beneficial and those that are deleterious has appeared to be heavily skewed toward maladaptive changes .", "T...	[ "The appearance of new mutations within a population provides the raw material for evolution .", "The consistent decline in fitness observed in classical mutation accumulation studies has provided support for the long-held view that deleterious mutations are more common than beneficial mutations .", "Here we pr...	[ "Beneficial mutations have long been considered extremely rare events and were thought to occur with a frequency of approximately one out of a billion times that a bacterium replicates its genome .", "Rare beneficial mutations would then be amplified by natural selection from the more frequent background of harmf...	2011
[ "Introduction", "Materials and Methods", "Results and Discussion" ]	[ "veterinary science" ]	Population Genetics of Trypanosoma evansi from Camel in the Sudan	journal.pntd.0001196	null	[ [ "Trypanosoma evansi is the most widely distributed of the pathogenic animal trypanosomes , affecting domesticated livestock in Asia , Africa and Central , South America , Canaries Island and recently in Europe ( Spain and France ) [1–2–3–4] ) .", "Until recently , countries were obligated to declare to th...	[ "Genetic variation of microsatellite loci is a widely used method for the analysis of population genetic structure of microorganisms .", "We have investigated genetic variation at 15 microsatellite loci of T . evansi isolated from camels in Sudan and Kenya to evaluate the genetic information partitioned within an...	[ "Trypanosomiasis due to Trypanosoma evansi is a widely distributed disease of livestock , affecting especially camelids and equines and is transmitted by biting flies .", "The disease is of great concern to many developing countries such as Sudan , where its large camel population estimated at over 4 . 6 million ...	2011
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "medicine", "bacterial diseases", "infectious diseases", "immunoassays", "immunology", "biology", "immunologic techniques", "rickettsia" ]	Cytokine Network in Scrub Typhus: High Levels of Interleukin-8 Are Associated with Disease Severity and Mortality	journal.pntd.0002648	null	[ [ "Scrub typhus is a multi-system infection caused by the obligate intracellular gram-negative , vector-borne bacteria Orientia tsutsugamushi ( O . tsutsugamushi ) .", "It is endemic in the Asia-Pacific region , with around one million cases yearly and one billion people at risk [1] .", "As it is transm...	[ "Scrub typhus , caused by Orientia tsutsugamushi , is endemic in the Asia-Pacific region .", "Mortality is high if untreated , and even with treatment as high as 10–20% , further knowledge of the immune response during scrub typhus is needed .", "The current study was aimed at comparing plasma levels of a varie...	[ "Scrub typhus is a potentially fatal disease affecting at least 1 million people yearly , with 1 billion at risk in the Asia-Pacific region .", "Caused by the bacterium Orientia tsutsugamushi , which is transmitted by mites , people with more outdoor activities , like farmers and construction workers , often low-...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "viruses", "virology", "in vitro", "eukaryotes", "homo (human)" ]	Evidence for Direct Involvement of the Capsid Protein in HIV Infection of Nondividing Cells	journal.ppat.0030156	null	[ [ "One of the properties that set HIV-1 and other lentiviruses apart from most of the other retroviruses is the ability to infect cells independent of the cell cycle [1 , 2] .", "This ability allows HIV-1 to propagate in nondividing cells in vivo such as resting CD4+ T cells [3] and terminally differentiate...	[ "HIV and other lentiviruses can productively infect nondividing cells , whereas most other retroviruses , such as murine leukemia virus , require cell division for efficient infection .", "However , the determinants for this phenotype have been controversial .", "Here , we show that HIV-1 capsid ( CA ) is invol...	[ "HIV and related viruses are unusual among retroviruses in their ability to replicate independently of cell-cycle progression of target cells .", "However , the determinants of this phenotype have been controversial .", "Here , we identified mutations on the surface of the capsid ( CA ) protein that reduce the ...	2007
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "urology", "medicine and health sciences", "anoxia", "pulmonology", "germ cells", "developmental biology", "oocytes", "evolutionary adaptation", "population biology", "embryos", "fecundity", "medical hypoxia", "embryology", "animal cells", "evolutionary genetics", "biochemistry", "po...	Adaptation to Temporally Fluctuating Environments by the Evolution of Maternal Effects	journal.pbio.1002388	What strategies do organisms evolve to cope with an environment that varies between generations? An experimental evolution study reveals that nematode mothers evolve glycogen provisioning to protect their embryos from fluctuating oxygen levels.	[ [ "All organisms live in temporally fluctuating environments , for example , when the environmental conditions change regularly across seasons or when environmental conditions change erratically across a range of time spans .", "Adaptation to these environments can happen by the evolution of different degre...	[ "All organisms live in temporally fluctuating environments .", "Theory predicts that the evolution of deterministic maternal effects ( i . e . , anticipatory maternal effects or transgenerational phenotypic plasticity ) underlies adaptation to environments that fluctuate in a predictably alternating fashion over ...	[ "Mothers can influence the phenotype of their offspring , independently of the genes that they transmit to them; such phenomena are known as “maternal effects . ”", "Theory suggests that maternal effects can be advantageous when the environment changes between generations , but a direct demonstration of this has ...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	MicroRNA-Gene Association As a Prognostic Biomarker in Cancer Exposes Disease Mechanisms	journal.pcbi.1003351	null	[ [ "Micro RNAs ( miRs ) are small , endogenous non-coding RNA molecules that control gene expression by inhibiting translation or inducing cleavage of target mRNAs .", "The role of miRs as key regulators of a wide variety of fundamental cellular processes , such as proliferation , apoptosis , differentiation...	[ "The transcriptional networks that regulate gene expression and modifications to this network are at the core of the cancer phenotype .", "MicroRNAs , a well-studied species of small non-coding RNA molecules , have been shown to have a central role in regulating gene expression as part of this transcriptional net...	[ "Despite major progress and improved understanding of Glioblastoma Multiforme , the disease is still associated with poor prognosis .", "The identification of genomic regulatory mechanisms , their affiliation with clinical outcome and the association between specific modifications in genome sequence that can expl...	2013
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "genome-wide association studies", "replication studies", "quantitative traits", "research design", "genomic databases", "mathematics", "statistics (mathematics)", "test statistics", "genome analysis", "research and analysis methods", "mathematical and statistical techniques", "statistical met...	Statistical correction of the Winner’s Curse explains replication variability in quantitative trait genome-wide association studies	journal.pgen.1006916	null	[ [ "Genome-wide association studies ( GWAS ) have identified thousands of genetic variants associated with complex human traits [1] .", "GWAS are most commonly two-stage designs , with a discovery study followed up by ( possibly several ) internal replication studies on independent samples .", "Due to th...	[ "Genome-wide association studies ( GWAS ) have identified hundreds of SNPs responsible for variation in human quantitative traits .", "However , genome-wide-significant associations often fail to replicate across independent cohorts , in apparent inconsistency with their apparent strong effects in discovery cohor...	[ "The majority of associations between common genetic variation and human traits come from genome-wide association studies , which have analyzed millions of single-nucleotide polymorphisms in millions of samples .", "These kinds of studies pose serious statistical challenges to discovering new associations .", "...	2017
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "developmental biology", "model organisms", "genetics", "biology", "neuroscience", "genetics and genomics" ]	The Rac GTP Exchange Factor TIAM-1 Acts with CDC-42 and the Guidance Receptor UNC-40/DCC in Neuronal Protrusion and Axon Guidance	journal.pgen.1002665	null	[ [ "In a developing nervous system , axonal growth happens via extension and migration of the growth cone , an actin-rich neuronal structure from which filopodial and lamellipodial structures emanate in order to sense the surrounding environment for appropriate guidance cues [1]–[5] .", "Guidance receptors s...	[ "The mechanisms linking guidance receptors to cytoskeletal dynamics in the growth cone during axon extension remain mysterious .", "The Rho-family GTPases Rac and CDC-42 are key regulators of growth cone lamellipodia and filopodia formation , yet little is understood about how these molecules interact in growth c...	[ "Axons extend great distances to make precise synaptic connections in the developing nervous system .", "Axons are guided to their targets by the growth cone , a dynamic structure at the axon distal tip that senses extracellular cues telling the axon where to go .", "In response to guidance cues , growth cones ...	2012
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[]	Reciprocity between Regulatory T Cells and Th17 Cells: Relevance to Polarized Immunity in Leprosy	journal.pntd.0004338	null	[ [ "Leprosy is a disease of immunological spectrum tightly correlating with the extent of pathology and clinical manifestation [1] .", "It is well known that T cell defect is a distinctive feature in lepromatous leprosy ( LL ) in contrast to that of tuberculoid leprosy ( TT ) patients .", "In between the...	[ "T cell defect is a common feature in lepromatous or borderline lepromatous leprosy ( LL/BL ) patients in contrast to tuberculoid or borderline tuberculoid type ( TT/BT ) patients .", "Tuberculoid leprosy is characterized by strong Th1-type cell response with localized lesions whereas lepromatous leprosy is hallm...	[ "Polarized T cell response ( Th1/Th2 biased ) to Mycobacterium leprae ( M . leprae ) is believed to be a critical element in the pathogenesis of leprosy and its varied clinical manifestations .", "However , immune response at the pathologic sites of leprosy is an extremely complex process , particularly in the li...	2016
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "medicine", "public health and epidemiology", "clinical research design", "infectious disease epidemiology", "african trypanosomiasis", "parasitic diseases", "phase ii", "neglected tropical diseases", "population biology", "infectious disease control", "infectious diseases", "phase iii", "ep...	Safety and Efficacy of the 10-Day Melarsoprol Schedule for the Treatment of Second Stage Rhodesiense Sleeping Sickness	journal.pntd.0001695	null	[ [ "Human African Trypanosomiasis ( HAT ) , better known as sleeping sickness , is transmitted through tsetse flies ( Glossina ssp . ) .", "The disease occurs in a chronic form caused by Trypanosoma brucei gambiense ( West and Central Africa ) and an acute form caused by Trypanosoma brucei rhodesiense ( East...	[ "Assessment of the safety and efficacy of a 10-day melarsoprol schedule in second stage T . b . rhodesiense patients and the effect of suramin-pretreatment on the incidence of encephalopathic syndrome ( ES ) during melarsoprol therapy .", "Sequential conduct of a proof-of-concept trial ( n = 60 ) and a utilizatio...	[ "Human African Trypanosomiasis ( HAT ) is a parasitic disease that occurs in a chronic form caused by T . b . gambiense in West and Central Africa and in an acute form caused by T . b . rhodesiense in East and South Africa .", "In the first stage of the disease parasites are detectable in blood and lymph .", "O...	2012
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "infectious diseases", "infectious diseases/neglected tropical diseases", "infectious diseases/helminth infections", "public health and epidemiology/infectious diseases", "hematology/anemias", "infectious diseases/protozoal infections", "infectious diseases/epidemiology and control of infectious disease...	Controlling Schistosomiasis: Significant Decrease of Anaemia Prevalence One Year after a Single Dose of Praziquantel in Nigerien Schoolchildren	journal.pntd.0000241	null	[ [ "Schistosoma haematobium is endemic in Niger , particularly throughout the Niger River valley and in villages in close proximity to permanent and temporary ponds [1]–[3] .", "The prevalence of infection is highly variable from one village to another .", "School-aged children are more often and more he...	[ "In the framework of the monitoring and evaluation of the Nigerien schistosomiasis and soil-transmitted helminth control programme , a follow-up of children took place in eight sentinel sites .", "The objective of the study was to assess the evolution of Schistosoma haematobium infection and anaemia in schoolchil...	[ "The World Health Organization's recommendation for the control of urinary schistosomiasis is to reduce morbidity by reducing the prevalence of heavy infections .", "In Niger , where urinary schistosomiasis is endemic along the Niger River valley and in proximity to ponds , a national control programme for schist...	2008
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine", "cell death", "infectious diseases", "cell biology", "cytomegalovirus infection", "biology", "molecular cell biology", "viral diseases" ]	MCMV-mediated Inhibition of the Pro-apoptotic Bak Protein Is Required for Optimal In Vivo Replication	journal.ppat.1003192	null	[ [ "The cytomegaloviruses ( CMV ) are a family of species-specific viruses that , after acute infection , persist for the life of the host in a latent form and periodically reactivate .", "In order to avoid elimination by the host immune system the CMV utilize an array of immune evasion strategies to interfe...	[ "Successful replication and transmission of large DNA viruses such as the cytomegaloviruses ( CMV ) family of viruses depends on the ability to interfere with multiple aspects of the host immune response .", "Apoptosis functions as a host innate defence mechanism against viral infection , and the capacity to inte...	[ "The cytomegaloviruses ( CMV ) are a family of viruses that establish a latent infection that lasts for the life of the host , with the virus able to reactivate when the host is immunosuppressed .", "We have used murine CMV ( MCMV ) as a model to understand how CMV interferes with the anti-viral immune response ....	2013
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "medicine and health sciences", "dysplasia", "pathology and laboratory medicine", "nuclear staining", "statistics", "cancers and neoplasms", "hormones", "oncology", "multivariate analysis", "histochemistry and cytochemistry techniques", "mathematics", "signs and symptoms", "immunologic techn...	Single-cell RNA-sequencing reveals transcriptional dynamics of estrogen-induced dysplasia in the ovarian surface epithelium	journal.pgen.1007788	null	[ [ "Ovarian cancer is the deadliest gynecological cancer with an overall 5-year survival rate of only 45% .", "However , if detected early , this survival rate increases to 92% [1] .", "These statistics demonstrate the importance of understanding the initiating events of ovarian cancer to better develop ...	[ "Estrogen therapy increases the risk of ovarian cancer and exogenous estradiol accelerates the onset of ovarian cancer in mouse models .", "Both in vivo and in vitro , ovarian surface epithelial ( OSE ) cells exposed to estradiol develop a subpopulation that loses cell polarity , contact inhibition , and forms mu...	[ "Women who take estrogen replacement therapy are at higher risk of developing ovarian cancer .", "When ovarian epithelial cells are exposed to estrogen , there is a heterogeneous cellular response , with some cells appearing unaffected , while others become disorganized and grow at accelerated rates consistent wi...	2018
[ "Introduction", "Methods", "Results", "Discussion" ]	[]	Toward Measuring Schistosoma Response to Praziquantel Treatment with Appropriate Descriptors of Egg Excretion	journal.pntd.0003821	null	[ [ "Schistosomiasis is a parasitic disease caused by blood flukes of the genus Schistosoma .", "The three main species infecting humans are S . haematobium ( causing urogenital schistosomiasis ) , S . japonicum , and S . mansoni ( the latter two responsible for intestinal schistosomiasis ) [1] .", "The b...	[ "The control of schistosomiasis emphasizes preventive chemotherapy with praziquantel , which aims at decreasing infection intensity and thus morbidity in individuals , as well as transmission in communities .", "Standardizing methods to assess treatment efficacy is important to compare trial outcomes across setti...	[ "To identify whether a person is infected with parasitic worms , stool or urine samples are examined for worm eggs .", "The drug praziquantel is used against the parasitic disease schistosomiasis .", "However , there is no definitive agreement as to how the efficacy of praziquantel is best expressed .", "We p...	2015
[ "Introduction", "Results", "Discussion", "Material and methods" ]	[ "flow cytometry", "medicine and health sciences", "rift valley fever virus", "vesicular stomatitis virus", "pathology and laboratory medicine", "pathogens", "microbiology", "viral structure", "retroviruses", "viruses", "immunodeficiency viruses", "rna viruses", "glycoproteins", "bunyavirus...	Interference with the production of infectious viral particles and bimodal inhibition of replication are broadly conserved antiviral properties of IFITMs	journal.ppat.1006610	null	[ [ "The interferon-induced transmembrane proteins ( IFITMs ) are a family of highly related proteins that present two transmembrane domains ( TM ) connected by a short linker region and an N and C-termini of variable length [1 , 2] .", "In humans , this family is composed of five expressed members: IFITM1 , ...	[ "IFITMs are broad antiviral factors that block incoming virions in endosomal vesicles , protecting target cells from infection .", "In the case of HIV-1 , we and others reported the existence of an additional antiviral mechanism through which IFITMs lead to the production of virions of reduced infectivity .", "...	[ "IFITMs are interferon-regulated proteins that inhibit a broad range of viruses .", "Until recently , IFITMs had been described to arrest incoming viral particles in target cells , by inducing their retention in endosomal vesicles .", "More recently in the case of HIV-1 , ours and other laboratories have highli...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biology" ]	Genome-Wide Crossover Distribution in Arabidopsis thaliana Meiosis Reveals Sex-Specific Patterns along Chromosomes	journal.pgen.1002354	null	[ [ "Crossovers ( COs ) are recombination events characterized by a reciprocal exchange of genetic material .", "In most eukaryotes , they are essential for the segregation of homologous chromosomes at the first meiotic division .", "When CO formation or localization is impaired , aneuploid gametes are fo...	[ "In most species , crossovers ( COs ) are essential for the accurate segregation of homologous chromosomes at the first meiotic division .", "Their number and location are tightly regulated .", "Here , we report a detailed , genome-wide characterization of the rate and localization of COs in Arabidopsis thalian...	[ "Reciprocal exchanges of genetic material ( crossovers ) between homologous chromosomes ensure their proper segregation to generate gametes .", "Their number and location along chromosomes are tightly regulated .", "We localized precisely the position of 13 , 535 crossovers in more than 3 , 000 plants of Arabid...	2011
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "genetics and genomics/complex traits", "virology/mechanisms of resistance and susceptibility, including host genetics", "genetics and genomics/genetics of disease", "immunology/genetics of the immune system", "infectious diseases/hiv infection and aids" ]	Common Genetic Variation and the Control of HIV-1 in Humans	journal.pgen.1000791	null	[ [ "The clinical outcome of HIV-1 infection is highly variable and determined by complex interactions between virus , host and environment .", "Several human genetic factors have been reported to modulate HIV-1 disease [1] , [2] , but current knowledge only explains a small fraction of the observed variabili...	[ "To extend the understanding of host genetic determinants of HIV-1 control , we performed a genome-wide association study in a cohort of 2 , 554 infected Caucasian subjects .", "The study was powered to detect common genetic variants explaining down to 1 . 3% of the variability in viral load at set point .", "W...	[ "The ability to spontaneously control HIV-1 upon infection is highly variable between individuals .", "To evaluate the contribution of variation in human genes to differences in plasma viral load and in disease progression rates , we performed a genome-wide association study in >2 , 500 HIV–infected individuals ....	2009
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biology and life sciences", "medicine and health sciences" ]	Cryptococcus gattii VGIII Isolates Causing Infections in HIV/AIDS Patients in Southern California: Identification of the Local Environmental Source as Arboreal	journal.ppat.1004285	null	[ [ "Outbreaks of infectious diseases caused by all major classes of microbial pathogens occur globally , annually , and these outbreaks pose public health challenges [1]–[4] .", "Advancing understanding of forces driving outbreaks to enhance our ability to predict , contain , and blunt their impact include:"...	[ "Ongoing Cryptococcus gattii outbreaks in the Western United States and Canada illustrate the impact of environmental reservoirs and both clonal and recombining propagation in driving emergence and expansion of microbial pathogens .", "C . gattii comprises four distinct molecular types: VGI , VGII , VGIII , and V...	[ "The environmentally-acquired human pathogen C . gattii is responsible for ongoing and expanding outbreaks in the Western United States and Canada .", "C . gattii comprises four distinct molecular types: VGI , VGII , VGIII , and VGIV .", "Molecular types VGI , VGII , and VGIII have been isolated from patients a...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "colorimetric assays", "cognitive neurology", "cellular stress responses", "medicine and health sciences", "luciferase", "neurodegenerative diseases", "enzymes", "cell processes", "enzymology", "neuroscience", "phosphatases", "biochemical analysis", "cognitive neuroscience", "enzyme assays...	NMNAT2:HSP90 Complex Mediates Proteostasis in Proteinopathies	journal.pbio.1002472	This study reveals NMNAT2 to be a dual-function neuronal maintenance factor that not only generates NAD to protect neurons from excitotoxicity but also moonlights as a chaperone to combat protein toxicity.	[ [ "Robust neuronal maintenance mechanisms are required to minimize or repair damage arising from intrinsic and extrinsic stressors .", "Nicotinamide mononucleotide adenylyl transferases ( NMNATs ) play important roles in neuronal maintenance in flies [1 , 2] and human [3–6] , and their overexpression provid...	[ "Nicotinamide mononucleotide adenylyl transferase 2 ( NMNAT2 ) is neuroprotective in numerous preclinical models of neurodegeneration .", "Here , we show that brain nmnat2 mRNA levels correlate positively with global cognitive function and negatively with AD pathology .", "In AD brains , NMNAT2 mRNA and protein...	[ "Pathological protein aggregates are found in many neurodegenerative diseases , and it has been hypothesized that these protein aggregates are toxic and cause neuronal death .", "Little is known about how neurons protect against pathological protein aggregates to maintain their health .", "Nicotinamide mononucl...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "phosphorylation", "cell motility", "medicine and health sciences", "luciferase", "pathology and laboratory medicine", "cardiovascular physiology", "gene regulation", "endothelial cells", "pathogens", "enzymes", "microbiology", "cancers and neoplasms", "enzymology", "epithelial cells", "...	The SH3BGR/STAT3 Pathway Regulates Cell Migration and Angiogenesis Induced by a Gammaherpesvirus MicroRNA	journal.ppat.1005605	null	[ [ "Kaposi’s sarcoma-associated herpesvirus ( KSHV ) is a gammaherpesvirus associated with AIDS-associated Kaposi’s sarcoma ( KS ) , primary effusion lymphoma ( PEL ) , and multicentric Castleman’s disease ( MCD ) [1] .", "KS is an angiogenic vascular tumor of endothelial spindle cells [2] .", "KS is cha...	[ "Kaposi’s sarcoma ( KS ) -associated herpesvirus ( KSHV ) is a gammaherpesvirus etiologically associated with KS , a highly disseminated angiogenic tumor of hyperproliferative spindle endothelial cells .", "KSHV encodes 25 mature microRNAs but their roles in KSHV-induced tumor dissemination and angiogenesis remai...	[ "Kaposi’s Sarcoma ( KS ) , caused by infection of Kaposi’s sarcoma ( KS ) -associated herpesvirus ( KSHV ) , is a tumor of endothelial cells characterized by angiogenesis and invasiveness .", "In vitro , KSHV-infected endothelial cells display an increased invasiveness and angiogenicity .", "KSHV encodes twelve...	2016
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "infectious diseases/helminth infections", "public health and epidemiology/preventive medicine", "infectious diseases/epidemiology and control of infectious diseases", "infectious diseases/neglected tropical diseases" ]	Integrated Mapping of Neglected Tropical Diseases: Epidemiological Findings and Control Implications for Northern Bahr-el-Ghazal State, Southern Sudan	journal.pntd.0000537	null	[ [ "Southern Sudan is one of a few African countries that have recently embarked on integrated control of some of their endemic neglected tropical diseases ( NTDs ) [1] .", "Integration typically targets those diseases for which safe and effective preventive chemotherapy ( PCT ) is readily available and ofte...	[ "There are few detailed data on the geographic distribution of most neglected tropical diseases ( NTDs ) in post-conflict Southern Sudan .", "To guide intervention by the recently established national programme for integrated NTD control , we conducted an integrated prevalence survey for schistosomiasis , soil-tr...	[ "Integrated control of neglected tropical diseases ( NTDs ) is being scaled up in a number of developing countries , because it is thought to be more cost-effective than stand-alone control programmes .", "Under this approach , treatments for onchocerciasis , lymphatic filariasis ( LF ) , schistosomiasis , soil-t...	2009
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genetics and genomics/genomics", "genetics and genomics/gene expression", "molecular biology/transcription elongation", "genetics and genomics/gene function", "molecular biology/dna repair" ]	Genome-Wide Analysis of Factors Affecting Transcription Elongation and DNA Repair: A New Role for PAF and Ccr4-Not in Transcription-Coupled Repair	journal.pgen.1000364	null	[ [ "Synthesis of an RNA transcript by RNA polymerase II ( RNAPII ) requires the successful completion of at least four steps in the transcription cycle: promoter binding and initiation , promoter clearance , elongation , and termination .", "While many studies have focused on the regulation of initiation , m...	[ "RNA polymerases frequently deal with a number of obstacles during transcription elongation that need to be removed for transcription resumption .", "One important type of hindrance consists of DNA lesions , which are removed by transcription-coupled repair ( TC-NER ) , a specific sub-pathway of nucleotide excisi...	[ "Dealing with DNA lesions is one of the most important tasks of both prokaryotic and eukaryotic cells .", "This is particularly relevant for damage occurring inside genes , in the DNA strands that are actively transcribed , because transcription cannot proceed through a damaged site and the persisting lesion can ...	2009
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[]	First-Time Detection of Mycobacterium bovis in Livestock Tissues and Milk in the West Bank, Palestinian Territories	journal.pntd.0002417	null	[ [ "Tuberculosis ( TB ) is included among the neglected diseases that disproportionally affect the world low-income populations .", "Bovine tuberculosis ( bTB ) is a zoonotic disease causing major public health concerns .", "It is caused by Mycobacterium bovis , a member of the Mycobacterium tuberculosis...	[ "Bovine tuberculosis , bTB , is classified by the WHO as one of the seven neglected zoonontic diseases that cause animal health problems and has high potential to infect humans .", "In the West Bank , bTB was not studied among animals and the prevalence of human tuberculosis caused by M . bovis is unknown .", "...	[ "Bovine tuberculosis ( caused by Mycobacterium bovis ) is a zoonotic disease causing major public health concerns .", "Animals , both wild and domestic , tested positive to bovine tuberculosis are being slaughtered and the affected herds are placed under temporary movement restrictions .", "Hence , bTB can have...	2013
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "molecular biology/bioinformatics", "computational biology/molecular genetics", "computational biology/metabolic networks", "computational biology/signaling networks" ]	An Integrated Approach for the Analysis of Biological Pathways using Mixed Models	journal.pgen.1000115	null	[ [ "To help increase power to detect microarray differential expression and to better interpret findings , gene-class testing or pathway analysis has become increasingly popular [1] .", "These approaches allow the integration of gene annotation databases such as Gene Ontology [2] and KEGG Pathway [3] to form...	[ "We compare the properties of this mixed models approach with nonparametric method GSEA and parametric method PAGE using a simulation study , and illustrate its application with a diabetes data set and a dose-response data set ." ]	[ "In microarray data analysis , when statistical testing is applied to each gene individually , one is often left with too many significant genes that are difficult to interpret or too few genes after a multiple comparison adjustment .", "Gene-class , or pathway-level testing , integrates gene annotation data such...	2008
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "cell biology/morphogenesis and cell biology", "cell biology/extra-cellular matrix", "cell biology/leukocyte signaling and gene expression", "cell biology/cytoskeleton" ]	A Proteomic and Cellular Analysis of Uropods in the Pathogen Entamoeba histolytica	journal.pntd.0001002	null	[ [ "The acquisition of cell polarity is a crucial requirement for motility in a variety of cells , including activated leukocytes and fast-moving amoebae .", "Cell polarization is defined by the presence of an anterioposterior cell axis and two functionally and morphologically distinct poles: the leading edg...	[ "Exposure of Entamoeba histolytica to specific ligands induces cell polarization via the activation of signalling pathways and cytoskeletal elements .", "The process leads to formation of a protruding pseudopod at the front of the cell and a retracting uropod at the rear .", "In the present study , we show that...	[ "Uropods are membrane folds formed at the rear of moving cells , e . g . lymphocytes during immune responses and the amoebic parasite Entamoeba histolytica during amoebiasis .", "Previous studies showed some surface receptors of E . histolytica , e . g . the Gal/GalNAc lectin , which is involved in adhesion , und...	2011
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "biotechnology", "carbohydrate metabolism", "machine learning algorithms", "protein metabolism", "chemical compounds", "applied mathematics", "ketones", "carbohydrates", "neuroscience", "organic compounds", "glucose", "glucose metabolism", "pyruvate", "simulation and modeling", "algorith...	Rapid Prediction of Bacterial Heterotrophic Fluxomics Using Machine Learning and Constraint Programming	journal.pcbi.1004838	null	[ [ "With the advent of systems biology tools , such as genomics , transcriptomics , proteomics , and metabolomics during the last decade , the understanding of intracellular metabolisms from genotype to phenotype has been dramatically boosted .", "Notably , 13C metabolic flux analysis ( 13C-MFA ) enables the...	[ "13C metabolic flux analysis ( 13C-MFA ) has been widely used to measure in vivo enzyme reaction rates ( i . e . , metabolic flux ) in microorganisms .", "Mining the relationship between environmental and genetic factors and metabolic fluxes hidden in existing fluxomic data will lead to predictive models that can...	[ "Metabolic information is important for disease treatment , bioprocess optimization , environmental remediation , biogeochemical cycle regulation , and our understanding of life’s origin and evolution .", "13C-MFA can quantify microbial physiology at the level of metabolic reaction rates .", "To speed up microb...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genome-wide association studies", "medicine", "genome analysis tools", "genomics", "pediatric oncology", "pediatrics and child health", "biology", "computational biology", "genetics and genomics", "pediatrics" ]	Phenotype Restricted Genome-Wide Association Study Using a Gene-Centric Approach Identifies Three Low-Risk Neuroblastoma Susceptibility Loci	journal.pgen.1002026	null	[ [ "Neuroblastoma is a pediatric cancer of the developing sympathetic nervous system and is the most common childhood solid tumor outside the central nervous system [1] , [2] .", "Its broad spectrum of clinical behaviors is the basis for ways to categorize neuroblastoma into three risk groups: high-risk , in...	[ "Neuroblastoma is a malignant neoplasm of the developing sympathetic nervous system that is notable for its phenotypic diversity .", "High-risk patients typically have widely disseminated disease at diagnosis and a poor survival probability , but low-risk patients frequently have localized tumors that are almost ...	[ "Neuroblastoma is the most common solid tumor outside the central nervous system and is accountable for 10% of the mortality rate of all children's cancers .", "It has distinctive clinical behaviors and is categorized into different risk groups: high-risk , intermediate-risk , and low-risk .", "Genome-wide asso...	2011
[ "Introduction", "Materials and Methods", "Results/Discussion" ]	[ "infectious diseases/viral infections", "virology/emerging viral diseases" ]	Dengue Virus Serotype 2 from a Sylvatic Lineage Isolated from a Patient with Dengue Hemorrhagic Fever	journal.pntd.0000423	null	[ [ "Dengue viruses cause dengue fever ( DF ) and dengue hemorrhagic fever ( DHF ) in the tropics from Southeast and Southern Asia , the Caribbean , and many countries in South and Central America , and outbreaks are reported with increasing frequency globally .", "The four distinct dengue virus serotypes ( D...	[ "Dengue viruses circulate in both human and sylvatic cycles .", "Although dengue viruses ( DENV ) infecting humans can cause major epidemics and severe disease , relatively little is known about the epidemiology and etiology of sylvatic dengue viruses .", "A 20-year-old male developed dengue hemorrhagic fever (...	[ "Dengue viruses are mosquito-borne RNA viruses that cause a spectrum of illness from mild disease to life-threatening dengue hemorrhagic fever ( DHF ) .", "Dengue viruses exist in two separate cycles in nature , circulating in either non-human primates or humans .", "The viruses that are endemic in humans today...	2009
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[]	MicroRNA Expression Profile in Human Macrophages in Response to Leishmania major Infection	journal.pntd.0002478	null	[ [ "The protozoan parasite Leishmania ( L . ) causes a heterogeneous group of tropical and subtropical neglected diseases known as leishmaniasis , with symptoms ranging from cutaneous lesions to fatal visceral leishmaniasis [1] .", "Leishmania parasites are obligate intracellular pathogens of their mammalian...	[ "Leishmania ( L . ) are intracellular protozoan parasites able to survive and replicate in the hostile phagolysosomal environment of infected macrophages .", "They cause leishmaniasis , a heterogeneous group of worldwide-distributed affections , representing a paradigm of neglected diseases that are mainly embedd...	[ "Leishmania parasites belong to different species , each one characterized by specific vectors and reservoirs , and causes cutaneous or visceral disease ( s ) of variable clinical presentation and severity .", "In its mammalian host , the parasite is an obligate intracellular pathogen infecting the monocyte/macro...	2013
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "medicine and health sciences", "enzyme-linked immunoassays", "body fluids", "pathology and laboratory medicine", "tropical diseases", "geographical locations", "parasitic diseases", "neglected tropical diseases", "immunologic techniques", "research and analysis methods", "serology", "south am...	Rapid diagnostic tests duo as alternative to conventional serological assays for conclusive Chagas disease diagnosis	journal.pntd.0005501	null	[ [ "Chagas disease is caused by infection with the kinetoplastid parasite Trypanosoma cruzi ( T . cruzi ) , generally transmitted by triatomine vectors that are endemic to the Americas .", "In recent decades , population movements from endemic to non-endemic regions and the chance of vector-independent trans...	[ "Chagas disease is caused by the parasite Trypanosoma cruzi .", "It affects several million people , mainly in Latin America , and severe cardiac and/or digestive complications occur in ~30% of the chronically infected patients .", "Disease acute stage is mostly asymptomatic and infection goes undiagnosed .", ...	[ "Chagas disease is a neglected tropical disease caused by the parasite Trypanosoma cruzi .", "It affects 6–7 million people , mainly in Latin America .", "An initial asymptomatic phase make the infection go undiagnosed and untreated , silently progressing into its chronic stage .", "About 30% of the chronical...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genomics", "cell biology", "evolutionary biology", "theoretical biology", "gene expression", "genetics", "biology and life sciences", "computational biology", "molecular cell biology", "evolutionary genetics" ]	Codon-by-Codon Modulation of Translational Speed and Accuracy Via mRNA Folding	journal.pbio.1001910	Secondary structure in mRNAs modulates the speed of protein synthesis codon-by-codon to improve accuracy at important sites while ensuring high speed elsewhere.	[ [ "Rapid cell growth demands expeditious protein synthesis , which requires a large number of ribosomes .", "Because ribosomes are limited during rapid cell growth [1] , fast translational elongation is desired to minimize ribosome sequestration and alleviate ribosome shortage [2]–[4] .", "However , sev...	[ "Rapid cell growth demands fast protein translational elongation to alleviate ribosome shortage .", "However , speedy elongation undermines translational accuracy because of a mechanistic tradeoff .", "Here we provide genomic evidence in budding yeast and mouse embryonic stem cells that the efficiency–accuracy ...	[ "Protein synthesis by ribosomal translation is a vital cellular process , but our understanding of its regulation has been poor .", "Because the number of ribosomes in the cell is limited , rapid growth relies on fast translational elongation .", "The accuracy of translation must also be maintained , and in an ...	2014
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "immunodeficiency viruses", "organismal evolution", "innate immune system", "medicine and health sciences", "infectious diseases", "immunity", "medical microbiology", "microbial evolution", "viral pathogens", "virology", "microbial pathogens", "biology and life sciences", "immunology", "mi...	Human APOBEC3 Induced Mutation of Human Immunodeficiency Virus Type-1 Contributes to Adaptation and Evolution in Natural Infection	journal.ppat.1004281	null	[ [ "The pathogenesis of HIV-1 infection correlates with the level of active viral replication and relates to a variety of factors specific to the virus , the host , and its immune system .", "Mutations , insertions , deletions and recombinations that confer changes in the activity of virally encoded genes an...	[ "Human APOBEC3 proteins are cytidine deaminases that contribute broadly to innate immunity through the control of exogenous retrovirus replication and endogenous retroelement retrotransposition .", "As an intrinsic antiretroviral defense mechanism , APOBEC3 proteins induce extensive guanosine-to-adenosine ( G-to-...	[ "Cytidine deaminases of the human APOBEC3 gene family act as an intrinsic defense mechanism against infection with HIV-1 and other viruses .", "The APOBEC3 proteins introduce mutations into the viral genome by inducing enzymatic modification of nucleotide sequences and inhibiting synthesis of cDNA strands from th...	2014
[ "Introduction", "Results and discussion", "Conclusion", "Materials and methods" ]	[ "z chromosomes", "sequence assembly tools", "genetic mapping", "genome analysis", "sequence motif analysis", "research and analysis methods", "sequence analysis", "sex chromosomes", "genomics", "sequence alignment", "bioinformatics", "chromosome biology", "chromosomal aberrations", "short ...	Repeated translocation of a gene cassette drives sex-chromosome turnover in strawberries	journal.pbio.2006062	null	[ [ "Sex chromosomes can be a strikingly diverse and evolutionarily labile component of eukaryotic genomes [1] .", "The defining feature of a sex chromosome , the sex-determining region ( SDR ) , has experienced similar restructuring in multiple independent instances of autosomes evolving into heteromorphic s...	[ "Turnovers of sex-determining systems represent important diversifying forces across eukaryotes .", "Shifts in sex chromosomes—but conservation of the master sex-determining genes—characterize distantly related animal lineages .", "Yet in plants , in which separate sexes have evolved repeatedly and sex chromoso...	[ "Sex chromosomes frequently restructure themselves during organismal evolution , often becoming highly differentiated .", "This dynamic process is poorly understood for most taxa , especially during the early stages typical of many dioecious flowering plants .", "We show that in wild strawberries , a female-spe...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "computational biology/sequence motif analysis", "computational biology/transcriptional regulation", "computational biology/comparative sequence analysis", "computational biology/evolutionary modeling", "computational biology/genomics", "evolutionary biology/bioinformatics" ]	Modeling the Evolution of Regulatory Elements by Simultaneous Detection and Alignment with Phylogenetic Pair HMMs	journal.pcbi.1001037	null	[ [ "A detailed understanding of the mechanisms underlying gene regulation , including precisely how these mechanisms are encoded in an individual's genomic DNA , is of prime importance both to biomedicine and to our knowledge of molecular biology and evolution .", "Given the wealth of genomic sequence data c...	[ "The computational detection of regulatory elements in DNA is a difficult but important problem impacting our progress in understanding the complex nature of eukaryotic gene regulation .", "Attempts to utilize cross-species conservation for this task have been hampered both by evolutionary changes of functional s...	[ "The computational detection of regulatory elements in DNA is a difficult but important problem for decoding eukaryotic gene regulation .", "Increasing sequence data has made it possible to utilize related genomes , but this is not as straightforward as it may seem , as the evolution of noncoding regulatory regio...	2010
[ "Introduction", "Methods", "Results", "Discussion", "Conclusions" ]	[ "invertebrates", "medicine and health sciences", "laboratory equipment", "engineering and technology", "pigments", "animals", "developmental biology", "materials science", "filter paper", "insect vectors", "infectious diseases", "aedes aegypti", "materials by attribute", "organic pigments"...	Darker eggs of mosquitoes resist more to dry conditions: Melanin enhances serosal cuticle contribution in egg resistance to desiccation in Aedes, Anopheles and Culex vectors	journal.pntd.0006063	null	[ [ "Mosquitoes of the genera Aedes , Anopheles and Culex transmit pathogens that are the causative agents of diverse diseases such as yellow fever , dengue , chikungunya , Zika and West Nile viruses , malaria and lymphatic filariasis [1–7] .", "Blocking mosquito life cycle is an effective way to hamper disea...	[ "Mosquito vectors lay their white eggs in the aquatic milieu .", "During early embryogenesis water passes freely through the transparent eggshell , which at this moment is composed of exochorion and endochorion .", "Within two hours the endochorion darkens via melanization but even so eggs shrink and perish if ...	[ "Mosquitoes transmit various causative agents of diseases and the blockage of vector life cycle is an effective way to hamper disease transmission .", "The egg is the least known life stage and understanding it can contribute with novel strategies for mosquito control .", "Mosquitoes lay eggs in water collectio...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	The NLRP3 Inflammasome Is a Pathogen Sensor for Invasive Entamoeba histolytica via Activation of α5β1 Integrin at the Macrophage-Amebae Intercellular Junction	journal.ppat.1004887	null	[ [ "Entamoeba histolytica , the etiologic agent of amebiasis , is a protozoan parasite of the human colon that colonizes about 10% of the world’s population resulting in 106 deaths/year and is endemic in areas that lack adequate water sanitation [1] .", "Infection is acquired by ingesting cysts that release ...	[ "Entamoeba histolytica ( Eh ) is an extracellular protozoan parasite of humans that invades the colon to cause life-threatening intestinal and extra-intestinal amebiasis .", "Colonized Eh is asymptomatic , however , when trophozoites adhere to host cells there is a considerable inflammatory response that is criti...	[ "Amebiasis caused by the enteric protozoan parasite Entamoeba histolytica is among the three top causes of death from parasitic infections worldwide , as a result of amebic colitis ( dysentery ) and liver or brain abscess .", "When Eh invades the intestinal barrier and contacts host tissue there is a profound inf...	2015
[ "Introduction", "Results", "Discussion", "Conclusions", "Materials and methods" ]	[ "medicine and health sciences", "toxins", "crystal structure", "pathology and laboratory medicine", "enzymes", "condensed matter physics", "enzymology", "toxic agents", "toxicology", "signs and symptoms", "lyases", "sequence motif analysis", "crystallography", "edema", "research and anal...	Calmodulin fishing with a structurally disordered bait triggers CyaA catalysis	journal.pbio.2004486	null	[ [ "Calmodulin ( CaM ) is a major mediator of calcium signaling in eukaryotic cells , ubiquitously distributed and highly conserved in the whole eukaryotic kingdom .", "This small acidic protein of 148 amino acids interacts with a wide variety of target proteins or enzymes to control their activities in resp...	[ "Once translocated into the cytosol of target cells , the catalytic domain ( AC ) of the adenylate cyclase toxin ( CyaA ) , a major virulence factor of Bordetella pertussis , is potently activated by binding calmodulin ( CaM ) to produce supraphysiological levels of cAMP , inducing cell death .", "Using a combina...	[ "Calmodulin is a widespread and highly conserved protein that interacts with a wide variety of eukaryotic proteins and enzymes , controlling their activities in response to calcium .", "The adenylate cyclase toxin ( CyaA ) of Bordetella pertussis , the causative agent of whooping cough , is one such calmodulin ta...	2017
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "medicine", "biochemistry", "biology", "glycoproteins", "glycobiology" ]	Recurrent Signature Patterns in HIV-1 B Clade Envelope Glycoproteins Associated with either Early or Chronic Infections	journal.ppat.1002209	null	[ [ "It has proven to be very difficult to elicit protective immunity through an HIV vaccine [1] , although a recent vaccine trial in Thailand , RV144 , yielded encouraging results [2] .", "A protective vaccine will need to elicit immune responses that interact effectively with the spectrum of circulating vir...	[ "Here we have identified HIV-1 B clade Envelope ( Env ) amino acid signatures from early in infection that may be favored at transmission , as well as patterns of recurrent mutation in chronic infection that may reflect common pathways of immune evasion .", "To accomplish this , we compared thousands of sequences...	[ "A single virus most often establishes HIV-1 infection .", "As a consequence , virus sampled early in infection is usually very homogeneous .", "A few months into the infection , the virus begins to accumulate mutations as it evolves to evade HIV-specific immune responses mounted by the infected host .", "Dur...	2011
[ "Introduction", "Results and Discussion", "Materials and Methods" ]	[ "biotechnology", "quantitative trait loci", "variant genotypes", "alleles", "genetic mapping", "molecular biology techniques", "genetic engineering", "research and analysis methods", "artificial gene amplification and extension", "chromosome biology", "molecular biology", "genetic loci", "ce...	Multi-locus Genotypes Underlying Temperature Sensitivity in a Mutationally Induced Trait	journal.pgen.1005929	null	[ [ "Genotype-by-environment interaction ( or ‘GxE’ ) occurs when genetically distinct individuals exhibit different phenotypic responses to the environment [1 , 2] .", "Work to date suggests that GxE is an important contributor to heritable variation in many agriculturally , evolutionarily , and medically re...	[ "Determining how genetic variation alters the expression of heritable phenotypes across conditions is important for agriculture , evolution , and medicine .", "Central to this problem is the concept of genotype-by-environment interaction ( or ‘GxE’ ) , which occurs when segregating genetic variation causes indivi...	[ "Individuals’ phenotypes are often determined through interactions between their genotypes and the environment ( or ‘GxE’ ) .", "Despite substantial research on this topic , the underlying causes of GxE are not fully understood .", "This stems , in part , from the fact that most mapping studies focused on GxE d...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "immunology/immunomodulation", "immunology/leukocyte activation", "immunology/immune response", "immunology/innate immunity" ]	Recognition of Lyso-Phospholipids by Human Natural Killer T Lymphocytes	journal.pbio.1000228	By identifying the lipid LPC as an endogenous antigen, recognized by the invariant subset of human NKT cells, this study establishes a novel link between these immunoregulatory cells and an inflammatory lipid mediator.	[ [ "Natural killer T ( NKT ) cells are a unique subpopulation of T lymphocytes that display innate-like characteristics and can potently modulate adaptive immune responses [1] , [2] .", "They are among the first cells to respond during microbial infections and produce a wide variety of cytokines that have mu...	[ "Natural killer T ( NKT ) cells are a subset of T lymphocytes with potent immunoregulatory properties .", "Recognition of self-antigens presented by CD1d molecules is an important route of NKT cell activation; however , the molecular identity of specific autoantigens that stimulate human NKT cells remains unclear...	[ "A central tenet of immunology is that cellular responses that protect us from pathogens result from molecular recognition of foreign compounds ( antigens ) .", "The role of self-antigens in immune activation is less clear .", "We show here that an endogenous lipid called lyso-phosphatidylcholine ( LPC ) is rec...	2009
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "death rates", "medicine and health sciences", "pathology and laboratory medicine", "infectious disease epidemiology", "demography", "immunology", "tropical diseases", "ethnicities", "vaccines", "preventive medicine", "neglected tropical diseases", "vaccination and immunization", "latin amer...	The Impact of the Newly Licensed Dengue Vaccine in Endemic Countries	journal.pntd.0005179	null	[ [ "Epidemiological models have been important in understanding the spread of infectious diseases and to evaluate intervention strategies like vector control and vaccination .", "Mathematical models were introduced into infectious disease epidemiology in the early 20th century , and a series of deterministic...	[ "With approximately 3 billion people at risk of acquiring the infection , dengue fever is now considered the most important mosquito-borne viral disease in the world , with 390 million dengue infections occurring every year , of which 96 million manifest symptoms with any level of disease severity .", "Treatment ...	[ "Caused by four antigenically related but distinct serotypes a tetravalent vaccine is needed to protect against the huge burden of dengue disease .", "Dengvaxia is a vaccine candidate now licensed in several countries for individuals 9–45 years of age living in endemic countries with at least 50% ( preferably 70%...	2016
[ "Introduction", "Results/Discussion", "Methods" ]	[ "physics", "statistical mechanics", "theoretical biology", "chemistry", "biology", "computational biology", "evolutionary biology", "biophysics", "physical chemistry" ]	Thermodynamic Basis for the Emergence of Genomes during Prebiotic Evolution	journal.pcbi.1002534	null	[ [ "All biological organisms are evolutionarily related .", "The salient characteristics of life ( reproduction and selection ) must have therefore emerged either gradually or abruptly from inanimate chemical processes some time in the early history of the Earth .", "Our ever-increasing knowledge on the ...	[ "The RNA world hypothesis views modern organisms as descendants of RNA molecules .", "The earliest RNA molecules must have been random sequences , from which the first genomes that coded for polymerase ribozymes emerged .", "The quasispecies theory by Eigen predicts the existence of an error threshold limiting ...	[ "A leading hypothesis for the origin of life describes a prebiotic world where RNA molecules started carrying genetic information for catalyzing their own replication .", "This origin of biological information is akin to the crystallization of ice from water , where ‘order’ emerges from ‘disorder . ’ What does th...	2012
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "veterinary immunology", "veterinary diseases", "zoonoses", "veterinary parasitology", "veterinary microbiology", "immunity", "leishmaniasis", "biology and life sciences", "immunology", "vaccination and immunization", "veterinary science", "parasitology", "veterinary medicine" ]	A Randomised, Double-Blind, Controlled Efficacy Trial of the LiESP/QA-21 Vaccine in Naïve Dogs Exposed to Two Leishmania infantum Transmission Seasons	journal.pntd.0003213	null	[ [ "Canine leishmaniosis ( CanL ) is an extremely variable and polymorphic disease , caused by progressive uncontrolled infection with the intracellular parasite Leishmania infantum ( in the Old World , synonym of L . chagasi in the New World ) transmitted by the bites of phlebotomine sand flies [1] .", "It ...	[ "Canine leishmaniasis is an important zoonosis caused by uncontrolled infection with Leishmania infantum , where an inappropriate immune response is not only responsible for permitting this intracellular parasite to multiply , but is also responsible for several of the pathological processes seen in this disease ."...	[ "Canine leishmaniasis is caused by uncontrolled infection with Leishmania infantum .", "The dog is also the principle reservoir of this parasite which can infect humans .", "The key determinant of the outcome of infection is the ability of the dog's immune system to respond appropriately .", "This should be m...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "mathematics", "genetics and genomics", "nematodes", "computational biology" ]	Improving the Caenorhabditis elegans Genome Annotation Using Machine Learning	journal.pcbi.0030020	null	[ [ "C . elegans is a free-living soil nematode with a cosmopolitan distribution .", "Its short life cycle , self-fertilizing propagation , simple anatomy , and the ease of genetic and experimental manipulations made C . elegans an important model system in biology .", "Today , C . elegans is one of the b...	[ "For modern biology , precise genome annotations are of prime importance , as they allow the accurate definition of genic regions .", "We employ state-of-the-art machine learning methods to assay and improve the accuracy of the genome annotation of the nematode Caenorhabditis elegans .", "The proposed machine l...	[ "Eukaryotic genes contain introns , which are intervening sequences that are excised from a gene transcript with the concomitant ligation of flanking segments called exons .", "The process of removing introns is called splicing .", "It involves biochemical mechanisms that to date are too complex to be modeled c...	2007
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biochemistry", "biochemistry/protein folding", "virology/antivirals, including modes of action and resistance", "infectious diseases/hiv infection and aids", "biochemistry/biomacromolecule-ligand interactions", "virology/host invasion and cell entry" ]	Asymmetric Deactivation of HIV-1 gp41 following Fusion Inhibitor Binding	journal.ppat.1000674	null	[ [ "Intermediate states of biological processes are increasingly common targets for inhibition [1] , [2] .", "The transient nature of such targets makes inhibitory potency a complex function of both equilibrium and nonequilibrium factors [3] .", "Here , we characterize the intermediate-state inhibition o...	[ "Both equilibrium and nonequilibrium factors influence the efficacy of pharmaceutical agents that target intermediate states of biochemical reactions .", "We explored the intermediate state inhibition of gp41 , part of the HIV-1 envelope glycoprotein complex ( Env ) that promotes viral entry through membrane fusi...	[ "Blocking HIV-1 entry into host cells is a viable strategy to prevent viral infection .", "Entry is mediated by viral surface proteins gp120 and gp41 , which undergo large structural changes upon encountering the host cell .", "One critical structural change involves the association of two distinct gp41 regions...	2009
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "theoretical biology", "biology and life sciences", "microbiology", "computational biology" ]	Ecological Consistency of SSU rRNA-Based Operational Taxonomic Units at a Global Scale	journal.pcbi.1003594	null	[ [ "Recent advances in sequencing technology have enabled researchers to characterize microbial diversity at previously unattainable scales .", "In large collaborative efforts , such as the Human Microbiome Project [1] , selected environments have been probed to depths of millions of sequences , but even sma...	[ "Operational Taxonomic Units ( OTUs ) , usually defined as clusters of similar 16S/18S rRNA sequences , are the most widely used basic diversity units in large-scale characterizations of microbial communities .", "However , it remains unclear how well the various proposed OTU clustering algorithms approximate ‘tr...	[ "To characterize the composition of microbial communities , researchers often sequence and quantify specific marker genes , particularly the SSU ( ‘small subunit’ ) ribosomal RNA gene .", "One crucial step in such studies is the clustering of sequences into Operational Taxonomic Units ( OTUs ) of closely related ...	2014
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "invertebrates", "body weight", "medicine and health sciences", "rna interference", "reporter genes", "animals", "animal models", "developmental biology", "drosophila melanogaster", "model organisms", "physiological parameters", "experimental organism systems", "gene types", "molecular gen...	Functional characterization of adaptive variation within a cis-regulatory element influencing Drosophila melanogaster growth	journal.pbio.2004538	null	[ [ "Gene expression variation is extensive both within and between species and is believed to underlie much of the phenotypic diversity observed among species , as well as among populations of the same species [1–2] .", "Furthermore , expression variation is thought to provide an abundant source of material ...	[ "Gene expression variation is a major contributor to phenotypic diversity within species and is thought to play an important role in adaptation .", "However , examples of adaptive regulatory polymorphism are rare , especially those that have been characterized at both the molecular genetic level and the organisma...	[ "Much of the phenotypic variation that is observed within species is thought to be caused by variation in gene expression .", "Variants within cis-regulatory elements , which affect the expression of nearby genes within the same DNA strand , are thought to be an abundant resource upon which natural selection can ...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genome analysis tools", "genetic networks", "functional genomics", "protein interactions", "biology", "genomics", "proteomics", "computational biology" ]	Network Topologies and Convergent Aetiologies Arising from Deletions and Duplications Observed in Individuals with Autism	journal.pgen.1003523	null	[ [ "Autism Spectrum Disorders ( ASD ) form a group of complex disorders affecting ∼1% of individuals [1] .", "ASD are characterised by impairments in social interaction , communication , and restricted and repetitive interests and behaviours [2] , although other symptoms such as intellectual disability , sei...	[ "Autism Spectrum Disorders ( ASD ) are highly heritable and characterised by impairments in social interaction and communication , and restricted and repetitive behaviours .", "Considering four sets of de novo copy number variants ( CNVs ) identified in 181 individuals with autism and exploiting mouse functional ...	[ "Autism Spectrum Disorders ( ASD ) are characterised by impairments in social interaction and communication , and restricted and repetitive behaviours .", "ASD are highly heritable and many different stretches of DNA have been found to be duplicated or deleted in individuals with ASD .", "We found that an unusu...	2013
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "antimicrobials", "carbohydrate metabolism", "medicine and health sciences", "chemical compounds", "monomers", "drugs", "microbiology", "carbohydrates", "glucose metabolism", "organic compounds", "glucose", "antibiotic resistance", "antibiotics", "pharmacology", "drug metabolism", "pol...	Chemogenomic model identifies synergistic drug combinations robust to the pathogen microenvironment	journal.pcbi.1006677	null	[ [ "The threat of antibiotic resistance coupled with a diminishing pipeline of new drugs has created a pressing need to enhance efficacy of existing antibiotics [1] .", "Combinations of antibiotics are now being increasingly used to enhance the efficacy of treatment regimens and concurrently reduce resistanc...	[ "Antibiotics need to be effective in diverse environments in vivo .", "However , the pathogen microenvironment can have a significant impact on antibiotic potency .", "Further , antibiotics are increasingly used in combinations to combat resistance , yet , the effect of microenvironments on drug-combination eff...	[ "The antibiotic resistance epidemic has created a pressing need to understand factors that influence antibiotic efficacy .", "An often-overlooked factor in the search for new treatments is the pathogen environment .", "Understanding the differences in pathogen sensitivity to antibiotics in lab conditions versus...	2018
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "medicine and health sciences", "body fluids", "enzyme-linked immunoassays", "immune physiology", "ears", "immunology", "sand flies", "saliva", "parasitic protozoans", "parasitic diseases", "protozoans", "leishmania", "antibodies", "insect vectors", "immunologic techniques", "research ...	Immunity to Lutzomyia whitmani Saliva Protects against Experimental Leishmania braziliensis Infection	journal.pntd.0005078	null	[ [ "Leishmaniasis develops when an infected sand fly bites the skin of the mammalian host , injecting saliva and the infective forms of Leishmania .", "Sand fly saliva includes molecules that modulate the host’s hemostatic , inflammatory and immune responses creating a favorable environment that facilitate p...	[ "Previous works showed that immunization with saliva from Lutzomyia intermedia , a vector of Leishmania braziliensis , does not protect against experimental infection .", "However , L . braziliensis is also transmitted by Lutzomyia whitmani , a sand fly species closely related to Lu .", "intermedia .", "Herei...	[ "The saliva from sand flies contains biologically active proteins that permit the insect to obtain a blood meal .", "When vertebrates are continuously exposed to these molecules , through insect biting , for example , they induce an immune response ( antibody and cell-mediated immunity ) in the vertebrate host ."...	2016
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "learning", "psychoses", "ecology and environmental sciences", "medicine and health sciences", "vertebrates", "social sciences", "neuroscience", "learning and memory", "animals", "osteichthyes", "cognitive psychology", "aquatic environments", "hallucinations", "bodies of water", "carps",...	Psychotic Experiences and Overhasty Inferences Are Related to Maladaptive Learning	journal.pcbi.1005328	null	[ [ "Psychotic symptoms are a core symptom of devastating psychiatric disorders such as schizophrenia .", "They comprise many different kinds of experiences , among others beliefs that are unfounded in the external reality ( delusions ) , and percepts in the absence of a causative stimulus ( hallucinations ) ...	[ "Theoretical accounts suggest that an alteration in the brain’s learning mechanisms might lead to overhasty inferences , resulting in psychotic symptoms .", "Here , we sought to elucidate the suggested link between maladaptive learning and psychosis .", "Ninety-eight healthy individuals with varying degrees of ...	[ "Predictive coding theories represent a unifying account of psychosis , stating that the central psychosis-related alteration affects the interplay between prior predictions and incoming information .", "Since every incoming information is imprecise and potentially allows for different interpretations , prior exp...	2017
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "learning", "decision making", "reaction time", "vertebrates", "social sciences", "mice", "neuroscience", "learning and memory", "animals", "mammals", "cognitive neuroscience", "cognitive psychology", "animal behavior", "cognition", "zoology", "foraging", "human learning", "behavio...	Mice learn to avoid regret	journal.pbio.2005853	null	[ [ "Regretful experiences comprise those in which an individual recognizes a better decision could have been made in the past .", "Humans assert a strong desire to avoid feeling regret [1] .", "Regret can have an immediate impact on influencing subsequent valuations , but it can also motivate individuals...	[ "Regret can be defined as the subjective experience of recognizing that one has made a mistake and that a better alternative could have been selected .", "The experience of regret is thought to carry negative utility .", "This typically takes two distinct forms: augmenting immediate postregret valuations to mak...	[ "Regret describes a unique postdecision phenomenon in which losses are realized as a fault of one’s own actions .", "Regret is often hypothesized to have an inherent negative utility , and humans will often incur costs so as to avoid the risk of future regret .", "However , current models of nonhuman decision-m...	2018
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[]	An Ex Vivo Model for Studying Hepatic Schistosomiasis and the Effect of Released Protein from Dying Eggs	journal.pntd.0003760	null	[ [ "The major neglected tropical disease schistosomiasis is caused by parasitic helminth worms of the genus Schistosoma .", "The disease affects 200 million people worldwide with many more at risk .", "The clinical features of schistosomiasis range from fever , headache and lethargy , to severe liver inf...	[ "We report the use of an ex vivo precision cut liver slice ( PCLS ) mouse model for studying hepatic schistosomiasis .", "In this system , liver tissue is unfixed , unfrozen , and alive for maintenance in culture and subsequent molecular analysis .", "Using thick naive mouse liver tissue and sterile culture con...	[ "Schistosomiasis is a major disease of humans caused by schistosome blood flukes .", "One of the primary sites of pathology is the liver of the infected host , and it is caused by the deposition of parasite eggs leading to an immune-fibrotic response .", "We have used an animal tissue model for this disease , w...	2015
[ "Background", "Materials and methods", "Results", "Discussion", "Study limitation", "Conclusions and recommendations" ]	[ "children", "medicine and health sciences", "pathology and laboratory medicine", "geographical locations", "parasitic diseases", "health care", "physiological processes", "age groups", "signs and symptoms", "pharmaceutics", "eating", "drug administration", "africa", "families", "people a...	Knowledge, practices and perceptions of geo-helminthes infection among parents of pre-school age children of coastal region, Kenya	journal.pntd.0005514	null	[ [ "Neglected tropical diseases ( NTDs ) are a cluster of tropical diseases that affect more than one billion people worldwide , mainly among poor populations .", "Soil-transmitted helminthes ( STHs ) which form part of the NTDs are associated with substantial acute and chronic morbidity , particularly among...	[ "Soil-transmitted helminthes ( STHs ) are common human parasitic diseases in most of the developing world particularly in Kenya .", "The ongoing National School-Based Deworming Programme ( NSBDP ) was launched in 2012 and is currently targeting 28 of the 47 endemic Counties .", "In an effort to improve treatmen...	[ "Soil-transmitted helminthes commonly known as worms , form part of the Neglected tropical diseases which are associated with substantial acute and chronic morbidity , particularly among children .", "Hookworm occurs throughout most of the country , with areas of highest prevalence being found in South-Western Ke...	2017
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "genetics and genomics/epigenetics", "genetics and genomics/gene expression" ]	Alternative Splicing of NURF301 Generates Distinct NURF Chromatin Remodeling Complexes with Altered Modified Histone Binding Specificities	journal.pgen.1000574	null	[ [ "The organization of DNA in nucleosomes has a vital function in regulating whether genetic information can be expressed .", "By altering nucleosome dynamics , genes can be rendered inaccessible or made available to the transcription machinery .", "There are a number of mechanisms by which altered chro...	[ "Drosophila NURF is an ISWI–containing chromatin remodeling complex that catalyzes ATP–dependent nucleosome sliding .", "By sliding nucleosomes , NURF can alter chromatin structure and regulate transcription .", "NURF301/BPTF is the only NURF–specific subunit of NURF and is instrumental in recruiting the comple...	[ "Changes in nucleosome dynamics have a profound effect on DNA transactions such as transcription , replication , and repair .", "Altered chromatin states can be induced by post-translational modification of the histone tails or energy-dependent nucleosome sliding mediated by ATP–dependent chromatin remodeling fac...	2009
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "systems biology", "genomics", "adaptation", "genome evolution", "evolutionary biology", "coevolution", "regulatory networks", "biology", "computational biology", "comparative genomics", "evolutionary selection", "evolutionary processes" ]	Regulatory Network Structure as a Dominant Determinant of Transcription Factor Evolutionary Rate	journal.pcbi.1002734	null	[ [ "The study of regulatory network evolution has so far mostly concentrated on cis-regulatory variation , such as the loss or gain of transcription factor ( TF ) binding sites in the promoter region of a gene .", "But trans-level variations are known to account for a significant amount of the expression var...	[ "The evolution of transcriptional regulatory networks has thus far mostly been studied at the level of cis-regulatory elements .", "To gain a complete understanding of regulatory network evolution we must also study the evolutionary role of trans-factors , such as transcription factors ( TFs ) .", "Here , we sy...	[ "Transcription factors ( TFs ) are proteins which regulate the expression of genes by interacting with DNA .", "Mutations in TF protein sequences can affect the expression levels of regulated genes throughout evolution .", "In this study , we look into the factors which cause the different TFs in baker's yeast ...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biology" ]	MOV10 RNA Helicase Is a Potent Inhibitor of Retrotransposition in Cells	journal.pgen.1002941	null	[ [ "MOV10 was originally identified as a protein that prevents infection of mice by Moloney murine leukemia virus [1] , [2] , and has been classified as a member of the UPF1p family of SF-1 ATP-dependent RNA helicases [3]–[6] .", "Evidence implicates MOV10 and its relatives in small RNA regulation of gene ex...	[ "MOV10 protein , a putative RNA helicase and component of the RNA–induced silencing complex ( RISC ) , inhibits retrovirus replication .", "We show that MOV10 also severely restricts human LINE1 ( L1 ) , Alu , and SVA retrotransposons .", "MOV10 associates with the L1 ribonucleoprotein particle , along with oth...	[ "LINE1s , the only active autonomous mobile DNA in humans , occupy at least 17% of our genome .", "It is believed that about 100 L1s are potentially active in any individual diploid genome .", "The L1 has also been responsible for genomic insertion of processed pseudogenes and more than a million non-autonomous...	2012
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "blood cells", "innate immune system", "medicine and health sciences", "antigen presentation", "immune cells", "immune physiology", "immunology", "microbiology", "cytotoxic t cells", "immune system proteins", "white blood cells", "memory t cells", "animal cells", "proteins", "antigens", ...	Proteome-wide analysis of CD8+ T cell responses to EBV reveals differences between primary and persistent infection	journal.ppat.1007110	null	[ [ "Human herpesviruses are ancient pathogens that have co-evolved with our species and its antecedents over millions of years , producing a finely balanced virus-host relationship in which both primary infection and subsequent life-long virus carriage are typically asymptomatic .", "By contrast , herpesviru...	[ "Human herpesviruses are antigenically rich agents that induce strong CD8+T cell responses in primary infection yet persist for life , continually challenging T cell memory through recurrent lytic replication and potentially influencing the spectrum of antigen-specific responses .", "Here we describe the first ly...	[ "Herpesviruses are carried by most people as lifelong asymptomatic infections but become life-threatening in immunocompromised individuals .", "This reflects the crucial role of T cells , especially CD8+ killer T cells , in controlling these agents .", "EBV is arguably the most pathogenic of the human herpesvir...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "neuroscience/behavioral neuroscience", "neuroscience/cognitive neuroscience", "neuroscience/motor systems" ]	Emergence of a Stable Cortical Map for Neuroprosthetic Control	journal.pbio.1000153	In this article, the authors show that the neural representation for control of a neuroprosthetic device undergoes a process of consolidation, after which it is stable, readily recalled, and resistant to interference.	[ [ "Research into the development of brain–machine interfaces ( BMIs ) [1] has flourished in the last decade , with impressive demonstrations of rodents , nonhuman primates , and humans controlling robots or computer cursors in real time [2]–[17] .", "Studies of closed-loop cortical BMIs have further demonst...	[ "Cortical control of neuroprosthetic devices is known to require neuronal adaptations .", "It remains unclear whether a stable cortical representation for prosthetic function can be stored and recalled in a manner that mimics our natural recall of motor skills .", "Especially in light of the mixed evidence for ...	[ "Brain–machine interfaces ( BMIs ) have the potential to revolutionize the care of neurologically impaired patients .", "Numerous studies have now shown the feasibility of direct “brain control” of a neuroprosthetic device , yet it remains unclear whether the neural representation for prosthetic control can becom...	2009
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Positive and Negative Regulation of Gli Activity by Kif7 in the Zebrafish Embryo	journal.pgen.1003955	null	[ [ "Hedgehog ( Hh ) proteins play a fundamental role in animal development , controlling cell type specification , proliferation and survival in a variety of contexts through a signaling pathway , the core components of which are shared across species [reviewed in 1] , [2] , [3] .", "Hh signaling also functi...	[ "Loss of function mutations of Kif7 , the vertebrate orthologue of the Drosophila Hh pathway component Costal2 , cause defects in the limbs and neural tubes of mice , attributable to ectopic expression of Hh target genes .", "While this implies a functional conservation of Cos2 and Kif7 between flies and vertebra...	[ "Hedgehog ( Hh ) proteins activate one of a handful of signaling pathways that orchestrate the development of animal embryos , controlling cell type specification , proliferation and survival in a variety of contexts .", "In Drosophila , the Cos2 protein plays a key role in modulating the response of cells to Hh ...	2013
[ "Introduction", "Materials and methods", "Results", "Discussion" ]	[ "medicine and health sciences", "secondary headaches", "pathology and laboratory medicine", "geographical locations", "tropical diseases", "vertebrates", "parasitic diseases", "animals", "mammals", "migraine", "headaches", "health care", "north america", "signs and symptoms", "neglected ...	The monetary burden of cysticercosis in Mexico	journal.pntd.0007501	null	[ [ "Cysticercosis is a public health and agricultural problem caused by the larvae of the zoonotic cestode Taenia solium .", "Humans are the definitive hosts of T . solium , with adult tapeworms found in the intestines after ingestion of undercooked pork containing cysticerci .", "Infection with the adul...	[ "Taenia solium cysticercosis is a public health and agricultural problem in many low and middle-income countries where health education , sanitation , pig management practices and meat inspection infrastructure are insufficient .", "Cysticercosis affects both human and animal health and has important economic con...	[ "Taenia solium cysticercosis is a parasitic disease , which can be transmitted between humans and pigs in areas of the world where pigs are raised in a traditional manner and latrines are not always used by the local population .", "Because cysticercosis affects humans and pigs , it is important to assess how muc...	2019
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Radial Frequency Analysis of Contour Shapes in the Visual Cortex	journal.pcbi.1004719	null	[ [ "To psychophysically investigate contour shape processing beyond local Gabor-like analysis Wilkinson et al . [1] introduced radial frequency patterns ( Fig 1A ) , closed contour shapes formed by sinusoidally modulating the radius of a base circle ( Fig 1C ) .", "Any closed shape , such as the outline of h...	[ "Cumulative psychophysical evidence suggests that the shape of closed contours is analysed by means of their radial frequency components ( RFC ) .", "However , neurophysiological evidence for RFC-based representations is still missing .", "We investigated the representation of radial frequency in the human visu...	[ "Current views suggest that neural representations of the visual environment are built from combinations of basis functions .", "For low-level visual feature analysis these basis functions are relatively well understood .", "It is not yet known , however , how primary visual features are combined into higher-le...	2016
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "genetics and genomics/genomics", "molecular biology/dna replication", "genetics and genomics/animal genetics", "molecular biology/recombination", "cell biology/cell growth and division", "molecular biology/chromosome structure", "genetics and genomics/chromosome biology", "genetics and genomics/disea...	Characterization of Oxidative Guanine Damage and Repair in Mammalian Telomeres	journal.pgen.1000951	null	[ [ "Telomeres are chromosome end nucleoprotein structures that are composed of telomere associated proteins and TTAGGG repeats in mammals [1] .", "Telomeres cap chromosome ends and prevent them from being recognized as broken DNA .", "Dysfunctional telomeres , emanating from loss of telomere repeats and/...	[ "8-oxo-7 , 8-dihydroguanine ( 8-oxoG ) and 2 , 6-diamino-4-hydroxy-5-formamidopyrimidine ( FapyG ) are among the most common oxidative DNA lesions and are substrates for 8-oxoguanine DNA glycosylase ( OGG1 ) –initiated DNA base excision repair ( BER ) .", "Mammalian telomeres consist of triple guanine repeats and...	[ "It has been proposed that oxidative DNA damage compromises telomere integrity .", "However , neither the types nor the consequences of oxidative DNA damage in telomeres have been fully explored .", "Oxidative base lesions , especially 8-oxoG and FapyG are among the most common oxidative DNA damage .", "These...	2010
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "motor systems", "computational neuroscience", "psychophysics", "biology", "sensory perception", "neuroscience" ]	Internal Representations of Temporal Statistics and Feedback Calibrate Motor-Sensory Interval Timing	journal.pcbi.1002771	null	[ [ "The ability to estimate motor-sensory time intervals in the subsecond range and react accordingly is fundamental in many behaviorally relevant circumstances [1] , such as dodging a blow or assessing causality ( ‘was it me producing that noise ? ’ ) .", "Since sensing of time intervals is inherently noisy...	[ "Humans have been shown to adapt to the temporal statistics of timing tasks so as to optimize the accuracy of their responses , in agreement with the predictions of Bayesian integration .", "This suggests that they build an internal representation of both the experimentally imposed distribution of time intervals ...	[ "Human performance in a timing task depends on the context of recently experienced time intervals .", "In fact , people may use prior experience to improve their timing performance .", "Given the relevance of time for both sensing and acting in the world , how humans learn and represent temporal information is ...	2012
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "sequencing techniques", "invertebrates", "medicine and health sciences", "cellular stress responses", "immunology", "cell processes", "parasitic diseases", "animals", "sequence assembly tools", "membrane proteins", "clinical medicine", "genome analysis", "molecular biology techniques", "a...	The Anisakis Transcriptome Provides a Resource for Fundamental and Applied Studies on Allergy-Causing Parasites	journal.pntd.0004845	null	[ [ "Foodborne diseases include a range of illnesses transmitted via the ingestion of foodstuffs contaminated with a variety of chemical compounds and pathogenic microorganisms , including parasites [1–3] .", "Whilst the global disease burden and costs linked to these illnesses are difficult to estimate , it ...	[ "Food-borne nematodes of the genus Anisakis are responsible for a wide range of illnesses ( = anisakiasis ) , from self-limiting gastrointestinal forms to severe systemic allergic reactions , which are often misdiagnosed and under-reported .", "In order to enhance and refine current diagnostic tools for anisakias...	[ "Nematodes within the genus Anisakis ( i . e . A . simplex and A . pegreffii , also known as herring worms ) are the causative agents of the fish-borne gastrointestinal illness known as ‘anisakiasis’ , with infections resulting in symptoms ranging from mild gastric forms to severe allergic reactions leading to urti...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "developmental biology/germ cells", "molecular biology/recombination", "cell biology", "molecular biology/chromosome structure", "molecular biology/dna repair" ]	Structural Maintenance of Chromosomes (SMC) Proteins Promote Homolog-Independent Recombination Repair in Meiosis Crucial for Germ Cell Genomic Stability	journal.pgen.1001028	null	[ [ "Homologous recombination ( HR ) utilizes an undamaged homologous DNA template to repair DNA double-strand breaks ( DSBs ) .", "The use of template-mediated repair minimizes the likelihood of DNA sequence alterations arising during the repair process .", "For mitotic cells following DNA replication , ...	[ "In meiosis , programmed DNA breaks repaired by homologous recombination ( HR ) can be processed into inter-homolog crossovers that promote the accurate segregation of chromosomes .", "In general , more programmed DNA double-strand breaks ( DSBs ) are formed than the number of inter-homolog crossovers , and the e...	[ "Sperm and oocytes are essential for the faithful transmission of genetic information during sexual reproduction .", "As germ cells mature into sperm and oocytes , DNA double-strand breaks ( DSBs ) are deliberately created on each chromosome and a subset of DSBs is repaired to form meiotic crossovers between homo...	2010
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genetics and genomics/genetics of disease", "rheumatology/bone and mineral metabolism" ]	Association of Variants at 1q32 and STAT3 with Ankylosing Spondylitis Suggests Genetic Overlap with Crohn's Disease	journal.pgen.1001195	null	[ [ "Ankylosing spondylitis ( AS ) is one of a group of common inflammatory rheumatic diseases known as spondyloarthritidies in which involvement of the spine and sacroiliac joints is prominent [1] .", "Heritability of the disease assessed by twin studies has been determined to be >90% [2] .", "Apart from...	[ "Ankylosing spondylitis ( AS ) is a common inflammatory arthritic condition .", "Overt inflammatory bowel disease ( IBD ) occurs in about 10% of AS patients , and in addition 70% of AS cases may have subclinical terminal ileitis .", "Spondyloarthritis is also common in IBD patients .", "We therefore tested Cr...	[ "Ankylosing spondylitis is a common inflammatory arthritis primarily affecting the spine and pelvis .", "The disease is highly heritable ( heritability>90% ) , and the major genetic allele for the disease , HLA-B27 , contributes approximately half the genetic risk for the condition .", "Ankylosing spondylitis a...	2010
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "medicine and health sciences", "toxins", "pathology and laboratory medicine", "anesthesiology", "vertebrates", "neuromuscular blockade", "electrophysiology", "neuroscience", "animals", "toxicology", "toxic agents", "health care", "paralysis", "signs and symptoms", "pharmaceutics", "re...	Neuromuscular Effects of Common Krait (Bungarus caeruleus) Envenoming in Sri Lanka	journal.pntd.0004368	null	[ [ "Globally snake envenoming is a major cause of morbidity and mortality in the rural tropics [1] .", "Neurotoxicity causing paralysis is one of the major clinical syndromes of snake envenoming , and occurs mainly with elapids ( Australasian elapids , American coral snakes , Asian kraits and some cobra spec...	[ "We aimed to investigate neurophysiological and clinical effects of common krait envenoming , including the time course and treatment response .", "Patients with definite common krait ( Bungarus caeruleus ) bites were recruited from a Sri Lankan hospital .", "All patients had serial neurological examinations an...	[ "Common krait bites cause muscular paralysis due to the venom disrupting communication between the nerves and muscles .", "This becomes life-threatening for the patient if there is paralysis of the muscles used for breathing .", "We studied the severity of paralysis , long term effects and the value of antiveno...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods", "Supporting Information" ]	[ "plant biology", "computational biology", "molecular biology", "genetics and genomics" ]	Genome-Wide Profiling and Analysis of Arabidopsis siRNAs	journal.pbio.0050057	There are a lot of small RNAs in Arabidopis that regulate other genes. These RNAs are produced by a number of enzymes; the authors have used mutants of these enzymes to see what each of them does.	[ [ "Most eukaryotes contain RNA-based silencing pathways that function at the transcriptional or posttranscriptional level to negatively regulate or control genes , repetitive sequences , viruses , and mobile elements [1 , 2] .", "At the heart of these silencing pathways are small RNAs , which arise from dou...	[ "Eukaryotes contain a diversified set of small RNA-guided pathways that control genes , repeated sequences , and viruses at the transcriptional and posttranscriptional levels .", "Genome-wide profiles and analyses of small RNAs , particularly the large class of 24-nucleotide ( nt ) short interfering RNAs ( siRNAs...	[ "The discovery of small RNA molecules that inactivate genes during normal growth and development or on invasion by viruses and other mobile genetic elements has profoundly altered our views about how genes are regulated .", "We set out to investigate the global patterns of small RNA formation and activity across ...	2007
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "body weight", "medicine and health sciences", "microbiome", "microbiology", "cancers and neoplasms", "ulcerative colitis", "oncology", "colitis", "physiological parameters", "mathematics", "statistics (mathematics)", "gastroenterology and hepatology", "obesity", "inflammatory bowel diseas...	Correcting for batch effects in case-control microbiome studies	journal.pcbi.1006102	null	[ [ "Data generated by high throughput methods like mass-spectrometry , second-generation sequencing , or microarrays are sensitive to experimental and computational processing [1 , 2] .", "This sensitivity gives rise to ‘batch effects’ between independent runs of an experiment .", "Even when different re...	[ "High-throughput data generation platforms , like mass-spectrometry , microarrays , and second-generation sequencing are susceptible to batch effects due to run-to-run variation in reagents , equipment , protocols , or personnel .", "Currently , batch correction methods are not commonly applied to microbiome sequ...	[ "Batch effects are obstacles to comparing results across studies .", "Traditional meta-analysis techniques for combining p-values from independent studies , like Fisher’s method , are effective but statistically conservative .", "If batch-effects can be corrected , then statistical tests can be performed on dat...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine", "animal genetics", "genetic mutation", "protein interactions", "gene regulation", "regulatory proteins", "dna-binding proteins", "dna transcription", "developmental biology", "molecular development", "dna", "rna synthesis", "epigenetics", "molecular genetics", "chromatin", ...	Mi2β Is Required for γ-Globin Gene Silencing: Temporal Assembly of a GATA-1-FOG-1-Mi2 Repressor Complex in β-YAC Transgenic Mice	journal.pgen.1003155	null	[ [ "The human β-globin locus is composed of five functional genes ( ε , Gγ , Aγ , δ , and β ) and a master regulatory region called the locus control region ( LCR ) .", "These genes are arrayed in the order in which they are progressively expressed during development .", "Expression of the β-like globin ...	[ "Activation of γ-globin gene expression in adults is known to be therapeutic for sickle cell disease .", "Thus , it follows that the converse , alleviation of repression , would be equally effective , since the net result would be the same: an increase in fetal hemoglobin .", "A GATA-1-FOG-1-Mi2 repressor compl...	[ "Sickle cell disease ( SCD ) is one of the most common genetic diseases , affecting millions of people worldwide .", "SCD affects red blood cells' shape and renders them ineffective , resulting in anemia along with attendant complications .", "The disease is caused by a single point mutation in the coding seque...	2012
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "taxonomy", "organismal evolution", "medicine and health sciences", "pathology and laboratory medicine", "influenza", "pathogens", "microbiology", "orthomyxoviruses", "epistasis", "viruses", "mutation", "phylogenetics", "data management", "rna viruses", "phylogenetic analysis", "microb...	Fitness cost of reassortment in human influenza	journal.ppat.1006685	null	[ [ "Influenza virus is a negative-sense single strand RNA virus .", "Humans can be infected by three phylogenetically and antigenically distinct influenza lineages—A , B and C—that co-circulate globally .", "Among these lineages , influenza A shows the fastest rate of evolution [1–4] .", "The genome ...	[ "Reassortment , which is the exchange of genome sequence between viruses co-infecting a host cell , plays an important role in the evolution of segmented viruses .", "In the human influenza virus , reassortment happens most frequently between co-existing variants within the same lineage .", "This process breaks...	[ "The genome of the human influenza virus consists of 8 disjoint RNA polymer segments .", "These segments can undergo reassortment: when two viruses co-infect a host cell , they can produce viral offspring with a new combination of segments .", "In this paper , we show that reassortment within a given influenza ...	2017
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "ecology and environmental sciences", "medicine and health sciences", "vector-borne diseases", "tropical diseases", "species delimitation", "biodiversity", "parasitic diseases", "parasitic protozoans", "seasons", "protozoans", "speciation", "neglected tropical diseases", "ecological metrics"...	Amazonian Triatomine Biodiversity and the Transmission of Chagas Disease in French Guiana: In Medio Stat Sanitas	journal.pntd.0004427	null	[ [ "Tropical and sub-tropical countries from all over the globe are vulnerable to two of the major scientific and socio-economic issues faced by today’s human societies; the loss of biodiversity and the burden of infectious diseases .", "These issues are linked one with another since a critical consequence o...	[ "The effects of biodiversity on the transmission of infectious diseases now stand as a cornerstone of many public health policies .", "The upper Amazonia and Guyana shield are hot-spots of biodiversity that offer genuine opportunities to explore the relationship between the risk of transmission of Chagas disease ...	[ "A major aspect of the evolution of Life on Earth is the contemporary loss of biodiversity .", "To understand the effects of biodiversity on biological phenomena is increasingly important .", "A key question is whether biodiversity facilitates or reduces infectious diseases transmission .", "Surprisingly , al...	2016

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