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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", "Model", "Results", "Discussion", "Materials and Methods" ]	[ "medicine and health sciences", "body fluids", "cardiovascular anatomy", "endothelial cells", "renal arteries", "epithelial cells", "hemodynamics", "arterioles", "arteries", "nephrons", "kidneys", "blood vessels", "animal cells", "biological tissue", "blood pressure", "hematology", "...	Modeling of Kidney Hemodynamics: Probability-Based Topology of an Arterial Network	journal.pcbi.1004922	null	[ [ "An important feature of the vascular system is its highly branched structure .", "It is assumed that the branching geometry of blood vessels is governed by defined principles [1–3] .", "Tree-like structures of arterial systems have been a subject of experimental and theoretical studies related to vas...	[ "Through regulation of the extracellular fluid volume , the kidneys provide important long-term regulation of blood pressure .", "At the level of the individual functional unit ( the nephron ) , pressure and flow control involves two different mechanisms that both produce oscillations .", "The nephrons are arra...	[ "By maintaining the volume and composition of the body fluids within narrow ranges , and by producing a set of hormones that affect the blood vessels , the kidneys provide important long-term regulation of blood pressure .", "Disturbances of kidney function can cause hypertension , a prevalent disease in modern s...	2016
[ "Introduction", "Results", "Discussion", "Methods" ]	[]	A Sensitized Screen for Genes Promoting Invadopodia Function In Vivo: CDC-42 and Rab GDI-1 Direct Distinct Aspects of Invadopodia Formation	journal.pgen.1005786	null	[ [ "Basement membrane ( BM ) is a dense , highly cross-linked extracellular matrix that surrounds most tissues and acts as a barrier to migrating cells [1] .", "During development and immune function , specialized cells acquire the ability to cross BM barriers to facilitate cell movement into new tissues [2–...	[ "Invadopodia are specialized membrane protrusions composed of F-actin , actin regulators , signaling proteins , and a dynamically trafficked invadopodial membrane that drive cell invasion through basement membrane ( BM ) barriers in development and cancer .", "Due to the challenges of studying invasion in vivo , ...	[ "During animal development specialized cells acquire the ability move and invade into other tissues to form complex organs and structures .", "Understanding this cellular behavior is important medically , as cancer cells can hijack the developmental program of invasion to metastasize throughout the body .", "On...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "host cells", "virulence factors and mechanisms", "dna viruses", "viral transmission and infection", "viral classification", "virology", "biology", "microbiology", "viral replication" ]	The Master Regulator of the Cellular Stress Response (HSF1) Is Critical for Orthopoxvirus Infection	journal.ppat.1003904	null	[ [ "The Poxviridae family is comprised of several human pathogens in the Orthopoxvirus genus , including monkeypox ( MPXV ) and smallpox ( Variola ) , which was eradicated through vaccination with vaccinia ( VACV ) .", "With a dramatic increase in human MPXV cases in Africa , the rise of VACV-like orthopoxvi...	[ "The genus Orthopoxviridae contains a diverse group of human pathogens including monkeypox , smallpox and vaccinia .", "These viruses are presumed to be less dependent on host functions than other DNA viruses because they have large genomes and replicate in the cytoplasm , but a detailed understanding of the host...	[ "Orthopoxviruses bring in many of the factors they need for replication and impair the host cell by preventing the expression of host proteins .", "Although orthopoxviruses are less reliant on the host than some viruses , host factors are still required for infection .", "Here , we report results from two genom...	2014
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "medicine", "infectious disease epidemiology", "epidemiology", "population biology", "biology" ]	Evaluating Paratransgenesis as a Potential Control Strategy for African Trypanosomiasis	journal.pntd.0002374	null	[ [ "African trypanosomiasis infects 30 , 000 people in sub-Saharan Africa .", "Without treatment , infection is almost always fatal [1] .", "In addition , losses in livestock production due to African trypanosomiasis are estimated at US$1 billion annually [2] .", "Currently , control efforts primaril...	[ "Genetic-modification strategies are currently being developed to reduce the transmission of vector-borne diseases , including African trypanosomiasis .", "For tsetse , the vector of African trypanosomiasis , a paratransgenic strategy is being considered: this approach involves modification of the commensal symbi...	[ "African sleeping sickness is a fatal disease occurring in sub-Saharan Africa .", "The parasites that cause African sleeping sickness are transmitted between humans and livestock by the tsetse fly .", "Controlling the spread of the parasite by tsetse flies has been proposed as a promising strategy for reducing ...	2013
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "trophozoites", "parasite groups", "morpholino", "rna interference", "giardia", "enzymes", "cell cycle and cell division", "cell processes", "enzymology", "nucleotides", "parasitic protozoans", "parasitology", "apicomplexa", "protozoans", "cytokinesis", "molecular biology techniques", ...	Identification and Validation of Small-Gatekeeper Kinases as Drug Targets in Giardia lamblia	journal.pntd.0005107	null	[ [ "Giardia lamblia is the most commonly reported intestinal protozoan parasite and the cause of giardiasis , a gastrointestinal illness resulting in diarrhea , nutrient malabsorption , vomiting , and weight loss [1] .", "It infects approximately 280 million people worldwide [2 , 3 , 4] .", "This disease...	[ "Giardiasis is widely acknowledged to be a neglected disease in need of new therapeutics to address toxicity and resistance issues associated with the limited available treatment options .", "We examined seven protein kinases in the Giardia lamblia genome that are predicted to share an unusual structural feature ...	[ "The eukaryotic protozoan Giardia lamblia is the most commonly reported intestinal parasite worldwide .", "Current treatments used to treat giardiasis include metronidazole and other nitroimidazole derivatives .", "However , emergence of metronidazole-resistance strains and adverse reactions to the treatments s...	2016
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "splenomegaly", "schistosoma", "invertebrates", "schistosoma mansoni", "parasite groups", "medicine and health sciences", "pathology and laboratory medicine", "plasmodium", "helminths", "parasitic diseases", "anemia", "animals", "parasitology", "apicomplexa", "signs and symptoms", "gas...	Antagonistic effects of Plasmodium-helminth co-infections on malaria pathology in different population groups in Côte d’Ivoire	journal.pntd.0007086	null	[ [ "Anemia is multifactorial .", "However , in low- and middle-income countries it is largely attributable to parasitic diseases , such as malaria and helminth infections [1] .", "Yet , the etiology of anemia differs between malaria and helminthiases .", "Plasmodium spp .", ", the malaria causing...	[ "Plasmodium spp .", "and helminths are co-endemic in many parts of the tropics; hence , co-infection is a common phenomenon .", "Interactions between Plasmodium and helminth infections may alter the host’s immune response and susceptibility and thus impact on morbidity .", "There is little information on the ...	[ "Malaria ( due to infection with Plasmodium spp . ) and parasitic worms ( for example soil-transmitted helminths and Schistosoma spp . ) are common in the tropics .", "Hence , people are often co-infected , depending on various factors .", "Interactions between Plasmodium and helminth infections may alter immun...	2019
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "medicine and health sciences", "toxins", "pathology and laboratory medicine", "engineering and technology", "pathogens", "vibrio", "tropical diseases", "microbiology", "toxic agents", "toxicology", "epithelial cells", "solutions", "bacterial diseases", "aqueous solutions", "vibrio chole...	Neutralization of cholera toxin with nanoparticle decoys for treatment of cholera	journal.pntd.0006266	null	[ [ "Diarrheal diseases are a major cause of morbidity and mortality in developing regions , with an estimated 3–5 million cases and over 100 , 000 deaths per year [1 , 2] .", "Diarrhea accounts for 1 in 9 childhood deaths worldwide , making it the second leading cause of death among children under the age of...	[ "Diarrheal diseases are a major cause of morbidity and mortality worldwide .", "In many cases , antibiotic therapy is either ineffective or not recommended due to concerns about emergence of resistance .", "The pathogenesis of several of the most prevalent infections , including cholera and enteroxigenic Escher...	[ "Diarrheal diseases are a major cause of suffering and death in the world , particularly in tropical regions with limited health care resources .", "Many of the most important diarrhea-causing microbes produce toxins that activate fluid secretion in the gut .", "A prototype pathogen in this category is the caus...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "immunology/cellular microbiology and pathogenesis", "immunology/antigen processing and recognition", "cell biology/leukocyte signaling and gene expression", "cell biology/cell signaling", "immunology/immunomodulation", "cell biology/membranes and sorting", "infectious diseases/viral infections", "vir...	DC-SIGN Mediated Sphingomyelinase-Activation and Ceramide Generation Is Essential for Enhancement of Viral Uptake in Dendritic Cells	journal.ppat.1001290	null	[ [ "Their interaction with myeloid dendritic cells ( DCs ) is believed to be central to the understanding of immunomodulation by viruses also including measles virus [1] , [2] , [3] , [4] .", "In the hematopoetic system , MV replication segregates with expression of CD150 , an Ig-like domain containing molec...	[ "As pattern recognition receptor on dendritic cells ( DCs ) , DC-SIGN binds carbohydrate structures on its pathogen ligands and essentially determines host pathogen interactions because it both skews T cell responses and enhances pathogen uptake for cis infection and/or T cell trans-infection .", "How these proce...	[ "Dendritic cells ( DCs ) bear receptors specialized on recognition of patterns specific to pathogens ( such as carbohydrates ) , which can either promote functional activation of these cells ( such as TLRs ) , which renders them capable of efficiently presenting antigens to T cells , or , as DC-SIGN , endocytic upt...	2011
[ "Introduction", "Results", "Discussion", "Methods" ]	[]	Impaired Systemic Tetrahydrobiopterin Bioavailability and Increased Dihydrobiopterin in Adult Falciparum Malaria: Association with Disease Severity, Impaired Microvascular Function and Increased Endothelial Activation	journal.ppat.1004667	null	[ [ "Malaria remains the most important parasitic infection in humans , causing an estimated 207 million cases and 627 , 000 deaths in 2010 [1 , 2] .", "Mortality from severe Plasmodium falciparum malaria has decreased with use of intravenous artesunate , but case fatality rates remain at 8% and 15% for Afric...	[ "Tetrahydrobiopterin ( BH4 ) is a co-factor required for catalytic activity of nitric oxide synthase ( NOS ) and amino acid-monooxygenases , including phenylalanine hydroxylase .", "BH4 is unstable: during oxidative stress it is non-enzymatically oxidized to dihydrobiopterin ( BH2 ) , which inhibits NOS .", "De...	[ "Vascular nitric oxide ( NO ) bioavailability is decreased in severe falciparum malaria and associated with microvascular dysfunction and increased endothelial activation .", "Nitric oxide synthase ( NOS ) requires tetrahydrobiopterin ( BH4 ) as a co-factor to convert L-arginine to NO , but when BH4 is low , NOS ...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "blood cells", "bacteriology", "medicine and health sciences", "immune cells", "immune physiology", "pathology and laboratory medicine", "spleen", "pathogens", "immunology", "microbiology", "operons", "dna transcription", "secretion systems", "signs and symptoms", "dna", "neutrophils",...	Fis Is Essential for Yersinia pseudotuberculosis Virulence and Protects against Reactive Oxygen Species Produced by Phagocytic Cells during Infection	journal.ppat.1005898	null	[ [ "Bacterial pathogens utilize both “defensive” and “offensive” strategies to survive in mammalian tissue sites and withstand the host immune response [1] .", "“Defensive” strategies often consist of physiological adaptations to stresses encountered in tissues , such as changes in pH or temperature , nutrie...	[ "All three pathogenic Yersinia species share a conserved virulence plasmid that encodes a Type 3 Secretion System ( T3SS ) and its associated effector proteins .", "During mammalian infection , these effectors are injected into innate immune cells , where they block many bactericidal functions , including the pro...	[ "The pathogenic members of the genus Yersinia share a conserved virulence plasmid that primarily serves to encode a Type 3 Secretion System and its associated effector proteins .", "During mammalian infection , these effectors are targeted toward phagocytic cells , where they neutralize a multitude of functions ,...	2016
[ "Introduction", "Materials and Methods", "Results and Discussion" ]	[ "chemical bonding", "classical mechanics", "chemical compounds", "phosphates", "vibration", "enthalpy", "thermodynamics", "hydrogen bonding", "physical chemistry", "entropy", "chemistry", "solvation", "free energy", "physics", "biochemistry", "biochemical simulations", "biology and l...	Characterization of Promiscuous Binding of Phosphor Ligands to Breast-Cancer-Gene 1 (BRCA1) C-Terminal (BRCT): Molecular Dynamics, Free Energy, Entropy and Inhibitor Design	journal.pcbi.1005057	null	[ [ "The tandem ~100-amino acid repeats of breast-cancer-gene 1 ( BRCA1 ) C-terminal ( BRCT ) are known to bind to phosphorylated proteins which are important for a number of tumor suppressor functions , which include , DNA repair , cell-cycle checkpoint , and transcription regulation [1–4] .", "The BRCT repe...	[ "Inhibition of the protein-protein interaction ( PPI ) mediated by breast-cancer-gene 1 C-terminal ( BRCT ) is an attractive strategy to sensitize breast and ovarian cancers to chemotherapeutic agents that induce DNA damage .", "Such inhibitors could also be used for studies to understand the role of this PPI in ...	[ "Promiscuous proteins are commonly observed in biological systems , such as modular domains that recognize phosphopeptides during signal transduction .", "The use of phosphopeptides and compounds with phosphate groups as inhibitors to protein–protein interactions have attracted increasing interest for years .", ...	2016
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "learning", "invertebrates", "medicine and health sciences", "sleep deprivation", "nervous system", "sleep", "social sciences", "neuroscience", "animals", "learning and memory", "sleep disorders", "animal models", "physiological processes", "drosophila melanogaster", "model organisms", ...	AMPK signaling linked to the schizophrenia-associated 1q21.1 deletion is required for neuronal and sleep maintenance	journal.pgen.1007623	null	[ [ "Recent genome-wide association studies have identified copy-number variants ( CNVs ) associated with high risk of schizophrenia and other neuropsychiatric disorders [1–4] .", "Sleep disturbance is one of the most common problems observed in individuals with psychiatric disorders [5] .", "Although the...	[ "The human 1q21 . 1 deletion of ten genes is associated with increased risk of schizophrenia .", "This deletion involves the β-subunit of the AMP-activated protein kinase ( AMPK ) complex , a key energy sensor in the cell .", "Although neurons have a high demand for energy and low capacity to store nutrients , ...	[ "The human 1q21 . 1 chromosomal deletion is associated with increased risk of schizophrenia .", "Because this deletion affects only a small number of genes , it provides a unique opportunity to identify the specific disease-causing gene ( s ) using animal models .", "Here , we report the use of a Drosophila mod...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods", "Accession numbers" ]	[ "cell biology", "physiology", "diabetes and endocrinology", "genetics and genomics" ]	COPI Complex Is a Regulator of Lipid Homeostasis	journal.pbio.0060292	A specific vesicle-trafficking machine is shown to be required for cells to use stored lipid, in bothDrosophila and mammalian cells.	[ [ "Lipid homeostasis is critical in health and disease , but remains poorly understood ( for review see [1] ) .", "Non-esterified free fatty acid ( NEFA ) is used for energy generation in beta-oxidation , membrane phospholipid synthesis , signaling , and in regulation of transcription factors such as the pe...	[ "Lipid droplets are ubiquitous triglyceride and sterol ester storage organelles required for energy storage homeostasis and biosynthesis .", "Although little is known about lipid droplet formation and regulation , it is clear that members of the PAT ( perilipin , adipocyte differentiation related protein , tail i...	[ "Fat cells , and cells in general , convert fatty acids into triglycerides that are stored in droplets for future use .", "Despite the enormous importance of lipid droplets in obesity and other disease processes , we know very little about how lipid reserves in droplets are formed and how those reserves are drawn...	2008
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genome evolution", "gene expression", "genetics", "biology", "genomics", "genetics and genomics" ]	Gene Expression Divergence is Coupled to Evolution of DNA Structure in Coding Regions	journal.pcbi.1002275	null	[ [ "Proper control of gene expression is central for the unique phenotype of each organism .", "Phenotypic diversity can be generated through changes in gene expression .", "Divergence in gene expression of a specific gene between closely related species can result from sequence changes in its coding reg...	[ "Sequence changes in coding region and regulatory region of the gene itself ( cis ) determine most of gene expression divergence between closely related species .", "But gene expression divergence between yeast species is not correlated with evolution of primary nucleotide sequence .", "This indicates that othe...	[ "The unique phenotype of each organism is partly determined by gene expression .", "Changes in gene expression are an important source of phenotypic variation , and can be caused by changes in regulatory and coding sequences of the gene itself ( cis ) and changes in regulatory factors ( trans ) .", "The contrib...	2011
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "engineering and technology", "gene regulation", "electrical circuits", "regulator genes", "gene types", "molecular biology techniques", "research and analysis methods", "gene mapping", "gene expression", "molecular biology", "toggle switches", "phenotypes", "gene regulatory networks", "ge...	Interrogating the topological robustness of gene regulatory circuits by randomization	journal.pcbi.1005456	null	[ [ "State-of-the-art molecular profiling techniques[1–4] have enabled the construction or inference of large gene regulatory networks underlying certain cellular functions , such as cell differentiation[5 , 6] and circadian rhythm[7 , 8] .", "However , it remains a challenge to understand the operating princ...	[ "One of the most important roles of cells is performing their cellular tasks properly for survival .", "Cells usually achieve robust functionality , for example , cell-fate decision-making and signal transduction , through multiple layers of regulation involving many genes .", "Despite the combinatorial complex...	[ "Cells are able to robustly carry out their essential biological functions , possibly because of multiple layers of tight regulation via complex , yet well-designed , gene regulatory networks involving a substantial number of genes .", "State-of-the-art genomics technology has enabled the mapping of these large g...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genetics and genomics/disease models", "biochemistry/protein folding", "neurological disorders", "cell biology/cellular death and stress responses" ]	Disease-Associated Mutant Ubiquitin Causes Proteasomal Impairment and Enhances the Toxicity of Protein Aggregates	journal.pgen.1000382	null	[ [ "As technology and medicine further extend the human lifespan , age-related diseases will become more prevalent .", "Alzheimer's disease ( AD ) is a neurodegenerative disorder that affects 20 million people worldwide and is the most common form of late-onset dementia [1] .", "The study of genetic muta...	[ "Protein homeostasis is critical for cellular survival and its dysregulation has been implicated in Alzheimer's disease ( AD ) and other neurodegenerative disorders .", "Despite the growing appreciation of the pathogenic mechanisms involved in familial forms of AD , much less is known about the sporadic cases .",...	[ "The accumulation of cytotoxic protein aggregates occurs in many neurodegenerative diseases .", "It is difficult to determine if the protein aggregates found in these diseases represent a cause or consequence of the disorder .", "Degradation pathways , such as the ubiquitin/proteasome system ( UPS ) , remove mi...	2009
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "medicine", "infectious diseases", "chagas disease", "nucleic acids", "neglected tropical diseases", "dna", "dna repair", "biology", "molecular cell biology", "parasitic diseases" ]	Oxidative Stress and DNA Lesions: The Role of 8-Oxoguanine Lesions in Trypanosoma cruzi Cell Viability	journal.pntd.0002279	null	[ [ "Oxidative stress is often defined as a situation in which the balance between oxidants and antioxidants is disrupted .", "The main source of oxidative stress in living organisms is reactive oxygen species ( ROS ) , which are molecules , such as hydrogen peroxide , superoxide and hydroxyl radicals , that ...	[ "The main consequence of oxidative stress is the formation of DNA lesions , which can result in genomic instability and lead to cell death .", "Guanine is the base that is most susceptible to oxidation , due to its low redox potential , and 8-oxoguanine ( 8-oxoG ) is the most common lesion .", "These characteri...	[ "The parasite Trypanosoma cruzi is the causative agent of Chagas disease , a malady endemic throughout Latin America .", "Studying the DNA repair machinery of this parasite could provide us with good insights about T . cruzi biology and virulence .", "We focused on the 8-oxoguanine ( 8-oxoG ) DNA lesion and its...	2013
[ "Introduction", "Materials and methods", "Results", "Discussion" ]	[ "animal types", "medicine and health sciences", "enzyme-linked immunoassays", "immune physiology", "chemical compounds", "picric acid", "immunology", "vertebrates", "animals", "mammals", "organic compounds", "primates", "nitrobenzenes", "bacterial diseases", "colobus", "antibodies", ...	Low antibody prevalence against Bacillus cereus biovar anthracis in Taï National Park, Côte d'Ivoire, indicates high rate of lethal infections in wildlife	journal.pntd.0005960	null	[ [ "Anthrax is a zoonosis occurring worldwide , characterized by septicemia and sudden death , mainly in herbivores .", "The disease is regularly observed in arid and savanna ecosystems , where animals ingest bacterial spores from soil while grazing [1–3] .", "In the past anthrax was thought to be exclus...	[ "Bacillus cereus biovar anthracis ( Bcbva ) is a member of the B . cereus group which carries both B . anthracis virulence plasmids , causes anthrax-like disease in various wildlife species and was described in several sub-Saharan African rainforests .", "Long-term monitoring of carcasses in Taï National Park , C...	[ "Anthrax is a deadly zoonosis , predominantly known to affect wild and domestic herbivores .", "It has long been assumed that the disease is exclusively caused by B . anthracis , but recently another member of the B . cereus group , Bacillus cereus biovar anthracis ( Bcbva ) , was found to carry both B . anthraci...	2017
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[]	The Immunology of a Healing Response in Cutaneous Leishmaniasis Treated with Localized Heat or Systemic Antimonial Therapy	journal.pntd.0004178	null	[ [ "Leishmaniasis , a vector-borne parasitic disease , remains a pressing global health concern with 12 million persons infected , 2 million new infections each year , limited therapeutic options and no effective vaccine [1] .", "Healing cutaneous leishmaniasis ( CL ) relies on the development of an effectiv...	[ "The effectiveness of systemic antimonial ( sodium stibogluconate , Pentostam , SSG ) treatment versus local heat therapy ( Thermomed ) for cutaneous leishmaniasis was studied previously and showed similar healing rates .", "We hypothesized that different curative immune responses might develop with systemic and ...	[ "Globally , leishmaniasis treatment relies on the use of antimonial drugs ( i . e . SSG ) .", "In an earlier study we showed that skin lesions due to L . major treated by the ThermoMed ( TM ) device healed at a similar rate and with less associated systemic toxicity than lesions treated with intravenous SSG .", ...	2015
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "public health and epidemiology/global health" ]	Feasibility, Drug Safety, and Effectiveness of Etiological Treatment Programs for Chagas Disease in Honduras, Guatemala, and Bolivia: 10-Year Experience of Médecins Sans Frontières	journal.pntd.0000488	null	[ [ "Discovered 100 years ago in 1909 , Chagas disease ( American trypanosomiasis ) is an endemic disease of the Americas , caused by infection with the protozoan parasite Trypanosoma cruzi .", "According to varying estimates , there are about 10–15 million existing cases , 50 , 000 new annual infections , an...	[ "Chagas disease ( American trypanosomiasis ) is a zoonotic or anthropozoonotic disease caused by the parasite Trypanosoma cruzi .", "Predominantly affecting populations in poor areas of Latin America , medical care for this neglected disease is often lacking .", "Médecins Sans Frontières/Doctors Without Borders...	[ "Chagas disease was discovered 100 years ago by the Brazilian physician Carlos Chagas .", "Predominantly affecting poor populations throughout Latin America , recognition and treatment of this parasitic disease are often neglected .", "Since 1999 , the international medical humanitarian aid organization Médecin...	2009
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "paraguay", "medicine and health sciences", "population dynamics", "geographical locations", "argentina", "population biology", "infectious disease control", "triatoma", "agrochemicals", "infectious diseases", "south america", "epidemiology", "disease vectors", "agriculture", "insecticid...	Distribution of Pyrethroid Resistant Populations of Triatoma infestans in the Southern Cone of South America	journal.pntd.0004561	null	[ [ "Chagas disease is the most important vector-borne infection in Latin America , affecting approximately 5–6 million individuals [1] .", "The disease is caused by the protozoa Trypanosoma cruzi ( Trypanosomatidae ) and the most frequent transmission mechanism is through the feces of infected blood-sucking ...	[ "A number of studies published during the last 15 years showed the occurrence of insecticide resistance in Triatoma infestans populations .", "The different toxicological profiles and mechanisms of resistance to insecticides is due to a genetic base and environmental factors , being the insecticide selective pres...	[ "The elimination of T . infestans in wide areas of the Southern Cone countries of South America and good results in other vector control initiatives showed the high susceptibility of triatomines to pyrethroid insecticides .", "Despite the constant efforts of vector control , the success was not complete in severa...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "sequencing techniques", "gene regulation", "biological cultures", "microbiology", "dna transcription", "ht1080 cells", "immunoprecipitation", "sequence motif analysis", "molecular biology techniques", "co-immunoprecipitation", "research and analysis methods", "sequence analysis", "small int...	Functional and Structural Mimicry of Cellular Protein Kinase A Anchoring Proteins by a Viral Oncoprotein	journal.ppat.1005621	null	[ [ "As obligate intracellular parasites , all viruses are critically dependent upon the host cell .", "Intensive selective pressure , rapid replicative cycle times and severe restrictions on viral genome size combine to drive virus evolution .", "As a consequence , viral regulatory proteins have been rel...	[ "The oncoproteins of the small DNA tumor viruses interact with a plethora of cellular regulators to commandeer control of the infected cell .", "During infection , adenovirus E1A deregulates cAMP signalling and repurposes it for activation of viral gene expression .", "We show that E1A structurally and function...	[ "Studies of human adenovirus ( HAdV ) , a small DNA tumor virus , illustrate the profound impact of viral proteins on multiple host functions .", "The multifunctional E1A proteins of HAdV are particularly adept at targeting key cellular regulators .", "Mechanistically , E1A alters or inhibits the normal functio...	2016
[ "Introduction", "Results/Discussion", "Materials and Methods" ]	[ "genetics and genomics/complex traits", "genetics and genomics/population genetics" ]	Genetic Architecture of Complex Traits and Accuracy of Genomic Prediction: Coat Colour, Milk-Fat Percentage, and Type in Holstein Cattle as Contrasting Model Traits	journal.pgen.1001139	null	[ [ "Genomic prediction of future phenotypes or genetic merit using dense SNP genotypes can be used for prediction of disease risk , for forensics , and for estimation of breeding values for use in selection of livestock , crops and forage species [1]–[4] .", "In dairy cattle , estimated breeding values predi...	[ "Prediction of genetic merit using dense SNP genotypes can be used for estimation of breeding values for selection of livestock , crops , and forage species; for prediction of disease risk; and for forensics .", "The accuracy of these genomic predictions depends in part on the genetic architecture of the trait , ...	[ "Prediction of future phenotypes or genetic merit using high-density SNP chips can be used for prediction of disease risk in humans , for forensics , and for selection of livestock , crops , and forage species .", "Key questions are how accurately these predictions can be made and on what parameters does the accu...	2010
[ "Introduction", "Results", "Discussion", "Material and methods" ]	[ "protein transport", "medicine and health sciences", "pathology and laboratory medicine", "viral transmission and infection", "hela cells", "pathogens", "biological cultures", "cell processes", "microbiology", "plasmid construction", "epithelial cells", "cell cultures", "dna construction", ...	Epithelial cells detect functional type III secretion system of enteropathogenic Escherichia coli through a novel NF-κB signaling pathway	journal.ppat.1006472	null	[ [ "Enteropathogenic and enterohemorrhagic E . coli ( EPEC and EHEC , respectively ) are important human pathogens that cause symptoms ranging from subclinical chronic colonization to acute , life threatening infections [1] .", "EPEC and EHEC form typical attaching and effacing ( AE ) lesions on intestinal e...	[ "Enteropathogenic Escherichia coli ( EPEC ) , a common cause of infant diarrhea , is associated with high risk of mortality in developing countries .", "The primary niche of infecting EPEC is the apical surface of intestinal epithelial cells .", "EPEC employs a type three secretion system ( TTSS ) to inject the...	[ "The intestine harbors a dense community of commensal bacteria that play a vital role in host health and homeostasis , but it is also the port of entry for many pathogens .", "An important function of the intestinal epithelial cells is coordinating the immune response to microbial signals , ranging from tolerance...	2017
[ "Introduction", "Results", "Discussion", "Methods" ]	[]	Network Signatures of Survival in Glioblastoma Multiforme	journal.pcbi.1003237	null	[ [ "Glioblastoma multiforme is the most common primary brain tumor in adults and , unfortunately , also the most fatal .", "While GBMs are categorized histologically , the nature of the disease leads to significant variability in both tumor classification and patient outcome .", "To more specifically def...	[ "To determine a molecular basis for prognostic differences in glioblastoma multiforme ( GBM ) , we employed a combinatorial network analysis framework to exhaustively search for molecular patterns in protein-protein interaction ( PPI ) networks .", "We identified a dysregulated molecular signature distinguishing ...	[ "Glioblastoma multiforme ( GBM ) is the most common and aggressive brain tumor in adults , and , while the median survival time for treated patients is approximately one year , subgroups of patients respond differently to the same treatments , with some patients showing little improvement and other patients living ...	2013
[ "Introduction", "Results/Discussion", "Materials and Methods" ]	[ "medicine", "protein interactions", "molecular dynamics", "molecular mechanics", "neuroscience", "toxicology", "ion channels", "protein structure", "nicotinic acetylcholine receptors", "proteins", "chemistry", "biology", "proteomics", "toxin binding", "macromolecular complex analysis", ...	Blockade of Neuronal α7-nAChR by α-Conotoxin ImI Explained by Computational Scanning and Energy Calculations	journal.pcbi.1002011	null	[ [ "Nicotinic acetylcholine receptors ( nAChRs ) are a large family of ligand-gated ion channels that mediate rapid synaptic transmission in the central and peripheral nervous system [1] , [2] .", "nAChRs are implicated in disorders such as Alzheimer's diseases , schizophrenia , depression , hyperactivity di...	[ "α-Conotoxins potently inhibit isoforms of nicotinic acetylcholine receptors ( nAChRs ) , which are essential for neuronal and neuromuscular transmission .", "They are also used as neurochemical tools to study nAChR physiology and are being evaluated as drug leads to treat various neuronal disorders .", "A numb...	[ "Conotoxins are peptide toxins extracted from the venom of carnivorous marine cone snails .", "Members of the α-conotoxin subfamily potently block nicotinic acetylcholine receptors ( nAChRs ) , which are involved in signal transmission between two neurons or between neurons and muscle fibers .", "nAChRs are imp...	2011
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "immunology/cellular microbiology and pathogenesis", "virology/persistence and latency", "molecular biology/transcription initiation and activation", "molecular biology/dna methylation", "microbiology/cellular microbiology and pathogenesis" ]	Epigenetic Regulation of HIV-1 Latency by Cytosine Methylation	journal.ppat.1000495	null	[ [ "In HIV-infected individuals , highly active anti-retroviral therapy ( HAART ) dramatically reduces HIV-1 plasma titers [1]–[3] and decreases morbidity and mortality [4] .", "However , a reservoir of latent virus persists within resting CD4+ T cells [5]–[8] and contributes to the reemergence of viremia up...	[ "Human immunodeficiency virus type 1 ( HIV-1 ) persists in a latent state within resting CD4+ T cells of infected persons treated with highly active antiretroviral therapy ( HAART ) .", "This reservoir must be eliminated for the clearance of infection .", "Using a cDNA library screen , we have identified methyl...	[ "Current drug therapies inhibit replication of the human immunodeficiency virus ( HIV ) .", "In patients undergoing these therapies , the amount of HIV is reduced to an undetectable level and HIV-related disease subsides .", "However , stopping antiviral drug therapy results in the quick return of HIV and of di...	2009
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "infectious diseases/neglected tropical diseases", "infectious diseases/skin infections", "infectious diseases/protozoal infections", "infectious diseases/tropical and travel-associated diseases", "immunology/immunity to infections" ]	CD8 Cells of Patients with Diffuse Cutaneous Leishmaniasis Display Functional Exhaustion: The Latter Is Reversed, In Vitro, by TLR2 Agonists	journal.pntd.0000871	null	[ [ "Leishmaniasis is a zoonotic disease that infects humans as well as a variety of mammalian species .", "Several Leishmania species , such as L . mexicana , L . amazonensis , L . braziliensis and L . aethiopica can cause two opposite clinical forms of cutaneous leishmaniasis: localized cutaneous leishmania...	[ "Leishmania mexicana ( Lm ) causes localized ( LCL ) and diffuse ( DCL ) cutaneous leishmaniasis .", "DCL patients have a poor cellular immune response leading to chronicity .", "It has been proposed that CD8 T lymphocytes ( CD8 ) play a crucial role in infection clearance , although the role of CD8 cytotoxicit...	[ "Leishmania mexicana causes localized and diffuse cutaneous leishmaniasis .", "Whereas the former is a benign form the disease , diffuse cutaneous leishmaniasis is a chronic disfiguring disease , for which no cure is available , and the immune cells of these patients respond poorly to the parasite .", "It has b...	2010
[ "Introduction", "Results/Discussion", "Materials and Methods", "Supporting Information" ]	[ "oncology", "viruses", "biochemistry", "molecular biology" ]	The Crystal Structure of the SV40 T-Antigen Origin Binding Domain in Complex with DNA	journal.pbio.0050023	Crystal structures of the SV40 large T antigen (T-ag) origin binding domain (obd) with and without DNA show how two T-ag obds orient head-to-head and engage with the major groove.	[ [ "Viral DNA replication involves a sequence of carefully orchestrated steps including recognition of the origin by a protein ( the initiator ) or proteins , melting of the origin DNA , replication protein A ( RPA ) -dependent unwinding of the DNA , and recruitment of polymerase and other replication factors ( ...	[ "DNA replication is initiated upon binding of “initiators” to origins of replication .", "In simian virus 40 ( SV40 ) , the core origin contains four pentanucleotide binding sites organized as pairs of inverted repeats .", "Here we describe the crystal structures of the origin binding domain ( obd ) of the SV40...	[ "How DNA replicates is a critical question for understanding life .", "DNA replication remains difficult to investigate in eukaryotes , where it involves a complex , multi-protein apparatus which initiates replication at multiple poorly-defined DNA sequences .", "This process is far easier to study in viral sys...	2007
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Influenza Virus Reassortment Is Enhanced by Semi-infectious Particles but Can Be Suppressed by Defective Interfering Particles	journal.ppat.1005204	null	[ [ "The influenza A virus ( IAV ) genome comprises eight segments of negative sense RNA , each of which encode at least one essential viral protein [1 , 2] .", "This genome structure supports the generation of viral diversity through two major mechanisms: genetic drift due to an error prone viral polymerase ...	[ "A high particle to infectivity ratio is a feature common to many RNA viruses , with ~90–99% of particles unable to initiate a productive infection under low multiplicity conditions .", "A recent publication by Brooke et al . revealed that , for influenza A virus ( IAV ) , a proportion of these seemingly non-infe...	[ "Since the genome of an influenza A virus has eight non-contiguous segments , two influenza A viruses can exchange genes readily when they infect the same cell .", "This process of reassortment is important to the evolution of the virus and is one reason why this pathogen is constantly changing .", "It has long...	2015
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "neuroscience/motor systems", "mathematics/statistics", "neuroscience/theoretical neuroscience" ]	A Granger Causality Measure for Point Process Models of Ensemble Neural Spiking Activity	journal.pcbi.1001110	null	[ [ "Neurons in the brain are known to exert measurable , directional influences on the firing activities of surrounding neurons , and a detailed analysis of these interactions improves our understanding of how the brain performs specific functions [1] .", "Attempts to identify associations between neurons , ...	[ "The ability to identify directional interactions that occur among multiple neurons in the brain is crucial to an understanding of how groups of neurons cooperate in order to generate specific brain functions .", "However , an optimal method of assessing these interactions has not been established .", "Granger ...	[ "Recent advances in multiple-electrode recording have made it possible to record the activities of multiple neurons simultaneously .", "This provides an opportunity to study how groups of neurons form functional ensembles as different brain areas perform their various functions .", "However , most of the method...	2011
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "rna interference", "rna stability", "gene function", "cell division", "molecular genetics", "biology", "molecular biology", "biochemistry", "rna", "cell biology", "nucleic acids", "genetics", "molecular cell biology", "genetics and genomics" ]	A Novel Role for the RNA–Binding Protein FXR1P in Myoblasts Cell-Cycle Progression by Modulating p21/Cdkn1a/Cip1/Waf1 mRNA Stability	journal.pgen.1003367	null	[ [ "The Fragile X-Related 1 ( FXR1 ) gene belongs to a small gene family that includes the Fragile X Mental Retardation 1 ( FMR1 ) and Fragile X-Related 2 ( FXR2 ) genes ( reviewed in [1] ) .", "Human FMR1 is located on chromosome Xq27 . 3 [2] and inactivation of FMR1 expression leads to the Fragile X syndro...	[ "The Fragile X-Related 1 gene ( FXR1 ) is a paralog of the Fragile X Mental Retardation 1 gene ( FMR1 ) , whose absence causes the Fragile X syndrome , the most common form of inherited intellectual disability .", "FXR1P plays an important role in normal muscle development , and its absence causes muscular abnorm...	[ "Muscle development is a complex process controlled by the timely expression of genes encoding crucial regulators of the muscle cell precursors called myoblasts .", "We know from previous studies that inactivation of the Fragile X related 1 ( FXR1 ) gene in various animal models ( mouse , frog , and zebrafish ) c...	2013
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "biochemistry", "cell biology", "diabetes and endocrinology", "biophysics", "neuroscience" ]	The Structural Basis of Gas-Responsive Transcription by the Human Nuclear Hormone Receptor REV-ERBβ	journal.pbio.1000043	The heme-regulated nuclear hormone receptor REV-ERB is one of the core transcription factors regulating circadian rhythms. We found that transcription by heme-bound REV-ERB is regulated by NO gas, and a crystal structure of the heme-bound protein uncovers the basis for heme and gas binding.	[ [ "The closely related REV-ERBα and REV-ERBβ proteins generally act as transcriptional repressors , either on their own , by recruiting co-repressor proteins [1–3] , or by competing with the Retinoid-related Orphan Receptors ( RORs ) α , β , or γ for the same DNA binding sites [4–6] .", "Physiologically , t...	[ "Heme is a ligand for the human nuclear receptors ( NR ) REV-ERBα and REV-ERBβ , which are transcriptional repressors that play important roles in circadian rhythm , lipid and glucose metabolism , and diseases such as diabetes , atherosclerosis , inflammation , and cancer .", "Here we show that transcription repr...	[ "Much of human biology , such as sleeping , eating , and even the prevalence of heart attacks , occurs in daily cycles .", "These cycles are orchestrated by a master “clock” located in the brain .", "The basic components of this clock are proteins that control the expression of important genes .", "In this st...	2009
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "infectious diseases", "medicine and health sciences", "mycetoma", "neglected tropical diseases", "tropical diseases", "fungal diseases" ]	A New Model for Management of Mycetoma in the Sudan	journal.pntd.0003271	null	[ [ "Mycetoma is a neglected tropical medical and health problem .", "It is a chronic , specific , granulomatous , progressive and disfiguring inflammatory disease caused by true fungi or by certain bacteria and hence it is usually classified into eumycetoma and actinomycetoma respectively [1] , [2] .", "...	[ "Patients with mycetoma usually present late with advanced disease , which is attributed to lack of medical and health facilities in endemic areas , poor health education and low socio-economic status .", "With this background , an integrated patient management model at the village level was designed to address t...	[ "The Mycetoma Research Centre ( MRC ) in Sudan adopted an integrated village management model in an attempt to encourage patients to present early for treatment .", "The model consisted of a house to house survey to detect mycetoma suspected patients and to refer them for further management , KAP , epidemiologica...	2014
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "medicine and health sciences", "medical doctors", "tropical diseases", "geographical locations", "social sciences", "parasitic diseases", "health care", "diabetes mellitus", "health care providers", "endocrine disorders", "neglected tropical diseases", "patients", "public and occupational h...	"I Cannot Be Worried": Living with Chagas Disease in Tropical Bolivia	journal.pntd.0005251	null	[ [ "Bolivia has the highest prevalence of CD in the world , with at least 6% of the population affected[1] .", "More than 99% of people with CD in Bolivia and worldwide are undiagnosed and untreated[15–17] .", "It was previously thought that treatment of adults with chronic CD was ineffective , and that ...	[ "Chagas disease ( CD ) profoundly affects the social and emotional dimensions of patients’ lives , and disproportionately impacts poor , marginalized populations in Latin America .", "Biomedical treatment for CD fails to reach up to 99% of the people affected , and in any case seldom addresses the emotional healt...	[ "An estimated 99% of people with Chagas disease do not receive treatment .", "I interviewed 63 patients with a diagnosis of Chagas disease at a rural clinic in an endemic area of Bolivia .", "Only 4 had obtained biomedical treatment .", "Although the departmental government provided free medication for Chagas...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "bacteriology", "bacterial physiology", "gene identification and analysis", "genetics", "molecular genetics", "comparative genomics", "biology", "genomics", "microbiology", "bacterial evolution", "bacterial biochemistry", "bacterial pathogens", "gram positive" ]	A PNPase Dependent CRISPR System in Listeria	journal.pgen.1004065	null	[ [ "Listeria monocytogenes is a gram-positive foodborne pathogenic bacterium that has evolved two distinct lifestyles: a saprophytic one , primarily in decaying vegetation and a parasitic one in the tissues of mammals and birds , causing a disease known as listeriosis .", "Infection in humans starts by the i...	[ "The human bacterial pathogen Listeria monocytogenes is emerging as a model organism to study RNA-mediated regulation in pathogenic bacteria .", "A class of non-coding RNAs called CRISPRs ( clustered regularly interspaced short palindromic repeats ) has been described to confer bacterial resistance against invadi...	[ "CRISPR-Cas systems confer to bacteria and archaea an adaptive immunity that protects them against invading bacteriophages and plasmids .", "In this study , we characterize a CRISPR ( RliB-CRISPR ) that is present in all L . monocytogenes strains at the same genomic locus but is never associated with a cas operon...	2014
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "virology/host invasion and cell entry", "virology/immunodeficiency viruses", "virology/new therapies, including antivirals and immunotherapy", "virology/antivirals, including modes of action and resistance" ]	CD4-Specific Designed Ankyrin Repeat Proteins Are Novel Potent HIV Entry Inhibitors with Unique Characteristics	journal.ppat.1000109	null	[ [ "The increasing need for a vaccine to control the HIV pandemic is undoubted , but recent failures of vaccine programs have made clear that it will be years to decades before a successful vaccination program can be installed [1] .", "In the meantime , drug based intervention strategies must be found to fil...	[ "Here , we describe the generation of a novel type of HIV entry inhibitor using the recently developed Designed Ankyrin Repeat Protein ( DARPin ) technology .", "DARPin proteins specific for human CD4 were selected from a DARPin DNA library using ribosome display .", "Selected pool members interacted specifical...	[ "There is an increasing need to develop inhibitors of HIV entry into target cells for both application in therapy and prevention .", "The development of specific HIV inhibitors as microbicides , agents that by topical application prevent infection , is considered particularly important in limiting the spread of H...	2008
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	EhVps32 Is a Vacuole-Associated Protein Involved in Pinocytosis and Phagocytosis of Entamoeaba histolytica	journal.ppat.1005079	null	[ [ "Entamoeba histolytica is the protozoan responsible for human amoebiasis , considered the third cause of death in the world due to parasitic diseases [1] .", "Phagocytosis is a key factor in the parasite virulence and several proteins involved in this event have been already unveiled [2–9] , among them th...	[ "Here , we investigated the role of EhVps32 protein ( a member of the endosomal-sorting complex required for transport ) in endocytosis of Entamoeba histolytica , a professional phagocyte .", "Confocal microscopy , TEM and cell fractionation revealed EhVps32 in cytoplasmic vesicles and also located adjacent to th...	[ "Trophozoites of E . histolytica represent an excellent model to study endosomal-sorting complex required for transport components due to their high endocytic activity and vesicle trafficking .", "The key role of EhVps32 on phagocytosis is supported by:", "i ) its presence on phagosomes ,", "ii ) its interact...	2015
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "circuit models", "computational neuroscience", "olfactory system", "biology", "sensory systems", "neuroscience" ]	Excitatory Local Interneurons Enhance Tuning of Sensory Information	journal.pcbi.1002563	null	[ [ "The olfactory system must accomplish two seemingly conflicting goals —generate distinct representations of different odors , yet maintain stable representations of a repeated odor despite variability introduced by noise .", "These conflicting ends , separability and reliability , are met as information a...	[ "Neurons in the insect antennal lobe represent odors as spatiotemporal patterns of activity that unfold over multiple time scales .", "As these patterns unspool they decrease the overlap between odor representations and thereby increase the ability of the olfactory system to discriminate odors .", "Using a real...	[ "The antennal lobe of insects and the olfactory bulb of vertebrates represent the first centers of the olfactory system where information about odor properties can be reorganized and optimized for further processing .", "Complex excitatory and inhibitory synaptic interactions within the antennal lobe and the olfa...	2012
[ "Introduction", "Results/Discussion" ]	[ "genome expression analysis", "statistics", "microbiology", "host-pathogen interaction", "immunodeficiency viruses", "mathematics", "biostatistics", "gene expression", "regulatory networks", "biology", "nonlinear dynamics", "viral replication", "differential equations", "systems biology", ...	24 Hours in the Life of HIV-1 in a T Cell Line	journal.ppat.1003161	null	[ [ "The life cycle of HIV-1 and its interaction with the host cell has been extensively studied [1] .", "However , previous analyses did not assess all relevant steps of viral replication in a longitudinal study in a single experimental system .", "Transcriptome ( and miRNA ) analyses have used microarra...	[ "HIV-1 infects CD4+ T cells and completes its replication cycle in approximately 24 hours .", "We employed repeated measurements in a standardized cell system and rigorous mathematical modeling to characterize the emergence of the viral replication intermediates and their impact on the cellular transcriptional re...	[ "Viral pathogens , such as HIV-1 , are fully dependent of the cellular machinery to complete the replication cycle .", "The cell offers a permissive environment , and deploys a number of antiviral defense strategies .", "The present work follows the process of infection of the cell with simultaneous measurement...	2013
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "cell physiology", "medicine and health sciences", "action potentials", "engineering and technology", "nervous system", "electrical circuits", "membrane potential", "junctional complexes", "electrophysiology", "neuroscience", "network analysis", "electrical synapses", "interneurons", "comp...	Electrical synapses regulate both subthreshold integration and population activity of principal cells in response to transient inputs within canonical feedforward circuits	journal.pcbi.1006440	null	[ [ "Electrical synapses are prevalent across many brain regions , including thalamus , hypothalamus , cerebellum , and the neocortex [1–3] .", "In contrast to neurotransmitter-based synapses , electrical synapses are a mode of intracellular communication that transmits signals almost instantaneously , and wi...	[ "As information about the world traverses the brain , the signals exchanged between neurons are passed and modulated by synapses , or specialized contacts between neurons .", "While neurotransmitter-based synapses tend to exert either excitatory or inhibitory pulses of influence on the postsynaptic neuron , elect...	[ "The roles that electrical synapses play in neural oscillations , network synchronization and rhythmicity are well established , but their roles in neuronal processing of transient inputs are much less understood .", "Here , we used computational models of canonical feedforward circuits and networks to investigat...	2019
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "sequence analysis", "virology", "emerging viral diseases", "biology", "computational biology", "microbiology", "viral evolution" ]	Dengue Virus Type 4 Phylogenetics in Brazil 2011: Looking beyond the Veil	journal.pntd.0001439	null	[ [ "Dengue virus ( DENV ) is a single stranded RNA virus , with four immunologically related serotypes ( DENV-1 , DENV-2 , DENV-3 and DENV-4 ) associated with Dengue Fever ( DF ) and Dengue Hemorrhagic Fever ( DHF ) [1] .", "The virus is widespread in tropical and Sub-Tropical areas of Asia , Africa and Amer...	[ "Dengue Fever and Dengue Hemorrhagic Fever are diseases affecting approximately 100 million people/year and are a major concern in developing countries .", "In the present study , the phylogenetic relationship of six strains of the first autochthonous cases of DENV-4 infection occurred in Sao Paulo State , Parana...	[ "Dengue virus infections are a major concern in developing countries , affecting approximately 100 million people/year .", "The virus has four immunologically related serotypes ( DENV-1 , DENV-2 , DENV-3 and DENV-4 ) associated with human disease .", "The virus is widespread in tropical and Sub-Tropical areas o...	2011
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biotechnology", "physics", "materials science", "nanomaterials", "materials physics", "biophysics theory", "biology", "biomaterials", "biophysics simulations", "biophysics", "computational biology", "material by attribute" ]	Dynamic Prestress in a Globular Protein	journal.pcbi.1002509	null	[ [ "The principle of ‘minimal frustration’ [1] , [2] underlies the thermodynamic picture of protein folding .", "According to this picture , proteins negotiate a rough , funnel-shaped energy landscape during the folding process , and eventually settle in a state that , as much as possible , satisfies the ene...	[ "A protein at equilibrium is commonly thought of as a fully relaxed structure , with the intra-molecular interactions showing fluctuations around their energy minimum .", "In contrast , here we find direct evidence for a protein as a molecular tensegrity structure , comprising a balance of tensed and compressed i...	[ "A tensegrity structure is one composed of members that are permanently under either tension or compression , and the balance of these tensile and compressive forces provides the structure with its mechanical stability .", "Macroscale tensegrity structures , which include Buckminster Fuller's geodesic domes , ach...	2012
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "invertebrates", "medicine and health sciences", "cytology", "immune physiology", "immunology", "vertebrates", "sand flies", "parasitic diseases", "dogs", "parasitic protozoans", "animals", "mammals", "parasitology", "protozoans", "leishmania", "ectoparasitic infections", "fleas", ...	Field Evaluation of Two Different Treatment Approaches and Their Ability to Control Fleas and Prevent Canine Leishmaniosis in a Highly Endemic Area	journal.pntd.0004987	null	[ [ "The veterinary importance of ectoparasites ( e . g . ticks and fleas ) is characterized by their impact on the health of companion animals [1] .", "Ectoparasites interact intensively with their animal hosts through blood feeding , and have the capacity to transmit pathogens of both medical and veterinary...	[ "This study investigated the efficacy of two collars for the treatment and prevention of flea infestations .", "Additionally the effect of these collars on the incidence of Leishmania infantum infection as compared with a group of vaccinated dogs was evaluated .", "A total of 224 young dogs from private animal ...	[ "Dogs are exposed to ectoparasites ( e . g . ticks and fleas ) and associated vector-borne infections .", "Among others , Leishmania infantum is a widespread protozoan of public health concern transmitted by phlebotomine sand flies .", "The prevention of canine leishmaniosis has become a priority in many endemi...	2016
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "medicine and health sciences", "protein interactions", "pathology and laboratory medicine", "enzymes", "pathogens", "purification techniques", "enzymology", "microbiology", "staphylococcus aureus", "plasmid construction", "dna construction", "molecular biology techniques", "cellular structu...	Regulation of the opposing (p)ppGpp synthetase and hydrolase activities in a bifunctional RelA/SpoT homologue from Staphylococcus aureus	journal.pgen.1007514	null	[ [ "Bacteria react to nutrient limitation via a stress response that is characterized by the synthesis of pyrophosphorylated GTP ( pppGpp ) or GDP ( ppGpp ) ( previously reviewed in [1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11] ) .", "Synthesis of ( p ) ppGpp , induced under these stress conditions ( stringe...	[ "The stringent response is characterized by ( p ) ppGpp synthesis resulting in repression of translation and reprogramming of the transcriptome .", "In Staphylococcus aureus , ( p ) ppGpp is synthesized by the long RSH ( RelA/SpoT homolog ) enzyme , RelSau or by one of the two short synthetases ( RelP , RelQ ) ."...	[ "The stringent response is a general stress response , which allows bacteria to survive nutrient limited conditions and to better tolerate antibiotic treatment .", "In the human pathogen , Staphylococcus aureus , the stringent response plays an important role for virulence , phagosomal escape and antibiotic toler...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biomacromolecule-ligand interactions", "medicine", "genetic mutation", "enzymes", "macromolecular assemblies", "gene function", "biocatalysis", "protein folding", "mitochondrial diseases", "chromosomal disorders", "membranes and sorting", "biology", "biophysics", "metabolism", "clinical...	Molecular Requirements for Peroxisomal Targeting of Alanine-Glyoxylate Aminotransferase as an Essential Determinant in Primary Hyperoxaluria Type 1	journal.pbio.1001309	The crystal structure of the peroxisome enzyme alanine-glyoxylate aminotransferase bound to its targeting receptor Pex5p explains why even minor fold defects prevent targeting of the enzyme and cause kidney disease.	[ [ "Primary hyperoxaluria type 1 ( PH1 ) is an autosomal recessive disorder that generally becomes symptomatic during childhood or adolescence and ultimately leads to renal failure , usually between the ages of 25 and 45 [1] .", "Although several therapeutic options have been established , the only curative ...	[ "Alanine-glyoxylate aminotransferase is a peroxisomal enzyme , of which various missense mutations lead to irreversible kidney damage via primary hyperoxaluria type 1 , in part caused by improper peroxisomal targeting .", "To unravel the molecular mechanism of its recognition by the peroxisomal receptor Pex5p , w...	[ "Peroxisomes are cell organelles contain proteins involved in various aspects of metabolism .", "Peroxisome proteins translocate from their site of synthesis in the cytoplasm across the organelle membrane in a fully folded and functional form .", "One such protein is the enzyme alanine–glyoxylate aminotransfera...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "signal transduction", "developmental biology", "model organisms", "organism development", "stem cells", "animal cells", "cell biology", "regeneration", "molecular development", "biology and life sciences", "cellular types", "morphogenesis", "cell signaling", "pattern formation", "resear...	zic-1 Expression in Planarian Neoblasts after Injury Controls Anterior Pole Regeneration	journal.pgen.1004452	null	[ [ "Regeneration is widespread in animals but still poorly understood .", "In animals with this ability , injury responses and positional cues likely interact to signal the production of missing structures .", "Across vertebrates and invertebrates , regeneration can involve either stem cells of high pote...	[ "Mechanisms that enable injury responses to prompt regenerative outgrowth are not well understood .", "Planarians can regenerate essentially any tissue removed by wounding , even after decapitation , due to robust regulation of adult pluripotent stem cells of the neoblast population .", "Formation of pole signa...	[ "Some animals are capable of regenerating organs damaged or removed by injury , and this ability likely requires precise control of secreted proteins that promote growth .", "Planarians are flatworms that can regenerate any missing tissues by regulating the activity of adult stem cells that can produce any specia...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biology", "molecular cell biology" ]	A Ubiquitin-specific Protease Possesses a Decisive Role for Adenovirus Replication and Oncogene-mediated Transformation	journal.ppat.1003273	null	[ [ "Human adenoviruses constitute a group of more than 60 adenovirus types .", "In general , adenoviruses cause self-limiting infections of the eye , or gastrointestinal and respiratory tract , which can lead to epidemic keratoconjunctivitis , diarreah , and severe acute respiratory diseases [1]–[9] .", ...	[ "Adenoviral replication depends on viral as well as cellular proteins .", "However , little is known about cellular proteins promoting adenoviral replication .", "In our screens to identify such proteins , we discovered a cellular component of the ubiquitin proteasome pathway interacting with the central regula...	[ "Adenoviral infections can result in severe outcomes leading to mortality especially in children undergoing immunosuppressive therapies .", "Unfortunately , no specific anti-adenoviral treatments are available to treat disseminated adenoviral infections .", "We have set out to identify host factors promoting ad...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "microbiology/immunity to infections", "immunology/immune response", "infectious diseases/bacterial infections", "immunology/immunity to infections", "infectious diseases/gastrointestinal infections" ]	The Microbiota Mediates Pathogen Clearance from the Gut Lumen after Non-Typhoidal Salmonella Diarrhea	journal.ppat.1001097	null	[ [ "Bacterial diarrhea is a global cause of morbidity and mortality .", "In most cases , the acute disease symptoms cease after a few days and the pathogen is eliminated from the gut .", "However , the mechanisms eliminating enteropathogenic bacteria from the gut lumen are poorly understood .", "Most...	[ "Many enteropathogenic bacteria target the mammalian gut .", "The mechanisms protecting the host from infection are poorly understood .", "We have studied the protective functions of secretory antibodies ( sIgA ) and the microbiota , using a mouse model for S . typhimurium diarrhea .", "This pathogen is a com...	[ "Numerous pathogens infect the gut .", "Protection against these infections is mediated by mucosal immune defenses including secreted IgA as well as by the competing intestinal microbiota .", "However , so far the relative importance of these two different defense mechanisms remains unclear .", "We addressed ...	2010
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "immunity", "immunity to infections", "biology and life sciences", "immunology", "vaccination and immunization" ]	Clinical and Parasitological Protection in a Leishmania infantum-Macaque Model Vaccinated with Adenovirus and the Recombinant A2 Antigen	journal.pntd.0002853	null	[ [ "Human VL is a severe systemic disease caused by protozoan parasites of the Leishmania donovani complex [1] .", "It remains one of the major infectious diseases primarily affecting some of the poorest regions of the world , with an estimated occurrence of approximately 0 . 2 to 0 . 4 million new cases of ...	[ "Visceral leishmaniasis ( VL ) is a severe vector-born disease of humans and dogs caused by Leishmania donovani complex parasites .", "Approximately 0 . 2 to 0 . 4 million new human VL cases occur annually worldwide .", "In the new world , these alarming numbers are primarily due to the impracticality of curren...	[ "Human visceral leishmaniasis causes significant morbidity and mortality , constituting an important global health problem .", "Absence of safe and cost effective anti-leishmanial drugs , together with emergence of drug resistance and HIV co-infection have posed a serious challenge to the disease containment .", ...	2014
[ "Introduction", "Results/Discussion", "Methods" ]	[ "genetics and genomics/genetics of disease" ]	Genome-Wide Analyses of Exonic Copy Number Variants in a Family-Based Study Point to Novel Autism Susceptibility Genes	journal.pgen.1000536	null	[ [ "The Autism spectrum disorders ( ASDs , MIM: 209850 ) are a heterogeneous group of childhood diseases characterized by abnormalities in social behavior and communication , as well as patterns of restricted and repetitive behaviors [1] .", "Twin studies have demonstrated much higher concordance rates of AS...	[ "The genetics underlying the autism spectrum disorders ( ASDs ) is complex and remains poorly understood .", "Previous work has demonstrated an important role for structural variation in a subset of cases , but has lacked the resolution necessary to move beyond detection of large regions of potential interest to ...	[ "Autism spectrum disorders ( ASDs ) are common neurodevelopmental syndromes with a strong genetic component .", "ASDs are characterized by disturbances in social behavior , impaired verbal and nonverbal communication , as well as repetitive behaviors and/or a restricted range of interests .", "To identify genes...	2009
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "infectious diseases/infectious diseases of the nervous system", "infectious diseases/neglected tropical diseases", "neurological disorders/infectious diseases of the nervous system", "public health and epidemiology/epidemiology", "infectious diseases/helminth infections", "public health and epidemiology/...	A Systematic Review of the Frequency of Neurocyticercosis with a Focus on People with Epilepsy	journal.pntd.0000870	null	[ [ "Scientific evidence is instrumental to improving global public health , as health policies should be based on accurate and meaningful data .", "In early 1990 , the first Global Burden of Diseases ( GBD ) study , commissioned by the World Bank , was launched to develop a method to estimate and compare the...	[ "The objective of this study is to conduct a systematic review of studies reporting the frequency of neurocysticercosis ( NCC ) worldwide .", "PubMed , Commonwealth Agricultural Bureau ( CAB ) abstracts and 23 international databases were systematically searched for articles published from January 1 , 1990 to Jun...	[ "Neurocysticercosis ( NCC ) is a parasitic infection of the brain caused by the tapeworm Taenia solium , which infects humans and pigs .", "There have been increasing case reports and epidemiological studies on this disease , but its global frequency has never been determined , partly due to the fact that blood t...	2010
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "medicine and health sciences", "reproductive system", "pathology and laboratory medicine", "maternal health", "obstetrics and gynecology", "viral transmission and infection", "pathogens", "microbiology", "viruses", "animal models", "developmental biology", "model organisms", "women's health...	Hydrocephalus and arthrogryposis in an immunocompetent mouse model of ZIKA teratogeny: A developmental study	journal.pntd.0005363	null	[ [ "Zika virus ( ZIKV ) is a mosquito-borne flavivirus that was initially thought to produce a benign disease characterized by mild fever , muscle and joint pain , rash and conjunctivitis [1] .", "However , the recent ZIKV epidemic in Brazil has been associated with severe transient , as well as irreversible...	[ "The teratogenic mechanisms triggered by ZIKV are still obscure due to the lack of a suitable animal model .", "Here we present a mouse model of developmental disruption induced by ZIKV hematogenic infection .", "The model utilizes immunocompetent animals from wild-type FVB/NJ and C57BL/6J strains , providing a...	[ "Previously thought to produce a harmless bout of fever associated with skin rash and muscle , or joint pain , the Zika virus ( ZIKV ) is an important cause of morbidity/mortality to human embryos/fetuses .", "Different from other models , here we report data from wild-type immunocompetent mice , rather than tran...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine", "immunology", "microbiology", "bacterial diseases", "renal transplantation", "immune defense", "bacterial pathogens", "infectious diseases", "biology", "gram negative", "clinical immunology", "immunity", "innate immunity", "nephrology" ]	Cyclosporine A Impairs Nucleotide Binding Oligomerization Domain (Nod1)-Mediated Innate Antibacterial Renal Defenses in Mice and Human Transplant Recipients	journal.ppat.1003152	null	[ [ "Urinary tract infection ( UTI ) often complicated by acute pyelonephritis ( APN ) , which is mainly caused by uropathogenic Escherichia coli ( UPEC ) , is the most frequent infectious complication following renal transplantation [1] , [2] .", "Despite improvement of the surgical procedures and the use of...	[ "Acute pyelonephritis ( APN ) , which is mainly caused by uropathogenic Escherichia coli ( UPEC ) , is the most common bacterial complication in renal transplant recipients receiving immunosuppressive treatment .", "However , it remains unclear how immunosuppressive drugs , such as the calcineurin inhibitor cyclo...	[ "Patients who have received a kidney graft are treated with immunosuppressive drugs , such as the cyclosporine A ( CsA ) .", "Transplanted patients under CsA are prone to bacterial infections .", "In this study , we used an experimental mouse model of kidney infection with Escherichia coli ( E . coli ) bacteria...	2013
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "medicine", "infectious diseases", "soil-transmitted helminths", "neglected tropical diseases" ]	Potential Drug Development Candidates for Human Soil-Transmitted Helminthiases	journal.pntd.0001138	null	[ [ "Soil-transmitted helminthiasis ( STH ) is caused primarily by four species of nematode worms , Ancylostoma duodenale and Necator americanus ( hookworms ) , Ascaris lumbricoides ( roundworm ) , and Trichuris trichiura ( whipworm ) , that parasitize the human gastrointestinal tract [1] .", "Some 2–3 billio...	[ "Few drugs are available for soil-transmitted helminthiasis ( STH ) ; the benzimidazoles albendazole and mebendazole are the only drugs being used for preventive chemotherapy as they can be given in one single dose with no weight adjustment .", "While generally safe and effective in reducing intensity of infectio...	[ "There are few drugs - none ideal - for the treatment and control of gastrointestinal helminths ( soil-transmitted nematodes ) which , as chronic infections jeopardize children's growth , learning and ultimately individual , community and country development .", "Drugs for helminths are not attractive in human me...	2011
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine", "bacterial diseases", "infectious diseases", "anthrax", "population modeling", "infectious disease modeling", "biology", "computational biology" ]	Quantitative Models of the Dose-Response and Time Course of Inhalational Anthrax in Humans	journal.ppat.1003555	null	[ [ "The causative microorganism of anthrax , Bacillus anthracis ( B . anthracis ) , is classified by the US Centers for Disease Control and Prevention ( CDC ) as a Category A ( highest priority ) bioterrorism pathogen , with the potential for causing a large number of infections and deaths after an effective aer...	[ "Anthrax poses a community health risk due to accidental or intentional aerosol release .", "Reliable quantitative dose-response analyses are required to estimate the magnitude and timeline of potential consequences and the effect of public health intervention strategies under specific scenarios .", "Analyses o...	[ "Anthrax poses a potential community health risk due to accidental or intentional aerosol release .", "We address the need for a transparent and defensible quantitative dose-response model for inhalational anthrax that is useful for risk assessors in estimating the magnitude and timeline of potential public healt...	2013
[ "Introduction", "Model", "Results", "Discussion" ]	[ "neurology", "biology and life sciences", "medicine and health sciences", "computational biology" ]	Bistable Dynamics Underlying Excitability of Ion Homeostasis in Neuron Models	journal.pcbi.1003551	null	[ [ "The Hodgkin–Huxley ( HH ) model is one of the most successful models in mathematical biology [1] .", "This formalism , i . e . , a HH–type model , describes voltage changes across cell membranes that result in excitability .", "Not only neurons are excitable cells , also myocytes , pancreatic –cells ...	[ "When neurons fire action potentials , dissipation of free energy is usually not directly considered , because the change in free energy is often negligible compared to the immense reservoir stored in neural transmembrane ion gradients and the long–term energy requirements are met through chemical energy , i . e . ...	[ "Theoretical neuroscience complements experimental and clinical neuroscience .", "Simulations and analytical insights help to interpret data and guide our principal understanding of the nervous systems in both health and disease .", "The Hodgkin—Huxley–formulation of action potentials is certainly one of the mo...	2014
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "neurological disorders/alzheimer disease", "neurological disorders/cognitive neurology and dementia", "genetics and genomics/genome projects", "genetics and genomics/genetics of disease", "genetics and genomics/population genetics" ]	Genome-Wide Association of Familial Late-Onset Alzheimer's Disease Replicates BIN1 and CLU and Nominates CUGBP2 in Interaction with APOE	journal.pgen.1001308	null	[ [ "Alzheimer's disease ( AD , MIM 104300 ) is by far the most common form of dementia in the elderly .", "Late onset Alzheimer's disease ( LOAD ) , defined by the onset of symptoms after age 60 years , has annual incidence rates increasing from 1% at 65–70 years to 6–8% at 85 years and older [1] .", "By...	[ "Late-onset Alzheimer's disease ( LOAD ) is the most common form of dementia in the elderly .", "The National Institute of Aging-Late Onset Alzheimer's Disease Family Study and the National Cell Repository for Alzheimer's Disease conducted a joint genome-wide association study ( GWAS ) of multiplex LOAD families ...	[ "Genetic factors are well-established to play a role in risk of Alzheimer's disease ( AD ) .", "However , it has been difficult to find genes that are involved in AD susceptibility , other than a small number of genes that play a role in early-onset , high-penetrant disease risk , and the APOE ε4 allele , which i...	2011
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "microbiology/parasitology" ]	A Cytochrome b561 with Ferric Reductase Activity from the Parasitic Blood Fluke, Schistosoma japonicum	journal.pntd.0000884	null	[ [ "Iron is an essential co-factor of many biological processes in nearly all organisms , and serves as a major strengthening and stabilizing metal in invertebrates [1] .", "Although iron is the second most abundant element on Earth and the fourth most abundant element in the crust , it exists in inorganic f...	[ "Iron has an integral role in numerous cellular reactions and is required by virtually all organisms .", "In physiological conditions , iron is abundant in a largely insoluble ferric state .", "Ferric reductases are an essential component of iron uptake by cells , reducing iron to the soluble ferrous form .", ...	[ "Parasites acquire their food from their hosts , either by feeding directly on tissues of the host , or by competing for ingested food .", "Adult schistosomes live within the vasculature of humans and rely on the blood cells and plasma they ingest and dissolved solutes they derive across their body surface , the ...	2010
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "medicine", "infectious diseases", "dengue fever", "neglected tropical diseases", "immunology", "dengue", "biology", "viral diseases" ]	Suppression of Virus Specific Immune Responses by IL-10 in Acute Dengue Infection	journal.pntd.0002409	null	[ [ "Dengue viral infections have become one of the most important mosquito borne viral infections in the world and are one of the major emerging infectious diseases .", "Dengue is a major public health problem in over 100 countries in the tropical and sub-tropical regions .", "It has been predicted that ...	[ "Elevated IL-10 has been shown to be associated with severe dengue infection ( DI ) .", "We proceeded to investigate the role of IL-10 in the pathogenesis of acute DI .", "Ex vivo and cultured IFNγ ELISpot assays for dengue virus ( DENV ) NS3 protein and non dengue viral proteins were carried out in 26 patients...	[ "Dengue viral infections have become one of the most important mosquito borne viral infections in the world and are one of the major emerging infectious diseases .", "The occurrence of dengue haemorrhagic fever is thought to result from a complex interplay between the virus , host genetics and host immune factors...	2013
[ "Introduction", "Results", "Discussion", "Material and Methods" ]	[ "computational biology/systems biology", "genetics and genomics/gene expression", "computational biology/transcriptional regulation", "developmental biology/plant growth and development", "plant biology/plant growth and development", "plant biology/plant genetics and gene expression", "genetics and geno...	A Systems Approach Reveals Regulatory Circuitry for Arabidopsis Trichome Initiation by the GL3 and GL1 Selectors	journal.pgen.1000396	null	[ [ "Position-dependent cell fate determination and pattern formation are unique aspects of the development of plant structures .", "The establishment of single-celled leaf hairs ( trichomes ) from pluripotent epidermal ( protodermal ) cells provides a powerful system to determine the genetic networks and pos...	[ "Position-dependent cell fate determination and pattern formation are unique aspects of the development of plant structures .", "The establishment of single-celled leaf hairs ( trichomes ) from pluripotent epidermal ( protodermal ) cells in Arabidopsis provides a powerful system to determine the gene regulatory n...	[ "The establishment of single-celled leaf hairs ( trichomes ) from pluripotent epidermal ( protodermal ) cells provides a powerful system to determine the gene regulatory networks involved in plant cell fate determination .", "Two transcription factors—GL1 and GL3—have been associated with the initiation of tricho...	2009
[ "Introduction", "Results", "Discussion", "Conclusions", "Methods" ]	[ "biochemistry", "mathematics", "statistics (mathematics)", "protein structure prediction", "proteins", "mathematical and statistical techniques", "protein structure", "statistical methods", "biology and life sciences", "physical sciences", "molecular biology", "research and analysis methods", ...	Improving Contact Prediction along Three Dimensions	journal.pcbi.1003847	null	[ [ "The large majority of cellular mechanisms are executed and controlled by the coordinated action of thousands of proteins , whose biological function is strongly connected to their three-dimensional ( 3D ) arrangement .", "As shown by Anfinsen almost 40 years ago [1] , the native three-dimensional structu...	[ "Correlation patterns in multiple sequence alignments of homologous proteins can be exploited to infer information on the three-dimensional structure of their members .", "The typical pipeline to address this task , which we in this paper refer to as the three dimensions of contact prediction , is to", "( i ) f...	[ "Proteins are large molecules that living cells make by stringing together building blocks called amino acids or peptides , following their blue-prints in the DNA .", "Freshly made proteins are typically long , structure-less chains of peptides , but shortly afterwards most of them fold into characteristic struct...	2014
[ "Introduction", "Methods", "Results", "Discussion" ]	[]	Association between Age and Severity to Leptospirosis in Children	journal.pntd.0002436	null	[ [ "Leptospirosis is an important zoonosis of worldwide distribution caused by pathogenic spirochaetes of the genus Leptospira .", "Humans usually become infected through contact with water or soil contaminated by the urine of mammalian reservoirs such as rodents , dogs , cattle and pigs [1] .", "Infecti...	[ "In endemic areas , leptospirosis is more common and more severe in adults compared with children .", "Reasons to explain this discrepancy remain unclear and limited data focusing on adolescents are available .", "The objective of the study was to describe disease spectrum and outcome differences in children an...	[ "Leptospirosis is endemic in tropical areas and seems to affect adults more often and more severely than children .", "Factors responsible for such differences have not been clearly established .", "However , host-related factors are believed to play a role in the development of severe leptospirosis .", "The ...	2013
[ "Introduction", "Materials and methods", "Results", "Discussion" ]	[ "medicine and health sciences", "african trypanosomiasis", "variant genotypes", "tropical diseases", "geographical locations", "uganda", "social sciences", "parasitic diseases", "parasitic protozoans", "neuroscience", "genetic mapping", "cognitive psychology", "protozoans", "neglected trop...	No evidence for association between APOL1 kidney disease risk alleles and Human African Trypanosomiasis in two Ugandan populations	journal.pntd.0006300	null	[ [ "The tsetse transmitted African trypanosomes are flagellated protozoa , a range of which cause disease in animals ( known as Nagana ) and humans ( Human African Trypanosomiasis , HAT , also known as sleeping sickness ) .", "These diseases are responsible for significant morbidity and mortality [1–3] and t...	[ "Human African trypanosomiasis ( HAT ) manifests as an acute form caused by Trypanosoma brucei rhodesiense ( Tbr ) and a chronic form caused by Trypanosoma brucei gambiense ( Tbg ) .", "Previous studies have suggested a host genetic role in infection outcomes , particularly for APOL1 .", "We have undertaken can...	[ "Human African Trypanosomiasis ( HAT ) occurs in two distinct disease forms; the acute form and the chronic form which are caused by microscopically indistinguishable hemo-parasites , Trypanosoma brucei rhodesiense and Trypanosoma brucei gambiense respectively .", "Uganda is the only country where both forms of t...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genetics", "biochemistry", "biology and life sciences", "microbiology" ]	Functional Interaction between Ribosomal Protein L6 and RbgA during Ribosome Assembly	journal.pgen.1004694	null	[ [ "The assembly of the 30S and 50S ribosomal subunits is a complex and tightly coordinated series of events that consists of the synthesis , processing and modification of 5S , 16S and 23S rRNA and the addition of more than 50 ribosomal proteins ( r-proteins ) [1] , [2] , [3] .", "The in vitro reconstitutio...	[ "RbgA is an essential GTPase that participates in the assembly of the large ribosomal subunit in Bacillus subtilis and its homologs are implicated in mitochondrial and eukaryotic large subunit assembly .", "How RbgA functions in this process is still poorly understood .", "To gain insight into the function of R...	[ "Ribosomes are complex macromolecular machines that carry out the essential function of protein synthesis in the cell .", "The assembly of ribosomal subunits is a multistep process that involves the accurate and timely assembly of 3 rRNA molecules and>50 ribosomal-proteins .", "In recent years many ribosome ass...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biotechnology", "biochemistry", "genome evolution", "plant genomics", "genetics", "biology and life sciences", "dna", "computational biology", "dna modification", "comparative genomics", "epigenomics", "plant biotechnology", "dna methylation", "epigenetics", "plant genetics" ]	Evolution of DNA Methylation Patterns in the Brassicaceae is Driven by Differences in Genome Organization	journal.pgen.1004785	null	[ [ "Cytosine methylation is a heritable epigenetic modification found in the genomes of organisms spanning the eukaryotic phylogeny [1] , [2] , [3] , [4] .", "It occurs in three nucleotide contexts , CG , CHG , or CHH ( where H is any nucleotide except G ) [5] , and is enriched in the repeat rich heterochrom...	[ "DNA methylation is an ancient molecular modification found in most eukaryotes .", "In plants , DNA methylation is not only critical for transcriptionally silencing transposons , but can also affect phenotype by altering expression of protein coding genes .", "The extent of its contribution to phenotypic divers...	[ "DNA methylation is an epigenetic mark that has received a great deal of attention in plants because it can be stably transmitted across generations .", "However , the rate of DNA methylation change , or epimutation , is greater than that of DNA mutation .", "In addition , different from DNA sequence , DNA meth...	2014
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "physiology/endocrinology", "computational biology/metabolic networks", "diabetes and endocrinology/type 2 diabetes" ]	Interpreting Metabolomic Profiles using Unbiased Pathway Models	journal.pcbi.1000692	null	[ [ "Disease heterogeneity has challenged the practice of medicine .", "Individuals with the same apparent disease at our current diagnostic resolution often show remarkable variation in prognosis and treatment responsiveness , presumably because a superficially similar disease state can arise from diverse co...	[ "Human disease is heterogeneous , with similar disease phenotypes resulting from distinct combinations of genetic and environmental factors .", "Small-molecule profiling can address disease heterogeneity by evaluating the underlying biologic state of individuals through non-invasive interrogation of plasma metabo...	[ "Human disease is complex , arising from the interaction of many genetic and environmental factors .", "Efforts to personalize treatment have been thwarted by “phenotypic heterogeneity” , the apparent similarity of disease states with diverse underlying causes .", "One approach to resolve this heterogeneity is ...	2010
[ "Introduction", "Theoretical Framework", "Results", "Discussion", "Methods" ]	[ "oxygen", "applied mathematics", "metabolic networks", "simulation and modeling", "algorithms", "mathematics", "metabolites", "algebra", "network analysis", "carbon", "molecular biology techniques", "research and analysis methods", "cell labeling", "computer and information sciences", "v...	Identification of Conserved Moieties in Metabolic Networks by Graph Theoretical Analysis of Atom Transition Networks	journal.pcbi.1004999	null	[ [ "Conserved moieties give rise to pools of metabolites with constant total concentration and dependent individual concentrations .", "These constant metabolite pools often consist of highly connected cofactors that are distributed throughout a metabolic network .", "Representative examples from energy ...	[ "Conserved moieties are groups of atoms that remain intact in all reactions of a metabolic network .", "Identification of conserved moieties gives insight into the structure and function of metabolic networks and facilitates metabolic modelling .", "All moiety conservation relations can be represented as nonneg...	[ "Conserved moieties are transferred between metabolites in internal reactions of a metabolic network but are not synthesised , degraded or exchanged with the environment .", "The total amount of a conserved moiety in the metabolic network is therefore constant over time .", "Metabolites that share a conserved m...	2016
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "biology", "zoology", "parasitology" ]	Introgressive Hybridization of Schistosoma haematobium Group Species in Senegal: Species Barrier Break Down between Ruminant and Human Schistosomes	journal.pntd.0002110	null	[ [ "In recent years , developments in molecular tools and their use in epidemiological studies have revealed several cases of hybridization and introgression in plants and animals [1]–[8] , although there are very few examples from metazoan parasites [7]–[8] .", "Hybridization can have a major impact on spec...	[ "Schistosomes are dioecious parasitic flatworms , which live in the vasculature of their mammalian definitive hosts .", "They are the causative agent of schistosomiasis , a disease of considerable medical and veterinary importance in tropical and subtropical regions .", "Schistosomes undergo a sexual reproducti...	[ "Schistosome blood flukes are transmitted through water contact and cause a severe debilitating disease in humans and their livestock .", "Understanding the biology and epidemiology of these parasites is essential to enable the development of better control strategies in endemic areas .", "Several species of sc...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "cell biology/leukocyte signaling and gene expression", "microbiology/immunity to infections", "immunology/immunomodulation", "immunology/innate immunity", "infectious diseases/bacterial infections", "infectious diseases/gastrointestinal infections", "immunology/leukocyte activation" ]	Commensal-Induced Regulatory T Cells Mediate Protection against Pathogen-Stimulated NF-κB Activation	journal.ppat.1000112	null	[ [ "Mechanisms of host protection by commensal organisms against infection vary depending on the nature of the pathogenic challenge .", "They range from mutual competition for nutrients and for microbial niches , to the production of specific anti-microbial peptides [1] , [2] .", "In addition , there is ...	[ "Host defence against infection requires a range of innate and adaptive immune responses that may lead to tissue damage .", "Such immune-mediated pathologies can be controlled with appropriate T regulatory ( Treg ) activity .", "The aim of the present study was to determine the influence of gut microbiota compo...	[ "The normal response to infection is rapid and effective clearance of pathogenic microbes .", "However , this immune response may occasionally cause collateral inflammatory damage to host tissue and in severe cases , such as systemic sepsis , results in organ failure .", "Various cellular mechanisms , including...	2008
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "medicine and health sciences", "enzyme-linked immunoassays", "pathology and laboratory medicine", "pathogens", "microbiology", "vertebrates", "animals", "mammals", "viruses", "research design", "hemorrhagic fever with renal syndrome", "hantavirus", "rna viruses", "signs and symptoms", "...	Severe fever with thrombocytopenia syndrome can masquerade as hemorrhagic fever with renal syndrome	journal.pntd.0007308	null	[ [ "Severe fever with thrombocytopenia syndrome ( SFTS ) is an emerging hemorrhagic fever and its pathogen SFTS virus ( SFTSV ) was first discovered in China in 2010 [1] .", "SFTSV is transmitted by tick bite and frequently spread from person-to-person [2–4]SFTSV is a negative-strand RNA virus belonging to t...	[ "Severe fever with thrombocytopenia syndrome ( SFTS ) is an emerging viral hemorrhagic fever with a high fatality rate and high frequency of person-to-person transmission and is caused by SFTSV , a tick-borne Phlebovirus .", "Because SFTS has similar clinical manifestations and epidemic characters ( such as spati...	[ "SFTS were clinically misdiagnosed as HFRS .", "It could cause particular concern in China .", "Physicians could not rely heavily on the exposure history .", "Both SFTS and HFRS patients are treated based on the clinical diagnosis in China .", "Laboratory confirmation of both diseases is not performed in cl...	2019
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biotechnology", "cell physiology", "cell motility", "liver", "tissue engineering", "immunology", "parasitic protozoans", "parasitology", "infectious disease immunology", "protozoans", "bioengineering", "extracellular space", "cell adhesion", "entamoeba histolytica", "hepatocytes", "am...	A New Human 3D-Liver Model Unravels the Role of Galectins in Liver Infection by the Parasite Entamoeba histolytica	journal.ppat.1004381	null	[ [ "The protozoan parasite Entamoeba histolytica is the etiological agent of human amoebiasis .", "The parasite has a simple life cycle alternating the contaminating cyst and the vegetative trophozoite form .", "Infection occurs upon uptake of cysts with contaminated water or food and their differentiati...	[ "Investigations of human parasitic diseases depend on the availability of appropriate in vivo animal models and ex vivo experimental systems , and are particularly difficult for pathogens whose exclusive natural hosts are humans , such as Entamoeba histolytica , the protozoan parasite responsible for amoebiasis .",...	[ "The study of liver infection is based on animal models , but the animal physiology does not always reflect the reality of the human host .", "This is particularly true for pathogens whose exclusive natural hosts are humans , such as Entamoeba histolytica , the protozoan parasite responsible for amoebiasis .", ...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "microbiology/medical microbiology", "microbiology/innate immunity", "microbiology/immunity to infections" ]	Vibrio cholerae Proteome-Wide Screen for Immunostimulatory Proteins Identifies Phosphatidylserine Decarboxylase as a Novel Toll-Like Receptor 4 Agonist	journal.ppat.1000556	null	[ [ "Innate and adaptive immunity are two arms of the immune system that help defend against invading microbes [1] , [2] .", "Innate immunity provides immediate defense against infection in a non-specific manner and also influences the antigen-specific adaptive immune response [3] , [4] .", "The innate re...	[ "Recognition of conserved bacterial components provides immediate and efficient immune responses and plays a critical role in triggering antigen-specific adaptive immunity .", "To date , most microbial components that are detected by host innate immune system are non-proteinaceous structural components .", "In ...	[ "Innate immune responses are the first line of defense and involve the early recognition of pathogenic microorganisms .", "Furthermore , these early innate responses can help shape and influence the development of more specific adaptive immune responses .", "One way that innate immunity is triggered is by activ...	2009
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "medicine and health sciences", "linguistics", "brain", "social sciences", "neuroscience", "learning and memory", "cognition", "computational neuroscience", "memory", "neuronal tuning", "animal cells", "amygdala", "false memories", "cellular neuroscience", "hippocampus", "entorhinal co...	Representation of abstract semantic knowledge in populations of human single neurons in the medial temporal lobe	journal.pbio.3000290	Single-neuron representations of stimuli in the human medial temporal lobe at the population level are governed by highly abstract semantic principles, but the attendant efficiency and potential for generalization comes at the cost of confusion between related stimuli.	[ [ "Cognitive faculties enabling flexible adaption of behaviour are at the heart of the human species’ evolutionary success .", "Cognition operates on abstract representations of knowledge derived from prior experience [1] .", "Abstraction can have two separate but related meanings [2] .", "First , f...	[ "Sensory experience elicits complex activity patterns throughout the neocortex .", "Projections from the neocortex converge onto the medial temporal lobe ( MTL ) , in which distributed neocortical firing patterns are distilled into sparse representations .", "The precise nature of these neuronal representations...	[ "What is the neuronal code for sensory experience in the human medial temporal lobe ( MTL ) ?", "Single-cell electrophysiology in the awake human brain during chronic , invasive epilepsy monitoring has previously revealed the existence of so-called concept cells .", "These cells have been found to increase thei...	2019
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "medicine and health sciences", "immune cells", "cardiovascular anatomy", "granulomas", "immunology", "tropical diseases", "collagens", "animal models", "bacterial diseases", "model organisms", "pharmaceutics", "experimental organism systems", "bacteria", "research and analysis methods", ...	Matrix metalloproteinase inhibitors enhance the efficacy of frontline drugs against Mycobacterium tuberculosis	journal.ppat.1006974	null	[ [ "Mycobacterium tuberculosis ( Mtb ) continues to pose a threat to global health .", "In 2015 , 10 . 4 million people were estimated to have become infected with Mtb and 1 . 8 million people died because of TB ( 0 . 4 million deaths within from TB/HIV co-infection ) , making Mtb the leading cause of death ...	[ "Mycobacterium tuberculosis ( Mtb ) remains a grave threat to world health with emerging drug resistant strains .", "One prominent feature of Mtb infection is the extensive reprogramming of host tissue at the site of infection .", "Here we report that inhibition of matrix metalloproteinase ( MMP ) activity by a...	[ "Mycobacterium tuberculosis ( Mtb ) continues to be the leading cause of death from a single infectious agent worldwide , leading to 1 . 8 million deaths in 2015 .", "The long treatment required ( 6–9 months ) , with all of its incumbent problems , can promote the emergence of multidrug-resistant ( MDR ) TB strai...	2018
[ "Introduction", "Methods", "Results", "Discussion" ]	[]	Impact of Community Mass Treatment with Azithromycin for Trachoma Elimination on the Prevalence of Yaws	journal.pntd.0003988	null	[ [ "Yaws , caused by Treponema pallidum subsp pertenue , is a non-venereal infection closely related to syphilis that predominantly affects children living in remote , rural communities in tropical countries[1] .", "Infection manifests as lesions of the skin , bone and cartilage and , untreated , may progres...	[ "Community mass treatment with 30mg/kg azithromycin is central to the new WHO strategy for eradicating yaws .", "Both yaws and trachoma— which is earmarked for elimination by 2020 using a strategy that includes mass treatment with 20mg/kg azithromycin—are endemic in the Pacific , raising the possibility of an int...	[ "Yaws is a bacterial infection closely related to syphilis .", "The WHO has launched a worldwide campaign to eradicate yaws by 2020 .", "This strategy relies on mass treatment of the whole community with the antibiotic azithromycin .", "Mass treatment with the same antibiotic is also recommended by WHO to tre...	2015
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "blood cells", "medicine and health sciences", "immune cells", "pathology and laboratory medicine", "antigen-presenting cells", "pathogens", "immunology", "microbiology", "retroviruses", "viruses", "infectious disease immunology", "rna viruses", "white blood cells", "animal cells", "medi...	Functional Activity of Monocytes and Macrophages in HTLV-1 Infected Subjects	journal.pntd.0003399	null	[ [ "Human T lymphotropic virus type 1 ( HTLV-1 ) infects about 15 to 20 million people worldwide , with endemic foci in virtually all continents [1] , [2] .", "A large proportion of individuals remain asymptomatic until the end of life , but a subgroup of infected individuals will develop a malignant lymphop...	[ "The Human T lymphotropic virus type-1 ( HTLV-1 ) infects predominantly T cells , inducing proliferation and lymphocyte activation .", "Additionally , HTLV-1 infected subjects are more susceptible to other infections caused by other intracellular agents .", "Monocytes/macrophages are important cells in the defe...	[ "HTLV-1 predominantly infects T cells , inducing cell proliferation and activation .", "While there is a larger amount of studies regarding T cells functions in HTLV-1 infected subjects , little is known about innate immunity .", "We evaluated monocyte and macrophage functions in HTLV-1 infected subjects .", ...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "systems biology", "genomics", "synthetic biology", "biology", "computational biology", "molecular cell biology", "molecular biology", "genetics and genomics" ]	Measurements of the Impact of 3′ End Sequences on Gene Expression Reveal Wide Range and Sequence Dependent Effects	journal.pcbi.1002934	null	[ [ "Studies aimed at understanding the determinants of gene expression have traditionally been focused on promoter and enhancer sequences .", "However , regulatory information is also encoded in other genomic regions such as the 5′ and 3′ untranslated regions ( UTRs ) and may even be embedded within the codi...	[ "A full understanding of gene regulation requires an understanding of the contributions that the various regulatory regions have on gene expression .", "Although it is well established that sequences downstream of the main promoter can affect expression , our understanding of the scale of this effect and how it i...	[ "A basic question in gene expression is the relative contribution of different regulatory layers and genomic regions to the differences in protein levels .", "In this work we concentrated on the effect of 3′ end sequences .", "For this , we constructed a library of yeast strains that differ only by a native 3′ ...	2013
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "medicine and health sciences", "disabilities", "pathology and laboratory medicine", "nervous system", "tropical diseases", "geographical locations", "pediatrics", "bacterial diseases", "signs and symptoms", "global health", "neglected tropical diseases", "africa", "public and occupational h...	The Burden of Leprosy in Cameroon: Fifteen Years into the Post-elimination Era	journal.pntd.0005012	null	[ [ "Leprosy is the oldest disease known to humanity , as recent genomic studies have traced Mycobacterium leprae , its causative agent , along human dispersal in the past 100 , 000 years [1] .", "It affects peripheral nerves , the skin and mucosa of the upper respiratory pathways [2] .", "Transmission is...	[ "Cameroon achieved the elimination target of leprosy in 2000 , and has maintained this status ever since .", "However , a number of health districts in the country continue to report significant numbers of leprosy cases .", "The aim of this study was to assess the burden of leprosy in Cameroon from 2000 to 2014...	[ "Cameroon achieved the elimination of leprosy in 2000 , however , a number of areas in the country continue to report high numbers of cases .", "We conducted this study to assess the burden of leprosy in Cameroon from 2000 to 2014 .", "We obtained and analysed leprosy data for this period from the National Cont...	2016
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[]	Narrow Bottlenecks Affect Pea Seedborne Mosaic Virus Populations during Vertical Seed Transmission but not during Leaf Colonization	journal.ppat.1003833	null	[ [ "Evolution of virus populations depends on several forces including mutation , recombination , genetic drift , selection and migration , acting concomitantly but exerting pressures that vary widely in direction and intensity .", "It makes therefore difficult to predict viral emergences or the durability o...	[ "The effective size of populations ( Ne ) determines whether selection or genetic drift is the predominant force shaping their genetic structure and evolution .", "Populations having high Ne adapt faster , as selection acts more intensely , than populations having low Ne , where random effects of genetic drift do...	[ "Short generation times and high mutation rates are the hallmarks of virus .", "They favor their fast adaptation as illustrated by their ability to overcome natural as well as man-made barriers such as host resistance or drug treatments .", "However , such a fast adaptation could be slowed down when genetic dri...	2014
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "genetics and genomics/gene discovery", "genetics and genomics/complex traits", "genetics and genomics/disease models", "genetics and genomics/genetics of disease", "mathematics/statistics", "genetics and genomics/medical genetics", "genetics and genomics/population genetics" ]	Enhanced Statistical Tests for GWAS in Admixed Populations: Assessment using African Americans from CARe and a Breast Cancer Consortium	journal.pgen.1001371	null	[ [ "Genome-wide association studies ( GWAS ) are the currently prevailing approach for identifying genetic variants with a modest effect on the risk of common disease , and have identified hundreds of common risk variants for a wide range of diseases and phenotypes [1] , [2] .", "Although GWAS have initially...	[ "While genome-wide association studies ( GWAS ) have primarily examined populations of European ancestry , more recent studies often involve additional populations , including admixed populations such as African Americans and Latinos .", "In admixed populations , linkage disequilibrium ( LD ) exists both at a fin...	[ "This paper presents improved methodologies for the analysis of genome-wide association studies in admixed populations , which are populations that came about by the mixing of two or more distant continental populations over a few hundred years ( e . g . , African Americans or Latinos ) .", "Studies of admixed po...	2011
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "blood cells", "dermatology", "medicine and health sciences", "immune cells", "pathology and laboratory medicine", "immunology", "cloning", "parasitic diseases", "nematode infections", "developmental biology", "skin infections", "molecular biology techniques", "neutrophils", "research and ...	Neutropenic Mice Provide Insight into the Role of Skin-Infiltrating Neutrophils in the Host Protective Immunity against Filarial Infective Larvae	journal.pntd.0004605	null	[ [ "Filarial nematodes constitute a large group of human pathogens ( i . e . Onchocerca volvulus , Brugia malayi , Brugia timori , Wuchereria bancrofti , Loa loa , Mansonella spp . ) infecting around 150 million people throughout the tropics with more than 1 . 5 billion at risk of infection .", "Filariases r...	[ "Our knowledge and control of the pathogenesis induced by the filariae remain limited due to experimental obstacles presented by parasitic nematode biology and the lack of selective prophylactic or curative drugs .", "Here we thought to investigate the role of neutrophils in the host innate immune response to the...	[ "Filariases are chronic debilitating diseases caused by parasitic nematodes affecting more than 150 million people worldwide .", "None of the current drugs are selective , neither able to eliminate the parasites nor to prevent new infections once the drug pressure has waned .", "Therefore , blocking the entry a...	2016
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "biology and life sciences", "immunology", "vaccination and immunization" ]	Natural and Vaccine-Mediated Immunity to Salmonella Typhimurium is Impaired by the Helminth Nippostrongylus brasiliensis	journal.pntd.0003341	null	[ [ "Models examining immunity to experimental infections primarily focus on responses to a single pathogen or vaccine in an immunologically naïve host .", "Such studies have shaped our understanding of how infections develop and are controlled .", "However , in reality individuals are exposed to multiple...	[ "The impact of exposure to multiple pathogens concurrently or consecutively on immune function is unclear .", "Here , immune responses induced by combinations of the bacterium Salmonella Typhimurium ( STm ) and the helminth Nippostrongylus brasiliensis ( Nb ) , which causes a murine hookworm infection and an expe...	[ "Vaccination studies in animal models have focused on understanding responses in young , previously naïve mice .", "In reality , humans are vaccinated or respond to infection in the context of a life-time of accumulated exposure to multiple , systemic infections and other vaccines , some of which are themselves a...	2014
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[]	Killer Cell Immunoglobulin-like Receptors and Their HLA Ligands are Related with the Immunopathology of Chagas Disease	journal.pntd.0003753	null	[ [ "Chagas disease , caused by the flagellate parasite Trypanosoma cruzi , currently affects around 6 million to 7 million people worldwide and about 25 million have the potential risk of becoming infected [1] .", "The disease is endemic and its development occurs in acute and chronic phases .", "The lat...	[ "The aim of this study was to investigate the influence of killer cell immunoglobulin-like receptor ( KIR ) genes and their human leucocyte antigen ( HLA ) ligands in the susceptibility of chronic Chagas disease .", "This case-control study enrolled 131 serologically-diagnosed Chagas disease patients ( 59 men and...	[ "Chagas disease is an infection caused by the haemoflagellate protozoan Trypanosoma cruzi .", "It is one of the most important public health problems in Latin America , and was first described by Carlos Justiniano Ribeiro das Chagas , a Brazilian physician and scientist , in 1909 .", "It is mostly vector-borne ...	2015
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "evolutionary biology", "non-clinical medicine", "animals", "developmental biology" ]	Animal Cell Differentiation Patterns Suppress Somatic Evolution	journal.pcbi.0030250	null	[ [ "Mature tissues of long-lived metazoans exhibit ongoing cell differentiation , with tissue-specific somatic stem cells dividing to renew populations of more differentiated cells that are not self-renewing .", "Although ongoing cell replacement is clearly necessary for long-lived organisms , it is not obvi...	[ "Cell differentiation in multicellular organisms has the obvious function during development of creating new cell types .", "However , in long-lived organisms with extensive cell turnover , cell differentiation often continues after new cell types are no longer needed or produced .", "Here , we address the ques...	[ "Darwinian natural selection and evolution is usually studied in populations of organisms .", "However , it is possible , in principle , in any population of cells , including the population of cells that constitutes a multicellular animal .", "Such “somatic” evolution among cells within an organism tends to re...	2007
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	A Bio-inspired Collision Avoidance Model Based on Spatial Information Derived from Motion Detectors Leads to Common Routes	journal.pcbi.1004339	null	[ [ "Anyone who has tried to catch flying flies will be familiar with their amazing performance .", "Within a fraction of a second , flies perform high-speed turns to avoid a predator or a collision with an obstacle .", "The collision avoidance decisions are produced in a fly’s brain with very limited neu...	[ "Avoiding collisions is one of the most basic needs of any mobile agent , both biological and technical , when searching around or aiming toward a goal .", "We propose a model of collision avoidance inspired by behavioral experiments on insects and by properties of optic flow on a spherical eye experienced during...	[ "The number of robots in our surroundings is increasing continually .", "They are used to rescue humans , inspect hazardous terrain or clean our homes .", "Over the past few decades , they have become more autonomous , safer and cheaper to build .", "Every autonomous robot needs to navigate in sometimes compl...	2015
[ "On Recent Approaches to Entropy and Epistasis" ]	[ "medicine and health sciences", "pathology and laboratory medicine", "pathogens", "microbiology", "retroviruses", "epistasis", "immunodeficiency viruses", "viruses", "mutation", "substitution mutation", "rna viruses", "pharmacology", "thermodynamics", "formal comment", "computer and info...	Epistasis and Entropy	journal.pgen.1006322	null	[ [ "Methods for inferring gene epistasis , or gene interactions , without fitness measurements are valuable for many reasons .", "It may be difficult or costly , if even possible , to accurately measure fitness for populations in nature .", "One approach depends on information theory .", "Briefly , e...	[ "Epistasis is a key concept in the theory of adaptation .", "Indicators of epistasis are of interest for large systems where systematic fitness measurements may not be possible .", "Some recent approaches depend on information theory .", "We show that considering shared entropy for pairs of loci can be mislea...	[ "Some recent approaches for identifying epistasis from sequence data depend on information theory .", "We show that considering shared entropy for pairs of loci can be misleading .", "The reason is that shared entropy does not imply epistasis for the pair .", "This observation holds true also in the absence o...	2016
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "phosphorylation", "chemical compounds", "enzymes", "enzymology", "organic compounds", "plasmid construction", "phosphatases", "regulator genes", "basic amino acids", "amino acids", "dna construction", "molecular biology techniques", "gene types", "mutagenesis and gene deletion techniques"...	Phosphorelay through the bifunctional phosphotransferase PhyT controls the general stress response in an alphaproteobacterium	journal.pgen.1007294	null	[ [ "Two-component regulatory pathways enable bacteria to react to changing environmental conditions .", "Classical two-component systems consist of a sensor histidine kinase and a response regulator; the histidine kinase autophosphorylates upon sensing appropriate environmental signals and subsequently trans...	[ "Two-component systems constitute phosphotransfer signaling pathways and enable adaptation to environmental changes , an essential feature for bacterial survival .", "The general stress response ( GSR ) in the plant-protecting alphaproteobacterium Sphingomonas melonis Fr1 involves a two-component system consistin...	[ "The general stress response ( GSR ) in alphaproteobacteria represents an essential feature for survival in stressful , constantly changing habitats .", "A variety of stresses are sensed by GSR-activating histidine kinases and lead to multiple stress resistance via the response regulator PhyR .", "Here , we des...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "taxonomy", "genome evolution", "ecology", "genome analysis", "genetics", "biology and life sciences", "comparative genomics", "molecular evolution", "computational biology", "evolutionary biology", "population genetics", "microbiology", "population biology", "microbial ecology" ]	Hidden Diversity in Honey Bee Gut Symbionts Detected by Single-Cell Genomics	journal.pgen.1004596	null	[ [ "Animals contain complex bacterial communities in their guts that can impact health status [1]–[3] .", "In mammals , the phylogenetic architecture of gut communities has been described as fan-like , with few deep- and intermediate-branching lineages , but with many shallow branches [3] .", "Most of th...	[ "Microbial communities in animal guts are composed of diverse , specialized bacterial species , but little is known about how gut bacteria diversify to produce genetically and ecologically distinct entities .", "The gut microbiota of the honey bee , Apis mellifera , presents a useful model , because it consists o...	[ "Gut microbial communities are often complex , consisting of bacteria from divergent phyla as well as multiple strains of each of the constituent species .", "But because the composition of these communities is typically assessed using 16S rRNA analyses , little is known about genomic changes associated with in s...	2014
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "phosphorylation", "medicine and health sciences", "immune physiology", "electrophoretic mobility shift assay", "immunology", "microbiology", "dna replication", "immunoprecipitation", "dna", "molecular biology techniques", "antibodies", "microbial genomics", "research and analysis methods", ...	Phosphorylated STAT5 directly facilitates parvovirus B19 DNA replication in human erythroid progenitors through interaction with the MCM complex	journal.ppat.1006370	null	[ [ "Human parvovirus B19 ( B19V ) is a small , non-enveloped parvovirus with a single-stranded ( ss ) DNA genome of 5 . 6 kb .", "It belongs to the genus Erythroparvovirus of the Parvoviridae family [1] .", "The B19V genome is flanked by identical inverted terminal repeats ( ITRs ) at both ends [2] .", ...	[ "Productive infection of human parvovirus B19 ( B19V ) exhibits high tropism for burst forming unit erythroid ( BFU-E ) and colony forming unit erythroid ( CFU-E ) progenitor cells in human bone marrow and fetal liver .", "This exclusive restriction of the virus replication to human erythroid progenitor cells is ...	[ "Human parvovirus B19 ( B19V ) infection can cause severe hematological disorders , a direct consequence of the death of infected human erythroid progenitor cells ( EPCs ) of the bone marrow and fetal liver .", "B19V replicates autonomously in human EPCs , and the erythropoietin ( EPO ) and EPO-receptor ( EPO-R )...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine", "biology" ]	Nuclear Hormone Receptor Regulation of MicroRNAs Controls Innate Immune Responses in C. elegans	journal.ppat.1003545	null	[ [ "Innate immunity is an evolutionarily conserved response to pathogens and forms the first line of defense for most organisms .", "When infected by pathogens , the nematode Caenorhabditis elegans mounts a rapid innate immune response and produces an array of anti-microbial genes , similar to other organism...	[ "Nuclear hormone receptors respond to small molecules such as retinoids or steroids and regulate development .", "Signaling in the conserved p38/PMK-1 MAP kinase pathway regulates innate immunity .", "In this study , we show that the Caenorhabditis elegans nuclear receptor DAF-12 negatively regulates the defens...	[ "When infected by the Pseudomonas aeruginosa , the nematode Caenorhabditis elegans invokes an innate immune response that protects the worm from pathogenic attack .", "The appropriate level of immune response in C . elegans requires the accurate regulation of multiple signal pathways , especially signals of repre...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "mutagenesis", "functional genomics", "mutagens", "genetics", "biology and life sciences", "genomics" ]	A Massively Parallel Pipeline to Clone DNA Variants and Examine Molecular Phenotypes of Human Disease Mutations	journal.pgen.1004819	null	[ [ "Owing to rapid advances in next-generation sequencing technologies , tens of thousands of disease-associated mutations [1] and millions of single nucleotide polymorphisms ( SNPs ) [2] , [3] have been identified in the human population .", "With the large number of ongoing whole-exome and whole-genome seq...	[ "Understanding the functional relevance of DNA variants is essential for all exome and genome sequencing projects .", "However , current mutagenesis cloning protocols require Sanger sequencing , and thus are prohibitively costly and labor-intensive .", "We describe a massively-parallel site-directed mutagenesis...	[ "With rapid advances in sequencing technologies , tens of millions of DNA variants have now been discovered in the human population .", "However , there are currently no experimental methods available for examining the impact of DNA variants in a high-throughput fashion .", "As a result , we have no functional ...	2014
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "blood cells", "nuclear import", "medicine and health sciences", "luciferase", "immune cells", "pathology and laboratory medicine", "european union", "enzymes", "pathogens", "cell processes", "immunology", "microbiology", "geographical locations", "enzymology", "retroviruses", "viruses...	The mutation of Transportin 3 gene that causes limb girdle muscular dystrophy 1F induces protection against HIV-1 infection	journal.ppat.1007958	null	[ [ "Productive HIV-1 infection requires the interaction with cellular co-factors at virtually all the steps of the viral replication cycle [1] .", "Viral entry depends on fusion of viral and cellular membranes through successive interactions with CD4 receptor combined with CXC chemokine receptor type 4 ( CXC...	[ "The causative mutation responsible for limb girdle muscular dystrophy 1F ( LGMD1F ) is one heterozygous single nucleotide deletion in the stop codon of the nuclear import factor Transportin 3 gene ( TNPO3 ) .", "This mutation causes a carboxy-terminal extension of 15 amino acids , producing a protein of unknown ...	[ "TNPO3 has been described as a key factor in the infection by the human immunodeficiency virus ( HIV-1 ) , the causative agent of AIDS .", "In 2013 , a relationship between a genetic defect in TNPO3 gene and a rare muscle disease named Limb Girdle Muscular Dystrophy 1F ( LGMD1F ) , with an autosomal dominant tran...	2019
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "sequencing techniques", "invertebrates", "parasite groups", "medicine and health sciences", "pathology and laboratory medicine", "parasite evolution", "population genetics", "microbiology", "parasitic diseases", "animals", "parasitic protozoans", "parasitology", "parasite physiology", "ge...	Differing Patterns of Selection and Geospatial Genetic Diversity within Two Leading Plasmodium vivax Candidate Vaccine Antigens	journal.pntd.0002796	null	[ [ "Plasmodium vivax causes 80 to 300 million infections per year and over 2 . 5 billion people remain at risk of infection despite malaria elimination efforts [1] .", "Now , concern over P . vivax is growing due to reports of increasingly severe disease [2] , emerging chloroquine resistance [3] , and multi-...	[ "Although Plasmodium vivax is a leading cause of malaria around the world , only a handful of vivax antigens are being studied for vaccine development .", "Here , we investigated genetic signatures of selection and geospatial genetic diversity of two leading vivax vaccine antigens – Plasmodium vivax merozoite sur...	[ "Plasmodium vivax causes tens of millions of malaria cases each year .", "Although some vaccines against P . vivax are being developed , little is known about the geospatial genetic diversity and selective constraints of the parasite surface antigens that these vaccines target .", "In order to create vaccines t...	2014
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "transfection", "cell death", "autophagic cell death", "medicine and health sciences", "vesicles", "pathology and laboratory medicine", "gene regulation", "hepacivirus", "pathogens", "cell processes", "condensed matter physics", "microbiology", "viruses", "rna viruses", "molecular biolog...	RACK1 mediates rewiring of intracellular networks induced by hepatitis C virus infection	journal.ppat.1008021	null	[ [ "Liver diseases caused by hepatitis C virus ( HCV ) constitute a significant health burden worldwide .", "Around 71 million people are chronically infected with HCV [1 , 2] , and more than 350 , 000 annual deaths are due to HCV infection , in most cases as a result of HCV-related liver cirrhosis and hepat...	[ "Hepatitis C virus ( HCV ) is a positive-strand RNA virus replicating in a membranous replication organelle composed primarily of double-membrane vesicles ( DMVs ) having morphological resemblance to autophagosomes .", "To define the mechanism of DMV formation and the possible link to autophagy , we conducted a y...	[ "All positive-strand RNA viruses replicate their genomes in distinct membrane-associated compartments designated replication organelles .", "The compartmentalization of viral replication machinery allows the enrichment and coordination of cellular and viral factors required for RNA replication and the evasion fro...	2019
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "plant science", "plant biology", "biology" ]	Specific Missense Alleles of the Arabidopsis Jasmonic Acid Co-Receptor COI1 Regulate Innate Immune Receptor Accumulation and Function	journal.pgen.1003018	null	[ [ "During their life cycle , plants have to fend off microbial pathogens including fungi , bacteria , viruses , and nematodes .", "To protect themselves , plants rely on the innate immune system of each plant cell to detect pathogen attack and subsequently activate disease resistance responses .", "The ...	[ "Plants utilize proteins containing nucleotide binding site ( NB ) and leucine-rich repeat ( LRR ) domains as intracellular innate immune receptors to recognize pathogens and initiate defense responses .", "Since mis-activation of defense responses can lead to tissue damage and even developmental arrest , proper ...	[ "To detect pathogen attack and subsequently trigger defense responses , plants utilize immune receptors composed of a nucleotide binding site ( NB ) domain and a C-terminal leucine-rich repeat ( LRR ) domain that function inside the cell .", "To identify regulators of NB–LRR protein accumulation and activity , we...	2012
[ "Introduction", "Material and methods", "Results", "Discussion" ]	[ "kala-azar", "medicine and health sciences", "decision making", "tropical diseases", "social sciences", "geographic information systems", "parasitic diseases", "neuroscience", "geoinformatics", "cognitive psychology", "cognition", "neglected tropical diseases", "infectious disease control", ...	SisLeish: A multi-country standardized information system to monitor the status of Leishmaniasis in the Americas	journal.pntd.0005868	null	[ [ "Leishmaniasis is an infectious disease caused by protozoan parasites of the genus Leishmania from the Trypanosomatidae family [1] .", "It is a vector borne disease transmitted by sandflies from the Psychodidae family , and the genus Lutzomyia is the most important vector in the Americas [2] .", "Leis...	[ "In the Americas , leishmaniasis is endemic in 18 countries , and from 2001 through 2015 , 17 countries reported 843 , 931 cases of cutaneous and mucocutaneous leishmaniasis , and 12 countries reported 52 , 176 cases of visceral leishmaniasis .", "A Regional Information System ( SisLeish ) was created in order to...	[ "Leishmaniasis is among the most neglected diseases and remains a challenge for surveillance and control programs .", "In response to this challenge , the Regional Program for Leishmaniasis ( PAHO/WHO ) , with the support of advisors and representatives from endemic countries , have created a Regional Information...	2017
[ "Introduction", "Materials and methods", "Results", "Discussion" ]	[ "sequencing techniques", "engineering and technology", "gene regulation", "decision analysis", "management engineering", "genome analysis", "sequence motif analysis", "epigenetics", "dna", "molecular biology techniques", "dna methylation", "chromatin", "research and analysis methods", "seq...	Probing instructions for expression regulation in gene nucleotide compositions	journal.pcbi.1005921	null	[ [ "The diversity of cell types and cellular functions is defined by specific patterns of gene expression .", "The regulation of gene expression involves a plethora of DNA/RNA-binding proteins that bind specific motifs present in various DNA/RNA regulatory regions .", "At the DNA level , transcription fa...	[ "Gene expression is orchestrated by distinct regulatory regions to ensure a wide variety of cell types and functions .", "A challenge is to identify which regulatory regions are active , what are their associated features and how they work together in each cell type .", "Several approaches have tackled this pro...	[ "Identifying a maximum of DNA determinants implicated in gene regulation will accelerate genetic analyses and precision medicine approaches by identifying key gene features .", "In that context decoding the sequence-level instructions for gene regulation is of prime importance .", "Among global efforts to achie...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Systemic Regulation of RAS/MAPK Signaling by the Serotonin Metabolite 5-HIAA	journal.pgen.1005236	null	[ [ "Human cancer is a complex polygenic disease caused by somatic mutations in oncogenes and tumor suppressor genes together with inherited polymorphisms in cancer susceptibility genes .", "Many of the oncogenes and tumor suppressor genes that are mutated in different cancer types have been investigated in d...	[ "Human cancer is caused by the interplay of mutations in oncogenes and tumor suppressor genes and inherited variations in cancer susceptibility genes .", "While many of the tumor initiating mutations are well characterized , the effect of genetic background variation on disease onset and progression is less under...	[ "Mutations that activate a RAS oncogene are found in a large proportion of human cancers .", "In this study , we have used the roundworm Caenorhabditis elegans ( C . elegans ) as a model to investigate how the genetic composition of the animal affects the outcome of oncogenic RAS mutations that activate the MAPK ...	2015
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "medicine", "infectious diseases", "public health and epidemiology", "social and behavioral sciences", "neglected tropical diseases", "anthropology", "public health" ]	Should I Get Screened for Sleeping Sickness? A Qualitative Study in Kasai Province, Democratic Republic of Congo	journal.pntd.0001467	null	[ [ "Human African Trypanosomiasis ( HAT ) or African sleeping sickness is a parasitic disease unique to sub-Saharan Africa .", "It is caused by protozoa of the Trypanosoma Genus of which the species T . brucei gambiense and T . brucei rhodesiense cause disease in humans .", "According to WHO figures [1] ...	[ "Control of human African trypanosomiasis ( sleeping sickness ) in the Democratic Republic of Congo is based on mass population active screening by mobile teams .", "Although generally considered a successful strategy , the community participation rates in these screening activities and ensuing treatment remain l...	[ "Active screening strategies are common disease control interventions in the context of poor and remote rural communities with no direct access to healthcare facilities .", "For such activities to be as effective as possible , it is necessary that they are well adapted to local socio-economic and cultural setting...	2012

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