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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", "Materials and Methods", "Results", "Discussion" ]	[ "blood cells", "cell motility", "medicine and health sciences", "immune cells", "respiratory infections", "pathology and laboratory medicine", "influenza", "pathogens", "immunology", "microbiology", "orthomyxoviruses", "pulmonology", "viruses", "respiratory system", "rna viruses", "cyt...	Live Imaging of Influenza Infection of the Trachea Reveals Dynamic Regulation of CD8+ T Cell Motility by Antigen	journal.ppat.1005881	null	[ [ "Influenza virus productively infects the epithelial cells that line the upper and lower respiratory tract and is restricted to this site by a requirement for a locally-expressed trypsin-like enzyme that activates the viral hemagglutinin ( HA ) protein .", "The specific epithelial cell types and location ...	[ "During a primary influenza infection , cytotoxic CD8+ T cells need to infiltrate the infected airways and engage virus-infected epithelial cells .", "The factors that regulate T cell motility in the infected airway tissue are not well known .", "To more precisely study T cell infiltration of the airways , we d...	[ "Influenza virus infects the cells that line the trachea and lung airways .", "Virus-specific cytotoxic ( cell killing ) T cells are the first line of adaptive immunity responsible for elimination of infected cells .", "We studied the cell movement , or motility , of these T cells responding to infection in the...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "antimicrobials", "antiretrovirals", "complement system", "medicine and health sciences", "immune physiology", "body fluids", "pathology and laboratory medicine", "pathogens", "drugs", "immunology", "microbiology", "retroviruses", "viruses", "immunodeficiency viruses", "clinical medicine...	Optimal Combinations of Broadly Neutralizing Antibodies for Prevention and Treatment of HIV-1 Clade C Infection	journal.ppat.1005520	null	[ [ "The ability to elicit potent broadly neutralizing antibodies through immunization remains an elusive goal in the development of an effective HIV-1 vaccine [1] .", "This has motivated major efforts over the past 6 years to isolate and characterize Env-specific antibodies from HIV-1-infected individuals wh...	[ "The identification of a new generation of potent broadly neutralizing HIV-1 antibodies ( bnAbs ) has generated substantial interest in their potential use for the prevention and/or treatment of HIV-1 infection .", "While combinations of bnAbs targeting distinct epitopes on the viral envelope ( Env ) will likely ...	[ "In recent years , a new generation of monoclonal antibodies has been isolated from HIV-1 infected individuals that exhibit broad and potent neutralizing activity when tested against diverse strains of virus .", "There is a high level of interest in the field in determining if these antibodies can be used to prev...	2016
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "bacteriology", "medicine and health sciences", "toxins", "pathology and laboratory medicine", "markov models", "microbiology", "operons", "toxicology", "toxic agents", "mathematics", "genome analysis", "bacterial genetics", "dna", "microbial genetics", "bacteria", "research and analys...	TASmania: A bacterial Toxin-Antitoxin Systems database	journal.pcbi.1006946	null	[ [ "Toxin-antitoxin systems ( TAS ) were originally known for their involvement in a process known as post-segregational killing ( PSK ) , a plasmid maintenance mechanism based on the differential decay of the products of two plasmid-encoded genes: a toxin gene and its antagonistic antitoxin [1–3] .", "The c...	[ "Bacterial Toxin-Antitoxin systems ( TAS ) are involved in key biological functions including plasmid maintenance , defense against phages , persistence and virulence .", "They are found in nearly all phyla and classified into 6 different types based on the mode of inactivation of the toxin , with the type II TAS...	[ "TASmania offers an extensive annotation of TA loci in a very large database of bacterial genomes , which represents a resource of crucial importance for the microbiology community .", "TASmania supports", "i ) the discovery of new TA families;", "ii ) the design of a robust experimental strategy by taking in...	2019
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biotechnology", "biomacromolecule-ligand interactions", "biochemistry", "rna", "genome analysis tools", "genomics", "protein interactions", "nucleic acids", "proteins", "gene expression", "genetics", "regulatory proteins", "biology", "recombinant proteins", "molecular cell biology", "...	Defining NELF-E RNA Binding in HIV-1 and Promoter-Proximal Pause Regions	journal.pgen.1004090	null	[ [ "RNA polymerase II ( Pol II ) is a molecular machine responsible for transcribing all protein coding genes in the eukaryotic genome in a highly regulated multistep process .", "With the help of specific and general transcription factors , it binds to promoters , rapidly initiates transcription , transcrib...	[ "The four-subunit Negative Elongation Factor ( NELF ) is a major regulator of RNA Polymerase II ( Pol II ) pausing .", "The subunit NELF-E contains a conserved RNA Recognition Motif ( RRM ) and is proposed to facilitate Poll II pausing through its association with nascent transcribed RNA .", "However , conflict...	[ "RNA polymerase II ( Pol II ) is a molecular machine that is responsible for transcribing all protein coding genes in the eukaryotic genome .", "Transcription by Pol II is a highly regulated process consisting of several rate-limiting steps .", "During transcription elongation , a number of transcription factor...	2014
[ "Introduction", "Results and Discussion", "Materials and Methods", "Supporting Information" ]	[ "cell biology", "evolutionary biology" ]	Birth and Rapid Subcellular Adaptation of a Hominoid-Specific CDC14 Protein	journal.pbio.0060140	Evolutionary and experimental analyses of the hominoid CDC14 retrogene uncover a novel mode for the emergence of new gene function: selectively driven subcellular adaptation of the encoded protein.	[ [ "Gene duplication has been important for the evolution of phenotypes specific to species and evolutionary lineages by providing the genetic raw material for the emergence of genes with new or altered functions [1] .", "Duplicate gene copies are commonly generated through duplication of gene-containing chr...	[ "Gene duplication was prevalent during hominoid evolution , yet little is known about the functional fate of new ape gene copies .", "We characterized the CDC14B cell cycle gene and the functional evolution of its hominoid-specific daughter gene , CDC14Bretro .", "We found that CDC14B encodes four different spl...	[ "Many new gene copies emerged by gene duplication in human and ape ( hominoid ) ancestors .", "However , little is known with respect to their functional evolution .", "We used a combination of evolutionary analyses and cell biology experiments to unveil the adaptive evolution of the hominoid-specific CDC14Bret...	2008
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	From Cell Differentiation to Cell Collectives: Bacillus subtilis Uses Division of Labor to Migrate	journal.pbio.1002141	In the bacterium Bacillus subtilis, cooperation between surfactin-producing and matrix-producing cells drives migration over solid surfaces by the formation of filamentous loops at the edge of the colony. The growth of filamentous loops and their folding properties determine the rate of migration.	[ [ "Many properties of biological systems come about through the interactions of the parts that compose such systems .", "These so-called collective properties are said to “emerge” from these interactions , because they cannot be produced by the parts separately [1–3] .", "The most remarkable collective ...	[ "The organization of cells , emerging from cell–cell interactions , can give rise to collective properties .", "These properties are adaptive when together cells can face environmental challenges that they separately cannot .", "One particular challenge that is important for microorganisms is migration .", "I...	[ "Some problems can be solved only when individuals act together .", "This applies to bacteria in the same way that it applies to humans .", "Here we study how bacteria overcome the environmental challenge of migration over a solid surface by bundling their forces .", "Migration can be a significant environmen...	2015
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "infectious diseases/protozoal infections", "public health and epidemiology/global health" ]	The International Limits and Population at Risk of Plasmodium vivax Transmission in 2009	journal.pntd.0000774	null	[ [ "The bulk of the global burden of human malaria is caused by two parasites: Plasmodium falciparum and P . vivax .", "Existing research efforts have focussed largely on P . falciparum because of the mortality it causes in Africa [1] , [2] .", "This focus is increasingly regarded as untenable [3]–[6] be...	[ "A research priority for Plasmodium vivax malaria is to improve our understanding of the spatial distribution of risk and its relationship with the burden of P . vivax disease in human populations .", "The aim of the research outlined in this article is to provide a contemporary evidence-based map of the global s...	[ "Growing evidence shows that Plasmodium vivax malaria is clinically less benign than has been commonly believed .", "In addition , it is the most widely distributed species of human malaria and is likely to cause more illness in certain regions than the more extensively studied P . falciparum malaria .", "Under...	2010
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "mathematics/statistics", "neuroscience", "neuroscience/theoretical neuroscience" ]	Hierarchical Models in the Brain	journal.pcbi.1000211	null	[ [ "To simplify notation we will use", "fx: = fx ( x ) = ∂xf = ∂f/∂x", "to denote the partial derivative of the function , f , with", "respect to the variable x .", "We also use x", "˙ = ∂tx", "for temporal derivatives .", "Furthermore , we will be dealing with variables in", "gen...	[ "This paper describes a general model that subsumes many parametric models for", "continuous data .", "The model comprises hidden layers of state-space or dynamic", "causal models , arranged so that the output of one provides input to another .", "The", "ensuing hierarchy furnishes a model for many types ...	[ "Models are essential to make sense of scientific data , but they may also play a", "central role in how we assimilate sensory information .", "In this paper , we", "introduce a general model that generates or predicts diverse sorts of data .", "As", "such , it subsumes many common models used in data ana...	2008
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "infectious diseases/bacterial infections", "infectious diseases/neglected tropical diseases", "public health and epidemiology", "infectious diseases/epidemiology and control of infectious diseases" ]	Trachoma in Western Equatoria State, Southern Sudan: Implications for National Control	journal.pntd.0000492	null	[ [ "Trachoma is caused by ocular infection with the obligate intracellular bacterium Chlamydia trachomatis .", "Ocular Chlamydia is spread through contact with eye discharge from the infected person and through transmission by eye-seeking flies [1] .", "The disease is associated with poor personal and en...	[ "Trachoma is thought to be common over large parts of Southern Sudan .", "However , many areas of the country , particularly west of the Nile , have not yet been surveyed .", "The aim of this study was to confirm whether trachoma extends into Western Equatoria State from neighboring Central Equatoria , where tr...	[ "Baseline data on trachoma prevalence is a prerequisite for intervention .", "Prior to the present study , all surveys in Southern Sudan reported trachoma prevalences that exceeded the threshold for large-scale intervention .", "This gave rise to the notion that the disease may be endemic throughout the country...	2009
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "livestock", "medicine and health sciences", "enzyme-linked immunoassays", "lao people", "pathology and laboratory medicine", "pathogens", "tropical diseases", "microbiology", "vertebrates", "parasitic diseases", "animals", "mammals", "health care", "ethnicities", "viruses", "sanitatio...	Endemicity of Zoonotic Diseases in Pigs and Humans in Lowland and Upland Lao PDR: Identification of Socio-cultural Risk Factors	journal.pntd.0003913	null	[ [ "Approximately two thirds ( 66 . 9% ) of the 6 . 4 million residents of Lao PDR reside in rural areas and most ( 83% ) of the 0 . 8 million households are considered agricultural holdings [1] .", "The majority of these employ mixed farming systems ( i . e . keeping both livestock and crops ) .", "In r...	[ "In Lao People’s Democratic Republic pigs are kept in close contact with families .", "Human risk of infection with pig zoonoses arises from direct contact and consumption of unsafe pig products .", "This cross-sectional study was conducted in Luang Prabang ( north ) and Savannakhet ( central-south ) Provinces ...	[ "In Lao PDR , pigs are an important source of food and income and are kept by many rural residents .", "This study investigated five diseases that are transmitted between pigs and humans ( zoonoses ) , namely hepatitis E , Japanese encephalitis , trichinellosis , cysticercosis and taeniasis .", "Humans and pigs...	2016
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "community ecology", "zoology", "ecology", "entomology", "biology", "species interactions", "biodiversity", "parasitology" ]	First Report of Colonies of Sylvatic Triatoma infestans (Hemiptera: Reduviidae) in the Paraguayan Chaco, Using a Trained Dog	journal.pntd.0001026	null	[ [ "Triatoma infestans ( Hemiptera , Reduviidae ) is the main vector of Chagas disease ( American trypanosomiasis ) in the Southern Cone of Latin America .", "Through the Southern Cone Initiative against Chagas disease , vectorial transmission to humans has been interrupted in Chile , Uruguay and Brazil , bu...	[ "In the Gran Chaco region , control of Triatoma infestans has been limited by persistent domestic infestations despite the efforts of the Vector Control Services .", "In Paraguay , this region is the highest endemic area in the country , showing high levels of indoor and outdoor infestation .", "Although sylvat...	[ "Confirmation of sylvatic colonies of Triatoma infestans has a significant connotation for Paraguay .", "Prior to our findings , we believed this vector —unlike in other regions of the Gran Chaco—was living exclusively in domestic and peridomestic habitats .", "We never considered the possibility of sylvatic sp...	2011
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "infectious diseases", "medicine and health sciences", "biology and life sciences", "immunology", "tropical diseases", "parasitic diseases" ]	Hyperreactive Onchocerciasis is Characterized by a Combination of Th17-Th2 Immune Responses and Reduced Regulatory T Cells	journal.pntd.0003414	null	[ [ "Onchocerciasis is a neglected tropical disease causing both health and socioeconomic problems [1] .", "Elicited by the parasitic nematode Onchocerca volvulus ( Ov ) , it is transmitted through the bite of infected black flies ( genus Simulium ) .", "Characteristic disease symptoms include dermatologi...	[ "Clinical manifestations in onchocerciasis range from generalized onchocerciasis ( GEO ) to the rare but severe hyperreactive ( HO ) /sowda form .", "Since disease pathogenesis is associated with host inflammatory reactions , we investigated whether Th17 responses could be related to aggravated pathology in HO ."...	[ "Onchocerciasis , also known as river blindness is a tropical disease causing health and socioeconomic problems in endemic communities especially sub-Saharan Africa .", "The disease is transmitted by a filarial nematode called Onchocerca volvulus , which is spread by the bite of infected Simulium black flies .", ...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "systems biology", "rna", "rna processing", "nucleic acids", "gene expression", "biology", "molecular cell biology" ]	The Conserved Intronic Cleavage and Polyadenylation Site of CstF-77 Gene Imparts Control of 3′ End Processing Activity through Feedback Autoregulation and by U1 snRNP	journal.pgen.1003613	null	[ [ "Pre-mRNA cleavage/polyadenylation ( C/P ) is a 3′ end processing mechanism employed by almost all protein-coding genes in eukaryotes [1] , [2] .", "The site for C/P , commonly known as the polyA site or pA , is typically defined by both upstream and downstream cis elements [3] , [4] .", "In metazoans...	[ "The human gene encoding the cleavage/polyadenylation ( C/P ) factor CstF-77 contains 21 exons .", "However , intron 3 ( In3 ) accounts for nearly half of the gene region , and contains a C/P site ( pA ) with medium strength , leading to short mRNA isoforms with no apparent protein products .", "This intron con...	[ "Autoregulation is commonly used in biological systems to control the homeostasis of certain activity , and cross-regulation coordinates multiple processes .", "We show that vertebrate genes encoding the cleavage/polyadenylation ( C/P ) factor CstF-77 contain a conserved intronic C/P site ( pA ) which regulates C...	2013
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "medicine and health sciences", "immune physiology", "spleen", "population genetics", "ploidy", "tropical diseases", "cloning", "departures from diploidy", "parasitic protozoans", "parasitic diseases", "protozoans", "leishmania", "copy number variation", "molecular biology techniques", "...	Genome wide comparison of Ethiopian Leishmania donovani strains reveals differences potentially related to parasite survival	journal.pgen.1007133	null	[ [ "Leishmania donovani , together with L . infantum , are the main causative agents of visceral leishmaniasis ( VL ) .", "The World Health Organization ( WHO ) estimates that this disease causes an estimated 200 , 000 to 400 , 000 new VL cases worldwide , and >40 , 000 deaths yearly .", "The majority of...	[ "Leishmania donovani is the main cause of visceral leishmaniasis ( VL ) in East Africa .", "Differences between northern Ethiopia/Sudan ( NE ) and southern Ethiopia ( SE ) in ecology , vectors , and patient sensitivity to drug treatment have been described , however the relationship between differences in parasit...	[ "Approximately 200 , 000–400 , 000 new cases of visceral leishmaniasis ( VL ) occur annually resulting in an estimated 40 , 000 deaths .", "Almost 90% of the reported cases are caused by the Leishmania donovani occurring primarily in East Africa and the Indian subcontinent .", "Parasites in East Africa are more...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "transfection", "rna-binding proteins", "medicine and health sciences", "luciferase", "senescence", "enzymes", "cell cycle and cell division", "carcinomas", "cell processes", "enzymology", "cancers and neoplasms", "oncology", "physiological processes", "developmental biology", "organism ...	RNA-Binding Protein FXR1 Regulates p21 and TERC RNA to Bypass p53-Mediated Cellular Senescence in OSCC	journal.pgen.1006306	null	[ [ "Cellular senescence is a critical biological process occurring in normal and aging cells either due to developmentally programmed or DNA damage-induced causes .", "Cancer cells escape senescence by utilizing either transcriptional and/or co-transcriptional gene regulatory processes to control gene expres...	[ "RNA-binding proteins ( RBP ) regulate numerous aspects of co- and post-transcriptional gene expression in cancer cells .", "Here , we demonstrate that RBP , fragile X-related protein 1 ( FXR1 ) , plays an essential role in cellular senescence by utilizing mRNA turnover pathway .", "We report that overexpressed...	[ "Understanding the mechanisms underlying evasion of cellular senescence in tumor cells is expected to provide better treatment outcomes .", "Here , we identify RNA-binding proteins FXR1 ( Fragile X-Related protein 1 ) , that is overexpressed in oral cancer tissues and cells bypasses cellular senescence through p5...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "animal models", "cellular structures", "caenorhabditis elegans", "signal transduction", "animal genetics", "model organisms", "signaling in cellular processes", "genetics", "biology", "molecular cell biology", "calcium signaling", "gene networks", "cytoskeleton", "gene function" ]	Filamin and Phospholipase C-ε Are Required for Calcium Signaling in the Caenorhabditis elegans Spermatheca	journal.pgen.1003510	null	[ [ "Mechanotransduction , the conversion of physical forces into biochemical signals , is a critical component of cell signaling [1] , [2] .", "Force sensation is essential during organism development and guides cell migration , differentiation , and morphogenesis [3] , [4] .", "Mechanotransduction is es...	[ "The Caenorhabditis elegans spermatheca is a myoepithelial tube that stores sperm and undergoes cycles of stretching and constriction as oocytes enter , are fertilized , and exit into the uterus .", "FLN-1/filamin , a stretch-sensitive structural and signaling scaffold , and PLC-1/phospholipase C-ε , an enzyme th...	[ "During organism development and normal physiological function cells sense , integrate , and respond to a variety of cues or signals including biochemical and mechanical stimuli .", "In this study we used Caenorhabditis elegans , a small transparent worm , to study filamin ( FLN-1 ) , a structural protein that ma...	2013
[ "Introduction", "Results/Discussion", "Materials and Methods" ]	[ "medicine", "biology" ]	DNase Sda1 Allows Invasive M1T1 Group A Streptococcus to Prevent TLR9-Dependent Recognition	journal.ppat.1002736	null	[ [ "The Gram-positive bacterium Group A Streptococcus ( GAS ) is a leading human pathogen , annually causing over 700 million cases of superficial infections such as pharyngitis or pyoderma , and more than 650 , 000 cases of invasive infections , including the potentially lethal conditions of necrotizing fasciit...	[ "Group A Streptococcus ( GAS ) has developed a broad arsenal of virulence factors that serve to circumvent host defense mechanisms .", "The virulence factor DNase Sda1 of the hyperinvasive M1T1 GAS clone degrades DNA-based neutrophil extracellular traps allowing GAS to escape extracellular killing .", "TLR9 is ...	[ "Group A Streptococcus ( GAS ) ranks among the top ten human pathogens causing fatal disease .", "GAS possesses an arsenal of virulence factors that circumvent the primary mammalian defence strategies , the innate immune system .", "Toll-like receptors ( TLRs ) , allow the host to detect pathogens by recognizin...	2012
[ "Introduction", "Methods", "Results/Discussion" ]	[]	pMD-Membrane: A Method for Ligand Binding Site Identification in Membrane-Bound Proteins	journal.pcbi.1004469	null	[ [ "Identification of a suitable ligand-binding site on a drug target is a crucial first step in structure-based computer aided drug discovery [1] .", "This is not a trivial task if the desired target site is an allosteric one that is not readily observable in average experimental structures [2] .", "Rec...	[ "Probe-based or mixed solvent molecular dynamics simulation is a useful approach for the identification and characterization of druggable sites in drug targets .", "However , thus far the method has been applied only to soluble proteins .", "A major reason for this is the potential effect of the probe molecules...	[ "We introduce a simulation-based method to identify allosteric ligand binding sites in membrane-associated proteins for which existing methods are inadequate .", "We applied the method on two mutant forms of an oncogenic protein called K-Ras .", "We show that the way in which the protein interacts with membrane...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "immunology/genetics of the immune system", "immunology/immunity to infections", "immunology/innate immunity" ]	Gamma-Linolenic and Stearidonic Acids Are Required for Basal Immunity in Caenorhabditis elegans through Their Effects on p38 MAP Kinase Activity	journal.pgen.1000273	null	[ [ "Polyunsaturated fatty acids ( PUFAs ) are a class of long chain fatty acids of 18 carbon atoms or more in length that contain two or more double bonds .", "PUFAs are classified into two groups , the omega-6 ( n-6 ) or the omega-3 ( n-3 ) fatty acids , depending on the position of the double bond ( n ) cl...	[ "Polyunsaturated fatty acids ( PUFAs ) form a class of essential micronutrients that play a vital role in development , cardiovascular health , and immunity .", "The influence of lipids on the immune response is both complex and diverse , with multiple studies pointing to the beneficial effects of long-chain fatt...	[ "Polyunsaturated fatty acids are vital for optimal physiological functions , including immunity .", "Much of these effects are mediated by eicosanoids , which are metabolites of arachidonic acid ( AA ) and eicosapentaenoic acid ( EPA ) .", "In mammals , PUFAs cannot be synthesized de novo .", "They are produc...	2008
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genetics and genomics/microbial evolution and genomics", "evolutionary biology/microbial evolution and genomics", "microbiology/microbial evolution and genomics" ]	Fate of the H-NS–Repressed bgl Operon in Evolution of Escherichia coli	journal.pgen.1000405	null	[ [ "The species Escherichia coli includes commensal strains residing in the intestine of humans and animals , as well as pathogenic strains causing various intestinal and extra-intestinal infections .", "This diversity in the life-style of E . coli is based on a significant genetic variability of their genom...	[ "In the enterobacterial species Escherichia coli and Salmonella enterica , expression of horizontally acquired genes with a higher than average AT content is repressed by the nucleoid-associated protein H-NS .", "A classical example of an H-NS–repressed locus is the bgl ( aryl-β , D-glucoside ) operon of E . coli...	[ "Horizontal gene transfer , an important mechanism in bacterial adaptation and evolution , requires mechanisms to avoid uncontrolled and possibly disadvantageous expression of the transferred genes .", "Recently , it was shown that the protein H-NS selectively silences genes gained by horizontal transfer in enter...	2009
[ "Introduction", "Methods", "Results and Discussion" ]	[ "medicine", "infectious diseases", "schistosomiasis", "medicinal chemistry", "stereochemistry", "organic chemistry", "neglected tropical diseases", "chemistry", "heterocycle structures", "synthetic chemistry", "organic compounds" ]	Resolution of Praziquantel	journal.pntd.0001260	null	[ [ "Schistosomiasis ( bilharziosis ) is termed a \"neglected\" tropical disease owing to the continuing low level of investment in treatments , prevention and research , yet the disease accounts for an extraordinarily high level of suffering around the world .", "[1] , [2] Schistosomiasis has been called a \...	[ "Praziquantel remains the drug of choice for the worldwide treatment and control of schistosomiasis .", "The drug is synthesized and administered as a racemate .", "Use of the pure active enantiomer would be desirable since the inactive enantiomer is associated with side effects and is responsible for the extre...	[ "The drug praziquantel ( PZQ ) is used very widely in both animal and human medicine , where it is the mainstay of the treatment of the neglected tropical disease schistosomiasis .", "The drug is currently manufactured and administered as a racemate ( 1∶1 mixture of enantiomers ) but for various reasons the large...	2011
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "veterinary diseases", "zoonoses", "veterinary epidemiology", "entomology", "biology and life sciences", "zoology", "veterinary science" ]	Evidence for Circulation of the Rift Valley Fever Virus among Livestock in the Union of Comoros	journal.pntd.0003045	null	[ [ "Rift Valley fever ( RVF ) is an arthropod-borne zoonotic disease caused by a RVF virus ( RVFV ) , a member of the Phlebovirus genus of the family Bunyaviridae [1] .", "RVFV causes significant morbidity and mortality among sheep , goats , cattle and also affects humans .", "In livestock , abortion sto...	[ "Rift Valley fever virus ( RVFV ) is an arthropod-borne phlebovirus reported to be circulating in most parts of Africa .", "Since 2009 , RVFV has been suspected of continuously circulating in the Union of Comoros .", "To estimate the incidence of RVFV antibody acquisition in the Comorian ruminant population , 1...	[ "Rift Valley fever ( RVF ) is a viral disease transmitted by mosquitoes to ruminants .", "The disease may affect humans and has a great impact on the economy of the affected country .", "RVF occurs mostly in African countries , but epidemics have been reported in Madagascar and in the Arabian Peninsula .", "I...	2014
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "medicine and health sciences", "microcephaly", "venezuela", "pathology and laboratory medicine", "pathogens", "sociology", "geographical locations", "microbiology", "social sciences", "social media", "viruses", "developmental biology", "rna viruses", "network analysis", "social networks...	Forecasting Zika Incidence in the 2016 Latin America Outbreak Combining Traditional Disease Surveillance with Search, Social Media, and News Report Data	journal.pntd.0005295	null	[ [ "The rapid spread of Zika virus has led to more than 400 , 000 suspected cases across the Americas since its introduction to Brazil in 2014 , and has triggered alerts around the globe[1] .", "This event has led to diverse interventions and travel warnings to affected areas , underscoring the importance of...	[ "Over 400 , 000 people across the Americas are thought to have been infected with Zika virus as a consequence of the 2015–2016 Latin American outbreak .", "Official government-led case count data in Latin America are typically delayed by several weeks , making it difficult to track the disease in a timely manner ...	[ "In the absence of access to real-time government-reported Zika case counts , we demonstrate the ability of Internet-based data sources to track the outbreak .", "Our model predictions fill a critical time-gap in existing Zika surveillance , given that early interventions and real-time surveillance are necessary ...	2017
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "neonatology", "medicine and health sciences", "pathology and laboratory medicine", "cost-effectiveness analysis", "maternal health", "markov models", "economic analysis", "pathogens", "immunology", "geographical locations", "microbiology", "social sciences", "reoviruses", "pediatrics", ...	Cost-effectiveness analysis of diarrhoea management approaches in Nigeria: A decision analytical model	journal.pntd.0006124	null	[ [ "Globally , diarrhoea is the second leading cause of death in children under 5 years [1] .", "There are about 1 . 7 billion annual cases of diarrhoea in the world and 760 , 000 annual deaths of children under 5 years due to diarrhoea [2] .", "In Nigeria , 11% of childhood deaths are caused by diarrhoe...	[ "Diarrhoea is a leading cause of death in Nigerian children under 5 years .", "Implementing the most cost-effective approach to diarrhoea management in Nigeria will help optimize health care resources allocation .", "This study evaluated the cost-effectiveness of various approaches to diarrhoea management namel...	[ "‘‘Cost-effectiveness analysis of diarrhoea management approaches in Nigeria: a decision analytical model” was an original research carried out due to the high prevalence and mortality rate due to diarrhoea in Nigeria .", "The study aims to determine which treatment approach for diarrhoea would be cost-effective ...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biochemistry/cell signaling and trafficking structures", "cell biology" ]	A Global Census of Fission Yeast Deubiquitinating Enzyme Localization and Interaction Networks Reveals Distinct Compartmentalization Profiles and Overlapping Functions in Endocytosis and Polarity	journal.pbio.1000471	Proteomic, localization, and enzymatic activity screens in fission yeast reveal how deubiquitinating enzyme localization and function are tuned.	[ [ "Posttranslational modifications govern protein function by modulating their structure , localization , dynamics , and/or stability .", "Ubiquitination of substrate proteins induces an array of specific responses depending on the extent and architecture of the modification .", "Proteins can be modifie...	[ "Ubiquitination and deubiquitination are reciprocal processes that tune protein stability , function , and/or localization .", "The removal of ubiquitin and remodeling of ubiquitin chains is catalyzed by deubiquitinating enzymes ( DUBs ) , which are cysteine proteases or metalloproteases .", "Although ubiquitin...	[ "The post-translational modification of proteins by conjugation of monomers or chains of ubiquitin is a regulatory mechanism for tuning protein stability , localization and function .", "Given these vital functions , ubiquitination has to be highly regulated so that protein degradation and cell signaling are cont...	2010
[ "Introduction", "Methods", "Results", "Discussion" ]	[]	Gatifloxacin Versus Ofloxacin for the Treatment of Uncomplicated Enteric Fever in Nepal: An Open-Label, Randomized, Controlled Trial	journal.pntd.0002523	null	[ [ "Enteric fever is endemic in Nepal and many other developing countries [1] , [2] , [3] .", "In industrialised countries , it is usually a disease imported by returning travellers [4] , most frequently from South Asia [5] .", "Enteric fever is a systemic infection caused by Salmonella enterica serovars...	[ "Fluoroquinolones are the most commonly used group of antimicrobials for the treatment of enteric fever , but no direct comparison between two fluoroquinolones has been performed in a large randomised trial .", "An open-label randomized trial was conducted to investigate whether gatifloxacin is more effective tha...	[ "Enteric fever , which comprises of typhoid and paratyphoid fevers , is common in many developing countries .", "It is also sometimes seen in the Western world in returning travellers .", "This present study of uncomplicated enteric fever in an outpatient setting in a hospital in Kathmandu , Nepal compared the ...	2013
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "genome-wide association studies", "genome expression analysis", "functional genomics", "rna stability", "genome analysis tools", "gene expression", "biology", "molecular biology", "microarrays", "genomics", "molecular cell biology", "computational biology", "genetics and genomics" ]	The Contribution of RNA Decay Quantitative Trait Loci to Inter-Individual Variation in Steady-State Gene Expression Levels	journal.pgen.1003000	null	[ [ "Substantial variation in gene expression levels exists in natural populations [1]–[5] .", "Over the past decade , we have learned that much of this inter-individual regulatory variation is associated with specific genetic polymorphisms , which can be identified by mapping expression quantitative trait lo...	[ "Recent gene expression QTL ( eQTL ) mapping studies have provided considerable insight into the genetic basis for inter-individual regulatory variation .", "However , a limitation of all eQTL studies to date , which have used measurements of steady-state gene expression levels , is the inability to directly dist...	[ "Recent studies of functional genetic variation in humans have identified numerous loci that are associated with variation in gene expression levels , called expression quantitative trait loci ( eQTLs ) .", "The mechanisms by which these loci affect gene expression , however , are still largely unknown .", "Spe...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "viral transmission and infection", "immunology", "microbiology", "host-pathogen interaction", "immunodeficiency viruses", "viral load", "animal models of infection", "biology", "pathogenesis", "microbial ecology", "ecology", "immunity", "virology" ]	SIVagm Infection in Wild African Green Monkeys from South Africa: Epidemiology, Natural History, and Evolutionary Considerations	journal.ppat.1003011	null	[ [ "Over 40 African nonhuman primate ( NHP ) species are naturally infected with simian immunodeficiency viruses ( SIVs ) [1]–[3] .", "Among these , African green monkeys ( AGMs ) ( Chlorocebus genus ) are the most numerous , most widely geographically spread and most commonly infected with SIV in the wild [...	[ "Pathogenesis studies of SIV infection have not been performed to date in wild monkeys due to difficulty in collecting and storing samples on site and the lack of analytical reagents covering the extensive SIV diversity .", "We performed a large scale study of molecular epidemiology and natural history of SIVagm ...	[ "We simultaneously assessed , for the first time in a natural host , the epidemiology , diversity and natural history of SIVagmVer infection in wild vervet populations from South Africa .", "We report that African green monkeys ( AGMs ) have likely been infected with SIVagm for a long period , ranging from the ti...	2013
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "public health and epidemiology/infectious diseases" ]	Imported Episodic Rabies Increases Patient Demand for and Physician Delivery of Antirabies Prophylaxis	journal.pntd.0000723	null	[ [ "Media-communicated health alerts are being used more-and-more frequently by public health decision-makers to prevent consequences of a sudden event , such as , emerging and episodic zoonotic diseases .", "The medical community must now consider these communications to be preventive intervention tools for...	[ "Imported cases threaten rabies reemergence in rabies-free areas .", "During 2000–2005 , five dog and one human rabies cases were imported into France , a rabies-free country since 2001 .", "The Summer 2004 event led to unprecedented media warnings by the French Public Health Director .", "We investigated med...	[ "Rabies has been eliminated from a large part of the European Union and , thus , any newly imported cases threaten its reemergence .", "The 2000–2005 data derived from the exhaustive surveillance system implemented in France was analyzed to evaluate the impact on demand for and delivery of antirabies prophylaxis ...	2010
[ "Introduction", "Results/Discussion", "Methods" ]	[ "genetics and genomics/microbial evolution and genomics", "genetics and genomics/comparative genomics", "computational biology/genomics", "evolutionary biology/genomics" ]	Additions, Losses, and Rearrangements on the Evolutionary Route from a Reconstructed Ancestor to the Modern Saccharomyces cerevisiae Genome	journal.pgen.1000485	null	[ [ "Inferring the genome organization and gene content of an extinct species has the potential to provide detailed information about the recent evolution of species descended from it .", "If we know what was present in the genome of an ancestor , we can deduce how a current-day descendant differs from it .",...	[ "Comparative genomics can be used to infer the history of genomic rearrangements that occurred during the evolution of a species .", "We used the principle of parsimony , applied to aligned synteny blocks from 11 yeast species , to infer the gene content and gene order that existed in the genome of an extinct anc...	[ "Genomes evolve in structure as well as in DNA sequence .", "We used data from 11 different yeast species to investigate the process of structural evolution of the genome on the evolutionary path leading to the bakers' yeast S . cerevisiae .", "We focused on an ancestor that existed about 100 million years ago ...	2009
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "infectious diseases", "biology and life sciences", "microbiology", "medicine and health sciences" ]	Assessment of Anthelmintic Efficacy of Mebendazole in School Children in Six Countries Where Soil-Transmitted Helminths Are Endemic	journal.pntd.0003204	null	[ [ "The soil-transmitted helminths ( STHs , Ascaris lumbricoides , Trichuris trichiura , and the two hookworm species , Necator americanus and Ancylostoma duodenale ) are responsible for the highest burden among all neglected tropical diseases ( NTDs ) [1] .", "Recent global estimates indicate that in 2010 m...	[ "Robust reference values for fecal egg count reduction ( FECR ) rates of the most widely used anthelmintic drugs in preventive chemotherapy ( PC ) programs for controlling soil-transmitted helminths ( STHs; Ascaris lumbricoides , Trichuris trichiura , and hookworm ) are still lacking .", "However , they are urgen...	[ "Soil-transmitted helminths ( STHs; roundworms , whipworms , and hookworms ) infect millions of children in sub-tropical and tropical countries , resulting in malnutrition , growth stunting , intellectual retardation , and cognitive deficits .", "To fight against STH , large-scale deworming programs are implement...	2014
[ "Introduction", "Results", "Discussion", "Material and methods" ]	[ "animal types", "body weight", "medicine and health sciences", "animal welfare", "vertebrates", "mice", "animals", "mammals", "biochemical analysis", "physiological parameters", "animal behavior", "bioassays and physiological analysis", "animal management", "eyes", "zoology", "research...	Laboratory mouse housing conditions can be improved using common environmental enrichment without compromising data	journal.pbio.2005019	null	[ [ "The provision of species-appropriate environmental enrichment—which can be defined as additions to the cage environment that allow natural motivated behaviors enabling the animals to control their environment [1]—is generally promoted as a way to improve animal welfare [1 , 2] and is also legally requested w...	[ "Animal welfare requires the adequate housing of animals to ensure health and well-being .", "The application of environmental enrichment is a way to improve the well-being of laboratory animals .", "However , it is important to know whether these enrichment items can be incorporated in experimental mouse husba...	[ "Adequate housing of laboratory animals is essential to guarantee their well-being .", "From a scientific perspective , physically and mentally healthy animals also contribute to increased validity and reproducibility of experimental results .", "The choice of nesting material or shelter type , referred to as e...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "telomere length", "telomeres", "cell biology", "chromosome biology", "chromosome structure and function", "molecular biology", "gene expression", "genetics", "gene regulation", "biology and life sciences", "epigenetics", "molecular biology techniques", "cloning", "chromatin", "genetic l...	Regulation of the Human Telomerase Gene TERT by Telomere Position Effect—Over Long Distances (TPE-OLD): Implications for Aging and Cancer	journal.pbio.2000016	null	[ [ "All mammalian telomeres ( the ends of linear chromosomes ) are composed of large tracts of repeated 5ʹ-TTAGGG sequences .", "Telomeres are well-conserved DNA end structures from yeast to mammals , and it is believed that the primary role of telomeres , in combination with shelterin proteins , is to provi...	[ "Telomerase is expressed in early human development and then becomes silenced in most normal tissues .", "Because ~90% of primary human tumors express telomerase and generally maintain very short telomeres , telomerase is carefully regulated , particularly in large , long-lived mammals .", "In the current repor...	[ "Telomerase is very tightly regulated in large , long-lived species such as humans .", "Telomerase is expressed during early human fetal development , turned off in most adult tissues , and then becomes reactivated in most human cancers .", "However , the exact mechanism ( s ) regulating these switches in expre...	2016
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "infectious diseases/neglected tropical diseases", "public health and epidemiology/infectious diseases", "public health and epidemiology/global health", "mathematics/statistics", "computational biology/ecosystem modeling" ]	Understanding Uncertainties in Model-Based Predictions of Aedes aegypti Population Dynamics	journal.pntd.0000830	null	[ [ "Aedes aegypti is one of the most important mosquito vectors of human viral diseases .", "It causes approximately 50 million cases of dengue fever per year , 500 , 000 cases of dengue hemorrhagic fever ( DHF ) or dengue shock syndrome ( DSS ) , and approximately 12 , 500 fatalities annually [1] , [2] .", ...	[ "Aedes aegypti is one of the most important mosquito vectors of human disease .", "The development of spatial models for Ae .", "aegypti provides a promising start toward model-guided vector control and risk assessment , but this will only be possible if models make reliable predictions .", "The reliability o...	[ "Dengue is one of the most important insect-vectored human viral diseases .", "The principal vector is Aedes aegypti , a mosquito that lives in close association with humans .", "Currently , there is no effective vaccine available and the only means for limiting dengue outbreaks is vector control .", "To help...	2010
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "meiosis", "chromosome structure and function", "centromeres", "cell division", "dna replication", "dna", "dna synthesis", "chromosome biology", "biology", "molecular biology", "cell biology", "nucleic acids", "dna recombination", "molecular cell biology" ]	Separation of DNA Replication from the Assembly of Break-Competent Meiotic Chromosomes	journal.pgen.1002643	null	[ [ "The meiotic cell division produces haploid gametes from diploid progenitors by segregating the maternally- and paternally-derived copies of each chromosome .", "The faithful distribution of homologous chromosomes in meiosis is facilitated in most organisms by the crossovers formed during homologous recom...	[ "The meiotic cell division reduces the chromosome number from diploid to haploid to form gametes for sexual reproduction .", "Although much progress has been made in understanding meiotic recombination and the two meiotic divisions , the processes leading up to recombination , including the prolonged pre-meiotic ...	[ "Sexually reproducing organisms rely on a specialized cell division called meiosis to produce genetically distinct gametes with half the chromosome number of the parent .", "The first stage of the meiotic cell division is the duplication of chromosomes , followed by the exchange of DNA between homologous chromoso...	2012
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "sequencing techniques", "herpes simplex virus", "vero cells", "medicine and health sciences", "pathology and laboratory medicine", "keratitis", "pathogens", "split-decomposition method", "biological cultures", "population genetics", "microbiology", "ocular anatomy", "viruses", "multiple a...	Quantitative Trait Locus Based Virulence Determinant Mapping of the HSV-1 Genome in Murine Ocular Infection: Genes Involved in Viral Regulatory and Innate Immune Networks Contribute to Virulence	journal.ppat.1005499	null	[ [ "Herpes simplex virus type 1 ( HSV-1 ) causes recurrent mucocutaneous lesions , is an increasing cause of genital herpes , and is the primary source of infectious blindness and sporadic encephalitis in the United States [1–4] .", "HSV-1 ocular infection in humans usually presents as conjunctivitis , which...	[ "Herpes simplex virus type 1 causes mucocutaneous lesions , and is the leading cause of infectious blindness in the United States .", "Animal studies have shown that the severity of HSV-1 ocular disease is influenced by three main factors; innate immunity , host immune response and viral strain .", "We previous...	[ "In addition to causing recurrent labial lesions , herpes simplex virus type 1 ( HSV-1 ) is also the primary source of infectious blindness in the United States .", "Animal studies have shown that the severity of infection is influenced by several factors , including viral strain .", "Conventional studies inves...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods", "Supporting Information" ]	[ "biochemistry", "infectious diseases", "microbiology", "biophysics" ]	Structural Basis for the Regulation Mechanism of the Tyrosine Kinase CapB from Staphylococcus aureus	journal.pbio.0060143	Structural analysis of a conserved bacterial tyrosine kinase fromStaphylococcus aureus provides the basis for deciphering its regulatory mechanism, leading to a model for its implication in extracellular polysaccharide synthesis.	[ [ "Protein phosphorylation–dephosphorylation represents one of the most powerful and versatile mechanisms of molecular regulation in living organisms .", "For many years , however , protein phosphorylation–dephosphorylation was considered to be exclusive to eukaryotes .", "It was only after a long perio...	[ "Bacteria were thought to be devoid of tyrosine-phosphorylating enzymes .", "However , several tyrosine kinases without similarity to their eukaryotic counterparts have recently been identified in bacteria .", "They are involved in many physiological processes , but their accurate functions remain poorly unders...	[ "An idiosyncratic new class of bacterial enzymes , bacterial tyrosine-kinases ( BY-kinases ) , has been characterized .", "These enzymes , which are involved in an increasing number of physiological processes ranging from stress resistance to pathogenicity , share no sequence similarities with eukaryotic kinases ...	2008
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biochemistry", "cellular stress responses", "genomics", "cell biology", "gene expression", "genetics", "biology and life sciences", "dna repair", "dna", "cell processes", "molecular cell biology", "dna transcription" ]	UVB Induces a Genome-Wide Acting Negative Regulatory Mechanism That Operates at the Level of Transcription Initiation in Human Cells	journal.pgen.1004483	null	[ [ "Proper cell homeostasis and function requires expression of the DNA encoded information .", "Maintenance of genome integrity and accurate replication is crucial for correctly regulated gene expression .", "Transcription of thousands of coding and non-coding RNAs by the RNA polymerase II ( Pol II ) is...	[ "Faithful transcription of DNA is constantly threatened by different endogenous and environmental genotoxic effects .", "Transcription coupled repair ( TCR ) has been described to stop transcription and quickly remove DNA lesions from the transcribed strand of active genes , permitting rapid resumption of blocked...	[ "Our genome is continuously exposed to genotoxic attacks that generate aberrant DNA structures .", "These can block the transcribing DNA-dependent RNA polymerase II ( Pol II ) enzyme and can lead to deleterious cellular processes .", "Cells have developed several mechanisms to stop Pol II , repair the roadblock...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "molecular cell biology", "cell biology", "biology and life sciences", "molecular biology" ]	RNA-Processing Protein TDP-43 Regulates FOXO-Dependent Protein Quality Control in Stress Response	journal.pgen.1004693	null	[ [ "A defining feature of all living cells is the ability to adapt to stress stimuli .", "This adaptive response is particularly important for maintaining protein homeostasis , which is critical for cellular functions .", "The cell employs a variety of protein quality control mechanisms in an effort to m...	[ "Protein homeostasis is critical for cell survival and functions during stress and is regulated at both RNA and protein levels .", "However , how the cell integrates RNA-processing programs with post-translational protein quality control systems is unknown .", "Transactive response DNA-binding protein ( TARDBP/...	[ "TDP-43 is linked to pathogenesis of major neurodegenerative diseases , including amyotrophic lateral sclerosis ( ALS ) and frontotemporal dementia ( FTD ) .", "How TDP-43 contributes to the development of these degenerative diseases remains unsolved , and the full range of TDP-43 functions has yet to be establis...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biology and life sciences", "immunology" ]	Expression of Suppressor of Cytokine Signaling 1 (SOCS1) Impairs Viral Clearance and Exacerbates Lung Injury during Influenza Infection	journal.ppat.1004560	null	[ [ "Influenza virus causes highly contagious acute respiratory disease .", "Despite vaccine availability , the virus remains a major worldwide health problem .", "Proper host immunity is essential for virus clearance and recovery , with T cells playing a major role [1] .", "Cytokines have pivotal eff...	[ "Suppressor of cytokine signaling ( SOCS ) proteins are inducible feedback inhibitors of cytokine signaling .", "SOCS1−/− mice die within three weeks postnatally due to IFN-γ-induced hyperinflammation .", "Since it is well established that IFN-γ is dispensable for protection against influenza infection , we gen...	[ "Cytokines are critical in regulating the balance between protective immunity and detrimental inflammation during influenza infection .", "Suppressor of cytokine signaling ( SOCS ) proteins are inducible feedback inhibitors of cytokine signaling .", "Using gene-deficient and infectious animal models , we determ...	2014
[ "Introduction", "Materials and methods", "Results", "Discussion" ]	[ "death rates", "invertebrates", "medicine and health sciences", "infectious disease epidemiology", "neighborhoods", "vector-borne diseases", "social sciences", "human mobility", "animals", "population biology", "infectious disease control", "insect vectors", "human geography", "infectious ...	Vector-borne disease risk indexes in spatially structured populations	journal.pntd.0006234	null	[ [ "Dengue , Zika and Chikungunya are deseases of major concern in many countries [1 , 2] .", "In particular , Dengue is of major importance due to its epidemiological magnitude [3 , 4] .", "On the other hand , in many countries Zika and Chikungunya can be considered as new diseases for which a great por...	[ "There are economic and physical limitations when applying prevention and control strategies for urban vector borne diseases .", "Consequently , there are increasing concerns and interest in designing efficient strategies and regulations that health agencies can follow in order to reduce the imminent impact of vi...	[ "A disease is called vector-borne when it is not transmitted directly among humans , but in a human-vector-human way .", "Examples of major importance , due to its epidemiological magnitude , are Dengue , Chikungunya and Zika tropical diseases , for which the main vector is the Aedes aegypti mosquito .", "Usual...	2018
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "parasite groups", "medicine and health sciences", "plasmodium", "gene regulation", "regulatory proteins", "microbiology", "dna-binding proteins", "parasitic diseases", "parasitic protozoans", "parasitology", "apicomplexa", "protozoans", "genome analysis", "transcription factors", "pharm...	Oxidative stress and protein damage responses mediate artemisinin resistance in malaria parasites	journal.ppat.1006930	null	[ [ "Malaria remains the most prevalent and deadly vector-borne disease in the world , with an estimated two hundred million cases and over four hundred thousand deaths recorded in 2015[1] .", "Currently , the cornerstone of global malaria control programs is artemisinin combination therapy ( ACT ) .", "A...	[ "Due to their remarkable parasitocidal activity , artemisinins represent the key components of first-line therapies against Plasmodium falciparum malaria .", "However , the decline in efficacy of artemisinin-based drugs jeopardizes global efforts to control and ultimately eradicate the disease .", "To better un...	[ "The emergence of artemisinin resistance within and beyond Southeast Asia is a looming threat that needs to be promptly addressed .", "With this in mind , we derived several artemisinin-resistant parasite lines in vitro in order to fully characterize the resistance phenotype at the cellular and molecular levels ....	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "animal models", "developmental biology", "model organisms", "molecular development", "biology" ]	Insulin Signaling Regulates Fatty Acid Catabolism at the Level of CoA Activation	journal.pgen.1002478	null	[ [ "The insulin/IGF signaling ( IIS ) pathway is a highly conserved and critical regulator of metabolism in mammals and in flies , where it senses organismal nutrient levels to regulate multiple physiological functions including carbohydrate metabolism , tissue growth and longevity [1]–[3] .", "Insulin regul...	[ "The insulin/IGF signaling pathway is a highly conserved regulator of metabolism in flies and mammals , regulating multiple physiological functions including lipid metabolism .", "Although insulin signaling is known to regulate the activity of a number of enzymes in metabolic pathways , a comprehensive understand...	[ "Type 2 diabetes , which is reaching epidemic proportions worldwide , is often associated with obesity and an imbalance in organismal lipid homeostasis .", "Therefore , understanding how insulin regulates lipid biosynthesis and breakdown is necessary .", "Surprisingly , the molecular mechanisms by which insulin...	2012
[ "Introduction", "Results/Discussion", "Materials and Methods" ]	[ "infectious diseases/infectious diseases of the nervous system", "evolutionary biology/microbial evolution and genomics", "computational biology/evolutionary modeling", "infectious diseases/viral infections", "public health and epidemiology/epidemiology", "public health and epidemiology/infectious disease...	Phylodynamics and Human-Mediated Dispersal of a Zoonotic Virus	journal.ppat.1001166	null	[ [ "Every year approximately 55 , 000 people die from rabies [1] .", "Over 99% of these deaths occur in developing countries where rabies virus ( RABV; negative-sense RNA virus , family Rhabdoviridae ) is endemic in the domestic dog [2] .", "Rabies has been neglected across much of Asia and Africa , desp...	[ "Understanding the role of humans in the dispersal of predominately animal pathogens is essential for their control .", "We used newly developed Bayesian phylogeographic methods to unravel the dynamics and determinants of the spread of dog rabies virus ( RABV ) in North Africa .", "Each of the countries studied...	[ "At least 15 million doses of anti-rabies post-exposure prophylaxis are administered annually worldwide , and an estimated 55 , 000 people die of rabies every year .", "Over 99% of these deaths occur in developing countries , predominantly in Asia and in Africa where rabies is endemic in domestic dogs .", "Desp...	2010
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "protein structure", "biology", "computational biology", "macromolecular structure analysis" ]	The Role of Local Backrub Motions in Evolved and Designed Mutations	journal.pcbi.1002629	null	[ [ "Proteins routinely incorporate amino acid changes over evolutionary time by adapting their conformation to the new sidechain .", "However , it remains a difficult task to predict such a conformational response , especially when subtle backbone adjustments are involved .", "This issue is of central im...	[ "Amino acid substitutions in protein structures often require subtle backbone adjustments that are difficult to model in atomic detail .", "An improved ability to predict realistic backbone changes in response to engineered mutations would be of great utility for the blossoming field of rational protein design ."...	[ "Protein design has the potential to generate useful molecules for medicine and chemistry , including sensors , drugs , and catalysts for arbitrary reactions .", "When protein design is carried out starting from an experimentally determined structure , as is often the case , one important aspect to consider is ba...	2012
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "animal models", "model organisms", "parasitology", "immunology", "biology", "zoology", "mouse", "immune response" ]	Kinetics of Antibody Response in BALB/c and C57BL/6 Mice Bitten by Phlebotomus papatasi	journal.pntd.0001719	null	[ [ "Sand flies ( Diptera: Phlebotominae ) serve as vectors of leishmaniasis , a neglected disease with symptoms ranging from non-lethal cutaneous to life-threatening visceral form .", "The causative agents of the disease are protozoan parasites of the genus Leishmania which are transmitted to the hosts by th...	[ "Phlebotomine sand flies are blood-sucking insects transmitting Leishmania parasites .", "In bitten hosts , sand fly saliva elicits specific immune response and the humoral immunity was shown to reflect the intensity of sand fly exposure .", "Thus , anti-saliva antibodies were suggested as the potential risk ma...	[ "Leishmania major is the causative agent of zoonotic cutaneous leishmaniasis and Phlebotomus papatasi serve as the major vector .", "In endemic foci , rodents are the natural reservoirs of this disease .", "Thus , we studied anti-P .", "papatasi saliva antibody response in BALB/c and C57BL/6 mice that are com...	2012
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "physics", "statistical mechanics", "computational neuroscience", "single neuron function", "biology", "sensory systems", "neuroscience", "coding mechanisms" ]	Balanced Synaptic Input Shapes the Correlation between Neural Spike Trains	journal.pcbi.1002305	null	[ [ "Correlations between the spike trains of neuron pairs are observed throughout the central nervous system [1] .", "The correlation between a pair of neurons' spike trains can change depending on the state of their neural circuit .", "For instance , correlated neural activity is altered by stimulus pro...	[ "Stimulus properties , attention , and behavioral context influence correlations between the spike times produced by a pair of neurons .", "However , the biophysical mechanisms that modulate these correlations are poorly understood .", "With a combined theoretical and experimental approach , we show that the ra...	[ "Neurons in sensory , motor , and cognitive regions of the nervous system integrate synaptic input and output trains of action potentials ( spikes ) .", "A critical feature of neural computation is the ability for neurons to modulate their spike train response to a given input , allowing task context or past hist...	2011
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine and health sciences", "biology and life sciences", "immunology", "microbiology", "parasitology" ]	MHC Class II Restricted Innate-Like Double Negative T Cells Contribute to Optimal Primary and Secondary Immunity to Leishmania major	journal.ppat.1004396	null	[ [ "The spectrum of disease collectively called Leishmaniasis is caused by several species of protozoan parasites belonging to the genus Leishmania .", "The disease is currently endemic in 88 countries , affecting an estimated 12 million people with over 1 . 5–2 million new cases and 70 , 000 deaths each yea...	[ "Although it is generally believed that CD4+ T cells play important roles in anti-Leishmania immunity , some studies suggest that they may be dispensable , and that MHC II-restricted CD3+CD4−CD8− ( double negative , DN ) T cells may be more important in regulating primary anti-Leishmania immunity .", "In addition...	[ "Although it is generally believed that CD4+ T cells mediate anti-Leishmania immunity , some studies suggest that CD3+CD4−CD8− ( double negative , DN ) T cells may play a more important role in regulating primary anti-Leishmania immunity .", "Here , we report that DN T cells extensively proliferate and produce ef...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	A Single Amino Acid in the Stalk Region of the H1N1pdm Influenza Virus HA Protein Affects Viral Fusion, Stability and Infectivity	journal.ppat.1003831	null	[ [ "The swine-origin H1N1 2009 influenza virus ( H1N1pdm ) caused an estimated 151 , 700 to 575 , 400 deaths worldwide during the first 12 months of the 2009 pandemic [1] , [2] , [3] .", "Children and young adults were most vulnerable to infection because they lacked pre-existing immunity to the H1N1pdm viru...	[ "The 2009 H1N1 pandemic ( H1N1pdm ) viruses have evolved to contain an E47K substitution in the HA2 subunit of the stalk region of the hemagglutinin ( HA ) protein .", "The biological significance of this single amino acid change was investigated by comparing A/California/7/2009 ( HA2-E47 ) with a later strain , ...	[ "Influenza viruses cause seasonal epidemics and occasional pandemics , representing a threat to public health .", "The trimeric hemagglutinin ( HA ) surface glycoprotein mediates viral entry and plays important roles in viral host restriction , transmission and pathogenesis .", "The HA protein binds to the rece...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "immunology/leukocyte signaling and gene expression", "oncology/gastrointestinal cancers", "cell biology/cell signaling" ]	Non-Canonical NF-κB Activation and Abnormal B Cell Accumulation in Mice Expressing Ubiquitin Protein Ligase-Inactive c-IAP2	journal.pbio.1000518	Loss of c-IAP2 ubiquitin ligase activity, which occurs in the lymphoma-causing c-IAP2/MALT1 fusion protein, activates non-canonical NF-κB signaling and results in B cell abnormalities characteristic of MALT lymphoma.	[ [ "The defining characteristic of the IAP ( Inhibitor of Apoptosis ) gene family is the presence of one or more baculovirus IAP repeats ( BIRs ) ( reviewed in [1] ) .", "These ∼70 amino acid regions mediate protein-protein interactions , and in the context of adjacent sequences are responsible for the assoc...	[ "Chromosomal translocations between loci encoding MALT1 and c-IAP2 are common in MALT lymphomas .", "The resulting fusion proteins lack the c-IAP2 RING domain , the region responsible for its ubiquitin protein ligase ( E3 ) activity .", "Ectopic expression of the fusion protein activates the canonical NF-κB sig...	[ "MALT ( mucosal associated lymphoid tissue ) lymphomas commonly express a mutant protein that contains a portion of the ubiquitin protein ligase cellular Inhibitor of Apoptosis 2 ( c-IAP2 ) and a portion of the paracaspase MALT1 .", "Expression of this fusion protein activates the anti-apoptotic transcription fac...	2010
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "invertebrates", "medicine and health sciences", "pathology and laboratory medicine", "china", "atmospheric science", "pathogens", "geographical locations", "microbiology", "vertebrates", "animals", "mammals", "viruses", "hemorrhagic fever with renal syndrome", "hantavirus", "rna viruses...	Meteorological factors and risk of hemorrhagic fever with renal syndrome in Guangzhou, southern China, 2006–2015	journal.pntd.0006604	null	[ [ "Hemorrhagic fever with renal syndrome ( HFRS ) is a rodent-borne zoonosis caused by different species of hantaviruses , characterized by varying degrees of bleeding diathesis , hypertension , and renal failure [1] .", "In Asia the majority of reported cases of HFRS have occurred in China and the annual i...	[ "The epidemic tendency of hemorrhagic fever with renal syndrome ( HFRS ) is on the rise in recent years in Guangzhou .", "This study aimed to explore the associations between meteorological factors and HFRS epidemic risk in Guangzhou for the period from 2006–2015 .", "We obtained data of HFRS cases in Guangzhou...	[ "The prevalence of HFRS was on the rise in recent years , especially in the large and medium-sized cities in China .", "We obtained data of HFRS cases in Guangzhou from the National Notifiable Disease Report System ( NNDRS ) during the period of 2006–2015 .", "Meteorological data were obtained from the Guangzho...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "infectious diseases/bacterial infections", "genetics and genomics/gene function" ]	A Transgenic Drosophila Model Demonstrates That the Helicobacter pylori CagA Protein Functions as a Eukaryotic Gab Adaptor	journal.ppat.1000064	null	[ [ "The human pathogen , Helicobacter pylori , infects the stomachs of at least half the world's population and chronic infection is associated with the development of diseases such as gastritis , peptic ulcers and gastric cancer [1] .", "A major virulence determinant of H . pylori is the cytotoxin associate...	[ "Infection with the human gastric pathogen Helicobacter pylori is associated with a spectrum of diseases including gastritis , peptic ulcers , gastric adenocarcinoma , and gastric mucosa–associated lymphoid tissue lymphoma .", "The cytotoxin-associated gene A ( CagA ) protein of H . pylori , which is translocated...	[ "Like many pathogens , the human gastric bacterium Helicobacter pylori orchestrates infection through the activity of proteins that it translocates into host cells .", "The H . pylori translocated protein , CagA , which shares no homology to any other proteins , is a significant risk factor for H . pylori–associa...	2008
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biophysics", "biochemistry" ]	Evolution of Complex RNA Polymerases: The Complete Archaeal RNA Polymerase Structure	journal.pbio.1000102	The complete archaeal RNA polymerase structure is strikingly similar to the equivalent eukaryotic enzyme. Rpo13, a newly identified archaeal-specific subunit, may explain the minimal set of cofactors required for archaeal transcription initiation.	[ [ "Gene expression in cellular organisms across the three kingdoms of life is carried out by multisubunit RNA polymerase ( RNAP ) enzymes .", "Eukaryotes have three different multisubunit nuclear RNAPs ( Pol I , II , and III ) , whereas Archaea and Bacteria have single enzymes [1] .", "A wealth of struc...	[ "The archaeal RNA polymerase ( RNAP ) shares structural similarities with eukaryotic RNAP II but requires a reduced subset of general transcription factors for promoter-dependent initiation .", "To deepen our knowledge of cellular transcription , we have determined the structure of the 13-subunit DNA-directed RNA...	[ "Transcription , the process of converting DNA into RNA ( which in turn is translated into proteins by ribosomes ) is carried out by the multisubunit RNA polymerase ( RNAP ) enzyme .", "Transcription is fundamental to all organisms across the three kingdoms of life—Eukarya , Bacteria , and Archaea—and can be divi...	2009
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "immunomodulation", "adaptive immunity", "immune cells", "immunity", "t cells", "immune defense", "immunology", "biology", "immune suppression", "immunity to infections", "immunoregulation", "immune response" ]	Th2 Cell-Intrinsic Hypo-Responsiveness Determines Susceptibility to Helminth Infection	journal.ppat.1003215	null	[ [ "Protective immunity to helminth parasites takes decades to acquire , if it develops at all , with over 1 billion people harbouring chronic infections [1] .", "Protection is mediated by the Th2 arm of immunity [2] , which is also responsible for causing allergic diseases such as asthma , atopic dermatitis...	[ "The suppression of protective Type 2 immunity is a principal factor driving the chronicity of helminth infections , and has been attributed to a range of Th2 cell-extrinsic immune-regulators .", "However , the intrinsic fate of parasite-specific Th2 cells within a chronic immune down-regulatory environment , and...	[ "Helminth parasites mount chronic infections in over 1 billion people worldwide , of which filarial nematode infections account for 120 million .", "A major barrier to the development of protective Th2 immunity lies in the dominant down-regulatory immune responses invoked during infection .", "Although this imm...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "developmental biology/stem cells", "molecular biology/transcription initiation and activation", "genetics and genomics/gene expression", "developmental biology/cell differentiation", "genetics and genomics/gene function", "cell biology/gene expression" ]	Id4, a New Candidate Gene for Senile Osteoporosis, Acts as a Molecular Switch Promoting Osteoblast Differentiation	journal.pgen.1001019	null	[ [ "Senile osteoporosis or age-related osteopenia is accompanied by increased bone marrow tissue adiposity [1] .", "Bone marrow adipocytes and osteoblasts are thought to originate from common mesenchymal stem cells ( MSCs ) .", "Therefore , it has been suggested that the excessive accumulation of marrow ...	[ "Excessive accumulation of bone marrow adipocytes observed in senile osteoporosis or age-related osteopenia is caused by the unbalanced differentiation of MSCs into bone marrow adipocytes or osteoblasts .", "Several transcription factors are known to regulate the balance between adipocyte and osteoblast different...	[ "Increased bone marrow adiposity is observed in the bone marrow of senile osteoporosis patients .", "This is caused by unbalanced differentiation of mesenchymal stem cells ( MSCs ) into osteoblast or adipocyte .", "Previous reports have indicated that several transcription factors play important roles in determ...	2010
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "virology/emerging viral diseases", "virology/viral replication and gene regulation", "virology/antivirals, including modes of action and resistance" ]	In Vitro Reconstitution of SARS-Coronavirus mRNA Cap Methylation	journal.ppat.1000863	null	[ [ "In 2003 , the severe acute respiratory syndrome coronavirus ( SARS-CoV ) , which was likely transmitted from bats , was responsible for a worldwide SARS-outbreak [1] .", "Coronaviruses belong to the order Nidovirales and are characterized by the largest positive-strand RNA ( ( + ) RNA ) genomes ( around ...	[ "SARS-coronavirus ( SARS-CoV ) genome expression depends on the synthesis of a set of mRNAs , which presumably are capped at their 5′ end and direct the synthesis of all viral proteins in the infected cell .", "Sixteen viral non-structural proteins ( nsp1 to nsp16 ) constitute an unusually large replicase complex...	[ "In 2003 , an emerging coronavirus ( CoV ) was identified as the etiological agent of severe acute respiratory syndrome ( SARS ) .", "SARS-CoV replicates and transcribes its large RNA genome using a membrane-bound enzyme complex containing a variety of viral nonstructural proteins .", "A critical step during RN...	2010
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "protons", "medicine and health sciences", "chemical compounds", "membrane potential", "ions", "electrophysiology", "carbohydrates", "organic compounds", "glucose", "sodium", "organisms", "fungi", "model organisms", "biological transport", "cations", "thermodynamics", "physical chemi...	A Thermodynamic Model of Monovalent Cation Homeostasis in the Yeast Saccharomyces cerevisiae	journal.pcbi.1004703	null	[ [ "System responses to cation induced stress play a pivotal role in a wide range of essential cellular processes .", "A major challenge for the cell is to maintain optimum cytoplasmic concentrations of cations even under rapidly changing external conditions and perturbations such as salt , osmotic , or alka...	[ "Cationic and heavy metal toxicity is involved in a substantial number of diseases in mammals and crop plants .", "Therefore , the understanding of tightly regulated transporter activities , as well as conceiving the interplay of regulatory mechanisms , is of substantial interest .", "A generalized thermodynami...	[ "Metals , and particularly their positively charged ions ( cations ) , are an integral part of our environment , and all living organisms are exposed to metals in their natural habitat .", "Even though significant efforts have already been made by experimental and theoretical analysis of the individual components...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "plant biology/plant-environment interactions", "plant biology/plant biochemistry and physiology" ]	A Continuum Model for Metabolic Gas Exchange in Pear Fruit	journal.pcbi.1000023	null	[ [ "Exchange of O2 and CO2 of plants with their environment is essential for metabolic processes such as photosynthesis and respiration .", "Plants do not have specialised systems for gas exchange but rely on apertures in the epidermis such as stomata and lenticels and the intercellular air space within the ...	[ "Exchange of O2 and CO2 of plants with their environment is essential for metabolic processes such as photosynthesis and respiration .", "In some fruits such as pears , which are typically stored under a controlled atmosphere with reduced O2 and increased CO2 levels to extend their commercial storage life , anoxi...	[ "Respiration plays an important role in the overall metabolism of plants , and certainly is related to gas exchange of plants with the environment .", "In roots and bulky storage organs such as fruit and tubers , where the length of the diffusion path may be considerable , anoxic conditions may even occur .", "...	2008
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "ecology and environmental sciences", "medicine and health sciences", "vegf signaling", "population dynamics", "cancer treatment", "cancers and neoplasms", "oncology", "systems science", "mathematics", "population biology", "conservation biology", "computer and information sciences", "system...	The complex ecosystem in non small cell lung cancer invasion	journal.pcbi.1006131	null	[ [ "Lung cancer is the second most prevalent type of cancer causing over 150 , 000 deaths per year in the United States [1] .", "Insufficient progress has been made in achieving efficacious treatments .", "One of the main barriers in developing new treatment strategies is the vast diversity between and w...	[ "Many tumors are characterized by genetic instability , producing an assortment of genetic variants of tumor cells called subclones .", "These tumors and their surrounding environments form complex multi-cellular ecosystems , where subclones compete for resources and cooperate to perform multiple tasks , includin...	[ "Cancer is an elusive disease due to the wide variety of cancer types and adaptability to treatment .", "How is this adaptability accomplished ?", "Loss of genetic stability , a hallmark of cancer , leads to the emergence of many different types of cancer cells within a tumor .", "This creates a complex ecosy...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "computer and information sciences", "mathematical computing", "model organisms", "mathematics", "cell biology", "theoretical biology", "biology and life sciences", "computing methods", "physical sciences", "yeast and fungal models", "molecular cell biology", "biophysics", "research and anal...	Fusion of Protein Aggregates Facilitates Asymmetric Damage Segregation	journal.pbio.1001886	Fusion of harmful aggregated proteins into larger clumps increases the asymmetry of segregation of damage at cell division, favoring the production of rejuvenated cells.	[ [ "A dividing cell can deal with damaged material in two different ways .", "First , the damaged material can be segregated asymmetrically during division , such that it is concentrated in one of the two newborn daughter cells , while the other cell is born clean .", "The damage is then removed from the...	[ "Asymmetric segregation of damaged proteins at cell division generates a cell that retains damage and a clean cell that supports population survival .", "In cells that divide asymmetrically , such as Saccharomyces cerevisiae , segregation of damaged proteins is achieved by retention and active transport .", "We...	[ "During their lifetime , cells accumulate damage that is inherited by the daughter cells when the mother cell divides .", "The amount of inherited damage determines how long the daughter cell will live and how fast it will age .", "We have discovered fusion of protein aggregates as a new strategy that cells use...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "developmental biology", "cell fate determination", "model organisms", "stem cells", "molecular development", "gene expression", "genetics", "epigenetics", "biology", "cell differentiation" ]	Lsd1 Restricts the Number of Germline Stem Cells by Regulating Multiple Targets in Escort Cells	journal.pgen.1004200	null	[ [ "Stem cells undergo self-renewing divisions in which at least one daughter retains its stem cell identity , while the second daughter may or may not differentiate , depending on intrinsic and extrinsic cues .", "A balance between stem cell self-renewal and differentiation must be maintained for proper org...	[ "Specialized microenvironments called niches regulate tissue homeostasis by controlling the balance between stem cell self-renewal and the differentiation of stem cell daughters .", "However the mechanisms that govern the formation , size and signaling of in vivo niches remain poorly understood .", "Loss of the...	[ "The mechanisms that govern the formation , size and signaling output of in vivo niches remain poorly understood .", "Studies of Drosophila germline stem cells ( GSCs ) have suggested that chromatin programming greatly influences the behavior of these cells and their progeny .", "Previous work has shown that lo...	2014
[ "Introduction", "Materials and methods", "Results", "Discussion" ]	[ "medicine and health sciences", "toxins", "immune physiology", "pathology and laboratory medicine", "immunology", "tropical diseases", "vertebrates", "animals", "mammals", "toxicology", "toxic agents", "toxicity", "routes of administration", "reptiles", "neglected tropical diseases", "...	A polyvalent coral snake antivenom with broad neutralization capacity	journal.pntd.0007250	null	[ [ "Coral snakes of the genus Micrurus and Micruroides represent a highly diverse neotropical monophyletic assembly of about 80 species distributed from the southern United States to northern Argentina [1] .", "Although uncommon ( 1–2% of the snake bites in the Americas ) [2–4] , Micrurus envenomation can be...	[ "Coral snakes of the genus Micrurus have a high diversity and wide distribution in the Americas .", "Despite envenomings by these animals being uncommon , accidents are often severe and may result in death .", "Producing an antivenom to treat these envenomings has been challenging since coral snakes are difficu...	[ "Coral snakes are distributed in the Americas form Southern United States to Argentina .", "These snakes cause envenomings that , despite not being common , often lead to death .", "The antivenoms currently produced to treat accidents caused by these snakes have limitations regarding the number of species venom...	2019
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "infectious diseases/infectious diseases of the nervous system", "cell biology", "microbiology/parasitology", "infectious diseases/tropical and travel-associated diseases", "microbiology/cellular microbiology and pathogenesis", "cell biology/cytoskeleton" ]	Plasmodium falciparum Adhesion on Human Brain Microvascular Endothelial Cells Involves Transmigration-Like Cup Formation and Induces Opening of Intercellular Junctions	journal.ppat.1001021	null	[ [ "Each year 3 . 2 billion people worldwide are exposed to the threat of malaria , resulting in around 2 million deaths [1] .", "Even with the best antiparasitic treatments , patients with cerebral malaria ( CM ) have no significant improvement in their prognosis , with an average fatality rate of 30 to 50%...	[ "Cerebral malaria , a major cause of death during malaria infection , is characterised by the sequestration of infected red blood cells ( IRBC ) in brain microvessels .", "Most of the molecules implicated in the adhesion of IRBC on endothelial cells ( EC ) are already described; however , the structure of the IRB...	[ "Cerebral malaria , a major cause of death during malaria infection , is characterised by the sequestration of infected red blood cells ( IRBC ) in brain microvessels .", "This study describes the interactions between plasmodium infected red blood cell and human brain endothelial cells .", "It highlights the ac...	2010
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "cell biology/microbial growth and development", "genetics and genomics/epigenetics", "biochemistry/protein chemistry" ]	DCAF26, an Adaptor Protein of Cul4-Based E3, Is Essential for DNA Methylation in Neurospora crassa	journal.pgen.1001132	null	[ [ "The Cul4-DDB1 complex , a major class of cullin-RING ubiquitin ligases ( CRLs ) , is evolutionarily conserved from yeasts to humans .", "Previous studies have indicated that Cul4-DDB1-regulated ubiquitination is linked to multiple processes , such as cell cycle regulation , DNA replication licensing , DN...	[ "DNA methylation is involved in gene silencing and genome stability in organisms from fungi to mammals .", "Genetic studies in Neurospora crassa previously showed that the CUL4-DDB1 E3 ubiquitin ligase regulates DNA methylation via histone H3K9 trimethylation .", "However , the substrate-specific adaptors of th...	[ "DNA associates with histones to form chromatin in eukaryotes .", "Epigenetics refers to DNA and histone modifications in chromatin that persist from one cell generation to the next , controlling gene expression and genome stability .", "These epigenetic changes are crucial for the development and differentiati...	2010
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine", "neurobiology of disease and regeneration", "animal genetics", "genetic mutation", "neuroscience", "gene function", "mutation types", "biology", "neurological disorders", "neurology", "neuromuscular diseases", "genetics", "genetics of disease", "genetics and genomics" ]	Charcot-Marie-Tooth–Linked Mutant GARS Is Toxic to Peripheral Neurons Independent of Wild-Type GARS Levels	journal.pgen.1002399	null	[ [ "Charcot-Marie-Tooth disease ( CMT ) is a heterogeneous group of inherited neuropathies affecting approximately 1 in 2 , 500 people [1] .", "CMT is divided into type 1 forms , characterized by demyelination and decreased nerve conduction velocity , type 2 or axonal forms , characterized by axon loss and r...	[ "Charcot-Marie-Tooth disease type 2D ( CMT2D ) is a dominantly inherited peripheral neuropathy caused by missense mutations in the glycyl-tRNA synthetase gene ( GARS ) .", "In addition to GARS , mutations in three other tRNA synthetase genes cause similar neuropathies , although the underlying mechanisms are not ...	[ "Mutations in the glycyl-tRNA synthetase gene ( GARS ) cause Charcot-Marie-Tooth disease type 2D , a disease characterized by neuronal axon loss in the arms and legs , resulting in weakness and sensory problems .", "The GARS protein is essential for protein synthesis in every cell , and it has been difficult to d...	2011
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "medicine and health sciences", "immune physiology", "pathology and laboratory medicine", "pathogens", "immunology", "tropical diseases", "microbiology", "vertebrates", "animals", "mammals", "viruses", "vaccines", "preventive medicine", "rabies", "rna viruses", "neglected tropical dise...	Protection of bats (Eptesicus fuscus) against rabies following topical or oronasal exposure to a recombinant raccoon poxvirus vaccine	journal.pntd.0005958	null	[ [ "Rabies is a fatal viral zoonotic disease known to humans for nearly four millennia that continues to cause significant public health concern with over 50 , 000 human deaths every year [1] .", "Fortunately , over 15 million people receive post-exposure prophylaxis for rabies exposure , which effectively p...	[ "Rabies is an ancient neglected tropical disease that causes tens of thousands of human deaths and millions of cattle deaths annually .", "In order to develop a new vaccine for potential use in bats , a reservoir of rabies infection for humans and animals alike , an in silico antigen designer tool was used to cre...	[ "Rabies remains a significant and costly zoonotic disease worldwide .", "While control of canine rabies can significantly diminish the threat to human health , spillover of rabies and related lyssaviruses from bats into terrestrial animals and humans continues to be an important issue .", "Here we describe the ...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine", "infectious diseases", "global health", "genetics", "immunology", "biology", "microbiology", "genetics and genomics" ]	Novel Chikungunya Vaccine Candidate with an IRES-Based Attenuation and Host Range Alteration Mechanism	journal.ppat.1002142	null	[ [ "Chikungunya ( CHIK ) virus ( CHIKV ) is a reemerging arboviral pathogen that has recently caused explosive urban outbreaks involving millions of persons in Africa and Asia .", "The virus was first isolated from a human in Tanzania in 1953 during a major epidemic [1] , and derives its name from a Makonde ...	[ "Chikungunya virus ( CHIKV ) is a reemerging mosquito-borne pathogen that has recently caused devastating urban epidemics of severe and sometimes chronic arthralgia .", "As with most other mosquito-borne viral diseases , control relies on reducing mosquito populations and their contact with people , which has bee...	[ "Chikungunya virus ( CHIKV ) is a mosquito-borne alphavirus that has reemerged since 2004 to cause millions of cases of severe and often persistent arthralgia .", "Because no licensed vaccine exists to prevent this disease , we utilized an attenuation approach to produce a live CHIKV vaccine candidate that elicit...	2011
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "cognitive neuroscience", "cognition", "decision making", "consciousness", "biology", "neuroscience", "neuroimaging" ]	How Awareness Changes the Relative Weights of Evidence During Human Decision-Making	journal.pbio.1001203	A combined behavioral and brain imaging study shows how sensory awareness and stimulus visibility can influence the dynamics of decision-making in humans.	[ [ "Many decisions can be formalized as a process of accumulation of evidence over time , ultimately favoring one alternative over another [1] , [2] .", "Evidence accumulation models have successfully captured the neural dynamics of simple decisions in a visual motion categorization task [3] as well as more ...	[ "Human decisions are based on accumulating evidence over time for different options .", "Here we ask a simple question: How is the accumulation of evidence affected by the level of awareness of the information ?", "We examined the influence of awareness on decision-making using combined behavioral methods and m...	[ "When making a decision , we gather evidence for the different options and ultimately choose on the basis of the accumulated evidence .", "A fundamental question is whether and how conscious awareness of the evidence changes this decision-making process .", "Here , we examined the influence of sensory awareness...	2011
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "growth control", "gene networks", "animal genetics", "genetic mutation", "functional genomics", "chromosome structure and function", "gene regulation", "dna transcription", "gene function", "animal models", "genetics of disease", "developmental biology", "model organisms", "organism devel...	Trps1 and Its Target Gene Sox9 Regulate Epithelial Proliferation in the Developing Hair Follicle and Are Associated with Hypertrichosis	journal.pgen.1003002	null	[ [ "Hypertrichosis is defined as excessive hair growth for a particular site of the body or age of a patient that is not hormone-dependent .", "Hypertrichoses are characterized on the basis of multiple criteria: cause ( genetic or acquired ) , age of onset , extent of hair distribution ( universal or localiz...	[ "Hereditary hypertrichoses are a group of hair overgrowth syndromes that are extremely rare in humans .", "We have previously demonstrated that a position effect on TRPS1 is associated with hypertrichosis in humans and mice .", "To gain insight into the functional role of Trps1 , we analyzed the late morphogene...	[ "The various ectodermal appendages found in nature have evolved over time to allow organisms to better adapt to their environment .", "These include hair , feathers , scales , nails , teeth , beaks , horns , and a wide array of eccrine glands .", "The hair follicle is an ectodermal appendage unique to mammals t...	2012
[ "Introduction", "Materials and methods", "Results", "Discussion" ]	[ "invertebrates", "medicine and health sciences", "pathology and laboratory medicine", "chikungunya infection", "engineering and technology", "transportation", "pathogens", "geographical locations", "microbiology", "tropical diseases", "animals", "viruses", "rna viruses", "neglected tropica...	Vector status of Aedes species determines geographical risk of autochthonous Zika virus establishment	journal.pntd.0005487	null	[ [ "In May 2015 , a Zika disease outbreak originated in Brazil , and by October 5 , 2016 , local transmission of the Zika virus had been reported in over 60 countries and territories , with over 750 thousand estimated cases [1] .", "The World Health Organization ( WHO ) previously predicted that the virus wo...	[ "The 2015-16 Zika virus pandemic originating in Latin America led to predictions of a catastrophic global spread of the disease .", "Since the current outbreak began in Brazil in May 2015 local transmission of Zika has been reported in over 60 countries and territories , with over 750 thousand confirmed and suspe...	[ "Between 1952 , when the Zika virus was first found in humans , and 2007 Zika disease outbreaks were limited to small isolated epidemics in equatorial Africa and tropical Asia .", "However , the recent outbreak , which began in Brazil in May 2015 , resulted over 750 thousand estimated cases and confirmed local tr...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "parasitology", "biology", "microbiology" ]	An Apicoplast Localized Ubiquitylation System Is Required for the Import of Nuclear-encoded Plastid Proteins	journal.ppat.1003426	null	[ [ "Apicomplexans are eukaryotic pathogens and responsible for important human and animal diseases including malaria and toxoplasmosis .", "The Apicomplexa evolved from single-celled photosynthetic algae , and their adaptation to animal parasitism likely predates the emergence of animals from water to land ....	[ "Apicomplexan parasites are responsible for numerous important human diseases including toxoplasmosis , cryptosporidiosis , and most importantly malaria .", "There is a constant need for new antimalarials , and one of most keenly pursued drug targets is an ancient algal endosymbiont , the apicoplast .", "The ap...	[ "The apicoplast is an essential parasite organelle derived from an algal endosymbiont .", "Most apicoplast proteins are nuclear encoded and post-translationally imported .", "Part of this journey utilizes the endoplasmic reticulum associated degradation or ERAD system of the algal endosymbiont .", "Typically ...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biotechnology/applied microbiology", "infectious diseases/neglected tropical diseases", "infectious diseases/viral infections", "public health and epidemiology/global health", "microbiology/applied microbiology", "infectious diseases/tropical and travel-associated diseases" ]	The Endosymbiotic Bacterium Wolbachia Induces Resistance to Dengue Virus in Aedes aegypti	journal.ppat.1000833	null	[ [ "Dengue fever and its associated condition , the highly lethal dengue hemorrhagic fever , are emerging globally as the most important arboviral diseases currently threatening human populations .", "Approximately 2 . 5 billion people are at risk of contracting dengue-associated disease , with an estimated ...	[ "Genetic strategies that reduce or block pathogen transmission by mosquitoes have been proposed as a means of augmenting current control measures to reduce the growing burden of vector-borne diseases .", "The endosymbiotic bacterium Wolbachia has long been promoted as a potential vehicle for introducing disease-r...	[ "Dengue fever and its associated condition , dengue hemorrhagic fever , are emerging globally as the most important arboviral diseases currently threatening human populations .", "Dengue virus is transmitted to humans by aedine mosquitoes , primarily Aedes aegypti and , to a lesser extent , Aedes albopictus .", ...	2010
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "infectious diseases", "veterinary diseases", "zoonoses", "medicine and health sciences", "respiratory infections", "sars", "veterinary virology", "common cold", "biology and life sciences", "viral diseases", "pulmonology", "veterinary science" ]	Targeting Membrane-Bound Viral RNA Synthesis Reveals Potent Inhibition of Diverse Coronaviruses Including the Middle East Respiratory Syndrome Virus	journal.ppat.1004166	null	[ [ "Prior to the emergence of the highly pathogenic severe acute respiratory syndrome-associated coronavirus ( SARS-CoV ) in 2003 [1]–[3] only two circulating human coronaviruses ( HCoVs ) , HCoV-229E [4] and HCoV-OC43 [5] causing relatively mild common cold-like respiratory tract infections , were known , and c...	[ "Coronaviruses raise serious concerns as emerging zoonotic viruses without specific antiviral drugs available .", "Here we screened a collection of 16671 diverse compounds for anti-human coronavirus 229E activity and identified an inhibitor , designated K22 , that specifically targets membrane-bound coronaviral R...	[ "Viruses that replicate in the host cell cytoplasm have evolved to employ host cell-derived membranes to compartmentalize genome replication and transcription .", "Specifically for positive-stranded RNA viruses , accumulating knowledge concerning the involvement , rearrangement and requirement of cellular membran...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "complement system", "immunity", "vector biology", "innate immunity", "anopheles", "immune defense", "immunology", "biology", "microbiology", "parasitology", "immune system" ]	The CLIP-Domain Serine Protease Homolog SPCLIP1 Regulates Complement Recruitment to Microbial Surfaces in the Malaria Mosquito Anopheles gambiae	journal.ppat.1003623	null	[ [ "The mosquito Anopheles gambiae is the main vector of Plasmodium falciparum malaria in sub-Saharan Africa and hence directly responsible for the death of hundreds of thousands of people every year and for a devastating socioeconomic burden especially in endemic countries .", "Mosquitoes launch a potent im...	[ "The complement C3-like protein TEP1 of the mosquito Anopheles gambiae is required for defense against malaria parasites and bacteria .", "Two forms of TEP1 are present in the mosquito hemolymph , the full-length TEP1-F and the proteolytically processed TEP1cut that is part of a complex including the leucine-rich...	[ "Mosquitoes are vectors of numerous human diseases including malaria .", "Disease transmission requires that microbes overcome the robust mosquito immune system .", "In the African malaria mosquito , the TEP1 protein that is homologous to mammalian complement factor C3 is shown to play a central role in mosquit...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "cancer genomics", "sequencing techniques", "medicine and health sciences", "basic cancer research", "oncology", "substitution mutation", "mutation", "sequence motif analysis", "epigenetics", "molecular biology techniques", "chromatin", "research and analysis methods", "sequence analysis", ...	Mutational Biases Drive Elevated Rates of Substitution at Regulatory Sites across Cancer Types	journal.pgen.1006207	null	[ [ "Most large-scale surveys of somatic mutation in cancer have focussed on protein-coding sequences , and catalogues of genes that carry recurrent mutations already number in the hundreds [1–3] , but it has long been speculated that driver mutations are likely to exist in the 98% of the genome sequence outside ...	[ "Disruption of gene regulation is known to play major roles in carcinogenesis and tumour progression .", "Here , we comprehensively characterize the mutational profiles of diverse transcription factor binding sites ( TFBSs ) across 1 , 574 completely sequenced cancer genomes encompassing 11 tumour types .", "We...	[ "Regulatory regions of the genome are important players in cancer initiation and progression .", "Here , we study the patterns of mutations accumulating at short DNA segments bound by regulatory proteins ( transcription factor binding sites ) across many cancer types and in the human population .", "We find str...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "plant science", "plant biology", "biology", "molecular cell biology" ]	Misregulation of AUXIN RESPONSE FACTOR 8 Underlies the Developmental Abnormalities Caused by Three Distinct Viral Silencing Suppressors in Arabidopsis	journal.ppat.1002035	null	[ [ "RNA silencing in Arabidopsis entails the activities of four distinct paralogs of the RNaseIII Dicer , producing small RNAs with specialized functions [1] .", "DICER-LIKE 1 ( DCL1 ) predominantly synthesizes microRNAs ( miRNAs ) , 19-to-24-nucleotide ( nt ) in length , from non-coding primary transcripts ...	[ "In Arabidopsis , micro ( mi ) RNAs and trans-acting ( ta-si ) RNAs synthesized directly or indirectly through the DICER-LIKE-1 ( DCL1 ) ribonuclease have roles in patterning and hormonal responses , while DCL2 , 3 , 4-dependent small-interfering ( si ) RNAs are mainly involved in silencing of transposable elements...	[ "In the plant and animal RNA silencing pathways , small RNA molecules known as micro ( mi ) RNA and short-interfering ( si ) RNAs have key roles in development and antiviral defense , respectively .", "In turn , viruses counteract this defense by deploying specific virulence factors , referred to as Viral Suppres...	2011
[ "Introduction", "Results/Discussion", "Methods" ]	[ "biochemistry/biocatalysis", "biochemistry/bioinformatics", "biochemistry/structural genomics" ]	A Structure-Based Approach for Detection of Thiol Oxidoreductases and Their Catalytic Redox-Active Cysteine Residues	journal.pcbi.1000383	null	[ [ "Compared to other amino acids in proteins , cysteine ( Cys ) residues are less frequent ,", "yet often more conserved and found in functionally important locations .", "Protein-based Cys thiols can be divided into several broad categories wherein these", "residues", "( i ) are engaged in stru...	[ "Cysteine ( Cys ) residues often play critical roles in proteins , for example , in", "the formation of structural disulfide bonds , metal binding , targeting proteins", "to the membranes , and various catalytic functions .", "However , the structural", "determinants for various Cys functions are not clear ...	[ "Among the 20 amino acids commonly found in proteins , cysteine ( Cys ) is special in", "that it is present more often than other residues in functionally important", "locations within proteins .", "Some of these functions include metal binding ,", "catalysis , structural stability , and posttranslational m...	2009
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biotechnology", "bioengineering", "biochemistry", "biology", "molecular cell biology", "neuroscience", "engineering" ]	A Genetically Encoded Tag for Correlated Light and Electron Microscopy of Intact Cells, Tissues, and Organisms	journal.pbio.1001041	null	[ [ "The most general techniques for imaging specific proteins within cells and organisms rely either on antibodies or genetic tags .", "EM is the standard technique for ultrastructural localization , but conventional EM immunolabeling remains challenging because of the need to develop high-affinity , high-se...	[ "Electron microscopy ( EM ) achieves the highest spatial resolution in protein localization , but specific protein EM labeling has lacked generally applicable genetically encoded tags for in situ visualization in cells and tissues .", "Here we introduce “miniSOG” ( for mini Singlet Oxygen Generator ) , a fluoresc...	[ "Electron microscopy ( EM ) once revolutionized cell biology by revealing subcellular anatomy at resolutions of tens of nanometers , well below the diffraction limit of light microscopy .", "Over the past two decades , light microscopy has been revitalized by the development of spontaneously fluorescent proteins ...	2011
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genetics", "biology and life sciences", "animal genetics" ]	A Splice Mutation in the PHKG1 Gene Causes High Glycogen Content and Low Meat Quality in Pig Skeletal Muscle	journal.pgen.1004710	null	[ [ "In past decades , thousands of quantitative trait loci ( QTLs ) have been detected for economically important traits in livestock through genetic linkage studies [1] .", "The recent availability of livestock genome sequences and high-density SNP chips has allowed detection of significant association of n...	[ "Glycolytic potential ( GP ) in skeletal muscle is economically important in the pig industry because of its effect on pork processing yield .", "We have previously mapped a major quantitative trait loci ( QTL ) for GP on chromosome 3 in a White Duroc × Erhualian F2 intercross .", "We herein performed a systems...	[ "Glycogen storage diseases ( GSD ) are a group of inherited disorders characterized by storage of excess glycogen , which are mainly caused by the abnormality of a particular enzyme essential for releasing glucose from glycogen .", "GSD-like conditions have been described in a wide variety of species .", "Pigs ...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine", "gene networks", "cancer genetics", "genetic mutation", "obstetrics and gynecology", "cancer risk factors", "cancers and neoplasms", "animal models", "oncology", "model organisms", "biology", "gynecological tumors", "mouse", "autosomal dominant", "genetic causes of cancer", ...	Stromal Liver Kinase B1 [STK11] Signaling Loss Induces Oviductal Adenomas and Endometrial Cancer by Activating Mammalian Target of Rapamycin Complex 1	journal.pgen.1002906	null	[ [ "The embryonic Müllerian ducts , which are composed of a simple columnar epithelium surrounded by mesenchymal cells , differentiate into the oviducts , uterus , cervix , and anterior portion of the vagina [1] .", "During differentiation , epithelial-mesenchymal communication plays an important role in spe...	[ "Germline mutations of the Liver Kinase b1 ( LKB1/STK11 ) tumor suppressor gene have been linked to Peutz-Jeghers Syndrome ( PJS ) , an autosomal-dominant , cancer-prone disorder in which patients develop neoplasms in several organs , including the oviduct , ovary , and cervix .", "We have conditionally deleted L...	[ "Peutz-Jeghers Syndrome patients have autosomal dominant mutations in the LKB1/STK11 gene and are prone to developing cancer , predominantly in the intestinal tract but also in other tissues , including the reproductive tracts and gonads .", "To elucidate the mechanisms disrupted by the loss of LKB1 in the reprod...	2012
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "biochemistry/molecular evolution", "genetics and genomics/microbial evolution and genomics", "genetics and genomics/bioinformatics" ]	Effect of Correlated tRNA Abundances on Translation Errors and Evolution of Codon Usage Bias	journal.pgen.1001128	null	[ [ "Protein production is the most energetically expensive metabolic process within a cell [1]–[4] .", "However , like all biological processes , protein translation is prone to errors .", "The biological importance of these translation errors and their impact on coding sequence evolution , especially th...	[ "Despite the fact that tRNA abundances are thought to play a major role in determining translation error rates , their distribution across the genetic code and the resulting implications have received little attention .", "In general , studies of codon usage bias ( CUB ) assume that codons with higher tRNA abunda...	[ "Codon usage bias ( CUB ) is a ubiquitous and important phenomenon .", "CUB is thought to be driven primarily due to selection against missense errors .", "For over 30 years , the standard model of translation errors has implicitly assumed that the relationship between translation errors and tRNA abundances are...	2010
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "infectious diseases/helminth infections", "genetics and genomics/population genetics", "evolutionary biology/evolutionary ecology", "evolutionary biology/evolutionary and comparative genetics" ]	DNA-Sequence Variation Among Schistosoma mekongi Populations and Related Taxa; Phylogeography and the Current Distribution of Asian Schistosomiasis	journal.pntd.0000200	null	[ [ "Schistosomiasis in humans along the lower Mekong river ( specifically Cambodia and southern Laos ) was first recognized in 1957 [1] and has proven a persistent public health problem in the region [2] .", "The species involved is the parasitic blood fluke Schistosoma mekongi Voge , Buckner & Bruce 1978 , ...	[ "Schistosomiasis in humans along the lower Mekong River has proven a persistent public health problem in the region .", "The causative agent is the parasite Schistosoma mekongi ( Trematoda: Digenea ) .", "A new transmission focus is reported , as well as the first study of genetic variation among S . mekongi po...	[ "Schistosomiasis is a disease caused by parasitic worms of the genus Schistosoma .", "In the lower Mekong river , schistosomiasis in humans is called Mekong schistosomiasis and is caused by Schistosoma mekongi .", "In the past , Mekong schistosomiasis was known only from the lower Mekong river .", "Here DNA-s...	2008
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Trm9-Catalyzed tRNA Modifications Regulate Global Protein Expression by Codon-Biased Translation	journal.pgen.1005706	null	[ [ "A striking feature of tRNA molecules is the large number of post-transcriptional modifications , representing up to 10% of the ribonucleoside content [1 , 2] .", "Ranging from simple base methylation to complex modifications involving multiple enzymatic steps , modified ribonucleosides are phylogenetical...	[ "Post-transcriptional modifications of transfer RNAs ( tRNAs ) have long been recognized to play crucial roles in regulating the rate and fidelity of translation .", "However , the extent to which they determine global protein production remains poorly understood .", "Here we use quantitative proteomics to show...	[ "Here we present evidence for a more complicated role for transfer RNAs ( tRNAs ) than as mere adapters that link the genetic code in messenger RNA ( mRNA ) to the amino acid sequence of a protein during translation .", "tRNAs have long been known to be modified with dozens of different chemical structures other ...	2015
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "phosphorylation", "luciferase", "nucleic acid synthesis", "enzymes", "messenger rna", "enzymology", "dna-binding proteins", "phosphatases", "dna transcription", "polymerases", "sequence motif analysis", "rna synthesis", "chemical synthesis", "research and analysis methods", "sequence an...	RSV hijacks cellular protein phosphatase 1 to regulate M2-1 phosphorylation and viral transcription	journal.ppat.1006920	null	[ [ "Human respiratory syncytial virus ( RSV ) is the leading cause of severe respiratory tract infections in infants worldwide and the primary cause of infant hospitalization for respiratory infections [1] .", "In addition , RSV is increasingly recognized as a significant cause of disease in the elderly popu...	[ "Respiratory syncytial virus ( RSV ) RNA synthesis occurs in cytoplasmic inclusion bodies ( IBs ) in which all the components of the viral RNA polymerase are concentrated .", "In this work , we show that RSV P protein recruits the essential RSV transcription factor M2-1 to IBs independently of the phosphorylation...	[ "Respiratory syncytial virus ( RSV ) is the leading cause of lower respiratory tract illness in infants .", "Since no vaccine and no potent antivirals are available against RSV , it is essential to better understand the mechanisms of viral replication to develop new antiviral strategies .", "Here we have invest...	2018
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "phosphorylation", "invertebrates", "medicine and health sciences", "body fluids", "animals", "notch signaling", "animal models", "developmental biology", "drosophila melanogaster", "model organisms", "experimental organism systems", "population biology", "insect vectors", "drosophila", ...	The non-canonical Notch signaling is essential for the control of fertility in Aedes aegypti	journal.pntd.0006307	null	[ [ "Mosquitoes are highly-effective vectors that transmit many devastating diseases , including malaria , dengue , and Zika .", "Together , these diseases are responsible for over one million deaths each year [1–4] .", "Of note , cases of dengue are reaching disastrous levels in Central and South America...	[ "The Notch signaling pathway is a highly evolutionarily-conserved cell-cell signaling pathway that regulates many events during development .", "It plays a pivotal role in the regulation of fundamental cellular processes , such as cell proliferation , stem cell maintenance , and differentiation during embryonic a...	[ "Mosquitoes transmit many devastating diseases , including malaria , dengue , and Zika , which together are responsible for over one million deaths per year .", "Major reasons for this tragic situation are the unavailability of effective vaccines and drugs for most mosquito-borne diseases , increased resistance o...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biology and life sciences", "medicine and health sciences" ]	Aberrant Autolysosomal Regulation Is Linked to The Induction of Embryonic Senescence: Differential Roles of Beclin 1 and p53 in Vertebrate Spns1 Deficiency	journal.pgen.1004409	null	[ [ "Autophagy is an evolutionarily conserved intracellular catabolic process whereby cytoplasmic proteins and organelles are engulfed into autophagosomes and subsequently degraded in autolysosomes , following fusion with lysosomes .", "Biologically significant roles of autophagy have been illuminated in a va...	[ "Spinster ( Spin ) in Drosophila or Spinster homolog 1 ( Spns1 ) in vertebrates is a putative lysosomal H+-carbohydrate transporter , which functions at a late stage of autophagy .", "The Spin/Spns1 defect induces aberrant autolysosome formation that leads to embryonic senescence and accelerated aging symptoms , ...	[ "Spinster homolog 1 ( Spns1 ) in vertebrates , as well as Spinster ( Spin ) in Drosophila , is a hypothetical lysosomal H+-carbohydrate transporter , which functions at a late stage of autophagy .", "The Spin/Spns1 defect induces aberrant autolysosome formation that leads to embryonic senescence and accelerated a...	2014
[ "Introduction", "Results/Discussion", "Materials and Methods" ]	[ "microbial evolution", "microbial pathogens", "biology", "evolutionary biology", "microbiology", "evolutionary genetics" ]	Genomics of Adaptation during Experimental Evolution of the Opportunistic Pathogen Pseudomonas aeruginosa	journal.pgen.1002928	null	[ [ "In the mid-1800's , Louis Pasteur advised microbiologists to think of the human body as a “culture vessel” for microbes , in the context of understanding immunity [1] .", "Pasteur's approach has been revised and updated several times [2] , [3] , with a recent review encouraging researchers to be attentiv...	[ "Adaptation is likely to be an important determinant of the success of many pathogens , for example when colonizing a new host species , when challenged by antibiotic treatment , or in governing the establishment and progress of long-term chronic infection .", "Yet , the genomic basis of adaptation is poorly unde...	[ "Pathogens face a hostile and often novel environment when infecting a new host , and adaptation to this environment can be critical to a pathogen's survival .", "The genetic basis of pathogen adaptation is in turn important for treatment , since the consistency with which therapies succeed may depend on the exte...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biochemistry", "proteins", "protein structure", "biology", "microbiology", "host-pathogen interaction", "bacterial pathogens" ]	VipD of Legionella pneumophila Targets Activated Rab5 and Rab22 to Interfere with Endosomal Trafficking in Macrophages	journal.ppat.1003082	null	[ [ "Legionella pneumophila is an opportunistic human pathogen that replicates inside macrophages , which are at the front line of immune defense .", "This Gram-negative bacterium causes Legionnaires' disease characterized by severe pneumonia or less acute Pontiac fever .", "By phagocytosis , the bacteria...	[ "Upon phagocytosis , Legionella pneumophila translocates numerous effector proteins into host cells to perturb cellular metabolism and immunity , ultimately establishing intracellular survival and growth .", "VipD of L . pneumophila belongs to a family of bacterial effectors that contain the N-terminal lipase dom...	[ "Legionella pneumophila is a pathogen bacterium that causes Legionnaires' disease accompanied by severe pneumonia .", "Surprisingly , this pathogen invades and replicates inside macrophages , whose major function is to detect and destroy invading microorganisms .", "How L . pneumophila can be “immune” to this p...	2012
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "medicine", "infectious diseases", "filariasis", "neglected tropical diseases", "parasitic diseases" ]	Live Brugia malayi Microfilariae Inhibit Transendothelial Migration of Neutrophils and Monocytes	journal.pntd.0001914	null	[ [ "The filarial parasite Brugia malayi is a causative agent of human lymphatic filariasis in South and South-East Asia .", "B . malayi is transmitted by mosquitoes , which take up the blood-borne microfilarial stage ( Mf ) of the parasite .", "For the majority of the day , Mf sequester predominantly in ...	[ "Lymphatic filariasis is a major tropical disease caused by the parasite Brugia malayi .", "Microfilariae ( Mf ) circulate in the peripheral blood for 2–3 hours in synchronisation with maximal feeding of the mosquito vector .", "When absent from the peripheral blood , Mf sequester in the capillaries of the lung...	[ "Brugia malayi is a nematode which causes lymphatic filariasis in South and South-East Asia .", "Most infected people harbour many millions of the microfilarial stage of the parasite in their blood stream and yet they show few visible symptoms of disease .", "Vascular endothelial cells ( EC ) line the blood ves...	2012
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "fish", "medicine and health sciences", "cardiovascular anatomy", "enzymes", "cardiac ventricles", "enzymology", "vertebrates", "dna-binding proteins", "animals", "animal models", "osteichthyes", "organisms", "developmental biology", "model organisms", "experimental organism systems", ...	The roles of SMYD4 in epigenetic regulation of cardiac development in zebrafish	journal.pgen.1007578	null	[ [ "Protein post-translational modifications ( PTMs ) are critical for the biological function of proteins .", "Histone modification is a common epigenetic mechanism that plays essential roles in the regulation of chromatin structure and gene expression .", "Different types of histone modifications , whi...	[ "SMYD4 belongs to a family of lysine methyltransferases .", "We analyzed the role of smyd4 in zebrafish development by generating a smyd4 mutant zebrafish line ( smyd4L544Efs1 ) using the CRISPR/Cas9 technology .", "The maternal and zygotic smyd4L544Efs1 mutants demonstrated severe cardiac malformations , inc...	[ "SMYD4 belongs to a SET and MYND domain-containing lysine methyltransferase .", "In zebrafish , smyd4 is ubiquitously expressed in early embryos and becomes enriched in the developing heart at 48 hours post-fertilization ( hpf ) .", "We generated a smyd4 mutant zebrafish line ( smyd4L544Efs*1 ) using the CRISPR...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "microbiology/immunity to infections", "genetics and genomics/genetics of the immune system", "immunology/immunomodulation", "genetics and genomics/gene expression", "immunology/innate immunity", "microbiology/cellular microbiology and pathogenesis" ]	Pseudomonas aeruginosa Suppresses Host Immunity by Activating the DAF-2 Insulin-Like Signaling Pathway in Caenorhabditis elegans	journal.ppat.1000175	null	[ [ "The innate immune system is a genetically-encoded host defense mechanism that constitutes the first line of defense against pathogens in plants and animals .", "Innate immunity in animals is evolutionarily ancient , and the molecular components of mammalian innate immunity are partly conserved in inverte...	[ "Some pathogens have evolved mechanisms to overcome host immune defenses by inhibiting host defense signaling pathways and suppressing the expression of host defense effectors .", "We present evidence that Pseudomonas aeruginosa is able to suppress the expression of a subset of immune defense genes in the animal ...	[ "Bacterial pathogens have evolved mechanisms to overcome the immune defenses that animals and plants deploy against them .", "In some cases , this involves directly interfering with the proper functioning of the immune system .", "Because pathogens that employ these strategies are often the most deadly and diff...	2008
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "systems biology", "theoretical biology", "immunology", "biology", "computational biology", "molecular cell biology", "genetics and genomics" ]	A Mathematical Model for the Reciprocal Differentiation of T Helper 17 Cells and Induced Regulatory T Cells	journal.pcbi.1002122	null	[ [ "CD4+ T cells are important components of the adaptive immune system in higher vertebrates .", "By producing various cytokines , they perform critical functions such as helping B cells to produce antibodies , activating CD8+ cytotoxic T cells , enhancing the innate immune system , and suppressing the immu...	[ "The reciprocal differentiation of T helper 17 ( TH17 ) cells and induced regulatory T ( iTreg ) cells plays a critical role in both the pathogenesis and resolution of diverse human inflammatory diseases .", "Although initial studies suggested a stable commitment to either the TH17 or the iTreg lineage , recent r...	[ "In order to perform complex functions upon pathogenic challenges , the immune system needs to efficiently deploy a repertoire of specialized cells by inducing the differentiation of precursor cells into effector cells .", "In a critical process of the adaptive immune system , one common type of precursor cell ca...	2011
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "public health and epidemiology", "evidence-based healthcare", "pediatrics and child health" ]	Schistosoma mansoni Infections in Young Children: When Are Schistosome Antigens in Urine, Eggs in Stool and Antibodies to Eggs First Detectable?	journal.pntd.0000938	null	[ [ "Throughout the last decade several large-scale preventive chemotherapy campaigns , waged against neglected tropical diseases , have progressively scaled up operations to reach nationwide coverage levels in Uganda [1] , [2] .", "For control of intestinal schistosomiasis , as caused by Schistosoma mansoni ...	[ "In Uganda , control of intestinal schistosomiasis with preventive chemotherapy is typically focused towards treatment of school-aged children; the needs of younger children are presently being investigated as in lakeshore communities very young children can be infected .", "In the context of future epidemiologic...	[ "In sub-Saharan Africa , intestinal schistosomiasis is a debilitating disease caused by a worm infection .", "To arrest disease progression , de-worming medications are given out , often en masse , to school-aged children .", "In Uganda , however , much younger children can be infected , and in lakeshore commun...	2011
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "transfection", "invertebrates", "medicine and health sciences", "luciferase", "body fluids", "pathology and laboratory medicine", "enzymes", "pathogens", "microbiology", "enzymology", "animals", "viruses", "lymph nodes", "rna viruses", "lymphatic system", "molecular biology techniques...	Mosquito cell-derived West Nile virus replicon particles mimic arbovirus inoculum and have reduced spread in mice	journal.pntd.0005394	null	[ [ "Arthropod-borne viruses are transmitted between arthropod vectors , such as ticks and mosquitos , and their vertebrate hosts .", "Mosquito-borne flaviviruses , such as dengue , Zika , and West Nile viruses ( WNV ) , are responsible for a variety of debilitating pathologies , including hemorrhagic fever ,...	[ "Half of the human population is at risk of infection by an arthropod-borne virus .", "Many of these arboviruses , such as West Nile , dengue , and Zika viruses , infect humans by way of a bite from an infected mosquito .", "This infectious inoculum is insect cell-derived giving the virus particles distinct qua...	[ "Many emerging viruses of public health concern are arthropod-borne , including tick-borne encephalitis , dengue , Zika , chikungunya , and West Nile viruses .", "The arboviruses are maintained in nature via virus-specific transmission cycles , involving arthropod ( e . g . mosquitos , midges , and ticks ) and ve...	2017
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "medicinal chemistry", "emerging infectious diseases", "chemistry", "biology", "microbiology", "parasitology", "parasite physiology" ]	Selective Inhibitors of Protozoan Protein N-myristoyltransferases as Starting Points for Tropical Disease Medicinal Chemistry Programs	journal.pntd.0001625	null	[ [ "Protozoan parasites are major causative agents of global infectious diseases that affect millions of people in tropical and sub-tropical regions of the world [1] .", "In the absence of effective vaccination strategies , treatment for many of these infections depends on chemotherapy and is reliant on “old...	[ "Inhibition of N-myristoyltransferase has been validated pre-clinically as a target for the treatment of fungal and trypanosome infections , using species-specific inhibitors .", "In order to identify inhibitors of protozoan NMTs , we chose to screen a diverse subset of the Pfizer corporate collection against Pla...	[ "Inhibition of N-myristoyltransferase has been validated pre-clinically as a target for the treatment of fungal and trypanosome infections , using species-specific inhibitors .", "In order to identify inhibitors of protozoan NMTs , we chose to screen a diverse subset of the Pfizer corporate collection against Pla...	2012
[ "Introduction", "Materials and methods", "Results", "Discussion" ]	[ "urology", "viral vaccines", "medicine and health sciences", "immune physiology", "viral transmission and infection", "immunology", "geographical locations", "microbiology", "vertebrates", "animals", "mammals", "vaccines", "preventive medicine", "infectious disease control", "antibodies"...	Partial cross-protection between Japanese encephalitis virus genotype I and III in mice	journal.pntd.0007601	null	[ [ "Japanese encephalitis virus ( JEV ) is the causative agent of Japanese encephalitis ( JE ) which is prevalent in ~25 Asia-Pacific countries , with the estimated number of human cases ranging from 50 , 000 to 175 , 000 each year [1] .", "Globally , approximately 75% of human cases happen in children and a...	[ "Genotype III ( GIII ) Japanese encephalitis virus ( JEV ) predominance has gradually been replaced by genotype I ( GI ) over the last 20 years in many Asian countries .", "This genotype shift raises concerns about the protective efficacy of Japanese encephalitis ( JE ) vaccines , as all of the currently licensed...	[ "Japanese encephalitis virus ( JEV ) is a mosquito-borne flavivirus that causes Japanese encephalitis ( JE ) in humans and reproductive disorders in pigs .", "JEV is phylogenetically classified into five genotypes .", "JEV genotype III ( GIII ) was historically dominant throughout most of Asia , but has been re...	2019
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "public and occupational health", "infectious diseases", "medicine and health sciences", "global health", "biology and life sciences", "immunology" ]	Immunogenicity of a Killed Bivalent (O1 and O139) Whole Cell Oral Cholera Vaccine, Shanchol, in Haiti	journal.pntd.0002828	null	[ [ "Cholera remains a public health problem for many of the world's poorest individuals .", "Approximately 3 million cases of diarrheal illness and 120 , 000 deaths are caused by V . cholerae annually [1] .", "Devastating epidemics occur when V . cholerae is introduced into an immunologically naive popul...	[ "Studies of the immunogenicity of the killed bivalent whole cell oral cholera vaccine , Shanchol , have been performed in historically cholera-endemic areas of Asia .", "There is a need to assess the immunogenicity of the vaccine in Haiti and other populations without historical exposure to Vibrio cholerae .", ...	[ "Studies evaluating the ability of the killed bivalent whole cell oral cholera vaccine , Shanchol , to elicit an immune response have been performed in historically cholera-endemic areas of Asia .", "There is a need to assess whether the vaccine is able to elicit an immune response in Haiti and other populations ...	2014
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "humoral immunity", "medicine", "infectious diseases", "immunity", "immunology", "biology", "microbiology", "viral diseases", "dengue", "immune response", "immunoglobulins" ]	In-Depth Analysis of the Antibody Response of Individuals Exposed to Primary Dengue Virus Infection	journal.pntd.0001188	null	[ [ "Dengue virus ( DENV ) complex consists of 4 serotypes .", "People exposed to primary DENV infections develop robust antibody responses that cross-react with all serotypes ( Reviewed in [1] ) .", "Despite the extensive cross-reactivity , individuals only develop long term , protective immunity against...	[ "Humans who experience a primary dengue virus ( DENV ) infection develop antibodies that preferentially neutralize the homologous serotype responsible for infection .", "Affected individuals also generate cross-reactive antibodies against heterologous DENV serotypes , which are non-neutralizing .", "Dengue cros...	[ "Dengue is a mosquito-borne viral disease of humans .", "The dengue virus complex is made up of four viruses designated as serotypes .", "People experiencing their first infection develop immune responses that prevent re-infection with the same serotype only .", "People experiencing a second infection with a ...	2011
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "developmental biology", "medicine and health sciences", "body fluids", "blood", "anatomy", "platelets", "biology and life sciences", "hematology" ]	A Loss of Function Screen of Identified Genome-Wide Association Study Loci Reveals New Genes Controlling Hematopoiesis	journal.pgen.1004450	null	[ [ "Erythrocytes and platelets ( thrombocytes in zebrafish ) are the most abundant cells in blood .", "In an individual , the number and volume of both erythrocytes and platelets are highly heritable and tightly regulated within narrow ranges , but there is a wide variation of these parameters in the populat...	[ "The formation of mature cells by blood stem cells is very well understood at the cellular level and we know many of the key transcription factors that control fate decisions .", "However , many upstream signalling and downstream effector processes are only partially understood .", "Genome wide association stud...	[ "In this manuscript we report on a follow-up study of the GWAS loci associated with the platelet size and number .", "A GWAS meta-analysis identified 68 genetic loci controlling platelet size and number .", "Only a quarter of those genes , however , are known regulators of hematopoiesis .", "To determine func...	2014
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "nucleic acid synthesis", "cell cycle and cell division", "cell processes", "fungi", "model organisms", "dna replication", "experimental organism systems", "dna", "mammalian genomics", "synthesis phase", "schizosaccharomyces", "dna synthesis", "chemical synthesis", "research and analysis m...	CDK activity provides temporal and quantitative cues for organizing genome duplication	journal.pgen.1007214	null	[ [ "The accurate duplication of the genetic material relies on a multilayered control of the initiation of DNA synthesis at replication origins .", "Origins fire at characteristic times during S phase and are activated with particular frequencies , or efficiencies , in a population of cells .", "Together...	[ "In eukaryotes , the spatial and temporal organization of genome duplication gives rise to distinctive profiles of replication origin usage along the chromosomes .", "While it has become increasingly clear that these programs are important for cellular physiology , the mechanisms by which they are determined and ...	[ "The duplication of the genetic material is a highly conserved and tightly regulated process that is essential for cell proliferation .", "DNA synthesis initiates at sites called origins that are distributed throughout the genome .", "Replication origins are not all used equivalently , and their patterns of act...	2018

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