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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" ]	[ "biology and life sciences", "microbiology", "virology" ]	The Evolutionary History and Spatiotemporal Dynamics of the Fever, Thrombocytopenia and Leukocytopenia Syndrome Virus (FTLSV) in China	journal.pntd.0003237	null	[ [ "In 2007 , the fever , thrombocytopenia and leukopenia syndrome ( FTLS; also called severe fever with thrombocytopenia syndrome , SFTS ) was first reported in Henan province , China [1] , [2] .", "Since then , this life-threatening disease has been reported in many Chinese provinces , including Hubei , An...	[ "In 2007 , a novel bunyavirus was found in Henan Province , China and named fever , thrombocytopenia and leukocytopenia syndrome virus ( FTLSV ) ; since then , FTLSV has been found in ticks and animals in many Chinese provinces .", "Human-to-human transmission has been documented , indicating that FTLSV should be...	[ "FTLSV is novel bunyavirus belonging to genus Phlebovirus and was first found in Huaiyangshan area .", "The epidemiology and pathogenesis of FTLSV remain poorly understood .", "This lack of information underscores the importance of analyzing the movement and genetic history of FTLSV in China .", "Recent advan...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "systems biology", "developmental biology", "mathematics", "theoretical biology", "genetics", "biology", "evolutionary biology", "nonlinear dynamics", "genetics and genomics" ]	Cryptic Patterning of Avian Skin Confers a Developmental Facility for Loss of Neck Feathering	journal.pbio.1001028	null	[ [ "The vertebrate skin carries a highly ordered arrangement of pigments and morphological structures such as hairs and feathers .", "These patterns in the skin occur on two distinct spatial scales .", "Repetitive patterns of follicles or of pigment spots and stripes are laid out in a periodic manner , w...	[ "Vertebrate skin is characterized by its patterned array of appendages , whether feathers , hairs , or scales .", "In avian skin the distribution of feathers occurs on two distinct spatial levels .", "Grouping of feathers within discrete tracts , with bare skin lying between the tracts , is termed the macropatt...	[ "The distribution of hairs or feathers across the body is not homogeneous , and many animals have characteristic regions of their skin with either profuse or reduced coverage .", "These features , such as manes , crests , or bald patches , are seen in diverse species , suggesting that they can be selectively adva...	2011
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "acoustics", "engineering and technology", "signal processing", "random variables", "neuroscience", "covariance", "signal filtering", "mathematics", "brain mapping", "discrete mathematics", "neuroimaging", "combinatorics", "research and analysis methods", "imaging techniques", "probabili...	Imaging of neural oscillations with embedded inferential and group prevalence statistics	journal.pcbi.1005990	null	[ [ "The role of neural oscillations in population codes of brain functions , and the possible mechanisms of inter-regional communication between brain regions are not entirely understood .", "Source imaging techniques with magnetoencephalography ( MEG ) or electroencephalography ( EEG ) are time-resolved , n...	[ "Magnetoencephalography and electroencephalography ( MEG , EEG ) are essential techniques for studying distributed signal dynamics in the human brain .", "In particular , the functional role of neural oscillations remains to be clarified .", "For that reason , imaging methods need to identify distinct brain reg...	[ "The oscillatory activity of the brain produces a repertoire of signal dynamics that is rich and complex .", "Noninvasive recording techniques such as scalp magnetoencephalography and electroencephalography ( MEG , EEG ) are key methods to advance our comprehension of the role played by neural oscillations in bra...	2018
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "schistosoma", "invertebrates", "medicine and health sciences", "immune physiology", "body fluids", "helminths", "immunology", "tropical diseases", "parasitic diseases", "animals", "vaccines", "preventive medicine", "urine", "neglected tropical diseases", "infectious disease control", ...	Safety and efficacy of the rSh28GST urinary schistosomiasis vaccine: A phase 3 randomized, controlled trial in Senegalese children	journal.pntd.0006968	null	[ [ "Schistosomiasis is a chronic parasitic disease caused by trematodes that lay eggs in the urinary or gastrointestinal tract blood vessels [1] .", "It is associated with gastrointestinal or genitourinary disorders , pain , anemia , malnutrition , fatigue , and reduced exercise tolerance .", "These effe...	[ "Urinary schistosomiasis , the result of infection by Schistosoma haematobium ( Sh ) , remains a major global health concern .", "A schistosome vaccine could represent a breakthrough in schistosomiasis control strategies , which are presently based on treatment with praziquantel ( PZQ ) .", "We report the safet...	[ "Vaccines represent an attractive tool in the fight against schistosomiasis .", "Pre-clinical immunization studies with the schistosome enzyme 28 kDa glutathione S-transferase ( 28GST ) have shown a significant reduction of schistosome egg production and subsequent pathology .", "The objective of the present ph...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biochemistry/molecular evolution", "computational biology/macromolecular structure analysis", "computational biology/comparative sequence analysis", "biochemistry/protein chemistry", "biochemistry/macromolecular chemistry" ]	Evolution of a Signaling Nexus Constrained by Protein Interfaces and Conformational States	journal.pcbi.1000962	null	[ [ "How is functional novelty generated when a protein is highly constrained by its many interactions with other proteins and by its critical role in the cell ?", "In these proteins , new mutations are likely to have deleterious consequences by disrupting some important function within the cell due to the hi...	[ "Heterotrimeric G proteins act as the physical nexus between numerous receptors that respond to extracellular signals and proteins that drive the cytoplasmic response .", "The Gα subunit of the G protein , in particular , is highly constrained due to its many interactions with proteins that control or react to it...	[ "Proteins evolve new protein-protein interactions through changes to their residues .", "Many residue changes are harmful because they disrupt important existing interactions and functions .", "The more interactions a protein participates in , the more difficult it is to make changes that are not harmful to the...	2010
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "animal types", "medicine and health sciences", "education", "immunology", "tropical diseases", "sociology", "vertebrates", "social sciences", "domestic animals", "animals", "mammals", "preventive medicine", "rabies", "neglected tropical diseases", "vaccination and immunization", "zool...	Rabies: Knowledge and Practices Regarding Rabies in Rural Communities of the Brazilian Amazon Basin	journal.pntd.0004474	null	[ [ "Rabies is an acute form of viral encephalomyelitis , which is almost invariably fatal , and affects mammals on all continents except Antarctica [1] .", "Transmission occurs through the inoculation of the virus , typically through bites , scratches or contact between skin lesions and the saliva of an infe...	[ "The occurrence of outbreaks of human rabies transmitted by Desmodus rotundus in Brazil in 2004 and 2005 reinforced the need for further research into this zoonosis .", "Studies of knowledge and practices related to the disease will help to define strategies for the avoidance of new cases , through the identifica...	[ "In 2004 and 2005 , the occurrence of outbreaks of human rabies caused by the hematophagous bat , Desmodus rotundus in the Brazilian Amazon , highlighted the role of this bat in the transmission of the disease and the importance of further research on this zoonosis in this region .", "In the present study , we in...	2016
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "invertebrates", "medicine and health sciences", "tropical diseases", "social sciences", "parasitic diseases", "animals", "data management", "filariasis", "pharmaceutics", "drug administration", "neglected tropical diseases", "lymphatic filariasis", "computer and information sciences", "lo...	How much will it cost to eradicate lymphatic filariasis? An analysis of the financial and economic costs of intensified efforts against lymphatic filariasis	journal.pntd.0005934	null	[ [ "Neglected tropical diseases ( NTDs ) are a heterogeneous group of helminthic , bacterial , viral , fungal and protozoan infections that cause chronic and debilitating disability [1] .", "However , research and development to combat NTDs have notoriously been underfunded [2] .", "NTDs persist in areas...	[ "Lymphatic filariasis ( LF ) , a neglected tropical disease ( NTD ) preventable through mass drug administration ( MDA ) , is one of six diseases deemed possibly eradicable .", "Previously we developed one LF elimination scenario , which assumes MDA scale-up to continue in all countries that have previously under...	[ "Lymphatic filariasis ( LF ) is a neglected tropical disease ( NTD ) that is targeted for elimination and is thought to be potentially eradicable through once yearly mass drug administration ( MDA ) using drugs that are currently donated to LF endemic countries by the pharmaceutical companies that manufacture them ...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	CAPER Is Vital for Energy and Redox Homeostasis by Integrating Glucose-Induced Mitochondrial Functions via ERR-α-Gabpa and Stress-Induced Adaptive Responses via NF-κB-cMYC	journal.pgen.1005116	null	[ [ "An efficient metabolic adaptation to nutrient status is essential to promote growth , reproduction and to safeguard survival and life span .", "Because most eukaryotes execute aerobic oxidation through genes encoded by the nuclear genome and the mitochondrial genome , eukaryotes must coordinate their two...	[ "Ever since we developed mitochondria to generate ATP , eukaryotes required intimate mito-nuclear communication .", "In addition , since reactive oxygen species are a cost of mitochondrial oxidative phosphorylation , this demands safeguards as protection from these harmful byproducts .", "Here we identified a c...	[ "Energy homeostasis is a vital prerequisite for optimal nutrient utilization and prolonged survival in an environment with fluctuating and frequently scarce food resources .", "Numerous studies have elucidated the important roles of mitochondrial energy in fasting status but less is known about the role of mitoch...	2015
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "public health and epidemiology/epidemiology", "infectious diseases/neglected tropical diseases", "public health and epidemiology/infectious diseases", "infectious diseases/viral infections" ]	Dengue Dynamics in Binh Thuan Province, Southern Vietnam: Periodicity, Synchronicity and Climate Variability	journal.pntd.0000747	null	[ [ "Recent estimates indicate that approximately 3 . 5 billion people , about 55% of the world's population , live in countries at risk for dengue infection [1] .", "Dengue ranks among the most important infectious diseases in many countries in the tropics and subtropics .", "Dengue virus ( DENV ) transm...	[ "Dengue is a major global public health problem with increasing incidence and geographic spread .", "The epidemiology is complex with long inter-epidemic intervals and endemic with seasonal fluctuations .", "This study was initiated to investigate dengue transmission dynamics in Binh Thuan province , southern V...	[ "Dengue has become a major international public health problem due to increasing geographic distribution and a transition from epidemic transmission with long inter-epidemic intervals to endemic transmission with seasonal fluctuation .", "Seasonal and multi-annual cycles in dengue incidence vary over time and spa...	2010
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "hst1p/sir2p", "genetic robustness", "duplication", "deacetylase", "repression", "molecular biology" ]	Substitution as a Mechanism for Genetic Robustness: The Duplicated Deacetylases Hst1p and Sir2p in Saccharomyces cerevisiae	journal.pgen.0030126	null	[ [ "The evolutionary role of gene duplication presents a paradox .", "Gene duplication provides a source of new genetic material that is free of selective constraint and can evolve novel functions [1 , 2] , but at the same time , gene duplication provides genetic robustness against deleterious mutations thro...	[ "How duplicate genes provide genetic robustness remains an unresolved question .", "We have examined the duplicated histone deacetylases Sir2p and Hst1p in Saccharomyces cerevisiae and find that these paralogs with non-overlapping functions can provide genetic robustness against null mutations through a substitut...	[ "Gene duplication is an important force in evolution , as it provides a source of new genetic material .", "However , the mechanisms by which duplicated genes are retained and diverge are understudied at the experimental level .", "We have examined a pair of duplicated histone deacetylases Hst1p and Sir2p from ...	2007
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "medicine and health sciences", "microcephaly", "pathology and laboratory medicine", "congenital anomalies", "statistics", "pathogens", "geographical locations", "microbiology", "time series analysis", "viruses", "developmental biology", "mathematics", "rna viruses", "eye diseases", "eye...	Impact evaluation of Zika epidemic on congenital anomalies registration in Brazil: An interrupted time series analysis	journal.pntd.0007721	null	[ [ "Zika is a vector-borne disease that has become an important concern for the global health agenda after the World Health Organization ( WHO ) declared a public health emergency of international concern ( PHEIC ) when it was associated with an epidemic of severe microcephaly cases[1–3] .", "Ever since the ...	[ "This study aimed to assess the impact of the Zika epidemic on the registration of birth defects in Brazil .", "We used an interrupted time series analysis design to identify changes in the trends in the registration of congenital anomalies .", "We obtained monthly data from Brazilian Live Birth Information Sys...	[ "Zika can be characterized as one of the most significant emerging arboviruses .", "The Zika epidemic in Brazil and the subsequent increase in the number of serious brain anomalies , such as microcephaly , has demonstrated the importance of analysing the impact of Zika infection on the rate of congenital anomalie...	2019
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "children", "body weight", "medicine and health sciences", "body fluids", "education", "sociology", "tropical diseases", "geographical locations", "social sciences", "parasitic diseases", "health care", "urine", "age groups", "south africa", "physiological parameters", "obesity", "ne...	The Accuracy of Praziquantel Dose Poles for Mass Treatment of Schistosomiasis in School Girls in KwaZulu-Natal, South Africa	journal.pntd.0004623	null	[ [ "Schistosomiasis remains an important health challenge in poor , rural communities , contributing to significant morbidity and mortality [1 , 2] .", "As a means to control schistosomiasis , the World Health Organization ( WHO ) advocates for regular treatment with praziquantel ( PZQ ) of at-risk populatio...	[ "More than 260 million people live with schistosomiasis and regular mass-treatment should be implemented to prevent morbidity .", "Praziquantel , dosed at 40 milligrams per kilogram bodyweight , is the drug of choice .", "During the last decades the WHO Tablet Pole–which estimates tablet need by height as repre...	[ "Schistosomiasis is an acute and chronic parasitic disease caused by Schistosoma worms , contributing to morbidity and mortality in 261 million people , mainly in poor , rural communities .", "In an effort to control schistosomiasis , the World Health Organization advocates for regular mass treatment to at-risk p...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genetics and genomics/comparative genomics", "genetics and genomics/functional genomics", "plant biology/plant-environment interactions", "genetics and genomics/plant genomes and evolution", "plant biology/plant biochemistry and physiology", "genetics and genomics/plant genetics and gene expression" ]	The Five AhMTP1 Zinc Transporters Undergo Different Evolutionary Fates towards Adaptive Evolution to Zinc Tolerance in Arabidopsis halleri	journal.pgen.1000911	null	[ [ "Adaptation of an organism to a challenging environment entails dramatic modifications in cellular , physiological , and regulatory processes .", "Gene duplications are postulated to be one of the main mechanisms providing raw genetic material for the origin of these adaptive modifications [1] .", "Co...	[ "Gene duplication is a major mechanism facilitating adaptation to changing environments .", "From recent genomic analyses , the acquisition of zinc hypertolerance and hyperaccumulation characters discriminating Arabidopsis halleri from its zinc sensitive/non-accumulator closest relatives Arabidopsis lyrata and Ar...	[ "Arabidopsis halleri has developed the characters of zinc hypertolerance and hyperaccumulation as compared to its close relatives Arabidopsis thaliana and Arabidopsis lyrata .", "Different candidate genes were proposed to account for the appearance of these characters in A . halleri .", "One of them is MTP1 ( M...	2010
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine", "public health and epidemiology", "emergence", "viral transmission and infection", "virology", "emerging viral diseases", "epidemiology", "infectious disease epidemiology", "biology", "evolutionary biology", "microbiology", "evolutionary processes", "viral evolution" ]	Transmission of Equine Influenza Virus during an Outbreak Is Characterized by Frequent Mixed Infections and Loose Transmission Bottlenecks	journal.ppat.1003081	null	[ [ "Studying the evolution of influenza A viruses ( IAVs ) across different scales – from the individual to the global population – is critical for understanding the risk of cross-species transmissions and the potential for emergence of novel pandemic viruses .", "Time-informed phylogenetic approaches have b...	[ "The ability of influenza A viruses ( IAVs ) to cross species barriers and evade host immunity is a major public health concern .", "Studies on the phylodynamics of IAVs across different scales – from the individual to the population – are essential for devising effective measures to predict , prevent or contain ...	[ "Influenza A viruses ( IAVs ) are major pathogens of humans and animals .", "Understanding how IAVs spread and evolve at different scales ( individual , regional , global ) in natural conditions is critical for preventing or managing influenza epidemics .", "A vast body of knowledge has been generated on the ev...	2012
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "cdna libraries", "sequencing techniques", "medicine and health sciences", "methods and resources", "gene regulation", "messenger rna", "cancers and neoplasms", "oncology", "immunoprecipitation", "forms of dna", "dna libraries", "molecular biology techniques", "dna", "rna sequencing", "s...	Refined RIP-seq protocol for epitranscriptome analysis with low input materials	journal.pbio.2006092	null	[ [ "Epitranscriptomics is a functionally relevant change to the transcriptome that depends on biochemical modifications of RNA , and it has emerged as a new layer of post-transcriptional regulation of gene expression [1–3] .", "To date , more than 150 types of internal RNA modifications have been identified ...	[ "N6-Methyladenosine ( m6A ) accounts for approximately 0 . 2% to 0 . 6% of all adenosine in mammalian mRNA , representing the most abundant internal mRNA modifications .", "m6A RNA immunoprecipitation followed by high-throughput sequencing ( MeRIP-seq ) is a powerful technique to map the m6A location transcriptom...	[ "N6-Methyladenosine ( m6A ) is one of the most abundant and conserved mRNA modifications .", "It has been reported to influence multiple steps of RNA life cycle and play an important role in the initiation and progression of human cancers .", "m6A RNA immunoprecipitation followed by high-throughput sequencing (...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "immunology/antigen processing and recognition", "microbiology/immunity to infections", "microbiology/parasitology", "infectious diseases/protozoal infections", "immunology/immunity to infections" ]	Direct Visualization of Peptide/MHC Complexes at the Surface and in the Intracellular Compartments of Cells Infected In Vivo by Leishmania major	journal.ppat.1001154	null	[ [ "The initiation of an adaptive immune response against a pathogen relies on the loading of microbial peptides onto Major Histocompatibility Complex ( MHC ) molecules in Antigen Presenting Cells ( APCs ) and on the recognition of these peptide/MHC complexes by T lymphocytes .", "Therefore , identifying the...	[ "Protozoa and bacteria infect various types of phagocytic cells including macrophages , monocytes , dendritic cells and eosinophils .", "However , it is not clear which of these cells process and present microbial antigens in vivo and in which cellular compartments parasite peptides are loaded onto Major Histocom...	[ "Phagocytosis is a cellular process that allows the engulfment of solid particles such as bacteria or parasites by the cell membrane and leads to the formation of an intracytoplasmic vesicle , the phagosome .", "Cell types that are capable of phagocytosis are called phagocytes and include monocytes , macrophages ...	2010
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "molecular cell biology", "virology", "viral packaging", "biology", "microbiology", "viral replication" ]	Hepatitis C Virus p7 is Critical for Capsid Assembly and Envelopment	journal.ppat.1003355	null	[ [ "Approximately 160 million people are chronically infected with HCV [1] and viral persistence is associated with severe liver diseases such as steatosis , cirrhosis and hepatocellular carcinoma [2] .", "HCV is an enveloped virus with a positive-strand RNA genome that encodes a polyprotein of about 3 , 000...	[ "Hepatitis C virus ( HCV ) p7 is a membrane-associated ion channel protein crucial for virus production .", "To analyze how p7 contributes to this process , we dissected HCV morphogenesis into sub-steps including recruitment of HCV core to lipid droplets ( LD ) , virus capsid assembly , unloading of core protein ...	[ "Viroporins are small hydrophobic viral membrane proteins which oligomerize and modulate membrane properties to facilitate virus propagation .", "Within their membrane environment these proteins can form membrane pores or channels which change the permeability of membranes for ions .", "These properties are kno...	2013
[ "Introduction", "Results/Discussion", "Methods" ]	[ "algorithms", "systems biology", "computer science", "genomics", "computer modeling", "biology", "computational biology", "neuroscience", "genetics and genomics" ]	Molecular Machines in the Synapse: Overlapping Protein Sets Control Distinct Steps in Neurosecretion	journal.pcbi.1002450	null	[ [ "Synapses are complex biological structures , which evolved into highly specialized computational units that play an important role in learning , memory formation and information processing in the brain [1] , [2] , [3] .", "A key process in the synapse is the remarkably fast and precisely timed secretion ...	[ "Activity regulated neurotransmission shapes the computational properties of a neuron and involves the concerted action of many proteins .", "Classical , intuitive working models often assign specific proteins to specific steps in such complex cellular processes , whereas modern systems theories emphasize more in...	[ "Synapses , which are small structures where information is transmitted between neurons , are the functional units of computation in the brain implicated in information processing , learning and memory .", "In the last few years several genes that are expressed in synapses have been linked to brain disorders such...	2012
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "immunology", "immune response", "biology" ]	Evaluation of a Typhoid/Paratyphoid Diagnostic Assay (TPTest) Detecting Anti-Salmonella IgA in Secretions of Peripheral Blood Lymphocytes in Patients in Dhaka, Bangladesh	journal.pntd.0002316	null	[ [ "Salmonella enterica serotype Typhi and Paratyphi A and B are human-restricted pathogens and are the causes of enteric fever .", "Salmonella enterica serotype Typhi ( S . Typhi ) infection causes approximately 20 million cases of enteric ( typhoid ) fever and over 200 , 000 deaths annually [1] .", "Sa...	[ "Rapid and reliable diagnostic assays for enteric ( typhoid and paratyphoid ) fever are urgently needed .", "We report the characterization of novel approach utilizing lymphocyte secretions , for diagnosing patients with enteric fever by the TPTest procedure .", "TPTest detects Salmonella-specific IgA responses...	[ "Salmonella enterica serotype Typhi and Paratyphi A are responsible for typhoid and paratyphoid fever respectively and the disease caused is known generally as enteric fever .", "Appropriate and early diagnosis of the disease is important for initiation of treatment of the patient with a suitable antibiotic .", ...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "bacteriology", "macromolecular assemblies", "microbiology", "host-pathogen interaction", "dna transcription", "escherichia coli", "epigenetics", "bacterial pathogens", "gene expression", "microbial pathogens", "biology", "dna modification", "biochemistry", "bacterial physiology", "genet...	An Epigenetic Switch Involving Overlapping Fur and DNA Methylation Optimizes Expression of a Type VI Secretion Gene Cluster	journal.pgen.1002205	null	[ [ "Type VI secretion systems ( T6SS ) are macromolecular assemblies encoded within the genome of most Gram negative bacteria [1]–[3] .", "They are composed of at least 13 subunits , called core components , which are believed to form a trans-envelope apparatus from the cytoplasm to the outside of the cell [...	[ "Type VI secretion systems ( T6SS ) are macromolecular machines of the cell envelope of Gram-negative bacteria responsible for bacterial killing and/or virulence towards different host cells .", "Here , we characterized the regulatory mechanism underlying expression of the enteroagregative Escherichia coli sci1 T...	[ "DNA methylation plays an important role in the regulation of genes involved in assembly of cell surface adhesins or appendages .", "Methylation at a GATC motif by the Dam methylase influences binding of transcriptional regulators , leading to variation in the gene expression pattern .", "In several cases , thi...	2011
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Systematic Dissection of the Sequence Determinants of Gene 3’ End Mediated Expression Control	journal.pgen.1005147	null	[ [ "The genomic region downstream to the open reading frame ( 3’ end region ) is commonly considered to affect expression at the post-transcriptional level through regulatory sequences that reside within the mRNA 3’ un-translated region ( 3’ UTR ) affecting mRNA stability and translation[1–3] .", "In additio...	[ "The 3’end genomic region encodes a wide range of regulatory process including mRNA stability , 3’ end processing and translation .", "Here , we systematically investigate the sequence determinants of 3’ end mediated expression control by measuring the effect of 13 , 000 designed 3’ end sequence variants on const...	[ "We present a large-scale experimental investigation into sequence determinants of 3’ end mediated gene expression regulation , by measuring 13 , 000 designed 3’ end sequences .", "While 3’ end sequences contribute to expression differences through a variety of mechanisms including mRNA stability and regulation o...	2015
[ "Introduction", "Results", "Discussion" ]	[ "medicine", "plant biology", "cardiovascular anatomy", "trees", "anatomy and physiology", "geometry", "neuroscience", "marine biology", "plant science", "mathematics", "computational neuroscience", "plants", "corals", "theoretical biology", "marine and aquatic sciences", "biology", "...	Geometric Theory Predicts Bifurcations in Minimal Wiring Cost Trees in Biology Are Flat	journal.pcbi.1002474	null	[ [ "Bifurcations are observed widely in nature [1] , such as in dendrites and axons of neurons [2] , plants [3] , rivers , capillaries [4] , [5] , [6] , bronchi and tracheal systems [7] , [8] , [9] and octo- and scleractinian corals [10] , [11] .", "Most studies have focused on characterizing tree geometry [...	[ "The complex three-dimensional shapes of tree-like structures in biology are constrained by optimization principles , but the actual costs being minimized can be difficult to discern .", "We show that despite quite variable morphologies and functions , bifurcations in the scleractinian coral Madracis and in many ...	[ "Morphology is constrained by function and vice-versa .", "Often , intricate morphology can be explained by optimization of a cost .", "However , in biology , the exact form of the cost function is seldom clear .", "Previously , for many different natural trees authors have reported that most bifurcations are...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "alternative splicing", "biochemistry", "rna", "developmental biology", "rna processing", "cell biology", "gene regulatory networks", "gene expression", "genetics", "gene regulation", "biology and life sciences", "cell differentiation", "computational biology", "molecular cell biology", ...	Regulation of mRNA Abundance by Polypyrimidine Tract-Binding Protein-Controlled Alternate 5′ Splice Site Choice	journal.pgen.1004771	null	[ [ "Eukaryotes rely on post-transcriptional control of their gene expression programs to a remarkable extent .", "A compelling example of this trend is the ability of many mammalian transcripts to undergo alternative splicing ( AS ) regulated by interplay between RNA-encoded cis-elements and trans-acting fac...	[ "Alternative splicing ( AS ) provides a potent mechanism for increasing protein diversity and modulating gene expression levels .", "How alternate splice sites are selected by the splicing machinery and how AS is integrated into gene regulation networks remain important questions of eukaryotic biology .", "Here...	[ "Mammalian gene expression is extensively controlled at the post-transcriptional level and understanding of the underlying mechanisms can provide important biomedical insights .", "Here we identified a number of novel alternate splicing ( AS ) events where the choice between competing splice sites ( ss ) is regul...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Spatial Heterogeneity in Drug Concentrations Can Facilitate the Emergence of Resistance to Cancer Therapy	journal.pcbi.1004142	null	[ [ "Cancer is a common genetic disease that results from accumulated ( epi- ) genetic changes in tumor cells [1–5] .", "Targeted cancer therapy is currently an area of active research [6] , and is under rapid development [7–10] .", "Targeted agents can send cancer into remission , but the response is oft...	[ "Acquired resistance is one of the major barriers to successful cancer therapy .", "The development of resistance is commonly attributed to genetic heterogeneity .", "However , heterogeneity of drug penetration of the tumor microenvironment both on the microscopic level within solid tumors as well as on the mac...	[ "Failure of cancer therapy is commonly attributed to the outgrowth of pre-existing resistant mutants already present prior to treatment , yet there is increasing evidence that the tumor microenvironment influences cell sensitivity to drugs and thus mediates the evolution of resistance during treatment .", "Here ,...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	TRIM30α Is a Negative-Feedback Regulator of the Intracellular DNA and DNA Virus-Triggered Response by Targeting STING	journal.ppat.1005012	null	[ [ "The innate immune system is the first barrier of defense against pathogens , and a variety of germline-encoded pattern recognition receptors ( PRRs ) , including Toll-like receptors ( TLRs ) , C-type lectin receptors ( CLRs ) , RIG-I-like receptors ( RLRs ) and NOD-like receptors ( NLRs ) , have evolved in t...	[ "Uncontrolled immune responses to intracellular DNA have been shown to induce autoimmune diseases .", "Homeostasis regulation of immune responses to cytosolic DNA is critical for limiting the risk of autoimmunity and survival of the host .", "Here , we report that the E3 ubiquitin ligase tripartite motif protei...	[ "Negative-feedback regulation is a broad and pivotal biological event to maintain the homeostasis of the host .", "Viral DNA species derived from DNA viruses or retroviruses can activate STING signaling to produce pro-inflammatory cytokines and type I interferon , which further recruit immune cells or induce inte...	2015
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "genomics", "genetic mutation", "genome evolution", "genomic evolution", "genetics", "biology", "evolutionary biology", "comparative genomics", "evolutionary genetics", "genetics and genomics" ]	Recombination Drives Vertebrate Genome Contraction	journal.pgen.1002680	null	[ [ "A link between the dynamics of intron evolution and recombination has been found in form of a negative relationship between recombination rate and intron size , seen in Drosophila [1] , [2] , humans [2] and chicken [3] .", "Two hypotheses based on natural selection have been proposed to explain this rela...	[ "Selective and/or neutral processes may govern variation in DNA content and , ultimately , genome size .", "The observation in several organisms of a negative correlation between recombination rate and intron size could be compatible with a neutral model in which recombination is mutagenic for length changes .", ...	[ "One major implication from genetic work done several decades ago is that the genome contains a lot of sequences that do not constitute genes or other functional elements .", "The total amount of DNA—the genome size—is thus not necessarily an indicator of DNA complexity or organismal complexity , an observation o...	2012
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "invertebrates", "medicine and health sciences", "rna interference", "viral transmission and infection", "microbiology", "animals", "salmonellosis", "animal models", "bacterial diseases", "drosophila melanogaster", "model organisms", "experimental organism systems", "epigenetics", "insect ...	p38b and JAK-STAT signaling protect against Invertebrate iridescent virus 6 infection in Drosophila	journal.ppat.1007020	null	[ [ "Like all multicellular organisms , insects face a constant threat of infection from a wide array of microorganisms , including viral , bacterial , and fungal pathogens .", "Insects combat these infections with both static and inducible defenses , including a chitinous exoskeleton , circulating phagocytes...	[ "The fruit fly Drosophila melanogaster is a powerful model system for the study of innate immunity in vector insects as well as mammals .", "For vector insects , it is particularly important to understand all aspects of their antiviral immune defenses , which could eventually be harnessed to control the transmiss...	[ "Mosquitoes and other biting insects transmit many harmful pathogens to humans , including parasites and viruses .", "In order to better protect humans from these diseases , we must gain a more complete understanding of how insects successfully—or unsuccessfully—combat these infections .", "While we know a grea...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	The RNAPII-CTD Maintains Genome Integrity through Inhibition of Retrotransposon Gene Expression and Transposition	journal.pgen.1005608	null	[ [ "RNA polymerase II ( RNAPII ) is the enzyme responsible for the transcription of a diverse set of genomic loci , including most protein coding genes , many non-coding genes , and retrotransposons .", "Rpb1 , the largest subunit of RNAPII , contains a unique C-terminal domain ( CTD ) that is composed of he...	[ "RNA polymerase II ( RNAPII ) contains a unique C-terminal domain that is composed of heptapeptide repeats and which plays important regulatory roles during gene expression .", "RNAPII is responsible for the transcription of most protein-coding genes , a subset of non-coding genes , and retrotransposons .", "Re...	[ "RNA Polymerase II ( RNAPII ) is the enzyme responsible for the transcription of all protein-coding genes , many non-coding genes and retrotransposons .", "RNAPII has a unique C-terminal domain ( CTD ) that is composed of repeats of a seven amino acid sequence and is conserved across species .", "The CTD functi...	2015
[ "Introduction", "Results and Discussion", "Materials and Methods" ]	[]	Germline Progenitors Escape the Widespread Phenomenon of Homolog Pairing during Drosophila Development	journal.pgen.1004013	null	[ [ "During meiosis , the germline nucleus undergoes extensive reorganization to accurately align homologous chromosomes along their entire length , enabling them to recombine and ultimately segregate from one another .", "Outside of the germline , however , homolog pairing , if it occurs at all , is usually ...	[ "Homolog pairing , which plays a critical role in meiosis , poses a potential risk if it occurs in inappropriate tissues or between nonallelic sites , as it can lead to changes in gene expression , chromosome entanglements , and loss-of-heterozygosity due to mitotic recombination .", "This is particularly true in...	[ "Meiosis is a specialized cell division that permits the transmission of genetic material to following generations .", "A pivotal step for this process is the pairing and recombination between homologous chromosomes .", "In the case of Drosophila , which supports organismal-wide homolog pairing throughout devel...	2013
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "genomics", "gene expression", "genetics", "population genetics", "biology", "human genetics", "genetics and genomics" ]	Patterns of Cis Regulatory Variation in Diverse Human Populations	journal.pgen.1002639	null	[ [ "One of the fundamental questions of human population genetics is the extent to which human populations from around the world differ from one another .", "Population differentiation can be seen from the perspective of history , where neutral DNA sequence variation is used to reconstruct the relationships ...	[ "The genetic basis of gene expression variation has long been studied with the aim to understand the landscape of regulatory variants , but also more recently to assist in the interpretation and elucidation of disease signals .", "To date , many studies have looked in specific tissues and population-based samples...	[ "Variation among individuals in the degree to which genes are expressed ( i . e . turned on or off ) is a characteristic exhibited by all species , and studies have identified regions of the genome harboring genetic variation affecting gene expression levels .", "To assess the degree of human inter-population var...	2012
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "invertebrates", "medicine and health sciences", "rna interference", "pathology and laboratory medicine", "caenorhabditis", "gene regulation", "pathogens", "regulatory proteins", "immunology", "microbiology", "dna-binding proteins", "animals", "pseudomonas aeruginosa", "animal models", "...	A conserved mitochondrial surveillance pathway is required for defense against Pseudomonas aeruginosa	journal.pgen.1006876	null	[ [ "All living organisms encounter unfavorable stimuli , including both abiotic stressors and pathogens that interfere with their fitness and survival .", "To recover their homeostatic balance , they activate conserved defense networks .", "These include classical immune ( innate and adaptive ) pathways ...	[ "All living organisms exist in a precarious state of homeostasis that requires constant maintenance .", "A wide variety of stresses , including hypoxia , heat , and infection by pathogens perpetually threaten to imbalance this state .", "Organisms use a battery of defenses to mitigate damage and restore normal ...	[ "It is increasingly clear that living organisms surveil their cellular structures and physiology to gain early warning about the presence and activity of pathogens or abiotic threats ( like hypoxia , hyper- or hypothermia , oxidative damage , etc . ) .", "Upon recognizing dysfunction , host defense networks are e...	2017
[ "Introduction", "Materials and methods", "Results", "Discussion" ]	[ "united states", "dengue virus", "medicine and health sciences", "pathology and laboratory medicine", "infectious disease epidemiology", "pathogens", "geographical locations", "microbiology", "north america", "viruses", "texas", "probability distribution", "mathematics", "rna viruses", "...	Downgrading disease transmission risk estimates using terminal importations	journal.pntd.0007395	null	[ [ "The explosive emergence of Zika virus ( ZIKV ) in the Americas in 2016 caught the global health community by surprise .", "Officials scrambled not only to control the disease at its source but also to anticipate and rapidly contain global transmission via infected travelers [1] .", "The rate at which...	[ "As emerging and re-emerging infectious arboviruses like dengue , chikungunya , and Zika threaten new populations worldwide , officials scramble to assess local severity and transmissibility , with little to no epidemiological history to draw upon .", "Indirect estimates of risk from vector habitat suitability ma...	[ "When novel infectious diseases like chikungunya or Zika emerge and threaten global spread , public health officials worldwide must assess the risk for local introductions and outbreaks .", "These assessments are made in anticipation of local case data , and officials must draw upon historic evidence from similar...	2019
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "medicine and health sciences", "solomon islands", "pruritus", "pathology and laboratory medicine", "education", "medical personnel", "sociology", "tropical diseases", "geographical locations", "social sciences", "parasitic diseases", "neuroscience", "health care", "health care providers",...	The diagnosis of scabies by non-expert examiners: A study of diagnostic accuracy	journal.pntd.0007635	null	[ [ "Human scabies is a parasitic skin condition caused by infestation with the mite Sarcoptes scabiei var .", "hominis .", "Scabies is a significant public health problem , affecting more than 200 million people globally , with the highest burden in low-resource settings in tropical and subtropical regio...	[ "Although scabies is estimated to be one of the most common skin conditions globally , prevalence data is not available in most settings .", "Disease mapping is required to develop and monitor successful control programs .", "Non-expert health workers are likely to play an important role in scabies mapping acti...	[ "Scabies is a parasitic infection that leads to significant morbidity worldwide .", "Mapping of scabies prevalence would improve the understanding of the true burden of disease and the need for control programs in specific countries and regions .", "The diagnosis of scabies in low resource settings , where the ...	2019
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biochemistry", "viral replication", "dna replication", "nucleic acids", "virology", "viral nucleic acid", "viruses and cancer", "dna", "biology", "dna recombination", "dna repair", "microbiology" ]	ATM and ATR Activities Maintain Replication Fork Integrity during SV40 Chromatin Replication	journal.ppat.1003283	null	[ [ "Faithful duplication of the genome is vital for cell proliferation .", "In metazoans , the consequences of inaccurate genome replication include cell death , premature aging syndromes , neuro-degeneration disorders , and susceptibility to cancer [1] , [2] .", "The DNA damage signaling protein kinases...	[ "Mutation of DNA damage checkpoint signaling kinases ataxia telangiectasia-mutated ( ATM ) or ATM- and Rad3-related ( ATR ) results in genomic instability disorders .", "However , it is not well understood how the instability observed in these syndromes relates to DNA replication/repair defects and failed checkpo...	[ "All cells have evolved pathways to maintain the integrity of the genetic information stored in their chromosomes .", "Endogenous and exogenous agents induce mutations and other damage in DNA , most frequently during DNA replication .", "Such DNA damage is under surveillance by a complex network of proteins tha...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "prokaryotic models", "plant science", "model organisms", "plant and algal models", "plant microbiology", "genetic screens", "gene identification and analysis", "genetics", "synthetic biology", "biology and life sciences", "microbiology", "computational biology", "research and analysis metho...	A Synthetic Community Approach Reveals Plant Genotypes Affecting the Phyllosphere Microbiota	journal.pgen.1004283	null	[ [ "The aerial parts of the plants , which are dominated by leaves , represent one of the largest terrestrial habitats for microorganisms [1]–[3] .", "This habitat , called the phyllosphere , is occupied by a diverse community of bacteria and fungi , which is important for plant health and growth [1]–[3] .",...	[ "The identity of plant host genetic factors controlling the composition of the plant microbiota and the extent to which plant genes affect associated microbial populations is currently unknown .", "Here , we use a candidate gene approach to investigate host effects on the phyllosphere community composition and ab...	[ "The leaves of plants are inhabited by a diverse community of microorganisms .", "These leaf inhabitants influence their hosts with respect to growth and resistance to abiotic and biotic stresses .", "Recent studies revealed that the bacterial communities associated with leaves undergo selection , resulting in ...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Spatiotemporal Analysis of Hepatitis C Virus Infection	journal.ppat.1004758	null	[ [ "Hepatitis C virus ( HCV ) belongs to the Flaviviridae family of enveloped , positive-stranded RNA viruses .", "Following productive entry into hepatocytes , the 9 . 6 kb HCV genome is translated to produce a single large polyprotein [1] , which is cleaved by viral and host proteases to yield ten distinct...	[ "Hepatitis C virus ( HCV ) entry , translation , replication , and assembly occur with defined kinetics in distinct subcellular compartments .", "It is unclear how HCV spatially and temporally regulates these events within the host cell to coordinate its infection .", "We have developed a single molecule RNA de...	[ "The stages of the viral life cycle are spatially and temporally regulated to coordinate the infectious process in a way that maximizes successful replication and spread .", "In this study , we used RNA in situ hybridization ( ISH ) to simultaneously detect HCV ( + ) and ( − ) RNAs and analyze the kinetics of HCV...	2015
[ "Introduction", "Results and discussion", "Materials and methods" ]	[ "engineering and technology", "bibliometrics", "sexual and gender issues", "sociology", "social sciences", "social media", "scientists", "network analysis", "social networks", "social communication", "science and technology workforce", "research and analysis methods", "computer and informati...	Women are underrepresented in computational biology: An analysis of the scholarly literature in biology, computer science and computational biology	journal.pcbi.1005134	null	[ [ "There is ample literature on the underrepresentation of women in STEM fields and the biases contributing to it .", "Those biases , though often subtle , are pervasive in several ways: they are often held and perpetuated by both men and women , and they are apparent across all aspects of academic and scie...	[ "While women are generally underrepresented in STEM fields , there are noticeable differences between fields .", "For instance , the gender ratio in biology is more balanced than in computer science .", "We were interested in how this difference is reflected in the interdisciplinary field of computational/quant...	[ "There are fewer women than men working in Science , Technology , Engineering and Mathematics ( STEM ) .", "However , some fields within STEM are more gender-balanced than others .", "For instance , biology has a relatively high proportion of women , whereas there are few women in computer science .", "But wh...	2017
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "blood cells", "invertebrates", "medicine and health sciences", "immune cells", "immunology", "parasitic diseases", "animals", "protein expression", "gastropods", "peptide libraries", "molecular biology techniques", "snails", "research and analysis methods", "immune system proteins", "wh...	Differential Protein Expression in the Hemolymph of Bithynia siamensis goniomphalos Infected with Opisthorchis viverrini	journal.pntd.0005104	null	[ [ "Opisthorchis viverrini affects over 10 million people in different countries of Greater Mekong sub-region including Thailand , southern Vietnam , Lao PDR and Cambodia [1] .", "In addition to the problems associated with infection in the definitive human host , chronic inflammation caused by this parasite...	[ "Bithynia siamensis goniomphalos is a freshwater snail that serves as the first intermediate host of the human liver fluke Opisthorchis viverrini .", "This parasite is a major public health problem in different countries throughout the Greater Mekong sub-region ( Thailand , southern Vietnam , Lao PDR and Cambodia...	[ "The control of snails involved in transmission of trematodes plays a key role in the fight against these parasitic diseases .", "While some snails have been studied thoroughly , only few genomic and proteomic studies have focused on Bithynia siamensis goniomphalos , the snail intermediate host for Opisthorchis v...	2016
[ "Introduction", "Method", "Results", "Discussion" ]	[ "genome-wide association studies", "medicine and health sciences", "body fluids", "quantitative trait loci", "applied mathematics", "simulation and modeling", "algorithms", "mathematics", "genome analysis", "lipid analysis", "research and analysis methods", "genomic signal processing", "mole...	Integrating molecular QTL data into genome-wide genetic association analysis: Probabilistic assessment of enrichment and colocalization	journal.pgen.1006646	null	[ [ "Genome-wide association studies ( GWAS ) have successfully identified many genomic loci that impact complex diseases and complex traits .", "Nevertheless , the molecular pathways that connect genetic variants to complex traits are still poorly understood , primarily because a considerable proportion of t...	[ "We propose a novel statistical framework for integrating the result from molecular quantitative trait loci ( QTL ) mapping into genome-wide genetic association analysis of complex traits , with the primary objectives of quantitatively assessing the enrichment of the molecular QTLs in complex trait-associated genet...	[ "Genome-wide association studies ( GWAS ) have been tremendously successful in identifying genetic variants that impact complex diseases .", "However , the roles of such studies in disease etiology remain poorly understood , primarily because a large proportion of the GWAS findings are located in the non-coding r...	2017
[ "Introduction", "Results and Discussion", "Methods" ]	[]	Functional Basis of Microorganism Classification	journal.pcbi.1004472	null	[ [ "In biology , the field of taxonomy is tasked with describing , naming , and classifying organisms; the latter according to some metrics of similarity .", "Van Leeuwenhoek’s observation of microscopic organisms launched centuries of classification based on morphology and physiology [1] .", "Since the ...	[ "Correctly identifying nearest “neighbors” of a given microorganism is important in industrial and clinical applications where close relationships imply similar treatment .", "Microbial classification based on similarity of physiological and genetic organism traits ( polyphasic similarity ) is experimentally diff...	[ "Taxonomic classification of microorganisms according to similarity is important for industrial and clinical applications where close relationships imply similar uses and/or treatments .", "Current microbial taxonomy is phylogeny-guided , i . e . , the organisms are grouped based on their evolutionary relationshi...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine", "immune cells", "cytokines", "immunology", "microbiology", "hepatitis", "hepatitis c", "infectious diseases", "inflammation", "viral immune evasion", "biology", "pathogenesis", "immune response", "immune system", "immunopathology", "monocytes", "immunity", "virology", ...	IL-1β Production through the NLRP3 Inflammasome by Hepatic Macrophages Links Hepatitis C Virus Infection with Liver Inflammation and Disease	journal.ppat.1003330	null	[ [ "Chronic inflammation is a major contributor to disease and is the basis of hepatitis C virus ( HCV ) -mediated liver damage .", "HCV is a hepatotropic , enveloped virus that carries a single-stranded positive-sense RNA genome , and chronically infects nearly 3% of the world's population [1] .", "HCV ...	[ "Chronic hepatitis C virus ( HCV ) infection is a leading cause of liver disease .", "Liver inflammation underlies infection-induced fibrosis , cirrhosis and liver cancer but the processes that promote hepatic inflammation by HCV are not defined .", "We provide a systems biology analysis with multiple lines of ...	[ "Hepatitis C virus ( HCV ) causes chronic infection of the liver and is a leading cause of liver inflammation , cirrhosis and liver cancer in nearly 200 million people worldwide .", "Importantly , hepatic inflammation during chronic HCV infection is considered to be the primary catalyst for progressive liver dise...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "flow cytometry", "engineering and technology", "enzymes", "enzymology", "light microscopy", "mutation", "microscopy", "materials science", "industrial engineering", "quality control", "chaperone proteins", "ligases", "research and analysis methods", "missense mutation", "proteins", "f...	Prefoldin Promotes Proteasomal Degradation of Cytosolic Proteins with Missense Mutations by Maintaining Substrate Solubility	journal.pgen.1006184	null	[ [ "The protein homeostasis network encompasses systems required by the cell to generate and maintain the correct levels , conformational state , and distribution of its proteome [1] .", "Misfolded proteins threaten this balance by triggering loss of function phenotypes , diverting resources away from produc...	[ "Misfolded proteins challenge the ability of cells to maintain protein homeostasis and can accumulate into toxic protein aggregates .", "As a consequence , cells have adopted a number of protein quality control pathways to prevent protein aggregation , promote protein folding , and target terminally misfolded pro...	[ "Most polypeptides by necessity must fold into three-dimensional structures in order to become functional proteins .", "Misfolding , either during or subsequent to initial folding , can result in toxic protein aggregation .", "As a consequence , cells have adopted a number of protein quality control pathways to...	2016
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "plant anatomy", "stem anatomy", "internodes", "brassica", "hormones", "plant science", "model organisms", "rice", "plant hormones", "membrane receptor signaling", "experimental organism systems", "hormone receptor signaling", "plants", "arabidopsis thaliana", "research and analysis meth...	The pea branching RMS2 gene encodes the PsAFB4/5 auxin receptor and is involved in an auxin-strigolactone regulation loop	journal.pgen.1007089	null	[ [ "Feedback signals are an essential component of dynamic biological systems to enable robustness and plasticity in development .", "While negative feedback can attenuate signals , positive feedback can amplify or prolong them [1 , 2] .", "Several positive and negative feedback mechanisms are likely inv...	[ "Strigolactones ( SLs ) are well known for their role in repressing shoot branching .", "In pea , increased transcript levels of SL biosynthesis genes are observed in stems of highly branched SL deficient ( ramosus1 ( rms1 ) and rms5 ) and SL response ( rms3 and rms4 ) mutants indicative of negative feedback cont...	[ "Plant shoot branching results from the precise regulation of bud growth versus dormancy .", "Positive and negative feedback mechanisms are likely involved in the dynamic control of this highly plastic trait .", "Strigolactones , the most recently discovered class of plant hormones , play a key role in controll...	2017
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "bacteriology", "cell motility", "medicine and health sciences", "pathology and laboratory medicine", "pathogens", "bacillus", "microbiology", "light microscopy", "flagellar motility", "biomechanics", "biological locomotion", "prokaryotic models", "model organisms", "microscopy", "cellul...	Genetic Analysis of Collective Motility of Paenibacillus sp. NAIST15-1	journal.pgen.1006387	null	[ [ "Migration is a critical mechanism by which bacteria survive and thrive in a particular environment .", "Motility enables bacteria to search for nutrients , avoid toxic compounds , and seek out favorable environmental niches that they can then colonize .", "The organelles responsible for mobility , fl...	[ "Bacteria have developed various motility mechanisms to adapt to a variety of solid surfaces .", "A rhizosphere isolate , Paenibacillus sp .", "NAIST15-1 , exhibited unusual motility behavior .", "When spotted onto 1 . 5% agar media , Paenibacillus sp .", "formed many colonies , each of which moved around a...	[ "Motility is crucial as it enables bacteria to seek out and colonize suitable environments .", "Here , a new isolate from the rhizosphere , Paenibacillus sp .", ", exhibited unusual motility behavior .", "When spotted on low wet , hard agar media , the bacterium formed many colonies , each of which moved arou...	2016
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "public health and epidemiology/infectious diseases" ]	The Costs and Cost-Effectiveness of Mass Treatment for Intestinal Nematode Worm Infections Using Different Treatment Thresholds	journal.pntd.0000402	null	[ [ "In 2008 the Copenhagen Consensus ranked five nutritional interventions among the top ten of more than 40 proposals to answer the question: what would be the best ways of advancing human welfare globally ?", "[1] Deworming and other nutrition programmes in school were ranked as the sixth best intervention...	[ "It is estimated that almost a half of all of people living in developing countries today are infected with roundworms , hookworms , or whipworms or combinations of these types of intestinal nematode worms .", "They can all be treated using safe , effective , and inexpensive single-dose generic drugs costing as l...	[ "Almost one in every two people in the developing world is infected with one or more types of intestinal nematode worms .", "When fewer than 50% of people are infected , most carry only a few worms; but when more than 50% are infected , the number carrying moderate to heavy numbers increases markedly , as does th...	2009
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine", "infectious diseases", "biology", "microbiology" ]	Identification of Alternatively Translated Tetherin Isoforms with Differing Antiviral and Signaling Activities	journal.ppat.1002931	null	[ [ "Tetherin ( BST-2/CD317/HM1 . 24 ) is an interferon ( IFN ) induced , type II transmembrane glycoprotein which has been shown to function as an intrinsic antiviral factor that restricts release of a broad range of enveloped viruses , including members of the arenavirus [1] , [2] , filovirus [2] , [3] , gamma-...	[ "Tetherin ( BST-2/CD317/HM1 . 24 ) is an IFN induced transmembrane protein that restricts release of a broad range of enveloped viruses .", "Important features required for Tetherin activity and regulation reside within the cytoplasmic domain .", "Here we demonstrate that two isoforms , derived by alternative t...	[ "Regulation of innate immunity is critical to maintain a balance between control of a perceived threat and immunopathology .", "The interferon induced cellular factor Tetherin has been shown to restrict budding of a broad range of enveloped viruses including the human immunodeficiency virus .", "Though Tetherin...	2012
[ "Introduction", "Methods", "Results", "Discussion" ]	[]	Rapid Emergence of Multidrug Resistant, H58-Lineage Salmonella Typhi in Blantyre, Malawi	journal.pntd.0003748	null	[ [ "Typhoid fever , caused by Salmonella enterica serovar Typhi remains one of the most important infectious diseases globally , responsible for an estimated 26 . 9 million infections and 269 , 000 deaths in 2010 [1] .", "The accuracy of this estimate in sub-Saharan Africa ( SSA ) is limited by the paucity o...	[ "Between 1998 and 2010 , S . Typhi was an uncommon cause of bloodstream infection ( BSI ) in Blantyre , Malawi and it was usually susceptible to first-line antimicrobial therapy .", "In 2011 an increase in a multidrug resistant ( MDR ) strain was detected through routine bacteriological surveillance conducted at ...	[ "Typhoid fever is a major cause of disease and death around the world , particularly in resource limited settings , although reports suggest that until recently it has been much less prominent in sub-Saharan Africa ( SSA ) than Asia .", "Estimates of the precise burden of this disease are , however , difficult , ...	2015
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "genome-wide association studies", "statistics", "metaanalysis", "metabolomics", "mathematics", "metabolites", "genome analysis", "molecular biology techniques", "information technology", "data processing", "discrete mathematics", "combinatorics", "research and analysis methods", "cell lab...	PAIRUP-MS: Pathway analysis and imputation to relate unknowns in profiles from mass spectrometry-based metabolite data	journal.pcbi.1006734	null	[ [ "Metabolomics is a powerful systematic approach for studying circulating molecules in biological samples [1 , 2] .", "Profiling technologies such as nuclear magnetic resonance ( NMR ) spectroscopy and liquid or gas chromatography followed by mass spectrometry ( LC-MS or GC-MS ) have been used to discover ...	[ "Metabolomics is a powerful approach for discovering biomarkers and for characterizing the biochemical consequences of genetic variation .", "While untargeted metabolite profiling can measure thousands of signals in a single experiment , many biologically meaningful signals cannot be readily identified as known m...	[ "Untargeted metabolomics can systematically profile thousands of metabolite signals in biological samples and is an increasingly popular approach for discovering biomarkers and predictors for human traits and diseases .", "However , currently , a significant portion of the measured signals cannot be identified as...	2019
[ "Introduction", "Methods", "Results", "Discussion" ]	[]	A Multiscale Model Evaluates Screening for Neoplasia in Barrett’s Esophagus	journal.pcbi.1004272	null	[ [ "The incidence of esophageal adenocarcinoma ( EAC ) has increased dramatically over the past few decades in the US and other Western countries , prompting numerous epidemiological and clinical studies to characterize etiologic , genetic , and environmental factors that may contribute to this alarming trend [1...	[ "Barrett’s esophagus ( BE ) patients are routinely screened for high grade dysplasia ( HGD ) and esophageal adenocarcinoma ( EAC ) through endoscopic screening , during which multiple esophageal tissue samples are removed for histological analysis .", "We propose a computational method called the multistage clona...	[ "Endoscopic screening for detecting cancer and cancer precursors in Barrett’s esophagus ( BE ) is currently informed by repeated systematic biopsying of the metaplastic BE tissue .", "Here we present a comprehensive multiscale model of the natural history of esophageal adenocarcinoma ( EAC ) , which describes the...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Genome-Wide Identification of the Target Genes of AP2-O, a Plasmodium AP2-Family Transcription Factor	journal.ppat.1004905	null	[ [ "Malarial parasites require two host animals during their life cycle and undergo multiple developmental changes in each host .", "According to these changes in the life cycle , parasites remarkably alter their repertoire of gene expression [1] .", "However , the corresponding regulatory mechanisms of ...	[ "Stage-specific transcription is a fundamental biological process in the life cycle of the Plasmodium parasite .", "Proteins containing the AP2 DNA-binding domain are responsible for stage-specific transcriptional regulation and belong to the only known family of transcription factors in Plasmodium parasites .", ...	[ "Although malarial parasites have a complex life cycle , they harbor only 30 transcription factors in their genome .", "The majority of these transcription factors belong to a single family referred to as the AP2 family .", "Our previous study suggested that stage-specific AP2 family transcription factors have ...	2015
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "allosteric regulation", "biochemistry", "computational chemistry", "molecular dynamics", "proteins", "protein folding", "enzyme regulation", "protein structure", "protein domains", "biology and life sciences", "chemistry", "enzymology", "computational biology", "physical sciences", "enz...	In the Multi-domain Protein Adenylate Kinase, Domain Insertion Facilitates Cooperative Folding while Accommodating Function at Domain Interfaces	journal.pcbi.1003938	null	[ [ "The presence of multiple domains in proteins can lead to interactions between partially folded domains and in turn to increased misfolding and aggregation [1] .", "Nevertheless , several multi-domain proteins fold reversibly in vitro [2] , [3] .", "Cooperative folding , the all or nothing folding of ...	[ "Having multiple domains in proteins can lead to partial folding and increased aggregation .", "Folding cooperativity , the all or nothing folding of a protein , can reduce this aggregation propensity .", "In agreement with bulk experiments , a coarse-grained structure-based model of the three-domain protein , ...	[ "Most individual protein domains fold in an all or nothing fashion .", "This cooperative folding is important because it reduces the existence of partially folded proteins which can stick to each other and create disease causing aggregates .", "However , numerous proteins have multiple domains , independent uni...	2014
[ "Introduction", "Methods", "Results", "Discussion" ]	[]	Vaccination with Leishmania infantum Acidic Ribosomal P0 but Not with Nucleosomal Histones Proteins Controls Leishmania infantum Infection in Hamsters	journal.pntd.0003490	null	[ [ "Leishmaniasis is a parasitic disease caused by protozoan from the genus Leishmania transmitted by the bite of infected sand flies .", "Leishmaniasis is one of the six major tropical diseases targeted by the World Health Organization [1] .", "The disease has a broad spectrum of clinical manifestations...	[ "Several intracellular Leishmania antigens have been identified in order to find a potential vaccine capable of conferring long lasting protection against Leishmania infection .", "Histones and Acid Ribosomal proteins are already known to induce an effective immune response and have successfully been tested in th...	[ "Visceral leishmaniasis caused by Leishmania infantum is the most severe form of leishmaniasis .", "The disease is fatal if not treated and there is no vaccine available for human use .", "In the search for potential antigens , the protective ability of conserved parasite protein families such as L . infantum h...	2015
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "medicine and health sciences", "tropical diseases", "social sciences", "parasitic diseases", "anemia", "health care", "bacterial diseases", "eye diseases", "neglected tropical diseases", "onchocerciasis", "public and occupational health", "infectious diseases", "health economics", "econom...	The Socioeconomic Benefit to Individuals of Achieving the 2020 Targets for Five Preventive Chemotherapy Neglected Tropical Diseases	journal.pntd.0005289	null	[ [ "Neglected tropical diseases ( NTDs ) are a group of debilitating infectious diseases that can result in death , but are more often associated with chronic , disabling and disfiguring morbidity [1] .", "Most of them affect forgotten people , with little political or financial capital , living in slums or ...	[ "Lymphatic filariasis ( LF ) , onchocerciasis , schistosomiasis , soil-transmitted helminths ( STH ) and trachoma represent the five most prevalent neglected tropical diseases ( NTDs ) .", "They can be controlled or eliminated by means of safe and cost-effective interventions delivered through programs of Mass Dr...	[ "The five most prevalent neglected tropical diseases ( NTDs ) are lymphatic filariasis ( LF ) , onchocerciasis , schistosomiasis , soil-transmitted helminths ( STH ) and trachoma .", "They can be controlled or eliminated by means of safe and cost-effective interventions delivered through programs of Mass Drug Adm...	2017
[ "Introduction", "Methods", "Results", "Discussion" ]	[]	Efficacy of Electrocuting Devices to Catch Tsetse Flies (Glossinidae) and Other Diptera	journal.pntd.0004169	null	[ [ "Since the early 1970s , electrocuting grids have been crucial in clarifying the behaviour of tsetse flies ( Diptera: Glossinidae ) and in informing the development of bait methods of sampling and controlling these insects [1 , 2] .", "Two main types of device have been used:", "( i ) the electric net...	[ "The behaviour of insect vectors has an important bearing on the epidemiology of the diseases they transmit , and on the opportunities for vector control .", "Two sorts of electrocuting device have been particularly useful for studying the behaviour of tsetse flies ( Glossina spp ) , the vectors of the trypanosom...	[ "With a view to refining studies of tsetse fly behaviour , we used a catch method , in the field in Zimbabwe , to assess and improve the efficiency of 0 . 5m2 electrocuting grids commonly used to sample tsetse that collide with netting while in flight or which alight on cloth .", "We found that the efficiency of ...	2015
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "bacteriology", "organismal evolution", "microbial mutation", "medicine and health sciences", "pathology and laboratory medicine", "bacteriophages", "pathogens", "microbiology", "pili and fimbriae", "pseudomonas aeruginosa", "viruses", "developmental biology", "microbial evolution", "micro...	Cross-resistance is modular in bacteria–phage interactions	journal.pbio.2006057	null	[ [ "Natural microbial communities are comprised of complex networks of species interactions , wherein each species may be engaged in ecological interactions with many other species [1–3] .", "In this community context , the evolutionary response of a focal species to a given pairwise species interaction can ...	[ "Phages shape the structure of natural bacterial communities and can be effective therapeutic agents .", "Bacterial resistance to phage infection , however , limits the usefulness of phage therapies and could destabilise community structures , especially if individual resistance mutations provide cross-resistance...	[ "Phage therapy is a promising alternative to antibiotics for treating bacterial infections .", "Yet as with antibiotics , bacteria readily evolve resistance to phage attack , including cross-resistance that protects against multiple phages at once and so limits the usefulness of phage cocktails .", "Here we sho...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "systems biology", "cell motility", "molecular cell biology", "biology", "biophysics", "genetics and genomics" ]	An Adhesion-Dependent Switch between Mechanisms That Determine Motile Cell Shape	journal.pbio.1001059	null	[ [ "Motile cell shape and speed emerge from nanometer-scale interactions among constituent elements , including the actin network , myosin , adhesions , and the cell membrane [1] .", "Cell-substrate adhesion strength has a dramatic , biphasic effect on cell migration velocity: cell speed increases between lo...	[ "Keratocytes are fast-moving cells in which adhesion dynamics are tightly coupled to the actin polymerization motor that drives migration , resulting in highly coordinated cell movement .", "We have found that modifying the adhesive properties of the underlying substrate has a dramatic effect on keratocyte morpho...	[ "Cell migration is important for many biological processes: white blood cells chase down and kill bacteria to guard against infection , epithelial cells crawl across open wounds to promote healing , and embryonic cells move collectively to form organs and tissues during embryogenesis .", "In all of these cases , ...	2011
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "bacteriology", "medicine and health sciences", "pathology and laboratory medicine", "pathogens", "microbiology", "organisms", "bacterial diseases", "enterobacteriaceae", "genome analysis", "bacterial genetics", "sequence motif analysis", "dna", "epigenetics", "molecular biology techniques...	Quantitative mapping of DNA phosphorothioatome reveals phosphorothioate heterogeneity of low modification frequency	journal.pgen.1008026	null	[ [ "Phosphorothioate ( PT ) modification of DNA , in which the non-bridging oxygen in the phosphate moiety of the sugar-phosphate backbone is replaced by sulfur , is widespread in prokaryotes in and R-configuration and a sequence-selective manner .", "PT modification was originally developed as an artificial...	[ "Phosphorothioate ( PT ) modifications of the DNA backbone , widespread in prokaryotes , are first identified in bacterial enteropathogens Escherichia coli B7A more than a decade ago .", "However , methods for high resolution mapping of PT modification level are still lacking .", "Here , we developed the PT-IC-...	[ "Phosphorothioate ( PT ) modification is a novel DNA modification , previous studies showed that PT modifications in E . coli occure at GpsAAC/GpsTTC motifs , but the modification frequency at each site are not known .", "In this study , we introduced two methods: PT-IC-seq , which could quantitatively characteri...	2019
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "developmental biology", "embryology", "animal genetics", "genetics", "molecular genetics", "biology", "morphogenesis", "pattern formation", "genetics and genomics", "cell fate determination", "gene function" ]	Morphogenesis and Cell Fate Determination within the Adaxial Cell Equivalence Group of the Zebrafish Myotome	journal.pgen.1003014	null	[ [ "The mechanisms that are utilised to generate individual cell types from a set of equivalently fated set of precursors remains a central experimental focus of developmental biology .", "Studies from invertebrate systems have defined the concept of an equivalence group , where small clusters of lineage rel...	[ "One of the central questions of developmental biology is how cells of equivalent potential—an equivalence group—come to adopt specific cellular fates .", "In this study we have used a combination of live imaging , single cell lineage analyses , and perturbation of specific signaling pathways to dissect the speci...	[ "How specific genes and signals act on initially identical cells to generate the different tissues of the body remains one of the central questions of developmental genetics .", "Zebrafish are a useful model system to tackle this question as the optically clear embryo allows direct imaging of forming tissues , tr...	2012
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "medicine and health sciences", "immune physiology", "vesicular stomatitis virus", "pathology and laboratory medicine", "vesicles", "nervous system", "gene regulation", "pathogens", "immunology", "microbiology", "neuroscience", "viruses", "rna viruses", "antibodies", "cellular structures...	Metabotropic glutamate receptor subtype 2 is a cellular receptor for rabies virus	journal.ppat.1007189	null	[ [ "Rabies is an almost always fatal disease caused by rabies virus ( RABV ) ; it still kills about 60 , 000 people worldwide per year [1] , most of whom are children in developing countries .", "Rabies has the highest case fatality rate among all infectious diseases , imposing a burden that is at the very l...	[ "Rabies virus ( RABV ) invades the central nervous system and nearly always causes fatal disease in humans .", "How RABV interacts with host neuron membrane receptors to become internalized and cause rabid symptoms is not yet fully understood .", "Here , we identified a novel receptor of RABV , which RABV uses ...	[ "Rabies virus ( RABV ) invades the central nervous system and nearly always causes fatal disease in humans .", "How RABV interacts with host neuron membrane receptors to become internalized and cause rabid symptoms is not yet fully understood .", "Here , we identified metabotropic glutamate receptor subtype 2 (...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine and health sciences", "body fluids", "nervous system", "gene regulation", "regulatory proteins", "brain", "dna-binding proteins", "social sciences", "neuroscience", "visual acuity", "physiological processes", "transcription factors", "vision", "eyes", "neuronal plasticity", "...	A Mouse Model for Conditional Secretion of Specific Single-Chain Antibodies Provides Genetic Evidence for Regulation of Cortical Plasticity by a Non-cell Autonomous Homeoprotein Transcription Factor	journal.pgen.1006035	null	[ [ "During postnatal life , the cerebral cortex passes through critical periods ( CPs ) of plasticity allowing the neuronal circuitry to shape in response to environmental stimuli .", "CPs are driven by the maturation of a subset of inhibitory interneurons , the fast-spiking parvalbumin-expressing GABAergic ...	[ "During postnatal life the cerebral cortex passes through critical periods of plasticity allowing its physiological adaptation to the environment .", "In the visual cortex , critical period onset and closure are influenced by the non-cell autonomous activity of the Otx2 homeoprotein transcription factor , which r...	[ "Classically , cell signaling is based on the secretion of molecules that bind cell surface receptors .", "Lipophilic agents can do without cell-surface receptors due to their ability to diffuse through the plasma membrane , but this is normally not the case for proteins , which cannot pass the membrane barrier ....	2016
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "medicine and health sciences", "physicians", "medical doctors", "medical personnel", "japan", "sociology", "geographical locations", "tropical diseases", "social sciences", "vector-borne diseases", "health care", "health care providers", "infectious disease control", "infectious diseases"...	Health preparedness plan for dengue detection during the 2020 summer Olympic and Paralympic games in Tokyo	journal.pntd.0006755	null	[ [ "Tokyo will be hosting the next Olympic and Paralympic games during the summer season in 2020 ( Tokyo 2020 ) [19] .", "Although Tokyo is located in a temperate climate zone , vector-borne disease will continue to be a major concern , as it was with the previous games .", "It was unexpected that a deng...	[ "Participants in mass gathering events are at risk of acquiring imported and locally endemic infectious diseases .", "The 2014 dengue outbreak in Tokyo gathered attention since it was the first time in 70 years for Japan to experience an autochthonous transmission .", "Preparation for emerging infectious threat...	[ "Dengue is a mosquito-borne disease that is most prevalent among the emerging arboviruses .", "Most patients recover from dengue without complications , but a small portion of cases may progress to severe dengue which carries a high mortality rate if left untreated .", "In 2014 , a dengue outbreak unexpectedly ...	2018
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "syllables", "learning", "ornithology", "linguistics", "vocalization", "vertebrates", "social sciences", "neuroscience", "animals", "learning and memory", "animal signaling and communication", "cognitive psychology", "animal behavior", "mathematics", "statistics (mathematics)", "bird s...	An automated approach to the quantitation of vocalizations and vocal learning in the songbird	journal.pcbi.1006437	null	[ [ "Songbird vocal learning shares many parallels with speech learning and is a powerful and tractable model system for elucidating neural and behavioral mechanisms underlying vocal control and vocal learning [1 , 2] .", "Birds , like humans , learn vocalizations early in life through exposure to the vocaliz...	[ "Studies of learning mechanisms critically depend on the ability to accurately assess learning outcomes .", "This assessment can be impeded by the often complex , multidimensional nature of behavior .", "We present a novel , automated approach to evaluating imitative learning .", "Conceptually , our approach ...	[ "Measuring learning outcomes is a critical objective of research into the mechanisms that support learning .", "Demonstration that a given manipulation results in better or worse learning outcomes requires an accurate and consistent measurement of learning quality .", "However , many behaviors ( e . g . speakin...	2018
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[]	A Retrospective Study on Genetic Heterogeneity within Treponema Strains: Subpopulations Are Genetically Distinct in a Limited Number of Positions	journal.pntd.0004110	null	[ [ "The genus Treponema comprises several uncultivable human and animal pathogens including Treponema pallidum ssp .", "pallidum ( TPA ) , the causative agent of syphilis , T . p .", "ssp .", "pertenue ( TPE , the causative agent of yaws ) , and T . p .", "ssp .", "endemicum ( TEN , the causa...	[ "Pathogenic uncultivable treponemes comprise human and animal pathogens including agents of syphilis , yaws , bejel , pinta , and venereal spirochetosis in rabbits and hares .", "A set of 10 treponemal genome sequences including those of 4 Treponema pallidum ssp .", "pallidum ( TPA ) strains ( Nichols , DAL-1 ,...	[ "The genus Treponema comprises several uncultivable human and animal pathogens including Treponema pallidum ssp .", "pallidum ( TPA ) , the causative agent of syphilis , T . p .", "ssp .", "pertenue ( TPE , the causative agent of yaws ) , and T . p .", "ssp .", "endemicum ( TEN , the causative agent of be...	2015
[ "Introduction", "Results and Discussion", "Materials and Methods" ]	[ "haplotypes", "major histocompatibility complex", "genetic polymorphism", "genome evolution", "clinical immunology", "natural selection", "genetics", "introgression", "biology and life sciences", "population genetics", "gene flow", "computational biology", "evolutionary biology", "immunolo...	Introgression from Domestic Goat Generated Variation at the Major Histocompatibility Complex of Alpine Ibex	journal.pgen.1004438	null	[ [ "The MHC is one of the most gene-dense regions and contains the most polymorphic functional genes in vertebrate genomes [1]–[3] .", "The major role of MHC gene products is the recognition of foreign peptides and their presentation to specialist immune cells in order to initiate an immune response [4] .", ...	[ "The major histocompatibility complex ( MHC ) is a crucial component of the vertebrate immune system and shows extremely high levels of genetic polymorphism .", "The extraordinary genetic variation is thought to be ancient polymorphisms maintained by balancing selection .", "However , introgression from related...	[ "The major histocompatibility complex ( MHC ) , a crucial component of the defense against pathogens , contains the most polymorphic functional genes in vertebrate genomes .", "The extraordinary genetic variation is generally considered to be ancient .", "We investigated whether a previously neglected mechanism...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "cell death", "invertebrates", "animal genetics", "gene regulation", "cell cycle and cell division", "cell processes", "animals", "gene function", "animal models", "drosophila melanogaster", "model organisms", "molecular genetics", "drosophila", "research and analysis methods", "gene exp...	An Intronic microRNA Links Rb/E2F and EGFR Signaling	journal.pgen.1004493	null	[ [ "MicroRNAs ( miRNAs ) are short non-coding RNAs that regulate the expression of mRNA targets , thereby modulating biological processes including development , proliferation , metabolism , homeostasis and tumorigenesis .", "While some miRNAs elicit strong effects , many miRNAs operate more subtly to buffer...	[ "The importance of microRNAs in the regulation of various aspects of biology and disease is well recognized .", "However , what remains largely unappreciated is that a significant number of miRNAs are embedded within and are often co-expressed with protein-coding host genes .", "Such a configuration raises the ...	[ "Animal genomes encode hundreds of microRNA genes that impact all areas of biology by limiting the expression of their targets .", "What remains largely unappreciated is that a significant proportion of microRNA genes are embedded within protein-coding genes , and are often co-expressed with their hosts , which r...	2014
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "geomorphology", "taxonomy", "medicine and health sciences", "pathology and laboratory medicine", "landforms", "pathogens", "topography", "tropical diseases", "microbiology", "treponematoses", "bacterial diseases", "phylogenetics", "data management", "phylogenetic analysis", "neglected t...	Development of a Multilocus Sequence Typing (MLST) scheme for Treponema pallidum subsp. pertenue: Application to yaws in Lihir Island, Papua New Guinea	journal.pntd.0006113	null	[ [ "Yaws is a highly contagious treponemal infection caused by the bacterium Treponema pallidum subsp .", "pertenue ( T . p . pertenue ) .", "It is transmitted by direct skin contact and is symptomatic predominantly in children <15 years of age , usually manifesting as chronic ulcers on the extremities ....	[ "Yaws is a neglected tropical disease , caused by Treponema pallidum subsp .", "pertenue .", "The disease causes chronic lesions , primarily in young children living in remote villages in tropical climates .", "As part of a global yaws eradication campaign initiated by the World Health Organization , we sough...	[ "Yaws is a neglected treponemal infection that is often transmitted among children in developing countries .", "Eradication programs in the 1940–50’s significantly reduced the incidence of yaws , but the disease has resurged .", "The World Health Organization has proposed to eliminate yaws by 2020 , and mass tr...	2017
[ "Introduction", "Results", "Discussion" ]	[ "velocity", "medicine and health sciences", "classical mechanics", "engineering and technology", "motion detectors", "social sciences", "neuroscience", "insect flight", "biological locomotion", "flight (biology)", "vision", "sensory physiology", "animal cells", "sensory receptors", "phys...	Local motion adaptation enhances the representation of spatial structure at EMD arrays	journal.pcbi.1005919	null	[ [ "Spatial vision is a fundamental challenge for animals moving in cluttered environments , and there is no exception for flying insects .", "Because of their small brains insects have to rely on parsimonious principles to compute spatial information about their environment .", "Possessing eyes that are...	[ "Neuronal representation and extraction of spatial information are essential for behavioral control .", "For flying insects , a plausible way to gain spatial information is to exploit distance-dependent optic flow that is generated during translational self-motion .", "Optic flow is computed by arrays of local ...	[ "Insects , with their limited brain resources and high performance in a wide behavioral repertoire , are exquisite model systems for studying parsimonious signal processing .", "They extract spatial information by actively shaping their self-motion ( e . g . when performing peering movements or during flight segm...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Production of Anti-LPS IgM by B1a B Cells Depends on IL-1β and Is Protective against Lung Infection with Francisella tularensis LVS	journal.ppat.1004706	null	[ [ "Francisella tularensis ( Ft ) is a Gram-negative bacterium that infects macrophages and other cell types causing tularemia [1] .", "Ft is considered a potential bioterrorism agent and is used as a prime model intracellular bacterium to study the strategies adopted by microbes to evade and minimize innate...	[ "The role of IL-1β and IL-18 during lung infection with the gram-negative bacterium Francisella tularensis LVS has not been characterized in detail .", "Here , using a mouse model of pneumonic tularemia , we show that both cytokines are protective , but through different mechanisms .", "Il-18-/- mice quickly su...	[ "Francisella tularensis is a Gram-negative bacterium that infects macrophages and other cell types causing tularemia .", "F . tularensis is considered a potential bioterrorism agent and is a prime model intracellular bacterium to study the interaction of pathogens with the host immune system .", "The role of th...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "oncology", "medicine", "dermatology", "public health and epidemiology", "biology", "geriatrics", "molecular cell biology", "public health" ]	Regulation of Nucleotide Excision Repair by UV-DDB: Prioritization of Damage Recognition to Internucleosomal DNA	journal.pbio.1001183	This study reveals the molecular mechanism by which the nucleotide excision repair protein DDB2 prioritises excision of UV-induced DNA lesions in the nucleosome landscape.	[ [ "Ultraviolet ( UV ) light generates mutagenic DNA lesions in the skin , primarily 6-4 pyrimidine-pyrimidone photoproducts ( 6-4PPs ) and cyclobutane pyrimidine dimers ( CPDs ) [1] whose cytotoxic , inflammatory , and carcinogenic effects are mitigated by nucleotide excision repair ( NER ) .", "Defects in ...	[ "How tightly packed chromatin is thoroughly inspected for DNA damage is one of the fundamental unanswered questions in biology .", "In particular , the effective excision of carcinogenic lesions caused by the ultraviolet ( UV ) radiation of sunlight depends on UV-damaged DNA-binding protein ( UV-DDB ) , but the m...	[ "Like all molecules in living organisms , DNA undergoes spontaneous decay and is constantly under attack by endogenous and environmental agents .", "Unlike other molecules , however , DNA—the blueprint of heredity—cannot be re-created de novo; it can only be copied .", "The original blueprint must therefore rem...	2011
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "medicine and health sciences", "breast tumors", "gene regulation", "cancers and neoplasms", "oncology", "alternative splicing", "genome analysis", "bioassays and physiological analysis", "research and analysis methods", "small interfering rnas", "genomics", "gene expression", "breast cancer...	Robust stratification of breast cancer subtypes using differential patterns of transcript isoform expression	journal.pgen.1006589	null	[ [ "Breast cancer is the most common carcinoma in women world-wide and is the second leading cause of cancer death in American women [1] .", "The vast majority of these tumors are adenocarcinomas that develop from the mammary epithelium .", "Pathologists categorize breast tumors based on expression of th...	[ "Breast cancer , the second leading cause of cancer death of women worldwide , is a heterogenous disease with multiple different subtypes .", "These subtypes carry important implications for prognosis and therapy .", "Interestingly , it is known that these different subtypes not only have different biological b...	[ "Breast cancer , the second leading cause of cancer death of women worldwide , is a heterogenous disease .", "Different subtypes of breast cancer display very different expression programs , and these expression programs are associated with different patient outcomes and with different treatment protocols .", "...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genetics and genomics/genomics", "genetics and genomics/microbial evolution and genomics", "microbiology/microbial physiology and metabolism" ]	High-Precision, Whole-Genome Sequencing of Laboratory Strains Facilitates Genetic Studies	journal.pgen.1000139	null	[ [ "Completion of the whole-genome sequencing of many organisms , ranging from bacteria to humans , has transformed the way in which biological research is conducted .", "Genome sequencing is mostly used as a resource to obtain the reference sequence information of laboratory species , and its full applicati...	[ "Whole-genome sequencing is a powerful technique for obtaining the reference sequence information of multiple organisms .", "Its use can be dramatically expanded to rapidly identify genomic variations , which can be linked with phenotypes to obtain biological insights .", "We explored these potential applicatio...	[ "In this manuscript , we describe novel applications of the newly developed Solexa sequencing technology .", "We aim to provide insights into the following questions: ( 1 ) Can whole-genome sequencing , while rapidly surveying mega-bases of genome information , also reliably identify variations at the base-pair r...	2008
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biotechnology", "genetics and genomics/functional genomics", "cell biology/microbial growth and development", "genetics and genomics/disease models", "genetics and genomics/gene function", "genetics and genomics/genetics of disease", "infectious diseases/bacterial infections", "microbiology/cellular ...	Analysis of Pools of Targeted Salmonella Deletion Mutants Identifies Novel Genes Affecting Fitness during Competitive Infection in Mice	journal.ppat.1000477	null	[ [ "Genetic screening remains one of the most efficient methods to identify genes associated with a phenotype of interest in bacteria .", "Array-based methods for these screens originated with the transposon-based “signature tagged mutagenesis” ( STM ) strategy that used unique signature sequences in each tr...	[ "Pools of mutants of minimal complexity but maximal coverage of genes of interest facilitate screening for genes under selection in a particular environment .", "We constructed individual deletion mutants in 1 , 023 Salmonella enterica serovar Typhimurium genes , including almost all genes found in Salmonella but...	[ "One strategy to define bacterial genes with a role during infection involves the screening of a pool of random transposon insertion mutants , where each mutant is identifiable by a specific motif or unique transcript .", "Changes in the survival of each mutant indicate a role of the mutated region during infecti...	2009
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "blood cells", "flow cytometry", "hiv infections", "medicine and health sciences", "immune cells", "enzyme-linked immunoassays", "pathology and laboratory medicine", "pathogens", "immunology", "microbiology", "cloning", "retroviruses", "viruses", "immunodeficiency viruses", "rna viruses"...	A Subset of Latency-Reversing Agents Expose HIV-Infected Resting CD4+ T-Cells to Recognition by Cytotoxic T-Lymphocytes	journal.ppat.1005545	null	[ [ "Current antiretroviral ( ARV ) treatment regimens effectively suppress HIV replication , but are unable to cure infection .", "Viral persistence in long term cellular reservoirs leaves even well-treated individuals with a lifelong commitment to drug regimens , burdened by co-morbidities such as cardiovas...	[ "Resting CD4+ T-cells harboring inducible HIV proviruses are a critical reservoir in antiretroviral therapy ( ART ) -treated subjects .", "These cells express little to no viral protein , and thus neither die by viral cytopathic effects , nor are efficiently cleared by immune effectors .", "Elimination of this ...	[ "Although modern therapies have greatly improved the lives of HIV-positive people with access to care , a cure remains elusive .", "This leaves these individuals burdened by a lifelong commitment to medication , and fails to fully restore health .", "Curing infection would likely require therapies that combine ...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biology and life sciences" ]	Low Levels of p53 Protein and Chromatin Silencing of p53 Target Genes Repress Apoptosis in Drosophila Endocycling Cells	journal.pgen.1004581	null	[ [ "Eukaryotic cells respond to DNA damage via multiple pathways .", "Checkpoints arrest the cell cycle and mobilize the DNA repair machinery to fix the damage [1] , [2] .", "If this genotoxic stress is severe , however , the cells can enter a quiescent state known as senescence , or initiate programmed ...	[ "Apoptotic cell death is an important response to genotoxic stress that prevents oncogenesis .", "It is known that tissues can differ in their apoptotic response , but molecular mechanisms are little understood .", "Here , we show that Drosophila polyploid endocycling cells ( G/S cycle ) repress the apoptotic r...	[ "In order to maintain genome integrity , eukaryotic cells have evolved multiple ways to respond to DNA damage stress .", "One of the major cellular responses is apoptosis , during which the cell undergoes programmed cell death in order to prevent the propagation of the damaged genome to daughter cells .", "Alth...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "transfection", "innate immune system", "medicine and health sciences", "immune physiology", "cytokines", "pathology and laboratory medicine", "gene regulation", "pathogens", "regulatory proteins", "immunology", "microbiology", "dna-binding proteins", "plasmid construction", "bacterial dis...	A Family of Salmonella Type III Secretion Effector Proteins Selectively Targets the NF-κB Signaling Pathway to Preserve Host Homeostasis	journal.ppat.1005484	null	[ [ "Bacterial pathogens that have sustained long-standing associations with their hosts have evolved complex adaptations to modulate host functions to ensure their survival and replication [1–3] .", "One of these adaptations is the type III protein secretion system ( T3SS ) , a complex multi-protein machine ...	[ "Microbial infections usually lead to host innate immune responses and inflammation .", "These responses most often limit pathogen replication although they can also result in host-tissue damage .", "The enteropathogenic bacteria Salmonella Typhimurium utilizes a type III secretion system to induce intestinal i...	[ "The inflammatory response to microbial pathogens usually limits their replication but it can also cause tissue damage .", "The enteropathogenic bacteria Salmonella Typhimurium stimulate host signal transduction pathways that result in inflammation .", "We show here that a family of related Salmonella Typhimuri...	2016
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "invertebrates", "medicine and health sciences", "body fluids", "chemical compounds", "ketones", "vertebrates", "animals", "mammals", "parasitic protozoans", "organic compounds", "glossina", "parasitology", "urine", "protozoans", "tsetse fly", "insect vectors", "veterinary science", ...	Zebra skin odor repels the savannah tsetse fly, Glossina pallidipes (Diptera: Glossinidae)	journal.pntd.0007460	null	[ [ "Tsetse flies ( Glossina sp . ) feed exclusively on blood and are the sole cyclical vectors of the trypanosome parasites that cause African trypanosomosis , a neglected tropical disease [1–3] .", "Two forms of the disease exist in sub-Saharan Africa , both of which are major constraints to development: Hu...	[ "African trypanosomosis , primarily transmitted by tsetse flies , remains a serious public health and economic challenge in sub-Saharan Africa .", "Interventions employing natural repellents from non-preferred hosts of tsetse flies represent a promising management approach .", "Although zebras have been identif...	[ "The use of repellents from non-preferred hosts represents an innovative approach to control animal African trypanosomosis by limiting contact between tsetse flies and livestock .", "Although zebras are non-preferred hosts , the possible chemical basis of their avoidance by tsetse flies is unknown .", "We hypot...	2019
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "transfection", "medicine and health sciences", "immune physiology", "nervous system", "gene regulation", "immunology", "microbiology", "neuroscience", "immunoprecipitation", "mitochondria", "co-immunoprecipitation", "bioenergetics", "molecular biology techniques", "antibodies", "cellula...	Prohibitin plays a critical role in Enterovirus 71 neuropathogenesis	journal.ppat.1006778	null	[ [ "Enterovirus 71 ( EV71 ) is a non-enveloped , positive-sense , single-stranded RNA virus , and causes hand , foot and mouth disease ( HFMD ) in humans .", "Being a close relative of poliovirus , EV71 is deemed as an important neurotropic virus worldwide [1] .", "Since its first isolation in California...	[ "A close relative of poliovirus , enterovirus 71 ( EV71 ) is regarded as an important neurotropic virus of serious public health concern .", "EV71 causes Hand , Foot and Mouth Disease and has been associated with neurological complications in young children .", "Our limited understanding of the mechanisms invol...	[ "A close relative of poliovirus , Enterovirus 71 ( EV71 ) causes Hand , Foot and Mouth Disease and has been associated with neurological complications in young children .", "The lack of effective therapeutics is largely due to our limited understanding of the mechanisms involved in EV71 neuropathogenesis .", "H...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genome evolution", "microbiology", "fungal physiology", "genome sequencing", "fungal evolution", "microbial evolution", "genome complexity", "mycology", "microbial pathogens", "comparative genomics", "biology", "pathogenesis", "genomics", "computational biology", "genetics and genomics"...	Comparative Genomic Analysis of Human Fungal Pathogens Causing Paracoccidioidomycosis	journal.pgen.1002345	null	[ [ "Paracoccidioides , a dimorphic fungal pathogen , has infected approximately 10 million people in Latin America [1] .", "Each year , thousands of these infections develop into a systemic mycosis termed paracoccidioidomycosis , which requires prolonged treatment and has a high rate of relapse and complicat...	[ "Paracoccidioides is a fungal pathogen and the cause of paracoccidioidomycosis , a health-threatening human systemic mycosis endemic to Latin America .", "Infection by Paracoccidioides , a dimorphic fungus in the order Onygenales , is coupled with a thermally regulated transition from a soil-dwelling filamentous ...	[ "Paracoccidioides sp .", "are fungal pathogens that cause paracoccidioidomycosis in humans .", "They are part of a larger group of dimorphic fungi causing pulmonary infections in immunocompetent people , whereas many other fungi cause opportunistic infections .", "We sequenced the genomes of two strains of Pa...	2011
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "animal models of infection", "viral vaccines", "adaptive immunity", "immunity", "virology", "biology", "microbiology" ]	Acute Neonatal Infections ‘Lock-In’ a Suboptimal CD8+ T Cell Repertoire with Impaired Recall Responses	journal.ppat.1003572	null	[ [ "The immune system of neonates is generally characterized as immature and more susceptible to infections with various pathogens [1]–[3] .", "Many of the most debilitating infections are inflicted by intracellular pathogens that are either vertically transmitted or acquired very early on in life ( e . g . ...	[ "Microbial infection during various stages of human development produces widely different clinical outcomes , yet the links between age-related changes in the immune compartment and functional immunity remain unclear .", "The ability of the immune system to respond to specific antigens and mediate protection in e...	[ "Newborns typically have a heightened sensitivity to infectious diseases , the reasons for which are not yet well understood .", "One contributing factor is the limited diversity of lymphocyte receptors early in life to recognize antigen and control infection .", "We have previously shown that antigen-specific ...	2013
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "biophysics/theory and simulation" ]	Formation and Growth of Oligomers: A Monte Carlo Study of an Amyloid Tau Fragment	journal.pcbi.1000238	null	[ [ "A century ago , Alois Alzheimer reported dense extracellular deposits and intracellular neuronal aggregates in the brain of a patient suffering from memory loss , focal symptoms , delusions , and hallucinations [1] .", "The extracellular deposits have been subsequently identified as amyloid plaques compo...	[ "Small oligomers formed early in the process of amyloid fibril formation may be the major toxic species in Alzheimer's disease .", "We investigate the early stages of amyloid aggregation for the tau fragment AcPHF6 ( Ac-VQIVYK-NH2 ) using an implicit solvent all-atom model and extensive Monte Carlo simulations of...	[ "It is believed that the self association of certain protein molecules into aggregated structures , known as amyloid fibrils , plays an important role in a variety of human diseases , such as Alzheimer's disease and Parkinson's disease .", "Although the ability to form such amyloid fibrils is a common property fo...	2008
[ "Introduction", "Results and discussion", "Materials and methods" ]	[ "ruminants", "population genetics", "vertebrates", "animals", "mammals", "invertebrate genomics", "genetic mapping", "molecular biology techniques", "population biology", "research and analysis methods", "gene mapping", "introgression", "molecular biology", "genetic loci", "animal genomi...	Genomic introgression mapping of field-derived multiple-anthelmintic resistance in Teladorsagia circumcincta	journal.pgen.1006857	null	[ [ "Anthelmintic resistance is already a global problem for agriculture and a growing concern in relation to human pathogens [1 , 2] .", "In the absence of effective vaccines , treatment and prophylaxis of helminthiases rely on a limited number of chemotherapeutic agents whose efficacy is increasingly underm...	[ "Preventive chemotherapy has long been practiced against nematode parasites of livestock , leading to widespread drug resistance , and is increasingly being adopted for eradication of human parasitic nematodes even though it is similarly likely to lead to drug resistance .", "Given that the genetic architecture o...	[ "Teladorsagia circumcincta is an economically significant nematode ( roundworm ) pathogen affecting sheep and goats in temperate regions of the world .", "The widespread use of prophylactic treatment has resulted in rapid selection for anthelmintic ( anti-worm drug ) resistance in this and other species of livest...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "diabetes and endocrinology/thyroid", "cell biology/cell signaling" ]	Persistent cAMP-Signals Triggered by Internalized G-Protein–Coupled Receptors	journal.pbio.1000172	Real-time monitoring of G-protein-coupled receptor (GPCR) signaling in native cells suggests that the receptor for thyroid stimulating hormone remains active after internalization, challenging the current model for GPCR signaling.	[ [ "G-protein–coupled receptor ( GPCR ) signaling is thought to involve a series of steps occurring at the cell surface: coupling of receptors to G-proteins , activation of G-proteins , and ultimately , triggering of G-protein-regulated effectors ( i . e . , adenylyl cyclase , phospholipase C , calcium channels ...	[ "G-protein–coupled receptors ( GPCRs ) are generally thought to signal to second messengers like cyclic AMP ( cAMP ) from the cell surface and to become internalized upon repeated or prolonged stimulation .", "Once internalized , they are supposed to stop signaling to second messengers but may trigger nonclassica...	[ "Cells respond to many environmental cues through the activity of cell surface receptor proteins , which sense these cues and convey that information to signaling molecules inside the cell .", "G-protein–coupled receptors ( GPCRs ) form the largest eukaryotic family of plasma membrane receptors .", "They conver...	2009
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[]	The Molecular Epidemiology and Evolution of Murray Valley Encephalitis Virus: Recent Emergence of Distinct Sub-lineages of the Dominant Genotype 1	journal.pntd.0004240	null	[ [ "Murray Valley encephalitis virus ( MVEV; genus Flavivirus , family Flaviviridae ) is the most important cause of arboviral encephalitis in Australia .", "It is a member of the Japanese encephalitis ( JE ) serocomplex , along with other medically important flaviviruses such as JE virus ( JEV ) and West Ni...	[ "Recent increased activity of the mosquito-borne Murray Valley encephalitis virus ( MVEV ) in Australia has renewed concerns regarding its potential to spread and cause disease .", "To better understand the genetic relationships between earlier and more recent circulating strains , patterns of virus movement , as...	[ "Murray Valley encephalitis virus is the most significant cause of mosquito-borne encephalitis in humans in Australia , and can also cause neurological disease in horses .", "This study reports an expanded phylogenetic study of this virus and the first molecular evolutionary analysis .", "Of the four recognized...	2015
[ "Introduction", "Results", "Discussion", "Material and Methods" ]	[ "sequencing techniques", "chromosome structure and function", "genomic databases", "telomeres", "model organisms", "protozoans", "genome analysis", "tetrahymena thermophila", "sequence motif analysis", "ciliate protozoans", "molecular biology techniques", "research and analysis methods", "se...	Programmed Minichromosome Elimination as a Mechanism for Somatic Genome Reduction in Tetrahymena thermophila	journal.pgen.1006403	null	[ [ "Eukaryotic chromosomes are the structural bases of inheritance , and contain key components such as centromeres and telomeres to maintain stability and facilitate transmission .", "Loss of chromosome integrity causes severe problems including tumorigenesis [1–3] .", "In order to maintain chromosome s...	[ "The maintenance of chromosome integrity is crucial for genetic stability .", "However , programmed chromosome fragmentations are known to occur in many organisms , and in the ciliate Tetrahymena the five germline chromosomes are fragmented into hundreds of minichromosomes during somatic nuclear differentiation ....	[ "Chromatin diminution was first discovered in the parasite Parascaris univalens by T . Boveri more than one century ago .", "This process eliminates a large proportion of the genome accompanying germline-soma differentiation during development .", "Ciliates also carry out DNA elimination that have been studied ...	2016
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "cell motility", "cancer cell migration", "gene regulation", "enzymes", "enzymology", "signaling networks", "fluorophotometry", "developmental biology", "gtpase signaling", "network analysis", "research and analysis methods", "small interfering rnas", "contractile proteins", "fluorescence ...	A MAPK-Driven Feedback Loop Suppresses Rac Activity to Promote RhoA-Driven Cancer Cell Invasion	journal.pcbi.1004909	null	[ [ "An estimated 90% of cancer deaths are caused by metastatic secondary tumours [1] , a process instigated as certain cells escape the primary tumour to migrate in , and invade through , the local micro-environment .", "Cancer cells can adopt a range of different migratory mechanisms to achieve such invasio...	[ "Cell migration in 3D microenvironments is fundamental to development , homeostasis and the pathobiology of diseases such as cancer .", "Rab-coupling protein ( RCP ) dependent co-trafficking of α5β1 and EGFR1 promotes cancer cell invasion into fibronectin ( FN ) containing extracellular matrix ( ECM ) , by potent...	[ "The majority of cancer-related fatalities are caused by the movement of cancer cells away from the primary site to form metastases , making understanding the signalling mechanisms which underpin cell migration and invasion through their local environment of paramount importance .", "Much has been discovered abou...	2016
[ "Introduction", "Results/Discussion", "Materials and Methods" ]	[ "genetics and genomics/gene function", "developmental biology/neurodevelopment", "genetics and genomics/gene discovery", "neuroscience/neurodevelopment" ]	Systematic Identification of Genes that Regulate Neuronal Wiring in the Drosophila Visual System	journal.pgen.1000085	null	[ [ "The adult visual system of Drosophila melanogaster is a powerful genetic model for exploring the molecular and cellular mechanisms involved in axon growth , guidance , and synaptic specificity [1] .", "The adult retina consists of some 800 ommatidia , each containing 8 photoreceptor cells ( R1–R8 ) that ...	[ "Forward genetic screens in model organisms are an attractive means to identify those genes involved in any complex biological process , including neural circuit assembly .", "Although mutagenesis screens are readily performed to saturation , gene identification rarely is , being limited by the considerable effor...	[ "In the nervous system , every neuronal process should know where to grow and when to establish contacts to the next-order neurons .", "During development , it is known that neural circuit formation is primarily determined by the genes .", "To identify these genes , we focused on the Drosophila visual circuitry...	2008
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "biochemistry", "rna", "rna processing", "nucleic acids", "proteins", "protein translation", "gene expression", "genetics", "biology" ]	NSUN4 Is a Dual Function Mitochondrial Protein Required for Both Methylation of 12S rRNA and Coordination of Mitoribosomal Assembly	journal.pgen.1004110	null	[ [ "Expression of mtDNA is essential for production of ATP through oxidative phosphorylation in all eukaryotes .", "Mammalian mtDNA encodes 13 polypeptides that are translated on mitochondrial ribosomes ( mitoribosomes ) and are essential for oxidative phosphorylation .", "The mammalian mitoribosomes are...	[ "Biogenesis of mammalian mitochondrial ribosomes requires a concerted maturation of both the small ( SSU ) and large subunit ( LSU ) .", "We demonstrate here that the m5C methyltransferase NSUN4 , which forms a complex with MTERF4 , is essential in mitochondrial ribosomal biogenesis as mitochondrial translation i...	[ "Mitochondria perform a number of essential functions in the cell , including synthesis of ATP via the oxidative phosphorylation ( OXPHOS ) system .", "Normal mitochondrial function requires coordinated expression of two genomes: mitochondria's own genome ( mtDNA ) , which encodes 13 respiratory chain subunits wi...	2014
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "physiology/cardiovascular physiology and circulation", "oncology/oncology agents", "computational biology/systems biology" ]	Structural Adaptation and Heterogeneity of Normal and Tumor Microvascular Networks	journal.pcbi.1000394	null	[ [ "Solid tumors require an internal vasculature in order to grow beyond a few mm in size and to metastasize [1] .", "Tumor vascular networks are known to be fundamentally different from normal vasculature ( e . g . [2]–[4] ) .", "Vessels are typically immature , tortuous , dilated , and hyperpermeable a...	[ "Relative to normal tissues , tumor microcirculation exhibits high structural and functional heterogeneity leading to hypoxic regions and impairing treatment efficacy .", "Here , computational simulations of blood vessel structural adaptation are used to explore the hypothesis that abnormal adaptive responses to ...	[ "Blood vessels of tumors have abnormal structures , being irregular and tortuous .", "Oxygen supply to tumors is heterogeneous , with regions of low oxygen that resist radiation treatment and some types of chemotherapy .", "Blood vessels undergo continual structural change ( adaptation ) in response to blood fl...	2009
[ "Introduction", "Materials and Methods", "Results", "Discussion", "Conclusions" ]	[ "medicine and health sciences", "body fluids", "tropical diseases", "parasitic diseases", "parasitic protozoans", "organisms", "protozoans", "dna replication", "neglected tropical diseases", "molecular biology techniques", "dna", "cellular structures and organelles", "extraction techniques",...	Development of a PCR Assay to Detect Low Level Trypanosoma cruzi in Blood Specimens Collected with PAXgene Blood DNA Tubes for Clinical Trials Treating Chagas Disease	journal.pntd.0005146	null	[ [ "Chagas disease ( CD ) is a tropical parasitic disease caused by the chronic infection with the protozoan T . cruzi .", "About 6 to 7 million people , primarily in Mexico and Central and South America , are estimated to be infected [1] .", "Left untreated , up to 30 to 40% of chronically infected pati...	[ "Chagas disease is caused by the parasitic infection of Trypanosoma cruzi ( T . cruzi ) .", "The STOP CHAGAS clinical trial was initiated in 2011 to evaluate posaconazole in treating Chagas disease , with treatment success defined as negative qualitative PCR results of detecting the parasites in blood specimens c...	[ "Chagas disease is caused by the infection of the protozoan parasite Trypanosoma cruzi ( T . cruzi ) and carries a significant tropical disease burden in the Western Hemisphere .", "The STOP CHAGAS study was a global clinical trial evaluating therapies for Chagas disease .", "PAXgene blood DNA tubes used by the...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Targeting HIV Reservoir in Infected CD4 T Cells by Dual-Affinity Re-targeting Molecules (DARTs) that Bind HIV Envelope and Recruit Cytotoxic T Cells	journal.ppat.1005233	null	[ [ "Advanced regimens of combination antiretroviral therapy ( cART ) prevent AIDS and suppress HIV replication to nearly undetectable levels in over 90% of treatment-naïve participants [1–3] .", "However , in nearly all cases , cART interruption results in resumption of viral replication [4 , 5] , which indi...	[ "HIV reservoirs and production of viral antigens are not eliminated in chronically infected participants treated with combination antiretroviral therapy ( cART ) .", "Novel therapeutic strategies aiming at viral reservoir elimination are needed to address chronic immune dysfunction and non-AIDS morbidities that e...	[ "Current HIV therapies prevent AIDS by dramatically reducing , but not eliminating , HIV infection .", "A reservoir of HIV-infected cells persists during long-term antiviral therapy , and individuals are at increased risk to develop non-AIDS illnesses , e . g . , accelerated heart , bone , or kidney disease .", ...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biochemistry", "developmental biology", "genetics", "biology", "molecular cell biology", "genetics and genomics" ]	Normal DNA Methylation Dynamics in DICER1-Deficient Mouse Embryonic Stem Cells	journal.pgen.1002919	null	[ [ "Most CpG dinucleotides in the mammalian genome are methylated [1] , much of this being present at localized centric ( minor satellite , MinS ) and pericentric ( major satellite , MajS ) repeats , and dispersed repeats or transposable elements ( TEs ) .", "Here DNA methylation plays a role in maintaining ...	[ "Reduced DNA methylation has been reported in DICER1-deficient mouse ES cells .", "Reductions seen at pericentric satellite repeats have suggested that siRNAs are required for the proper assembly of heterochromatin .", "More recent studies have postulated that the reduced methylation is an indirect effect: the ...	[ "In mammalian cells , DNA methylation is required for the maintenance of genome stability .", "Recent studies have shown that the genome-wide levels of DNA methylation can be reduced in DICER1-deficient mouse embryonic stem ( ES ) cells , suggesting that the activity of DNA methylating enzymes ( DNMTs ) may be re...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biology" ]	Matefin/SUN-1 Phosphorylation Is Part of a Surveillance Mechanism to Coordinate Chromosome Synapsis and Recombination with Meiotic Progression and Chromosome Movement	journal.pgen.1003335	null	[ [ "Sexually reproducing organisms must halve their genome prior to gamete formation to maintain genome size in succeeding generations .", "During meiosis , one cycle of DNA replication is followed by two successive rounds of nuclear divisions , resulting in four nuclei that can develop into haploid gametes ...	[ "Faithful chromosome segregation during meiosis I depends on the establishment of a crossover between homologous chromosomes .", "This requires induction of DNA double-strand breaks ( DSBs ) , alignment of homologs , homolog association by synapsis , and repair of DSBs via homologous recombination .", "The succ...	[ "During meiosis , one round of replication is followed by two divisions to produce haploid gametes .", "During the first meiotic division , faithful segregation is facilitated by the formation between the parental homologs of a physical tether called crossover .", "Crossovers require the introduction of DNA dou...	2013
[ "Introduction", "Results/Discussion", "Materials and Methods" ]	[ "systems biology", "mathematics", "applied mathematics", "biology", "computational biology", "nonlinear dynamics" ]	A Whole-Body Model for Glycogen Regulation Reveals a Critical Role for Substrate Cycling in Maintaining Blood Glucose Homeostasis	journal.pcbi.1002272	null	[ [ "Glucose is the major metabolic fuel of mammals , with its maintenance at appropriate levels within the body being crucial for normal function , while dysregulation is associated with diseases such as diabetes mellitus , galactosemia and glycogen storage diseases [1] .", "Maintaining glucose levels requir...	[ "Timely , and sometimes rapid , metabolic adaptation to changes in food supply is critical for survival as an organism moves from the fasted to the fed state , and vice versa .", "These transitions necessitate major metabolic changes to maintain energy homeostasis as the source of blood glucose moves away from in...	[ "Homeostasis of blood glucose concentrations during circadian shifts in survival-related activities , sleep and food availability is crucial for the survival of mammals .", "This process depends upon glucose intake , short-term storage as glycogen , and gluconeogenesis .", "The integration of hepatic glycogen a...	2011
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "developmental biology", "plant science", "plant microbiology", "plant biology", "microbial pathogens", "plant cell biology", "biology", "microbial growth and development", "microbiology", "host-pathogen interaction", "bacterial pathogens" ]	Protection of Sinorhizobium against Host Cysteine-Rich Antimicrobial Peptides Is Critical for Symbiosis	journal.pbio.1001169	A bacterial membrane protein, BacA, protects Sinorhizobium meliloti against the antimicrobial activity of host peptides, enabling the peptides to induce bacterial persistence rather than bacterial death.	[ [ "The alpha-proteobacterium Sinorhizobium meliloti forms a symbiosis within specialized root organs , called nodules with Medicago species of leguminous plants , including the agriculturally important alfalfa and the model legume Medicago truncatula [1] .", "The bacteria induce the organogenesis of nodules...	[ "Sinorhizobium meliloti differentiates into persisting , nitrogen-fixing bacteroids within root nodules of the legume Medicago truncatula .", "Nodule-specific cysteine-rich antimicrobial peptides ( NCR AMPs ) and the bacterial BacA protein are essential for bacteroid development .", "However , the bacterial fac...	[ "Certain bacterial species have the unique capacity to enter into eukaryotic host cells and establish prolonged infections , which can be beneficial ( e . g . bacterial-legume symbiosis ) or detrimental ( e . g . chronic disease ) for the host .", "However , the mechanisms by which bacteria persist in host cells ...	2011
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "population ecology", "ecology", "population modeling", "virology", "biology", "computational biology", "microbiology", "host-pathogen interaction" ]	Heterogeneous Host Susceptibility Enhances Prevalence of Mixed-Genotype Micro-Parasite Infections	journal.pcbi.1002097	null	[ [ "Models of micro-parasitic infection and transmission have been instrumental to the study of infectious disease dynamics [1] , [2] .", "The insights reaped from these models , together with the advent of an evolutionary biology framework , have revolutionized our understanding of infectious diseases , and...	[ "Dose response in micro-parasite infections is usually shallower than predicted by the independent action model , which assumes that each infectious unit has a probability of infection that is independent of the presence of other infectious units .", "Moreover , the prevalence of mixed-genotype infections was gre...	[ "What elements are indispensable in the description of the most basic host-pathogen interactions ?", "The simplest models of infection generally fail to predict how many host plants or animals will become infected , and which virus genotypes will be present in these infected hosts .", "These simple models of in...	2011
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Luminal Progenitors Restrict Their Lineage Potential during Mammary Gland Development	journal.pbio.1002069	Stem cells in the embryonic mammary gland that express the Notch1 receptor are initially multipotent and highly regenerative, but they progressively restrict their lineage potential to the lumen of the mammary duct, where they may give rise to breast cancer.	[ [ "The mammary gland is composed of two epithelial compartments: an inner layer , which contains luminal cells , and an outer myoepithelial layer in direct contact with the basal membrane .", "These two cell lineages originate from mammary stem cells ( MaSC ) that were initially found to reside in the basal...	[ "The hierarchical relationships between stem cells and progenitors that guide mammary gland morphogenesis are still poorly defined .", "While multipotent basal stem cells have been found within the myoepithelial compartment , the in vivo lineage potential of luminal progenitors is unclear .", "Here we used the ...	[ "Tissue-specific stem cells are believed to be multipotent , thus able to generate all cell types of their tissue of origin .", "In the mammary gland epithelium , however , the existence of multipotent versus unipotent adult stem cells is currently under debate .", "In this study , we have identified and charac...	2015
[ "Introduction", "Methods", "Inclusion criteria", "Results", "Discussion" ]	[ "recombination-based assay", "medicine and health sciences", "enzyme-linked immunoassays", "pathology and laboratory medicine", "tropical diseases", "parasitic diseases", "parasitic protozoans", "biochemical analysis", "enzyme assays", "protozoans", "neglected tropical diseases", "molecular bi...	Rapid immunochromatographic tests for the diagnosis of chronic Chagas disease in at-risk populations: A systematic review and meta-analysis	journal.pntd.0007271	null	[ [ "Chagas disease ( CD ) is a parasitic disease affecting more than 8 million people and causing 806 , 170 DALYs lost , annually , in the endemic countries of Latin America ( LA ) [1] .", "It is caused by the protozoan parasite Trypanosoma cruzi , generally transmitted by insect vectors .", "Following i...	[ "Despite of a high disease burden , mainly in Latin America , Chagas disease ( CD ) is underdiagnosed and undertreated .", "Rapid diagnostic tests ( RDTs ) might improve the access to diagnosis .", "The aim of this study is to review the accuracy of commercially available RDTs used in field conditions for the d...	[ "Chagas disease ( CD ) is a parasitic disease that can affect seriously the health status of affected individuals .", "People with CD , mainly living in remote areas of Latin America , often face major barriers to the disease recognition , diagnosis and treatment .", "The World Health Organization recommends th...	2019
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "reverse transcriptase-polymerase chain reaction", "phosphorylation", "precipitates", "enzyme-linked immunoassays", "hela cells", "293t cells", "enzymes", "biological cultures", "enzymology", "immunoprecipitation", "cell cultures", "molecular biology techniques", "immunologic techniques", ...	MAVS activates TBK1 and IKKε through TRAFs in NEMO dependent and independent manner	journal.ppat.1006720	null	[ [ "The innate immune system is the first line of defense against microbial infection .", "Germline encoded pattern recognition receptors ( PRRs ) , such as Toll-like receptors ( TLRs ) , RIG-I-like receptors ( RLRs ) and NOD-like receptors ( NLRs ) [1] , recognize conserved molecular structures known as pat...	[ "Mitochondrial antiviral-signaling protein ( MAVS ) transmits signals from RIG-I-like receptors after RNA virus infections .", "However , the mechanism by which MAVS activates downstream components , such as TBK1 and IKKα/β , is unclear , although previous work suggests the involvement of NEMO or TBK1-binding pro...	[ "Innate immunity is the first line of defense against virus infection .", "RIG-I-like receptors ( RLRs ) recognize various viral RNA from RNA viruses and initiate host antiviral responses to produce type I interferons ( IFNs ) and other cytokines .", "RLRs sense distinct types of viruses by sharing a common ada...	2017
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "biomacromolecule-ligand interactions", "physics", "biochemistry", "protein chemistry", "protein interactions", "proteins", "protein structure", "biology", "biophysics", "drug discovery" ]	A Role for Both Conformational Selection and Induced Fit in Ligand Binding by the LAO Protein	journal.pcbi.1002054	null	[ [ "Molecular recognition plays important roles in many biological processes .", "For example , enzymes must recognize their substrates and drugs must be designed to have specific binding partners .", "Unfortunately , our understanding of how ligand binding occurs remains incomplete .", "In particula...	[ "Molecular recognition is determined by the structure and dynamics of both a protein and its ligand , but it is difficult to directly assess the role of each of these players .", "In this study , we use Markov State Models ( MSMs ) built from atomistic simulations to elucidate the mechanism by which the Lysine- ,...	[ "Protein-ligand interactions are crucial to chemistry , biology and medicine .", "Many studies have been conducted to probe the mechanism of protein-ligand binding , leading to the development of the induced fit and conformational selection models .", "Unfortunately , experimentally probing the atomistic detail...	2011
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biophysics/protein folding", "biochemistry/protein folding", "biophysics/theory and simulation", "biochemistry/theory and simulation", "computational biology/molecular dynamics" ]	Unfolding Simulations Reveal the Mechanism of Extreme Unfolding Cooperativity in the Kinetically Stable α-Lytic Protease	journal.pcbi.1000689	null	[ [ "α-lytic protease ( αLP ) , a prokaryotic serine protease of the chymotrypsin family , has evolved an unusual energetic landscape , providing it a functional advantage over its metazoan homologs .", "Unlike most proteins , αLP's active state is not stabilized by thermodynamics , but by a large kinetic bar...	[ "Kinetically stable proteins , those whose stability is derived from their slow unfolding kinetics and not thermodynamics , are examples of evolution's best attempts at suppressing unfolding .", "Especially in highly proteolytic environments , both partially and fully unfolded proteins face potential inactivation...	[ "Proteins , synthesized as linear polymers of amino acids , fold up into compact native states , burying their hydrophobic amino acids into their interiors .", "Protein folding minimizes the non-specific interactions that unfolded protein chains can make , which include aggregation with other proteins and degrada...	2010

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