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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", "Templatize infrastructure with version control", "Embrace ephemerality: Image data and software", "Use containers", "Manage security and privacy as code", "Use managed services instead of reinventing them", "Develop serverless applications", "Be agile: Iterate with small releases", ...	[ "cloud computing", "education", "engineering and technology", "computer hardware", "data management", "scientists", "science and technology workforce", "research and analysis methods", "computer and information sciences", "computing methods", "research assessment", "computer networks", "peop...	Eleven quick tips for architecting biomedical informatics workflows with cloud computing	journal.pcbi.1005994	null	[ [ "Cloud computing is the on-demand use of computational hardware , software , and networks provided by a third party [1] .", "The rise of the internet allowed companies to offer fully internet-based file storage services , including Amazon Web Services’ Simple Storage Service , which launched in 2006 [2] ....	[ "Cloud computing has revolutionized the development and operations of hardware and software across diverse technological arenas , yet academic biomedical research has lagged behind despite the numerous and weighty advantages that cloud computing offers .", "Biomedical researchers who embrace cloud computing can r...	[ "Cloud computing has revolutionized the tech sector , but academia is slow to adopt .", "These 11 quick tips are geared towards helping academic researchers and their teams harness the power of cloud computing by utilizing the design patterns that have evolved in the past decade .", "Cloud computing can increas...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "microbiology/cellular microbiology and pathogenesis", "microbiology/innate immunity" ]	NOD2, RIP2 and IRF5 Play a Critical Role in the Type I Interferon Response to Mycobacterium tuberculosis	journal.ppat.1000500	null	[ [ "Mycobacterium tuberculosis ( Mtb ) , the causative agent of human tuberculosis , is an exquisitely adapted obligate human pathogen that is thought to persist within as many as one billion individuals worldwide [1] .", "This bacterium's ability to survive and replicate inside a modified phagosomal compart...	[ "While the recognition of microbial infection often occurs at the cell surface via Toll-like receptors , the cytosol of the cell is also under surveillance for microbial products that breach the cell membrane .", "An important outcome of cytosolic recognition is the induction of IFNα and IFNβ , which are critical...	[ "Bacterial and viral infection stimulates production of several cytokines and chemokines that are thought to protect the host against infection .", "The bacterial strain known to cause tuberculosis elicits production of type I interferons , yet it was unclear how the bacteria isolated within the cell was capable ...	2009
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "plant anatomy", "classical mechanics", "pavement cells", "gene regulation", "plant cell biology", "cell cycle and cell division", "cell processes", "regulatory proteins", "dna-binding proteins", "cell differentiation", "hormones", "developmental biology", "plant science", "plant hormones"...	The CIN-TCP transcription factors promote commitment to differentiation in Arabidopsis leaf pavement cells via both auxin-dependent and independent pathways	journal.pgen.1007988	null	[ [ "Cells in an early organ primordium undergo active proliferation to generate sufficient number , while increasingly more cells exit division cycle and enter differentiation at later stages of organ growth , thus ensuring a mature organ with defined size [1 , 2] .", "While genes that drive cell cycle progr...	[ "Cells in organ primordia undergo active proliferation at an early stage to generate sufficient number , before exiting proliferation and entering differentiation .", "However , how the actively proliferating cells are developmentally reprogrammed to acquire differentiation potential during organ maturation is un...	[ "Cells in a young organ primordium proliferate to generate sufficient number , before they exit division cycle and enter differentiation programme at later stages .", "While factors that drive cell cycle progression have been identified and studied in detail in diverse eukaryotic species , developmental factors t...	2019
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "infectious diseases/bacterial infections", "microbiology/cellular microbiology and pathogenesis" ]	A Novel Extracytoplasmic Function (ECF) Sigma Factor Regulates Virulence in Pseudomonas aeruginosa	journal.ppat.1000572	null	[ [ "The human opportunistic pathogen Pseudomonas aeruginosa is known for a high proportion of regulatory genes in its genome [1] .", "This is not only due to the number of two-component regulatory systems , but this bacterium also contain a large number of different cell-surface signaling ( CSS ) systems [2]...	[ "Next to the two-component and quorum sensing systems , cell-surface signaling ( CSS ) has been recently identified as an important regulatory system in Pseudomonas aeruginosa .", "CSS systems sense signals from outside the cell and transmit them into the cytoplasm .", "They generally consist of a TonB-dependen...	[ "Pseudomonas aeruginosa is a versatile pathogen; these bacteria are able to cause an infection in humans and other mammals , zebrafish , insects , nematodes and even plants .", "P . aeruginosa evolved an impressive amount of gene regulation systems to be able to express the right virulence genes under the right c...	2009
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biochemistry", "signal transduction", "cell biology", "proteins", "chaperone proteins", "biology and life sciences", "molecular cell biology" ]	Modulation of STAT3 Folding and Function by TRiC/CCT Chaperonin	journal.pbio.1001844	Levels, folding, and function of the infamous cancer and inflammatory disease-related signaling molecule Stat3 are regulated by interaction with the chaperonin TRiC; manipulation of this interaction is a therapeutic avenue for exploration.	[ [ "Signal transducer and activator of transcription 3 ( Stat3 ) is a member of a family of seven closely related proteins responsible for the transmission of peptide hormone signals from the extracellular surface of cells to the nucleus [1] , [2] .", "Mice deficient in Stat3 died during early embryogenesis ...	[ "Signal transducer and activator of transcription 3 ( Stat3 ) transduces signals of many peptide hormones from the cell surface to the nucleus and functions as an oncoprotein in many types of cancers , yet little is known about how it achieves its native folded state within the cell .", "Here we show that Stat3 i...	[ "Stat3 is a multidomain transcription factor that contributes to many cellular functions by transmitting signals for over 40 peptide hormones from the cell surface to the nucleus .", "Understanding how multidomain proteins achieve their fully folded and functional state is of substantial biological interest .", ...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	SCARN a Novel Class of SCAR Protein That Is Required for Root-Hair Infection during Legume Nodulation	journal.pgen.1005623	null	[ [ "In most eukaryotic cells , the reversible association of G-actin subunits can result in the dynamic formation of actin filaments that play essential roles in changing cell shape and controlling nuclear localization .", "In addition , actin filaments form a framework along which vesicles and proteins can ...	[ "Rhizobial infection of legume root hairs requires a rearrangement of the actin cytoskeleton to enable the establishment of plant-made infection structures called infection threads .", "In the SCAR/WAVE ( Suppressor of cAMP receptor defect/WASP family verpolin homologous protein ) actin regulatory complex , the c...	[ "Characterization of Lotus japonicus mutants defective for nodule infection by rhizobia led to the identification of a gene we named SCARN .", "Two of the five alleles caused formation of branched root-hairs in uninoculated seedlings , suggesting SCARN plays a role in the microtubule and actin-regulated polar gro...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genetics and genomics", "genetics and genomics/population genetics" ]	GC-Biased Evolution Near Human Accelerated Regions	journal.pgen.1000960	null	[ [ "Understanding the forces that have shaped the evolution of the human genome is one of the most exciting problems in modern genomics .", "Two approaches to this problem are focused on identification and characterization of those genomic regions that have evolved the slowest and fastest along the human lin...	[ "Regions of the genome that have been the target of positive selection specifically along the human lineage are of special importance in human biology .", "We used high throughput sequencing combined with methods to enrich human genomic samples for particular targets to obtain the sequence of 22 chromosomal sampl...	[ "The search for functional regions in the human genome , beyond the protein-coding portion , often relies on signals of conservation across species .", "The Human Accelerated Regions ( HARs ) are strongly conserved elements , ranging in size from 100–400 bp , that show an unexpected number of human-specific chang...	2010
[ "Results", "Discussion", "Materials and methods" ]	[ "syllables", "linguistics", "medicine and health sciences", "engineering and technology", "nervous system", "signal processing", "social sciences", "neuroscience", "brain mapping", "neuroimaging", "research and analysis methods", "syntax", "imaging techniques", "phonemes", "short reports...	Perceptually relevant speech tracking in auditory and motor cortex reflects distinct linguistic features	journal.pbio.2004473	null	[ [ "Participants listened to single sentences and indicated after each trial which ( out of 4 ) target words occurred in the sentence .", "Participants reported the correct target word , on average , in 69 . 7 ± 7 . 1% ( mean ± SD ) of trials , with chance level being 25% .", "Performance of individual p...	[ "During online speech processing , our brain tracks the acoustic fluctuations in speech at different timescales .", "Previous research has focused on generic timescales ( for example , delta or theta bands ) that are assumed to map onto linguistic features such as prosody or syllables .", "However , given the h...	[ "How we comprehend speech—and how the brain encodes information from a continuous speech stream—is of interest for neuroscience , linguistics , and research on language disorders .", "Previous work that examined dynamic brain activity has addressed the issue of comprehension only indirectly , by contrasting intel...	2018
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "medicine and health sciences", "membrane potential", "electrophysiology", "membrane proteins", "mutation", "protein structure prediction", "protein structure", "sequence motif analysis", "cellular structures and organelles", "research and analysis methods", "sequence analysis", "bioinformatic...	A lipophilicity-based energy function for membrane-protein modelling and design	journal.pcbi.1007318	null	[ [ "Membrane proteins have essential biological roles as receptors , channels , and transporters .", "Over the past decade , significant progress has been made in the design of membrane proteins , including the first design of membrane-integral inhibitors [1] , a transporter [2 , 3] , and a de novo designed ...	[ "Membrane-protein design is an exciting and increasingly successful research area which has led to landmarks including the design of stable and accurate membrane-integral proteins based on coiled-coil motifs .", "Design of topologically more complex proteins , such as most receptors , channels , and transporters ...	[ "Membrane proteins comprise a third of the genome and have essential roles as intermediaries between the cell and its environment .", "Despite exciting recent progress in membrane-protein modelling and design , however , these fields lag far behind advances in soluble proteins , chiefly because of inaccurate mode...	2019
[ "Introduction", "Results and discussion", "Materials and methods" ]	[ "biotechnology", "antimicrobials", "synthetic biotechnology", "medicine and health sciences", "pathology and laboratory medicine", "engineering and technology", "pathogens", "drugs", "synthetic biology", "microbiology", "staphylococcus aureus", "pseudomonas aeruginosa", "antibiotic resistanc...	Synergy between conventional antibiotics and anti-biofilm peptides in a murine, sub-cutaneous abscess model caused by recalcitrant ESKAPE pathogens	journal.ppat.1007084	null	[ [ "ESKAPE pathogens ( E . faecium , S . aureus , K . pneumoniae , A . baumannii , P . aeruginosa , E . cloacae ) are recognized to be responsible for the majority of difficult-to-treat community-acquired , healthcare-associated , and nosocomial infections [1] .", "Multidrug-resistant bacteria represent majo...	[ "With the antibiotic development pipeline running dry , many fear that we might soon run out of treatment options .", "High-density infections are particularly difficult to treat due to their adaptive multidrug-resistance and currently there are no therapies that adequately address this important issue .", "Her...	[ "There has been enormous publicity about the inexorable rise of resistance and the dearth of new therapies .", "However less attention has been placed on adaptively multidrug-resistant high density bacterial infections for which antibiotics are highly used but no effective therapies currently exist .", "Here we...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine", "infectious diseases", "immune cells", "cytokines", "monocytes", "clinical immunology", "immunity", "hiv", "innate immunity", "immune activation", "t cells", "immunity to infections", "immunology", "biology", "immunoregulation", "viral diseases", "immune response", "imm...	The Th17/Treg Ratio, IL-1RA and sCD14 Levels in Primary HIV Infection Predict the T-cell Activation Set Point in the Absence of Systemic Microbial Translocation	journal.ppat.1003453	null	[ [ "High levels of immune activation occur early in primary HIV infection ( PHI ) and the CD8 T-cell activation set point ( i . e . the steady state level of activation following PHI ) is a strong predictor of subsequent CD4 T-cell loss independently of viral load [1] .", "Generalized immune activation is kn...	[ "Impairment of the intestinal barrier and subsequent microbial translocation ( MT ) may be involved in chronic immune activation , which plays a central role in HIV pathogenesis .", "Th17 cells are critical to prevent MT . The aim of the study was to investigate , in patients with primary HIV infection ( PHI ) , ...	[ "Generalized immune activation is pivotal in the pathogenesis of HIV disease .", "Impairment in the gut mucosal barrier allows the translocation of microbial flora from the gut towards the circulation .", "Translocated microbial products , together with HIV replication , contribute to chronic immune activation ...	2013
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "medicine", "infectious diseases", "disease mapping", "geography", "social and behavioral sciences", "global health", "epidemiology", "african trypanosomiasis", "neglected tropical diseases", "spatial analysis", "human geography" ]	Incorporating Scale Dependence in Disease Burden Estimates: The Case of Human African Trypanosomiasis in Uganda	journal.pntd.0002704	null	[ [ "Developed by the World Health Organization ( WHO ) in the early 1990s as part of the creation of the Global Burden of Disease Study ( GBD ) , the Disability Adjusted Life Year ( DALY ) is a standardized metric that has been utilized widely in the two decades since to estimate the global and regional impact o...	[ "The WHO has established the disability-adjusted life year ( DALY ) as a metric for measuring the burden of human disease and injury globally .", "However , most DALY estimates have been calculated as national totals .", "We mapped spatial variation in the burden of human African trypanosomiasis ( HAT ) in Ugan...	[ "Since the 1990s the World Health Organisation has established the disability-adjusted life year ( DALY ) as a metric for the burden of human disease and injury .", "However , disease burden has primarily been estimated at the national scale , which does not account for sub-country variations in burden levels .",...	2014
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[]	Efficient Optimization of Stimuli for Model-Based Design of Experiments to Resolve Dynamical Uncertainty	journal.pcbi.1004488	null	[ [ "Since experiments can be expensive and time consuming , it is important that they are planned to generate useful data .", "Traditional design of experiments is a well established field and has led to many advances in biology and medicine .", "The data obtained from strategically designed experiments ...	[ "This model-based design of experiments ( MBDOE ) method determines the input magnitudes of an experimental stimuli to apply and the associated measurements that should be taken to optimally constrain the uncertain dynamics of a biological system under study .", "The ideal global solution for this experiment desi...	[ "Many mathematical models that have been developed for biological systems are limited because the complex systems are not well understood , the parameters are not known , and available data is limited and noisy .", "On the other hand , experiments to support model development are limited in terms of costs and tim...	2015
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "microbiology", "host-pathogen interaction", "gene function", "genome sequencing", "fungi", "sequence analysis", "mycology", "gene expression", "microbial pathogens", "comparative genomics", "biology", "proteomics", "pathogenesis", "biochemistry", "genetics", "genomics", "computation...	Genomic and Proteomic Analyses of the Fungus Arthrobotrys oligospora Provide Insights into Nematode-Trap Formation	journal.ppat.1002179	null	[ [ "Nematode-trapping fungi are a heterogeneous group of organisms broadly distributed in terrestrial and aquatic ecosystems [1] , [2] .", "These fungi are capable of developing specific trapping devices such as adhesive networks , adhesive knobs , and constricting rings to capture nematodes and then extract...	[ "Nematode-trapping fungi are “carnivorous” and attack their hosts using specialized trapping devices .", "The morphological development of these traps is the key indicator of their switch from saprophytic to predacious lifestyles .", "Here , the genome of the nematode-trapping fungus Arthrobotrys oligospora Fre...	[ "The fungus Arthrobotrys oligospora has multiple lifestyles .", "It's not only a nematode pathogen , but also a saprophyte , a pathogen of other fungi , and a colonizer of plant roots .", "As a nematode pathogen , A . oligospora forms adhesive networks to capture nematodes and is a model organism for understand...	2011
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "geomorphology", "invertebrates", "medicine and health sciences", "body fluids", "pathology and laboratory medicine", "togaviruses", "chikungunya infection", "european union", "landforms", "pathogens", "italian people", "topography", "tropical diseases", "microbiology", "geographical loc...	Vector competence of Italian Aedes albopictus populations for the chikungunya virus (E1-226V)	journal.pntd.0006435	null	[ [ "Chikungunya virus ( CHIKV ) is a zoonotic arthropod-borne virus ( Togaviridae family , Alphavirus genus ) , historically endemic in Africa .", "Since its first isolation during an outbreak in Tanzania in 1952 , several epidemics in African and Asian continents were reported .", "The re-emergence of C...	[ "Chikungunya virus ( CHIKV ) is an emerging arbovirus , belonging to the Togaviridae family , Alphavirus genus , transmitted by Aedes spp .", "mosquitoes .", "Since 2007 , two different CHIKV strains ( E1-226A and E1-226V ) have been responsible for outbreaks in European countries , including Italy , sustained ...	[ "Aedes albopictus is a proven vector of more than 20 different arboviruses and , as demonstrated by experimental infections , is an efficient vector of chikungunya virus ( CHIKV ) in several countries .", "In Italy this widespread species caused the first outbreak of CHIKV in Europe in 2007 ( Emilia-Romagna regio...	2018
[ "Introduction", "Results/Discussion", "Materials and Methods" ]	[ "biochemistry", "protein interactions", "proteins", "protein structure", "biology", "computational biology" ]	The Structural Pathway of Interleukin 1 (IL-1) Initiated Signaling Reveals Mechanisms of Oncogenic Mutations and SNPs in Inflammation and Cancer	journal.pcbi.1003470	null	[ [ "Interleukin-1 ( IL-1 ) is a large family of cytokines ( small cell signaling proteins ) that mediate innate immune responses to defend the host against pathogens .", "The IL-1 family has 11 member proteins ( IL-1F1 to IL-1F11 ) and they are encoded by 11 distinct human and mouse genes [1]–[3] .", "Th...	[ "Interleukin-1 ( IL-1 ) is a large cytokine family closely related to innate immunity and inflammation .", "IL-1 proteins are key players in signaling pathways such as apoptosis , TLR , MAPK , NLR and NF-κB .", "The IL-1 pathway is also associated with cancer , and chronic inflammation increases the risk of tum...	[ "Structural pathways are important because they provide insight into signaling mechanisms; help understand the mechanism of disease-related mutations; and help in drug discovery .", "While extremely useful , common pathway diagrams lacking structural data are unable to provide mechanistic insight to explain oncog...	2014
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "molecular dynamics", "condensed matter physics", "dna-binding proteins", "probability distribution", "mathematics", "polymerases", "network analysis", "protein structure", "crystallography", "crystallization", "research and analysis methods", "computer and information sciences", "solid stat...	Same but not alike: Structure, flexibility and energetics of domains in multi-domain proteins are influenced by the presence of other domains	journal.pcbi.1006008	null	[ [ "A large proportion of proteins , coded in the genomes of diverse organisms , is constituted of more than one domain [1 , 2] .", "Multi-domain proteins have evolved from single-domain proteins through many duplication and adaptive events [3] .", "Duplication and shuffling of domains have led to the em...	[ "The majority of the proteins encoded in the genomes of eukaryotes contain more than one domain .", "Reasons for high prevalence of multi-domain proteins in various organisms have been attributed to higher stability and functional and folding advantages over single-domain proteins .", "Despite these advantages ...	[ "High prevalence of multi-domain proteins in proteomes has been attributed to higher stability and functional and folding advantages of the multi-domain proteins .", "Influence of tethering of domains on the overall properties of proteins has been well studied but its influence on the properties of the constituen...	2018
[ "Introduction", "Results/Discussion", "Materials and Methods" ]	[ "biochemistry", "neurological disorders", "computational biology", "biophysics" ]	Systematic In Vivo Analysis of the Intrinsic Determinants of Amyloid β Pathogenicity	journal.pbio.0050290	A systematic analysis of Alzheimer disease amyloid β peptide variants inDrosophila brain demonstrates that their predicted propensity to form protofibrillar aggregates correlates best with toxicity.	[ [ "A wide range of proteins has been found to convert into extracellular amyloid fibrils , or amyloid-like intracellular inclusions , under physiological conditions [1 , 2] .", "Such proteins have largely been identified through their association with disease , although a number have been found to have bene...	[ "Protein aggregation into amyloid fibrils and protofibrillar aggregates is associated with a number of the most common neurodegenerative diseases .", "We have established , using a computational approach , that knowledge of the primary sequences of proteins is sufficient to predict their in vitro aggregation prop...	[ "A wide range of diseases , including diabetes and common brain diseases of old age , are characterised by the deposition of protein in the affected tissues .", "Alzheimer disease , the most common neurodegenerative disorder , is caused by the aggregation and deposition of a peptide called Aβ in the brain .", "...	2007
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "gene function", "dna replication", "dna", "metabolic pathways", "biology", "molecular biology", "systems biology", "biochemistry", "nitrogen metabolism", "nucleic acids", "genetics", "molecular cell biology", "metabolism", "genetics and genomics" ]	Natural Polymorphism in BUL2 Links Cellular Amino Acid Availability with Chronological Aging and Telomere Maintenance in Yeast	journal.pgen.1002250	null	[ [ "The observation that dietary restriction promotes longevity in organisms ranging from yeast to primates raises the expectation that molecular mechanisms mediating this lifespan extension may also be shared among species .", "In support of the idea that related genetic circuitry controls aging in differen...	[ "Aging and longevity are considered to be highly complex genetic traits .", "In order to gain insight into aging as a polygenic trait , we employed an outbred Saccharomyces cerevisiae model , generated by crossing a vineyard strain RM11 and a laboratory strain S288c , to identify quantitative trait loci that cont...	[ "Dietary restriction promotes longevity in many species , ranging from yeast to primates , and delays aging-related pathologies including cancer in rodent models .", "There is considerable interest in understanding how nutrient limitation mediates these beneficial effects .", "Much of what we have learned about...	2011
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "children", "medicine and health sciences", "immune physiology", "infectious disease epidemiology", "immunology", "geographical locations", "age groups", "antibodies", "families", "genetic epidemiology", "immune system proteins", "infectious diseases", "proteins", "epidemiology", "people...	Cyclical Patterns of Hand, Foot and Mouth Disease Caused by Enterovirus A71 in Malaysia	journal.pntd.0004562	null	[ [ "Hand , foot and mouth disease ( HFMD ) is a common childhood disease , characterized by vesicles on the hands and feet , and ulcers in the mouth .", "Enterovirus A71 ( EV-A71 ) is one of the main causative agents of HFMD apart from coxsackieviruses ( CV ) A6 , A10 , and A16 [1–3] .", "EV-A71 , which ...	[ "Enterovirus A71 ( EV-A71 ) is an important emerging pathogen causing large epidemics of hand , foot and mouth disease ( HFMD ) in children .", "In Malaysia , since the first EV-A71 epidemic in 1997 , recurrent cyclical epidemics have occurred every 2–3 years for reasons that remain unclear .", "We hypothesize ...	[ "Enterovirus A71 ( EV-A71 ) is a major cause of hand , foot , and mouth disease ( HFMD ) in children .", "Since the first outbreak in Malaysia in 1997 , EV-A71 epidemics have occurred every 2–3 years , in 2000 , 2003 , 2006 , 2008/2009 , and 2012 .", "As the reasons for this cyclical pattern are not known , we ...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biochemistry", "molecular cell biology", "protein interactions", "proteins", "protein structure", "biology", "microbiology", "parasitology" ]	Structural and Functional Insights into the Malaria Parasite Moving Junction Complex	journal.ppat.1002755	null	[ [ "Plasmodium spp .", ", and P . falciparum in particular , are devastating global pathogens that place nearly half the human population at risk to malaria , leading to more than 250 million cases yearly and over one million deaths [1] .", "The success of the malaria parasite can be attributed to its in...	[ "Members of the phylum Apicomplexa , which include the malaria parasite Plasmodium , share many features in their invasion mechanism in spite of their diverse host cell specificities and life cycle characteristics .", "The formation of a moving junction ( MJ ) between the membranes of the invading apicomplexan pa...	[ "Malaria arises from infection of erythrocytes by single-cell parasites belonging to the genus Plasmodium , the species P . falciparum causing the most severe forms of the disease .", "The formation of a moving junction ( MJ ) between the membranes of the parasite and its host cell is essential for invasion .", ...	2012
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[]	Natural Terpenoids from Ambrosia Species Are Active In Vitro and In Vivo against Human Pathogenic Trypanosomatids	journal.pntd.0002494	null	[ [ "Natural products have been a major source of drugs mainly for treating infectious diseases and cancer [1] .", "About 75% of anti-infective drugs approved from 1981 to 2002 are derived from natural sources .", "Many of them were isolated from plants and have shown antiparasitic activity .", "The f...	[ "Among the natural compounds , terpenoids play an important role in the drug discovery process for tropical diseases .", "The aim of the present work was to isolate antiprotozoal compounds from Ambrosia elatior and A . scabra .", "The sesquiterpene lactone ( STL ) cumanin was isolated from A . elatior whereas t...	[ "In addition to the primary metabolism necessary for life , plants have a secondary metabolism that generates compounds , which aid in their growth and development .", "A common role of secondary metabolites is defense mechanisms to fight off animals , pest and pathogens .", "Pharmacognosy takes advantage of th...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biochemistry", "rna", "micrornas", "plant science", "plant disease resistance", "gene expression", "genetics", "gene regulation", "biology and life sciences", "plant pathology" ]	The miR9863 Family Regulates Distinct Mla Alleles in Barley to Attenuate NLR Receptor-Triggered Disease Resistance and Cell-Death Signaling	journal.pgen.1004755	null	[ [ "Plants have evolved two major classes of immune receptors for pathogen recognition and defense activation [1] .", "Pattern recognition receptors ( PRRs ) detect conserved pathogen associated molecular patterns ( PAMP ) and trigger PAMP-triggered immunity ( PTI ) [2] , whilst intracellular NB-LRR ( NLR ) ...	[ "Barley ( Hordeum vulgare L . ) Mla alleles encode coiled-coil ( CC ) , nucleotide binding , leucine-rich repeat ( NB-LRR ) receptors that trigger isolate-specific immune responses against the powdery mildew fungus , Blumeria graminis f .", "sp .", "hordei ( Bgh ) .", "How Mla or NB-LRR genes in grass species...	[ "Plants rely on cell-surface and intracellular immune receptors to sense pathogen invasion and to mediate defense responses .", "However , uncontrolled activation of immune responses is harmful to plant growth and development .", "Small RNAs have recently been shown to fine-tune the expression of intracellular ...	2014
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "medicine and health sciences", "brown adipose tissue", "messenger rna", "long non-coding rnas", "cell differentiation", "developmental biology", "adipocytes", "connective tissue cells", "genome analysis", "adipocyte differentiation", "lipids", "genomics", "animal cells", "fats", "gene e...	Dynamic transcriptome changes during adipose tissue energy expenditure reveal critical roles for long noncoding RNA regulators	journal.pbio.2002176	null	[ [ "Obesity has reached an epidemic proportion in both developed and developing nations , resulting in a steep rise in healthcare expenses and a growing population with associated comorbidities and chronic illnesses [1] .", "An attractive approach for obesity therapy is to augment the mass and activities of ...	[ "Enhancing brown fat activity and promoting white fat browning are attractive therapeutic strategies for treating obesity and associated metabolic disorders .", "To provide a comprehensive picture of the gene regulatory network in these processes , we conducted a series of transcriptome studies by RNA sequencing ...	[ "Fat accumulation is a major health problem in many countries , but unlike white fat—which stores calories—brown fat is packed with mitochondria to burn energy .", "Therefore , promoting “browning” of white fat and enhancing brown fat activity are seen as promising therapeutic strategies to fight obesity .", "L...	2017
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "sequencing techniques", "organismal evolution", "medicine and health sciences", "chemical compounds", "pathology and laboratory medicine", "pathogens", "geographical locations", "microbiology", "australia", "organic compounds", "viruses", "rna viruses", "amino acid substitution", "phyloge...	Archival Isolates Confirm a Single Topotype of West Nile Virus in Australia	journal.pntd.0005159	null	[ [ "West Nile virus ( Family Flaviviridae; Genus Flavivirus ) is a mosquito-borne virus which can cause disease in humans , horses and birds .", "In humans , the disease can manifest as a fever with rash and , infrequently , neurological disease including meningitis , encephalitis and acute flaccid paralysis...	[ "West Nile virus is globally wide-spread and causes significant disease in humans and animals .", "The evolution of West Nile virus Kunjin subtype in Australia ( WNVKUN ) was investigated using archival samples collected over a period of 50 years .", "Based on the pattern of fixed amino acid substitutions and t...	[ "West Nile virus is endemic in Australia , and is considered benign in relation to strains that circulate globally .", "In 2011 , a more pathogenic variant emerged which caused disease in horses .", "To understand the evolution of the virus , and as a background to the emergence of the pathogenic strain , we us...	2016
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "medicine", "infectious diseases", "schistosomiasis", "neglected tropical diseases", "parasitic diseases" ]	Long-Term Impact of the World Bank Loan Project for Schistosomiasis Control: A Comparison of the Spatial Distribution of Schistosomiasis Risk in China	journal.pntd.0001620	null	[ [ "Schistosomiasis japonica , a disease caused by the trematode Schistosoma japonicum , has a documented history of more than 2100 years in China [1] .", "It severely impacts the health of residents within endemic areas , causing substantial morbidity such as wasting , weakness , ascites and growth retardat...	[ "The World Bank Loan Project ( WBLP ) for controlling schistosomiasis in China was implemented during 1992–2001 .", "Its short-term impact has been assessed from non-spatial perspective , but its long-term impact remains unclear and a spatial evaluation has not previously been conducted .", "Here we compared th...	[ "Schistosomiasis japonica is an important disease in China with a documented history of more than 2 , 100 years .", "The World Bank Loan Project ( WBLP ) implemented during 1992–2001 contributed greatly to China's schistosomiasis control .", "This study shows that the long-term impact of WBLP strategy on schist...	2012
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "mast cells", "cell physiology", "medicine and health sciences", "neurochemistry", "pathology and laboratory medicine", "chemical compounds", "vomiting", "vertebrates", "marmosets", "neuroscience", "animals", "mammals", "organic compounds", "animal models", "primates", "physiological p...	Histamine release from intestinal mast cells induced by staphylococcal enterotoxin A (SEA) evokes vomiting reflex in common marmoset	journal.ppat.1007803	null	[ [ "Staphylococcal enterotoxins ( SEs ) produced by Staphylococcus aureus ( S . aureus ) have emetic activity and are causative agents of bacterial food poisoning .", "The primary symptoms of staphylococcal food poisoning include nausea , abdominal cramping and vomiting , which develop up to 1–6 h after inge...	[ "Staphylococcal enterotoxins ( SEs ) produced by Staphylococcus aureus are known as causative agents of emetic food poisoning .", "We previously demonstrated that SEA binds with submucosal mast cells and evokes mast cell degranulation in a small emetic house musk shrew model .", "Notably , primates have been re...	[ "Staphylococcal enterotoxin A ( SEA ) is a bacterial toxin that has been recognized as a leading causative agent of staphylococcal food poisoning since 1930 .", "The primary symptoms of staphylococcal food poisoning are nausea and emesis , which develop up to 1–6 h after ingestion of the causative foods contamina...	2019
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "invertebrates", "cell cycle and cell division", "cell processes", "cloning", "departures from diploidy", "animals", "animal models", "mitosis", "drosophila melanogaster", "model organisms", "experimental organism systems", "cytokinesis", "genome analysis", "molecular biology techniques", ...	A Cyclin A—Myb-MuvB—Aurora B network regulates the choice between mitotic cycles and polyploid endoreplication cycles	journal.pgen.1008253	null	[ [ "Endoreplication is a common cell cycle variant that entails periodic genome duplication without cell division and results in large polyploid cells [1] .", "Two variations on endoreplication are the endocycle , a repeated G/S cycle that completely skips mitosis , and endomitosis , wherein cells enter but ...	[ "Endoreplication is a cell cycle variant that entails cell growth and periodic genome duplication without cell division , and results in large , polyploid cells .", "Cells switch from mitotic cycles to endoreplication cycles during development , and also in response to conditional stimuli during wound healing , r...	[ "Endoreplication is a cell cycle variant that entails cell growth and periodic genome duplication without cell division , and results in large , polyploid cells .", "Cells switch from mitotic division cycles to endoreplication cycles during development , and also in response to conditional stimuli during wound he...	2019
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "medicine", "disease mapping", "infectious diseases", "public health and epidemiology", "epidemiology", "global health", "dengue fever", "neglected tropical diseases", "dengue", "viral diseases", "epidemiological methods", "disease informatics" ]	Refining the Global Spatial Limits of Dengue Virus Transmission by Evidence-Based Consensus	journal.pntd.0001760	null	[ [ "Despite increased interest in dengue in recent years , the global distribution of dengue remains highly uncertain .", "Estimates for the population at risk range from 30% [1] to 54 . 7% [2] of the world's population ( 2 . 05–3 . 74 billion ) while the Centers for Disease Control ( CDC ) and the World Hea...	[ "Dengue is a growing problem both in its geographical spread and in its intensity , and yet current global distribution remains highly uncertain .", "Challenges in diagnosis and diagnostic methods as well as highly variable national health systems mean no single data source can reliably estimate the distribution ...	[ "Previous attempts to map the current global distribution of dengue virus transmission have produced variable results , particularly in Africa , reflecting the lack of accuracy in both diagnostic and locational information of reported dengue cases .", "In this study , instead of excluding these less informed poin...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genetics and genomics/nuclear structure and function", "cell biology", "genetics and genomics/chromosome biology" ]	Sequential Assembly of Centromeric Proteins in Male Mouse Meiosis	journal.pgen.1000417	null	[ [ "Accurate chromosome segregation in mitosis is crucial to maintain a diploid chromosome number .", "Errors in chromosome segregation result in aneuploid daughter cells which are prone to become malignant .", "The centromere is the chromosome domain that directs this segregation process since it is inv...	[ "The assembly of the mitotic centromere has been extensively studied in recent years , revealing the sequence and regulation of protein loading to this chromosome domain .", "However , few studies have analyzed centromere assembly during mammalian meiosis .", "This study specifically targets this approach on mo...	[ "The centromere is a chromosome domain essential for the correct partitioning of chromosomes during mitotic and meiotic cell divisions .", "The characterization of the centromeric proteins and their sequential assembly have been extensively studied in mammalian mitosis , since defective chromosome segregation is ...	2009
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine", "infectious diseases", "biology", "microbiology" ]	The Salmonella Deubiquitinase SseL Inhibits Selective Autophagy of Cytosolic Aggregates	journal.ppat.1002743	null	[ [ "Salmonella enterica is a facultative intracellular pathogen that survives and replicates in a variety of hosts .", "The virulence traits of Salmonella include the Salmonella pathogenicity-island ( SPI ) -1- and -2-encoded type 3 secretion systems ( T3SSs ) , which are important for invasion of host cells...	[ "Cell stress and infection promote the formation of ubiquitinated aggregates in both non-immune and immune cells .", "These structures are recognised by the autophagy receptor p62/sequestosome 1 and are substrates for selective autophagy .", "The intracellular growth of Salmonella enterica occurs in a membranou...	[ "Ubiquitination can target substrates to a number of fates , including autophagy , the essential cellular process that allows cells to degrade cytosolic material .", "Although Salmonella enterica resides in a vacuolar compartment during infection , it translocates several virulence proteins into the host cell cyt...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Exome Sequencing in an Admixed Isolated Population Indicates NFXL1 Variants Confer a Risk for Specific Language Impairment	journal.pgen.1004925	null	[ [ "Language deficits form a central feature of many developmental disorders and account for a high number of pediatric referrals and statements of special educational need [1] .", "These language impairments often represent a secondary clinical feature of a more pertinent developmental disability such as Do...	[ "Children affected by Specific Language Impairment ( SLI ) fail to acquire age appropriate language skills despite adequate intelligence and opportunity .", "SLI is highly heritable , but the understanding of underlying genetic mechanisms has proved challenging .", "In this study , we use molecular genetic tech...	[ "Children affected by Specific Language Impairment ( SLI ) have unexpected problems learning to talk and understand language , despite developing normally in all other areas .", "This disorder runs in families but we do not understand how the genetic contributions work , or which genetic mechanisms might be impor...	2015
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "plant anatomy", "medicine and health sciences", "pathology and laboratory medicine", "population genetics", "brassica", "plant science", "model organisms", "coevolution", "experimental organism systems", "plant pathology", "population biology", "plants", "arabidopsis thaliana", "research ...	Cucumber mosaic virus infection as a potential selective pressure on Arabidopsis thaliana populations	journal.ppat.1007810	null	[ [ "It is commonly accepted that hosts and pathogens coevolve [1] .", "This concept rests on the assumption that pathogens are virulent parasites , defining virulence as the negative impact of infection on the host fitness .", "As a consequence , hosts will evolve defences to limit pathogen infection , o...	[ "It has been proposed that in wild ecosystems viruses are often plant mutualists , whereas agroecosystems favour pathogenicity .", "We seek evidence for virus pathogenicity in wild ecosystems through the analysis of plant-virus coevolution , which requires a negative effect of infection on the host fitness .", ...	[ "Plant-virus coevolution has not been demonstrated in any wild system , and it has been proposed that viruses often would be mutualistic symbionts , rather than pathogens , in wild plant ecosystems .", "We analyse if viruses are virulent pathogens of plants in wild ecosystems and , consequently , plants have evol...	2019
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "evolutionary biology", "genetics", "biology", "model organisms" ]	Rapid Sequential Spread of Two Wolbachia Variants in Drosophila simulans	journal.ppat.1003607	null	[ [ "The vertically-transmitted intracellular bacterium Wolbachia may be the most widespread [1]–[3] and evolutionarily significant endosymbiont [4] , [5] of insects and other arthropods .", "Wolbachia induce many reproductive manipulations within hosts that increase their chance of spreading through females ...	[ "The maternally inherited intracellular bacteria Wolbachia can manipulate host reproduction in various ways that foster frequency increases within and among host populations .", "Manipulations involving cytoplasmic incompatibility ( CI ) , where matings between infected males and uninfected females produce non-vi...	[ "Wolbachia are bacteria that live within the cells of arthropod hosts and are widespread in many groups of insects .", "These bacteria can rapidly spread through a population through a process of cytoplasmic incompatibility whereby females uninfected by Wolbachia show embryo death when they mate with males carryi...	2013
[ "Introduction", "Materials and Methods", "Results/Discussion" ]	[ "genetics and genomics/genomics", "molecular biology/dna replication", "genetics and genomics/gene expression", "genetics and genomics/functional genomics", "genetics and genomics/gene function", "cell biology/gene expression" ]	Mechanisms of Cell Cycle Control Revealed by a Systematic and Quantitative Overexpression Screen in S. cerevisiae	journal.pgen.1000120	null	[ [ "The budding yeast Saccharomyces cerevisiae undergoes a cell cycle similar to other eukaryotic organisms except for the lack of nuclear envelope dissolution during mitosis and the production of daughter cells via budding , and thus budding yeast has become a model system for studying eukaryotic cell cycle pro...	[ "Regulation of cell cycle progression is fundamental to cell health and reproduction , and failures in this process are associated with many human diseases .", "Much of our knowledge of cell cycle regulators derives from loss-of-function studies .", "To reveal new cell cycle regulatory genes that are difficult ...	[ "All cells require proper cell cycle regulation; failure leads to numerous human diseases .", "Cell cycle mechanisms are broadly conserved across eukaryotes , with many key regulatory genes known .", "Nonetheless , our knowledge of regulators is incomplete .", "Many classic studies have analyzed yeast loss-of...	2008
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "blood cells", "flow cytometry", "medicine and health sciences", "immune cells", "immune physiology", "spleen", "immunology", "parasitic diseases", "parasitic protozoans", "parasitology", "parasitemia", "protozoans", "antibodies", "quantitative parasitology", "research and analysis metho...	Trypanosoma brucei Co-opts NK Cells to Kill Splenic B2 B Cells	journal.ppat.1005733	null	[ [ "Trypanosoma brucei brucei , T . congolense and T . vivax cause Animal African Trypanosomiasis , which severely constrains cattle ranching and integrated agriculture in sub-Saharan Africa [1] .", "In addition , two sub-species of T . brucei , namely T . b .", "gambiense and T . b .", "rhodesiense ...	[ "After infection with T . brucei AnTat 1 . 1 , C57BL/6 mice lost splenic B2 B cells and lymphoid follicles , developed poor parasite-specific antibody responses , lost weight , became anemic and died with fulminating parasitemia within 35 days .", "In contrast , infected C57BL/6 mice lacking the cytotoxic granule...	[ "Trypanosomiasis-susceptible mammals that are infected with African trypanosomes develop anemia , lose weight , lose immune competence and have an increased susceptibility to secondary infections .", "Our earlier studies in the T . b .", "brucei AnTat 1 . 1 mouse model of African trypanosomiasis show that infec...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Decline of FoxP3+ Regulatory CD4 T Cells in Peripheral Blood of Children Heavily Exposed to Malaria	journal.ppat.1005041	null	[ [ "FoxP3+ regulatory CD4 T cells ( Tregs ) play a central role in preventing autoimmunity and maintaining self-tolerance .", "In the setting of infection , Tregs help to maintain the delicate balance between pathogen-specific immunity and immune-mediated pathology .", "Preserving this equilibrium requir...	[ "FoxP3+ regulatory CD4 T cells ( Tregs ) help to maintain the delicate balance between pathogen-specific immunity and immune-mediated pathology .", "Prior studies suggest that Tregs are induced by P . falciparum both in vivo and in vitro; however , the factors influencing Treg homeostasis during acute and chronic...	[ "In malaria endemic regions , immunity is slow to develop and does not provide substantial protection against reinfection .", "Rather , following repeated exposure , older children and adults eventually develop protection from most symptomatic manifestations of the infection .", "This may be due in part to the ...	2015
[ "Introduction", "Methods", "Results", "Discussion" ]	[]	The Impact of Climatic Risk Factors on the Prevalence, Distribution, and Severity of Acute and Chronic Trachoma	journal.pntd.0002513	null	[ [ "The neglected tropical disease ( NTD ) trachoma , caused by Chlamydia trachomatis , is the world's leading cause of infectious blindness [1] and an important cause of chronic discomfort in 57 endemic countries , mainly in Africa [2] .", "Over 40 million people are infected with C . trachomatis , 8 millio...	[ "Trachoma is the most common cause of infectious blindness .", "Hot , dry climates , dust and water scarcity are thought to be associated with the distribution of trachoma but the evidence is unclear .", "The aim of this study was to evaluate the epidemiological evidence regarding the extent to which climatic f...	[ "Trachoma – the leading cause of infectious blindness – is spread through contact with infected persons by hands and towels , and by ‘eye-seeking flies . ’ Trachoma prevalence is high in areas characterised by poverty , inadequate water supply , and poor sanitation .", "Trachoma is controlled by the SAFE strategy...	2013
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "genome-wide association studies", "genetic association studies", "genome analysis", "genetics", "biology and life sciences", "computational biology", "human genetics" ]	Principal Component Analysis Characterizes Shared Pathogenetics from Genome-Wide Association Studies	journal.pcbi.1003820	null	[ [ "Comorbidity studies show that some distinct diseases tend to co-occur [1]–[6] , pointing to a shared genetic and/or environmental component .", "In the era of genome-wide association studies ( GWASs ) , direct evidence of shared genetic risk factors of diseases comes to light [7] .", "For example , w...	[ "Genome-wide association studies ( GWASs ) have recently revealed many genetic associations that are shared between different diseases .", "We propose a method , disPCA , for genome-wide characterization of shared and distinct risk factors between and within disease classes .", "It flips the conventional GWAS p...	[ "Epidemiological studies have revealed distinct diseases that tend to co-occur in individuals .", "As genome-wide association studies ( GWASs ) have increased in numbers , more evidence regarding the genetic nature of this shared disease etiology is revealed .", "Here , we present a novel method that utilizes p...	2014
[ "Introduction", "Materials and methods", "Results", "Discussion" ]	[ "genome-wide association studies", "medicine and health sciences", "breast tumors", "volcanology", "magma", "statistics", "cancers and neoplasms", "oncology", "developmental biology", "mathematics", "test statistics", "genome analysis", "geology", "morphogenesis", "research and analysis ...	Powerful gene set analysis in GWAS with the Generalized Berk-Jones statistic	journal.pgen.1007530	null	[ [ "A common objective in genetic association studies is to search for associations between phenotypes and genomic constructs that are larger than a Single Nucleotide Polymorphism ( SNP ) .", "One popular unit of analysis is the set of all SNPs that are located near a list of related genes; inference on thes...	[ "A common complementary strategy in Genome-Wide Association Studies ( GWAS ) is to perform Gene Set Analysis ( GSA ) , which tests for the association between one phenotype of interest and an entire set of Single Nucleotide Polymorphisms ( SNPs ) residing in selected genes .", "While there exist many tools for pe...	[ "Researchers are frequently interested in the association between a biologically related set of genes—for example , a particular immune response pathway—and a complex phenotype .", "Such associations are often explored by applying various gene set analysis methods to genotype data from genome-wide association stu...	2019
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biotechnology", "medicine and health sciences", "functional genomics", "health care", "genome analysis", "genetic elements", "dna", "gene regions", "molecular genetics", "pharmacoeconomics", "health economics", "gene expression", "biochemistry", "gene regulatory networks", "genetics", ...	Genome-Wide Discovery of Drug-Dependent Human Liver Regulatory Elements	journal.pgen.1004648	null	[ [ "Adverse reactions to drug treatment constitute a substantial health problem that is a leading cause of morbidity and mortality in hospitalized patients [1] .", "Differential expression of drug metabolizing enzymes and drug transporters is a major determinant of inter-individual drug response variability ...	[ "Inter-individual variation in gene regulatory elements is hypothesized to play a causative role in adverse drug reactions and reduced drug activity .", "However , relatively little is known about the location and function of drug-dependent elements .", "To uncover drug-associated elements in a genome-wide mann...	[ "Drug response varies between individuals and can be caused by genetic factors .", "Nucleotide variation in gene regulatory elements can have a significant effect on drug response , but due to the difficulty in identifying these elements , they remain understudied .", "Here , we used various genomic assays to a...	2014
[ "Introduction", "Methods", "Results", "Discussion" ]	[]	Multiscale Mechanical Model of the Pacinian Corpuscle Shows Depth and Anisotropy Contribute to the Receptor’s Characteristic Response to Indentation	journal.pcbi.1004370	null	[ [ "Mechanoreceptors , a major component of the somatosensory system , detect specific physical stimuli and produce neural signals that give rise to sensations such as touch and pain [1] .", "Cutaneous mechanoreceptors respond to mechanical stimuli and consist of afferent nerve fibers surrounded by specializ...	[ "Cutaneous mechanoreceptors transduce different tactile stimuli into neural signals that produce distinct sensations of touch .", "The Pacinian corpuscle ( PC ) , a cutaneous mechanoreceptor located deep within the dermis of the skin , detects high frequency vibrations that occur within its large receptive field ...	[ "We performed computer simulations of the mechanical behavior of the Pacinian corpuscle ( PC ) , a sensory receptor in the skin that helps detect short-term contact and high-frequency vibration .", "The PC is composed of a series of tissue layers , and we found that this characteristic structure may explain the r...	2015
[ "Introduction", "Materials and methods", "Results", "Discussion" ]	[ "biogeography", "ecology and environmental sciences", "medicine and health sciences", "mitochondrial dna", "population genetics", "geographical locations", "uganda", "genetic mapping", "aquatic environments", "forms of dna", "bodies of water", "dna", "population biology", "infectious disea...	Genetic diversity and population structure of the tsetse fly Glossina fuscipes fuscipes (Diptera: Glossinidae) in Northern Uganda: Implications for vector control	journal.pntd.0005485	null	[ [ "The tsetse fly ( genus Glossina ) is the major vector of human African trypanosomiasis ( HAT ) and animal African trypanosomiasis ( AAT ) .", "The diseases occur throughout sub-Saharan Africa , causing extensive morbidity and mortality in humans and livestock [1][2] .", "Human disease is caused by tw...	[ "Uganda is the only country where the chronic and acute forms of human African Trypanosomiasis ( HAT ) or sleeping sickness both occur and are separated by < 100 km in areas north of Lake Kyoga .", "In Uganda , Glossina fuscipes fuscipes is the main vector of the Trypanosoma parasites responsible for these diseas...	[ "Northern Uganda is an epidemiologically important region affected by human African trypanosomiasis ( HAT ) because it harbors both forms of the HAT disease ( T . b . gambiense and T . b . rhodesiense ) .", "The geographic location of this region creates the risk that these distinct foci could merge , which would...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine", "developmental biology", "clinical immunology", "immunology", "biology" ]	Development and Function of Invariant Natural Killer T Cells Producing TH2- and TH17-Cytokines	journal.pbio.1001255	Four distinct subsets of invariant natural killer T (NKT) cells are shown to differentiate in the thymus, then migrate to peripheral tissues where they retain their phenotypic and functional characteristics.	[ [ "Natural killer T ( NKT ) cells , unlike conventional T cells bearing diverse antigen receptors , are characterized by the expression of an invariant T cell receptor ( TCR ) , Vα14Jα18 paired with Vβ8 , Vβ7 , or Vβ2 in mice [1] and the Vα24Jα18/Vβ11 pair in humans [2] , [3] , that recognizes glycolipid antige...	[ "There is heterogeneity in invariant natural killer T ( iNKT ) cells based on the expression of CD4 and the IL-17 receptor B ( IL-17RB ) , a receptor for IL-25 which is a key factor in TH2 immunity .", "However , the development pathway and precise function of these iNKT cell subtypes remain unknown .", "IL-17R...	[ "T cells are a diverse group of immune cells involved in cell-mediated acquired immunity .", "One subset of T cells is the innate-like invariant natural killer T ( iNKT ) cells that recognize glycolipid ligands on target cells instead of peptides .", "We know that functionally distinct subtypes of iNKT cells ar...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods", "Supporting Information" ]	[ "mathematics", "saccharomyces", "homo (human)", "computational biology" ]	Discovering Motifs in Ranked Lists of DNA Sequences	journal.pcbi.0030039	null	[ [ "This paper examines the problem of discovering “interesting” sequence motifs in biological sequence data .", "A widely accepted and more formal definition of this task is: given a target set and a background set of sequences ( or a background model ) , identify sequence motifs that are enriched in the ta...	[ "Computational methods for discovery of sequence elements that are enriched in a target set compared with a background set are fundamental in molecular biology research .", "One example is the discovery of transcription factor binding motifs that are inferred from ChIP–chip ( chromatin immuno-precipitation on a m...	[ "A computational problem with many applications in molecular biology is to identify short DNA sequence patterns ( motifs ) that are significantly overrepresented in a target set of genomic sequences relative to a background set of genomic sequences .", "One example is a target set that contains DNA sequences to w...	2007
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "death rates", "larvicides", "invertebrates", "medicine and health sciences", "demography", "population dynamics", "binomials", "animals", "age groups", "adults", "mathematics", "algebra", "pest control", "population biology", "insect vectors", "polynomials", "agrochemicals", "epid...	Assessment of the Effectiveness of a Seasonal-Long Insecticide-Based Control Strategy against Aedes albopictus Nuisance in an Urban Area	journal.pntd.0004463	null	[ [ "In the case of major malaria and Dengue vector species , which are the most frequent targets of insecticide-based interventions , the most important parameter to define the effectiveness of a treatment is its impact on disease transmission and morbidity/mortality .", "In the absence of disease transmissi...	[ "Seasonal-long larvicide treatments and/or outdoor space-spray applications of insecticides are frequently applied to reduce Aedes albopictus nuisance in urban areas of temperate regions , where the species has become a permanent pest affecting people’s quality of life and health .", "However , assessments of the...	[ "Due to the considerable nuisance created by the aggressive day-time biting behaviour of the “tiger mosquito , ” insecticide treatments are largely employed in urban areas of temperate regions where this tropical species has become a permanent pest .", "These include treatments of catch basins with lethal product...	2016
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "biotechnology", "biochemistry", "biochemical simulations", "medicine and health sciences", "pharmacogenetics", "biology and life sciences", "pharmacology", "computational biology", "biophysics", "pharmacogenomics", "biophysical simulations" ]	Molecular Insights into the Dynamics of Pharmacogenetically Important N-Terminal Variants of the Human β2-Adrenergic Receptor	journal.pcbi.1004006	null	[ [ "G protein-coupled receptors ( GPCRs ) constitute a family of membrane proteins that serve as important communication mediators in cellular signal transduction [1] , [2] .", "GPCRs are thus critical in the modulation of several signaling related disorders [3] , [4] and constitute more than 25% of all huma...	[ "The human β2-adrenergic receptor ( β2AR ) , a member of the G-protein coupled receptor ( GPCR ) family , is expressed in bronchial smooth muscle cells .", "Upon activation by agonists , β2AR causes bronchodilation and relief in asthma patients .", "The N-terminal polymorphism of β2AR at the 16th position , Arg...	[ "The human β2-adrenergic receptor ( β2AR ) is an important member of the GPCR family and a mutation at the 16th position , Arg16Gly , is commonly found in the population .", "This variation in asthma patients is linked to differential ( good/bad ) response to the drug albuterol , an agonist of the β2AR .", "To ...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Myopathic Lamin Mutations Cause Reductive Stress and Activate the Nrf2/Keap-1 Pathway	journal.pgen.1005231	null	[ [ "The human LMNA gene exemplifies the rich source of genetic variation that exists in the human genome .", "Over 283 sequence variants and 460 disease-causing mutations have been identified to date .", "These mutations cause at least 13 distinct clinical diseases , called laminopathies , which have mai...	[ "Mutations in the human LMNA gene cause muscular dystrophy by mechanisms that are incompletely understood .", "The LMNA gene encodes A-type lamins , intermediate filaments that form a network underlying the inner nuclear membrane , providing structural support for the nucleus and organizing the genome .", "To b...	[ "Mutations in the human LMNA gene cause muscular dystrophy that is often accompanied by heart disease .", "The LMNA gene makes proteins that form a network on the inner side of the nuclear envelope , a structure that reinforces the cell nucleus .", "How mutations in the LMNA gene cause muscle disease is not wel...	2015
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "biotechnology", "medicine and health sciences", "infectious disease epidemiology", "immunology", "microbiology", "synthetic bioengineering", "immunodeficiency viruses", "protein engineering", "plant science", "sexually transmitted diseases", "population modeling", "plant pathology", "evolut...	Immuno-epidemiological Modeling of HIV-1 Predicts High Heritability of the Set-Point Virus Load, while Selection for CTL Escape Dominates Virulence Evolution	journal.pcbi.1003899	null	[ [ "Human immunodeficiency virus type 1 ( HIV-1 ) evolves under two levels of selection .", "On the one hand , there is within-host selection for immune escape .", "On the other hand , selection on the population-level acts on infectiousness and virulence .", "In this paper , we explore how these two...	[ "It has been suggested that HIV-1 has evolved its set-point virus load to be optimized for transmission .", "Previous epidemiological models and studies into the heritability of set-point virus load confirm that this mode of adaptation within the human population is feasible .", "However , during the many cycle...	[ "HIV-1 is a relatively young virus , being introduced in the human population somewhere between 1884 and 1924 .", "Yet , previous studies suggest that the virus has already evolved to be efficiently transmitted among humans .", "Efficient transmission occurs when the set-point virus load , the semi-stable numbe...	2014
[ "Introduction", "Results and Discussion", "Materials and Methods" ]	[ "genome evolution", "population genetics", "microbiology", "escherichia coli", "mutation", "coevolution", "evolutionary adaptation", "bacterial pathogens", "genetic polymorphism", "medical microbiology", "microbial pathogens", "evolutionary genetics", "microbial ecology", "ecology", "nat...	Ex Uno Plures: Clonal Reinforcement Drives Evolution of a Simple Microbial Community	journal.pgen.1004430	null	[ [ "Illuminating the laws that produce Darwin's “tangled bank” remains one of the great challenges of biology , one that requires understanding how differences among forms are selected for , and how interdependence among forms is generated .", "In natural environments , meeting this challenge is complicated ...	[ "A major goal of genetics is to define the relationship between phenotype and genotype , while a major goal of ecology is to identify the rules that govern community assembly .", "Achieving these goals by analyzing natural systems can be difficult , as selective pressures create dynamic fitness landscapes that va...	[ "The variability of natural systems makes it difficult to deduce how organisms' genotypes manifest as phenotypes , and how communities of interacting organisms arise .", "Using laboratory experimental evolution we can control this variation .", "We previously showed that a population of E . coli that originated...	2014
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "invertebrates", "medicine and health sciences", "rna interference", "nervous system", "electrophysiology", "neuroscience", "animals", "animal models", "multivariate analysis", "drosophila melanogaster", "model organisms", "mathematics", "morphometry", "statistics (mathematics)", "bioass...	A New Fiji-Based Algorithm That Systematically Quantifies Nine Synaptic Parameters Provides Insights into Drosophila NMJ Morphometry	journal.pcbi.1004823	null	[ [ "Normal brain function relies on functional neuronal networks in which neurons connect and communicate with one another .", "Communication primarily takes place at chemical synapses , where neurotransmitters are released from the presynaptic compartment of a neuron and activate receptors at the postsynapt...	[ "The morphology of synapses is of central interest in neuroscience because of the intimate relation with synaptic efficacy .", "Two decades of gene manipulation studies in different animal models have revealed a repertoire of molecules that contribute to synapse development .", "However , since such studies oft...	[ "Altered synapse function underlies cognitive disorders such as intellectual disability , autism and schizophrenia .", "The morphology of synapses is crucial for their function but is often described using only a small number of parameters or categories .", "As a consequence , it is still unknown how different ...	2016
[ "Introduction", "Results", "Discussion", "Conclusion", "Materials and methods" ]	[ "cell physiology", "medicine and health sciences", "fish", "nervous system", "vertebrates", "electrophysiology", "green fluorescent protein", "neuroscience", "animals", "cell polarity", "animal models", "osteichthyes", "developmental biology", "luminescent proteins", "model organisms", ...	Hair cell identity establishes labeled lines of directional mechanosensation	journal.pbio.2004404	null	[ [ "Two of the most highly conserved sensory-neural maps in vertebrates are those underlying postural control during locomotion and rheotaxis [1–8] .", "These sensory-motor processes originate from the action of mechanoreceptive hair cells residing , respectively , in the inner ear and in the lateral line [9...	[ "Directional mechanoreception by hair cells is transmitted to the brain via afferent neurons to enable postural control and rheotaxis .", "Neuronal tuning to individual directions of mechanical flow occurs when each peripheral axon selectively synapses with multiple hair cells of identical planar polarization .",...	[ "Mechanosensory systems are essential for maintaining posture , gaze , and body orientation during locomotion .", "Such stability requires a coherent representation in the brain of the location and movement of mechanical stimuli .", "In fishes , mechanical stimuli at a given position activate direction-sensitiv...	2018
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "medicine", "antivirals", "infectious diseases", "mechanisms of resistance and susceptibility", "genomics", "hepatitis", "mathematics", "hepatitis b", "viral persistence and latency", "gene therapy", "virology", "microbiology", "biology", "nonlinear dynamics", "viral diseases", "infect...	Predictors of Hepatitis B Cure Using Gene Therapy to Deliver DNA Cleavage Enzymes: A Mathematical Modeling Approach	journal.pcbi.1003131	null	[ [ "To date , cure of most chronic viral infections has remained an impossible goal .", "Replicating forms of hepatitis B virus ( HBV ) , Herpes Simplex Virus ( HSV ) and Human Immunodeficiency Virus ( HIV ) can be targeted with potent small molecule therapies , thereby decreasing the burden of disease assoc...	[ "Most chronic viral infections are managed with small molecule therapies that inhibit replication but are not curative because non-replicating viral forms can persist despite decades of suppressive treatment .", "There are therefore numerous strategies in development to eradicate all non-replicating viruses from ...	[ "Innovative new approaches are being developed to eradicate viral infections that until recently were considered incurable .", "We are interested in engineering DNA cleavage enzymes that can cut and incapacitate persistent viruses .", "One hurdle is that these enzymes must be delivered to infected cells as gene...	2013
[ "Introduction", "Results/Discussion", "Materials and Methods" ]	[ "cell biology/neuronal and glial cell biology", "neuroscience/sensory systems", "cell biology/cell signaling", "cell biology/morphogenesis and cell biology", "cell biology/developmental molecular mechanisms", "cell biology/neuronal signaling mechanisms", "neuroscience/neurodevelopment", "developmental...	Hydrogen Peroxide Promotes Injury-Induced Peripheral Sensory Axon Regeneration in the Zebrafish Skin	journal.pbio.1000621	Production of H2O2 by injured zebrafish skin cells promotes the regeneration of nearby somatosensory axon terminals, thus coordinating wound healing of the skin with sensory reinnervation.	[ [ "Successful wound repair and regeneration requires coordination between the various cell types that make up the injured tissue .", "For example , following injuries that damage both epidermis and sensory endings , wounded epidermis promotes the regeneration of nerve fibers [1] , [2] .", "Conversely , ...	[ "Functional recovery from cutaneous injury requires not only the healing and regeneration of skin cells but also reinnervation of the skin by somatosensory peripheral axon endings .", "To investigate how sensory axon regeneration and wound healing are coordinated , we amputated the caudal fins of zebrafish larvae...	[ "Touch-sensing neurons project axonal processes that branch extensively within the outer layers of skin to detect touch stimuli .", "Recovering from skin injuries thus requires not only repair of damaged skin tissue but also regeneration of the sensory axons innervating it .", "To study whether skin wound heali...	2011
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "medicine and health sciences", "data acquisition", "statistics", "enzymes", "enzymology", "mathematics", "forecasting", "pharmacology", "molecular biology techniques", "enzyme inhibitors", "research and analysis methods", "computer and information sciences", "proteins", "mathematical and ...	Predicting kinase inhibitors using bioactivity matrix derived informer sets	journal.pcbi.1006813	null	[ [ "Early-stage drug discovery involves a search for pharmacologically active compounds ( hits ) that produce a desired response in an assay of protein function or disease-related phenotype .", "The active compounds serve as starting points for further structural optimization , with the ultimate goal of deve...	[ "Prediction of compounds that are active against a desired biological target is a common step in drug discovery efforts .", "Virtual screening methods seek some active-enriched fraction of a library for experimental testing .", "Where data are too scarce to train supervised learning models for compound prioriti...	[ "In the early stages of drug discovery efforts , computational models are used to predict activity and prioritize compounds for experimental testing .", "New targets commonly lack the data necessary to build effective models , and the screening needed to generate that experimental data can be costly .", "We see...	2019
[ "Introduction", "Materials and methods", "Results", "Discussion" ]	[ "blood cells", "urology", "medicine and health sciences", "immune cells", "body fluids", "pathology and laboratory medicine", "viral transmission and infection", "pathogens", "immunology", "microbiology", "vertebrates", "animals", "mammals", "retroviruses", "viruses", "immunodeficiency...	Differential impact of transplantation on peripheral and tissue-associated viral reservoirs: Implications for HIV gene therapy	journal.ppat.1006956	null	[ [ "Timothy Brown , known as the Berlin Patient , has recently reached 11 years of HIV-free remission in the absence of combination antiretroviral therapy ( cART ) [1–3] .", "Intensive studies have postulated three central tenants that led to his functional cure .", "First , the conditioning regimen that...	[ "Autologous transplantation and engraftment of HIV-resistant cells in sufficient numbers should recapitulate the functional cure of the Berlin Patient , with applicability to a greater number of infected individuals and with a superior safety profile .", "A robust preclinical model of suppressed HIV infection is ...	[ "Over the past decade , multiple strategies have been investigated for HIV Cure .", "Especially notable are cell-based approaches , inspired by the cure of the Berlin Patient , who was transplanted with hematopoietic stem cells from a donor that carried a mutation at the CCR5 locus .", "This mutation renders ce...	2018
[ "Introduction", "Materials and methods", "Results", "Discussion" ]	[ "acceleration", "invertebrates", "medicine and health sciences", "classical mechanics", "social sciences", "neuroscience", "insect flight", "biological locomotion", "animals", "flight (biology)", "simulation and modeling", "animal anatomy", "vision", "insect vectors", "zoology", "resea...	Modeling visual-based pitch, lift and speed control strategies in hoverflies	journal.pcbi.1005894	null	[ [ "Flying insects are subjected to a broad range of disturbances , for which fast , robust sensorimotor reflexes compensate .", "The flight stabilization performance of flies are even more impressive in view of the intrinsic aerodynamic instability of their flapping flight [1–4] .", "Compensating for th...	[ "To avoid crashing onto the floor , a free falling fly needs to trigger its wingbeats quickly and control the orientation of its thrust accurately and swiftly to stabilize its pitch and hence its speed .", "Behavioural data have suggested that the vertical optic flow produced by the fall and crossing the visual f...	[ "On the basis of vision-based feedback control of optic flow occurring during insects’ flight , we developed a dynamic model that accounts for the pitch orientation and speed in plummeting flies .", "We compared the hoverflies’ responses with our model and showed that an optic-flow based control strategy can be u...	2018
[ "Introduction", "Results/Discussion", "Materials and methods" ]	[ "united states", "biogeography", "ecology and environmental sciences", "animal genetics", "z chromosomes", "population dynamics", "population genetics", "geographical locations", "north america", "animal behavior", "mathematics", "bird genetics", "population biology", "zoology", "statist...	Deconstructing isolation-by-distance: The genomic consequences of limited dispersal	journal.pgen.1006911	null	[ [ "The movement of individuals over the landscape ( dispersal ) influences biological processes and diversity at many levels [1] , ranging from interactions between individuals to the persistence of populations or species over time [2–4] .", "Limited dispersal is also central to generating and maintaining s...	[ "Geographically limited dispersal can shape genetic population structure and result in a correlation between genetic and geographic distance , commonly called isolation-by-distance .", "Despite the prevalence of isolation-by-distance in nature , to date few studies have empirically demonstrated the processes that...	[ "Dispersal is a fundamental component of the life history of most organisms and therefore influences many biological processes .", "Dispersal is particularly important in creating genetic structure on the landscape .", "We often observe a pattern of decreased genetic relatedness between individuals as geographi...	2017
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "animal types", "medicine and health sciences", "immunology", "tropical diseases", "geographical locations", "vertebrates", "australia", "domestic animals", "pets and companion animals", "dogs", "animals", "mammals", "simulation and modeling", "preventive medicine", "rabies", "neglecte...	Modelling targeted rabies vaccination strategies for a domestic dog population with heterogeneous roaming patterns	journal.pntd.0007582	null	[ [ "Rabies is a viral encephalitis , estimated to cause approximately 59 , 000 human deaths worldwide; of these deaths , 99% are caused by dog bites [1] .", "Currently , the rabies-free communities of the Northern Peninsula Area ( NPA ) , Queensland , Australia are at risk of a rabies incursion due to proxim...	[ "Australia is currently canine rabies free .", "However , communities located on the northern coastline–such as the Northern Peninsula Area ( NPA ) , Queensland–are at risk of an incursion due to their large populations of susceptible free-roaming dogs and proximity to rabies-infected Indonesian islands .", "A ...	[ "Australia is currently free of canine rabies .", "However , northern communities are at risk of an incursion .", "The free-roaming dogs in the at-risk communities of the Northern Peninsula Area , Queensland , Australia , display various roaming behaviours which affect how they interact with each other and subs...	2019
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "sequencing techniques", "medicine and health sciences", "reproductive system", "vertebrates", "animals", "mammals", "animal models", "primates", "developmental biology", "model organisms", "experimental organism systems", "genetic elements", "molecular biology techniques", "mammalian geno...	Anthropoid primate–specific retroviral element THE1B controls expression of CRH in placenta and alters gestation length	journal.pbio.2006337	null	[ [ "The complex process of completing gestation and initiating parturition must be tightly controlled to prevent the dangerous consequences of preterm or postterm birth to the mother and offspring .", "In humans , corticotropin-releasing hormone ( CRH ) production by the placenta increases exponentially with...	[ "Pregnancy and parturition are intricately regulated to ensure successful reproductive outcomes .", "However , the factors that control gestational length in humans and other anthropoid primates remain poorly defined .", "Here , we show the endogenous retroviral long terminal repeat transposon-like human elemen...	[ "The proper timing of delivery is critical during pregnancy; if too early or too late , the baby will be at risk of serious health problems and even death .", "Corticotropin-releasing hormone ( CRH ) is a protein that can be detected in maternal blood , and its concentration correlates with the timing of birth ."...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Systematic Identification of Cyclic-di-GMP Binding Proteins in Vibrio cholerae Reveals a Novel Class of Cyclic-di-GMP-Binding ATPases Associated with Type II Secretion Systems	journal.ppat.1005232	null	[ [ "Cyclic diguanosine monophosphate ( c-di-GMP ) is a ubiquitous bacterial nucleotide secondary signaling molecule that regulates cellular processes in response to environmental and cellular stimuli .", "The elements of this canonical pathway of signal production , signal transduction , altered activity and...	[ "Cyclic-di-GMP ( c-di-GMP ) is a ubiquitous bacterial signaling molecule that regulates a variety of complex processes through a diverse set of c-di-GMP receptor proteins .", "We have utilized a systematic approach to identify c-di-GMP receptors from the pathogen Vibrio cholerae using the Differential Radial Capi...	[ "Cyclic-di-GMP ( c-di-GMP ) is a ubiquitous bacterial signaling molecule that regulates important bacterial functions , including virulence , antibiotic resistance , biofilm formation and cell division .", "The list of known c-di-GMP receptors is clearly incomplete .", "Here we utilized a systematic and unbiase...	2015
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "medicine and health sciences", "simulation and modeling", "multivariate analysis", "molecular motors", "actin motors", "mathematics", "statistics (mathematics)", "pharmaceutics", "motor proteins", "research and analysis methods", "contractile proteins", "proteins", "mathematical and statist...	Allosteric modulation of cardiac myosin dynamics by omecamtiv mecarbil	journal.pcbi.1005826	null	[ [ "Sarcomeric modulators are small molecules that can modify the function of proteins in the sarcomere , the fundamental repeating unit of skeletal and cardiac muscle cells .", "New promising avenues for the pharmacological treatment of different muscle and heart diseases rely on direct sarcomeric modulator...	[ "New promising avenues for the pharmacological treatment of skeletal and heart muscle diseases rely on direct sarcomeric modulators , which are molecules that can directly bind to sarcomeric proteins and either inhibit or enhance their activity .", "A recent breakthrough has been the discovery of the myosin activ...	[ "Cardiac myosin is a motor protein responsible for the contraction of the heart muscle .", "New strategies for the cure of heart diseases are currently being developed by using myosin modulators , which are small molecules that can interact with myosin and modify its activity .", "The advantage of this approach...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "haplotypes", "medicine and health sciences", "major histocompatibility complex", "genetic polymorphism", "genetics of the immune system", "clinical immunology", "genetics", "biology and life sciences", "population genetics", "immunology", "evolutionary biology" ]	Dominant Sequences of Human Major Histocompatibility Complex Conserved Extended Haplotypes from HLA-DQA2 to DAXX	journal.pgen.1004637	null	[ [ "The human major histocompatibility complex ( MHC ) is a highly polymorphic genomic region of over 3 Mb on chromosome 6p21 .", "MHC polymorphisms include critical determinants for tissue transplantation success and show strong correlation both with many genetic diseases and with ethnic origin .", "Hap...	[ "We resequenced and phased 27 kb of DNA within 580 kb of the MHC class II region in 158 population chromosomes , most of which were conserved extended haplotypes ( CEHs ) of European descent or contained their centromeric fragments .", "We determined the single nucleotide polymorphism and deletion-insertion polym...	[ "The human major histocompatibility complex ( MHC ) is a gene-dense region highly enriched in immune response genes .", "MHC genetic variation is among the highest in the human genome and is associated with both tissue transplant compatibility and many genetic disorders .", "Long-range ( 1–3 Mb ) MHC haplotypes...	2014
[ "Introduction", "Results/Discussion", "Materials and Methods" ]	[ "biotechnology", "plant genomes", "developmental biology", "plant science", "organism development", "plant development", "leaf development", "meristem development", "plant growth and development", "plant genomics", "genetics", "biology and life sciences", "organogenesis", "plant genetics",...	Genome-Wide Analysis of leafbladeless1-Regulated and Phased Small RNAs Underscores the Importance of the TAS3 ta-siRNA Pathway to Maize Development	journal.pgen.1004826	null	[ [ "Small RNAs are important regulators of development , particularly in plants , where many of the abundant and conserved microRNAs ( miRNAs ) target transcription factors that direct or reinforce cell fate decisions [1] .", "Consequently , mutations in genes required for miRNA processing or function condit...	[ "Maize leafbladeless1 ( lbl1 ) encodes a key component in the trans-acting short-interfering RNA ( ta-siRNA ) biogenesis pathway .", "Correlated with a great diversity in ta-siRNAs and the targets they regulate , the phenotypes conditioned by mutants perturbing this small RNA pathway vary extensively across speci...	[ "Mutations in maize leafbladeless1 ( lbl1 ) that disrupt ta-siRNA biogenesis give rise to plants with thread-like leaves that have lost top/bottom polarity .", "We used genomic approaches to identify lbl1-dependent small RNAs and their targets to determine the basis for these polarity defects .", "This revealed...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "diabetes and endocrinology/obesity", "ecology/behavioral ecology", "genetics and genomics/functional genomics" ]	Down-Regulation of Honey Bee IRS Gene Biases Behavior toward Food Rich in Protein	journal.pgen.1000896	null	[ [ "Multicellular animals have distinct energy demands but can modulate their growth and energy consumption in response to nutrient availability [1] , [2] .", "This state of metabolic homeostasis is central to health and lifespan .", "Metabolic homeostasis is maintained by physiological feedback mechanis...	[ "Food choice and eating behavior affect health and longevity .", "Large-scale research efforts aim to understand the molecular and social/behavioral mechanisms of energy homeostasis , body weight , and food intake .", "Honey bees ( Apis mellifera ) could provide a model for these studies since individuals vary ...	[ "Food choice , food handling , and eating are aspects of food-related behavior that can become pathological , as seen in the public health problems of obesity and diabetes .", "Thus , the insight that molecules from the body can bind to brain cells and signal and change food-related behavior is of biomedical inte...	2010
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "medicine", "biology" ]	Genome-Wide Gene-Environment Study Identifies Glutamate Receptor Gene GRIN2A as a Parkinson's Disease Modifier Gene via Interaction with Coffee	journal.pgen.1002237	null	[ [ "Common disorders are thought to have both genetic and environmental components .", "Genome-wide association studies ( GWAS ) have successfully identified numerous susceptibility loci for many common disorders ranging from behavioral traits such as addiction and substance abuse to infectious and immune-re...	[ "Our aim was to identify genes that influence the inverse association of coffee with the risk of developing Parkinson's disease ( PD ) .", "We used genome-wide genotype data and lifetime caffeinated-coffee-consumption data on 1 , 458 persons with PD and 931 without PD from the NeuroGenetics Research Consortium ( ...	[ "Parkinson's disease ( PD ) , like most common disorders , involves interactions between genetic make-up and environmental exposures that are unique to each individual .", "Caffeinated-coffee consumption may protect some people from developing PD , although not all benefit equally .", "In a genome-wide search ,...	2011
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "antimicrobials", "medicine and health sciences", "pathology and laboratory medicine", "pneumococcus", "pathogens", "drugs", "microbiology", "staphylococcus aureus", "electromagnetic radiation", "antibiotic resistance", "antibiotics", "pharmacology", "population biology", "bacteria", "ba...	Collective Resistance in Microbial Communities by Intracellular Antibiotic Deactivation	journal.pbio.2000631	null	[ [ "Antibiotics are indispensable for fighting bacterial infections .", "Yet the rapid emergence of resistance during the last decades renders current drugs increasingly ineffective and poses a serious threat to human health [1] .", "Drug action and bacterial resistance mechanisms are well understood in ...	[ "The structure and composition of bacterial communities can compromise antibiotic efficacy .", "For example , the secretion of β-lactamase by individual bacteria provides passive resistance for all residents within a polymicrobial environment .", "Here , we uncover that collective resistance can also develop vi...	[ "Antibiotic-resistant bacterial infections are on the rise and pose a serious threat to society .", "The influence of genetic resistance mechanisms on antibiotic therapy is well described .", "However , other factors , such as epigenetic resistance or the impact of the environment on antibiotic therapy , are le...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biomacromolecule-ligand interactions", "biochemistry", "enzyme structure", "protein interactions", "proteins", "enzymes", "protein structure", "macromolecular assemblies", "genetics", "biology", "microbiology", "biophysics", "genetics and genomics" ]	Conformational Change-Induced Repeat Domain Expansion Regulates Rap Phosphatase Quorum-Sensing Signal Receptors	journal.pbio.1001512	Structure-function studies reveal hojavascript:popupCustomFlags(‘pbiology’,%2013052,%20‘Submission’)w a family of bacterial cell-cell signaling peptides function mechanistically to regulate their cytoplasmic target receptors.	[ [ "Quorum sensing is a bacterial cell–cell communication process mediated by secreted signaling molecules .", "At low cell density , the concentration of the quorum-sensing signals is negligible and bacteria act as individuals .", "At high cell density , the concentration of the signals is sufficient to...	[ "The large family of Gram-positive quorum-sensing receptors known as the RNPP proteins consists of receptors homologous to the Rap , NprR , PlcR , and PrgX proteins that are regulated by imported oligopeptide autoinducers .", "Rap proteins are phosphatases and transcriptional anti-activators , and NprR , PlcR , a...	[ "The bacterial cell–cell communication process known as quorum sensing regulates important social behaviors including antibiotic production , motility , virulence , biofilm formation , sporulation , bioluminescence , and genetic competence .", "Gram-positive bacteria secrete oligopeptide quorum-sensing signals th...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "molecular cell biology", "gene expression", "genetics", "molecular genetics", "biology", "population genetics", "genetics of disease", "genetics and genomics" ]	Admixture Mapping in Lupus Identifies Multiple Functional Variants within IFIH1 Associated with Apoptosis, Inflammation, and Autoantibody Production	journal.pgen.1003222	null	[ [ "Systemic lupus erythematosus ( SLE , [MIM 152700] ) is a clinically heterogeneous autoimmune disease with a strong genetic component , characterized by inflammation , dysregulation of type-1 interferon responses and autoantibodies directed towards nuclear components .", "SLE overwhelmingly targets women ...	[ "Systemic lupus erythematosus ( SLE ) is an inflammatory autoimmune disease with a strong genetic component .", "African-Americans ( AA ) are at increased risk of SLE , but the genetic basis of this risk is largely unknown .", "To identify causal variants in SLE loci in AA , we performed admixture mapping follo...	[ "African-Americans ( AA ) are at increased risk of systemic lupus erythematosus ( SLE ) , but the genetic basis of this risk increase is largely unknown .", "We used admixture mapping to localize disease-causing genetic variants that differ in frequency across populations .", "This approach is advantageous for ...	2013
[ "Introduction", "Material and Methods", "Results", "Discussion" ]	[]	A Genome-Wide Association Study of a Biomarker of Nicotine Metabolism	journal.pgen.1005498	null	[ [ "Nicotine is a neuro-stimulant with high addiction potential [1] .", "Similar to other drugs causing dependence , nicotine increases dopamine levels in the nucleus accumbens and activates the mesolimbic brain reward pathway [2] .", "Nicotine metabolism rate varies significantly between individuals and...	[ "Individuals with fast nicotine metabolism typically smoke more and thus have a greater risk for smoking-induced diseases .", "Further , the efficacy of smoking cessation pharmacotherapy is dependent on the rate of nicotine metabolism .", "Our objective was to use nicotine metabolite ratio ( NMR ) , an establis...	[ "Nicotine metabolism rate significantly varies between individuals and affects smoking behavior .", "Individuals with fast nicotine metabolism typically smoke more and thus have a greater risk for smoking-induced diseases .", "Further , the efficacy of smoking cessation pharmacotherapy is dependent on nicotine ...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "virology/viral replication and gene regulation", "cell biology/membranes and sorting", "infectious diseases/viral infections", "biochemistry/macromolecular assemblies and machines", "molecular biology" ]	SARS-Coronavirus Replication/Transcription Complexes Are Membrane-Protected and Need a Host Factor for Activity In Vitro	journal.ppat.1000054	null	[ [ "Following infection and genome translation , positive-strand RNA ( +RNA ) viruses establish a cytoplasmic enzyme complex that directs the amplification and expression of their genome .", "The viral RNA-dependent RNA polymerase ( RdRp ) is the central enzyme of this ‘replication/transcription complex’ ( R...	[ "SARS-coronavirus ( SARS-CoV ) replication and transcription are mediated by a replication/transcription complex ( RTC ) of which virus-encoded , non-structural proteins ( nsps ) are the primary constituents .", "The 16 SARS-CoV nsps are produced by autoprocessing of two large precursor polyproteins .", "The RT...	[ "The SARS-coronavirus ( SARS-CoV ) , which causes the life-threatening severe acute respiratory syndrome , replicates in the cytoplasm of infected host cells .", "A critical early step in the SARS-CoV life cycle is the formation of a replication/transcription complex ( RTC ) that drives viral genome replication a...	2008
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine", "biology" ]	The Herpes Simplex Virus-1 Transactivator Infected Cell Protein-4 Drives VEGF-A Dependent Neovascularization	journal.ppat.1002278	null	[ [ "Herpes simplex virus-type 1 ( HSV-1 ) is a neurotropic member of the alpha herpesvirus family with worldwide seroprevalence rates ranging from between 50–90% .", "[1] , [2] .", "Primary infection is usually mild or asymptomatic in the immunocompetent host and typically occurs in childhood or early ad...	[ "Herpes simplex virus-1 ( HSV-1 ) causes lifelong infection affecting between 50 and 90% of the global population .", "In addition to causing dermal lesions , HSV-1 is a leading cause of blindness resulting from recurrent corneal infection .", "Corneal disease is characterized by loss of corneal immunologic pri...	[ "Herpes simplex virus-type 1 is the leading cause of infectious corneal blindness in the industrialized world .", "Most of the morbidity associated with the virus is due to the host response to episodic reactivation of latent virus .", "Corneal immunologic privilege is associated with a number of factors includ...	2011
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "mobile genetic elements", "genome complexity", "computer and information sciences", "systems science", "mathematics", "genome evolution", "statistics (mathematics)", "population modeling", "genetic elements", "genetics", "transposable elements", "biology and life sciences", "physical scienc...	Large-Scale Genomic Analysis Suggests a Neutral Punctuated Dynamics of Transposable Elements in Bacterial Genomes	journal.pcbi.1003680	null	[ [ "Transposable elements ( TE ) are pieces of DNA that encode the enzymatic capability to change location and proliferate within the host genome through a process called transposition .", "They are widely distributed in prokaryotes and eukaryotes , and in some cases they constitute substantial fractions of ...	[ "Insertion sequences ( IS ) are the simplest and most abundant form of transposable DNA found in bacterial genomes .", "When present in multiple copies , it is thought that they can promote genomic plasticity and genetic exchange , thus being a major force of evolutionary change .", "The main processes that det...	[ "Insertion sequences ( IS ) are mobile genetic elements found in most prokaryotic genomes .", "They are able to autonomously change position and proliferate in chromosomes .", "The nature of the coevolutionary dynamics of IS with the genome that hosts them is a matter of debate: Do IS proliferate to the point o...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "neurological disorders/neuromuscular diseases", "genetics and genomics/gene expression", "genetics and genomics/disease models", "genetics and genomics/genetics of disease", "neuroscience/neurodevelopment", "neurological disorders/neurogenetics", "neuroscience/neurobiology of disease and regeneration" ...	Alternative Splicing Events Are a Late Feature of Pathology in a Mouse Model of Spinal Muscular Atrophy	journal.pgen.1000773	null	[ [ "Autosomal recessive Spinal Muscular Atrophy ( SMA ) is a leading genetic cause of infant mortality , with a carrier frequency of 1∶50 and an annual incidence of 1 in 10 , 000 live births [1] .", "Affected individuals develop symmetrical , proximal weakness resulting from neurogenic muscle atrophy , and u...	[ "Spinal muscular atrophy is a severe motor neuron disease caused by inactivating mutations in the SMN1 gene leading to reduced levels of full-length functional SMN protein .", "SMN is a critical mediator of spliceosomal protein assembly , and complete loss or drastic reduction in protein leads to loss of cell via...	[ "The identification of mutations in the Survival Motor Neuron ( SMN ) gene as the cause of the severe motor neuron disorder spinal muscular atrophy is one of a number of discoveries implicating selective motor neuron vulnerability to defects in processing of RNA and its associated ribonucleoprotein complexes .", ...	2009
[ "Introduction", "Methodology", "Results and discussion", "Conclusion" ]	[ "medicine and health sciences", "neurocysticercosis", "tropical diseases", "vertebrates", "parasitic diseases", "animals", "mammals", "neuroscience", "neglected tropical diseases", "infectious disease control", "neuroimaging", "research and analysis methods", "infectious diseases", "swine"...	Target product profiles for the diagnosis of Taenia solium taeniasis, neurocysticercosis and porcine cysticercosis	journal.pntd.0005875	null	[ [ "Neurocysticercosis ( NCC ) is a Neglected Tropical Disease caused by infection with the cestode parasite Taenia solium .", "NCC is endemic in many low- and middle-income countries [1] and is the most frequent cause of acquired epilepsy in those countries and probably the world [2] .", "In endemic are...	[ "Target Product Profiles ( TPPs ) are process tools providing product requirements to guide researchers , developers and manufacturers in their efforts to develop effective and useful products such as biologicals , drugs or diagnostics .", "During a WHO Stakeholders Meeting on Taenia solium diagnostics , several ...	[ "Diagnosing the different manifestations of Taenia solium ( taeniasis and neurocysticercosis in humans , and pig cysticercosis ) presents many challenges .", "The current paper describes the Optimal and Minimal attributes of the diagnostic tests that would be fit for a variety of diagnostic purposes , presented i...	2017
[ "Introduction", "Results", "Discussion", "Methods", "Web resources" ]	[ "alleles", "genetic mapping", "simulation and modeling", "mutation", "molecular biology techniques", "research and analysis methods", "sequence analysis", "gene mapping", "bioinformatics", "sequence alignment", "chromosome biology", "molecular biology", "genetic loci", "haplotypes", "cel...	An estimator of first coalescent time reveals selection on young variants and large heterogeneity in rare allele ages among human populations	journal.pgen.1008340	null	[ [ "The age of an allele of a given frequency can be reveal the forces acting upon it , with rare alleles being particularly sensitive to recent evolutionary processes [1] .", "A functional allele that is younger than expected given its frequency is likely to have been under directional selection .", "Th...	[ "Allele age has long been a focus of population genetic research , primarily because it can be an important clue to the fitness effects of an allele .", "By virtue of their effects on fitness , alleles under directional selection are expected to be younger than neutral alleles of the same frequency .", "We deve...	[ "We developed a way to estimate the time when a copy of a gene most recently shared ancestry with other copies of that gene .", "This is also an estimate of the upper bound of when a mutation has arisen , and it can be used to study the ages of alleles that are found in a population .", "The method can be appli...	2019
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Chronic DNA Replication Stress Reduces Replicative Lifespan of Cells by TRP53-Dependent, microRNA-Assisted MCM2-7 Downregulation	journal.pgen.1005787	null	[ [ "In preparation for DNA replication , “licensing” of replication origins occurs during late M to early G1 phase [1 , 2] .", "These replication origins are selected and bound by the origin recognition complex ( ORC ) [3] .", "ORCs further recruit CDC6 and CDT1 to eventually load the MCM2-7 heterohexame...	[ "Circumstances that compromise efficient DNA replication , such as disruptions to replication fork progression , cause a state known as DNA replication stress ( RS ) .", "Whereas normally proliferating cells experience low levels of RS , excessive RS from intrinsic or extrinsic sources can trigger cell cycle arre...	[ "Duplication of the genome by DNA replication is essential for cell proliferation .", "DNA replication is initiated from many sites ( “origins” ) along chromosomes that are bound by replication licensing proteins , including MCM2-7 .", "They are also core components of the replication helicase complex that unwi...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genetics and genomics/gene expression", "plant biology/plant genetics and gene expression", "computational biology/systems biology", "computational biology/transcriptional regulation" ]	Network Modeling Reveals Prevalent Negative Regulatory Relationships between Signaling Sectors in Arabidopsis Immune Signaling	journal.ppat.1001011	null	[ [ "To understand the regulation of a particular biological process , it is important to elucidate what structural features of the signaling network regulating the process govern the behavior of the signaling network as a whole [1] , [2] .", "With a complex signaling network , in which components are highly ...	[ "Biological signaling processes may be mediated by complex networks in which network components and network sectors interact with each other in complex ways .", "Studies of complex networks benefit from approaches in which the roles of individual components are considered in the context of the network .", "The ...	[ "When a plant detects pathogen attack , this information is conveyed through a molecular signaling network to turn on a large variety of immune responses .", "We investigated how this plant immune signaling network was organized using the model plant Arabidopsis .", "Wild type and mutant plants with defects in ...	2010
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "medicine", "biology" ]	Discovering Thiamine Transporters as Targets of Chloroquine Using a Novel Functional Genomics Strategy	journal.pgen.1003083	null	[ [ "Chloroquine ( CQ ) and other quinoline-containing compounds have been major antimalarial drugs for many decades .", "They are also effective treatments for systematic lupus erythematosus , rheumatoid arthritis , and many other rheumatic and skin diseases [1] .", "In recent years , their effects in tr...	[ "Chloroquine ( CQ ) and other quinoline-containing antimalarials are important drugs with many therapeutic benefits as well as adverse effects .", "However , the molecular targets underlying most such effects are largely unknown .", "By taking a novel functional genomics strategy , which employs a unique combin...	[ "By using a novel SL/DS methodology in the model organism yeast , we discovered that the antimalarial drug CQ inhibits thiamine transporters and consequently causes thiamine ( vitamin B1 ) deficiency and growth defects .", "This mechanism of action ( MOA ) is conserved in human cells and possibly also in other or...	2012
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "blood cells", "invertebrates", "medicine and health sciences", "immune cells", "helminths", "immunology", "parasitic diseases", "animals", "nematode infections", "brugia", "white blood cells", "animal cells", "eosinophilia", "hematology", "helminth infections", "eosinophils", "eukar...	Interleukin-4 activated macrophages mediate immunity to filarial helminth infection by sustaining CCR3-dependent eosinophilia	journal.ppat.1006949	null	[ [ "Infections by helminth parasites are frequently accompanied by overt eosinophilia at parasitized tissue niches[1] .", "In animal models of infection , eosinophils are functionally important in the immune effector response directed at tissue-invading helminths[2–8] but can also drive pathology[2] and are ...	[ "Eosinophils are effectors in immunity to tissue helminths but also induce allergic immunopathology .", "Mechanisms of eosinophilia in non-mucosal tissues during infection remain unresolved .", "Here we identify a pivotal function of tissue macrophages ( Mϕ ) in eosinophil anti-helminth immunity using a BALB/c ...	[ "Helminths parasitize approximately one quarter of the global population .", "Medically-important helminths , including filariae responsible for elephantiasis and river blindness , are targeted for elimination as a public health problem .", "Currently there are no vaccines or immunotherapeutics available for fi...	2018
[ "Introduction", "Results", "Discussion", "Material and Methods" ]	[]	The EBNA-2 N-Terminal Transactivation Domain Folds into a Dimeric Structure Required for Target Gene Activation	journal.ppat.1004910	null	[ [ "Epstein-Barr virus ( EBV ) is a γ-herpesvirus that establishes a lifelong asymptomatic infection in the majority of human adults .", "EBV infection or reactivation can cause significant morbidity and mortality in immunocompromised transplant recipients of allogeneic hematopoietic stem cells or solid orga...	[ "Epstein-Barr virus ( EBV ) is a γ-herpesvirus that may cause infectious mononucleosis in young adults .", "In addition , epidemiological and molecular evidence links EBV to the pathogenesis of lymphoid and epithelial malignancies .", "EBV has the unique ability to transform resting B cells into permanently pro...	[ "Epstein-Barr virus is an oncogenic γ-herpesvirus that may cause infectious mononucleosis in young adults and fatal lymphoproliferative disorders in immunocompromised patients and is associated with the pathogenesis of Burkitt's lymphoma , nasopharyngeal and gastric carcinoma .", "Epstein-Barr virus nuclear antig...	2015
[ "Introduction", "Results", "Discussion", "Models" ]	[ "systems biology", "biology", "computational biology", "genetics and genomics" ]	Effect of Network Architecture on Synchronization and Entrainment Properties of the Circadian Oscillations in the Suprachiasmatic Nucleus	journal.pcbi.1002419	null	[ [ "In mammals , the suprachiasmatic nucleus ( SCN ) of the hypothalamus constitutes the central circadian pacemaker [1] , [2] .", "The SCN comprises about 20000 densely packed neurons organized into bilateral pairs of nuclei on each side of the third ventricle , above the optic chiasm [2] ( Fig . 1 ) .", ...	[ "In mammals , the suprachiasmatic nucleus ( SCN ) of the hypothalamus constitutes the central circadian pacemaker .", "The SCN receives light signals from the retina and controls peripheral circadian clocks ( located in the cortex , the pineal gland , the liver , the kidney , the heart , etc . ) .", "This hiera...	[ "In order to adapt to their cycling environment , virtually all living organisms have developed an internal timer , the circadian clock .", "In mammals , the circadian pacemaker is composed of about 20 , 000 neurons , called the suprachiasmatic nucleus ( SCN ) located in the hypothalamus .", "The SCN receives l...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine and health sciences", "in situ hybridization", "bmp signaling", "molecular probe techniques", "vertebrates", "animals", "animal models", "osteichthyes", "developmental biology", "model organisms", "molecular biology techniques", "embryos", "endocrine cells", "digestive system", ...	Four and a Half LIM Domains 1b (Fhl1b) Is Essential for Regulating the Liver versus Pancreas Fate Decision and for β-Cell Regeneration	journal.pgen.1005831	null	[ [ "Bone morphogenetic protein ( Bmp ) signaling plays an essential role in inducing the liver at the expense of Pdx1-expressing ventral pancreas and intestinal progenitors in different animal models [1–5] .", "In murine and zebrafish endodermal progenitors , Bmp signaling activates liver genes by affecting ...	[ "The liver and pancreas originate from overlapping embryonic regions , and single-cell lineage tracing in zebrafish has shown that Bone morphogenetic protein 2b ( Bmp2b ) signaling is essential for determining the fate of bipotential hepatopancreatic progenitors towards the liver or pancreas .", "Despite its pivo...	[ "Lineage-specific multipotent progenitors play crucial roles in embryonic development , regeneration in adult tissues , and diseases such as cancer .", "Bone morphogenetic protein ( Bmp ) signaling is critical for regulating the cell fate choice of liver versus pancreas , two essential organs of body metabolism ....	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "animal models", "developmental biology", "model organisms", "genetics", "biology", "genetics and genomics" ]	lin-28 Controls the Succession of Cell Fate Choices via Two Distinct Activities	journal.pgen.1002588	null	[ [ "Tissue and organ formation in animals requires that diverse cell types arise in proper succession from a common pool of progenitors .", "Mutations in the heterochronic genes of the nematode Caenorhabditis elegans either skip or reiterate developmental events , indicating that they encode components of a ...	[ "lin-28 is a conserved regulator of cell fate succession in animals .", "In Caenorhabditis elegans , it is a component of the heterochronic gene pathway that governs larval developmental timing , while its vertebrate homologs promote pluripotency and control differentiation in diverse tissues .", "The RNA bindi...	[ "As tissues form , different cell types are generated from a common pool of undifferentiated cells .", "The mechanisms that control this developmental timing are largely unknown .", "In the nematode Caenorhabditis elegans , the heterochronic genes control a succession of cell fates in progressively differentiat...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "developmental biology", "genetics", "biology", "molecular cell biology", "genetics and genomics" ]	SOX9 Governs Differentiation Stage-Specific Gene Expression in Growth Plate Chondrocytes via Direct Concomitant Transactivation and Repression	journal.pgen.1002356	null	[ [ "Chondrogenesis and the formation of bone by endochondral ossification depend on progressive steps of cell differentiation .", "Mesenchymal cells condense and differentiate into chondrocytes in a pattern that will define the eventual shape of the different skeletal elements .", "These chondrocytes pro...	[ "Cartilage and endochondral bone development require SOX9 activity to regulate chondrogenesis , chondrocyte proliferation , and transition to a non-mitotic hypertrophic state .", "The restricted and reciprocal expression of the collagen X gene , Col10a1 , in hypertrophic chondrocytes and Sox9 in immature chondroc...	[ "Chondrogenic differentiation is a key process in the formation of endochondral bone .", "Despite the wealth of information about gene expression patterns and signaling pathways important for this process , it is not clear how differentiation state-specificity of transcription is controlled .", "The transcripti...	2011
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "kala-azar", "medicine and health sciences", "medical doctors", "pathology and laboratory medicine", "medical personnel", "tropical diseases", "parasitic diseases", "health care", "health care providers", "women's health", "signs and symptoms", "neglected tropical diseases", "information tec...	“It’s just a fever”: Gender based barriers to care-seeking for visceral leishmaniasis in highly endemic districts of India: A qualitative study	journal.pntd.0007457	null	[ [ "Visceral leishmaniasis ( VL ) or Kala azar , is a vector-borne disease caused by the protozoan Leishmania donovani and transmitted through the bite of the phlebotomine sand fly .", "Up to 100 , 000 cases are estimated to occur globally every year [1] , and the disease is normally fatal within two years i...	[ "Diagnosis and treatment for visceral leishmaniasis ( VL ) is considered to be delayed amongst poor , rural women in highly endemic districts of Bihar and Jharkhand .", "The objective of this study was to assess and understand barriers to VL diagnosis and treatment for women in endemic districts with a high burde...	[ "India bears the greatest burden of a fatal parasitic disease called visceral leishmaniasis ( VL ) , popularly known as Kala Azar .", "The disease is confined mostly to hot spots in Bihar and Jharkhand in the eastern part of the country .", "Amongst factors hampering efforts to eliminate VL are delays from the ...	2019
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biochemistry", "model organisms", "molecular cell biology", "genetics", "biology", "genomics", "evolutionary biology", "proteomics" ]	NatF Contributes to an Evolutionary Shift in Protein N-Terminal Acetylation and Is Important for Normal Chromosome Segregation	journal.pgen.1002169	null	[ [ "N-terminal acetylation ( N-Ac ) is a common modification of proteins , but its general role has remained rather enigmatic .", "For specific proteins , N-Ac is recognized as an important regulator of function and localization [1]–[4] .", "Recently , it was suggested that it may act as a general destab...	[ "N-terminal acetylation ( N-Ac ) is a highly abundant eukaryotic protein modification .", "Proteomics revealed a significant increase in the occurrence of N-Ac from lower to higher eukaryotes , but evidence explaining the underlying molecular mechanism ( s ) is currently lacking .", "We first analysed protein N...	[ "Small chemical groups are commonly attached to proteins in order to control their activity , localization , and stability .", "An abundant protein modification is N-terminal acetylation , in which an N-terminal acetyltransferase ( NAT ) catalyzes the transfer of an acetyl group to the very N-terminal amino acid ...	2011
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "molecular biology/dna repair", "genetics and genomics/chromosome biology" ]	SUMO-Targeted Ubiquitin Ligase, Rad60, and Nse2 SUMO Ligase Suppress Spontaneous Top1–Mediated DNA Damage and Genome Instability	journal.pgen.1001320	null	[ [ "Efficient DNA repair suppresses spontaneous genetic alterations that otherwise lead to cell death or transformation .", "Posttranslational modifications ( PTMs ) can enhance the efficiency of individual repair processes and proteins and/or channel repair through appropriate pathways ( e . g . [1] , [2] )...	[ "Through as yet undefined proteins and pathways , the SUMO-targeted ubiquitin ligase ( STUbL ) suppresses genomic instability by ubiquitinating SUMO conjugated proteins and driving their proteasomal destruction .", "Here , we identify a critical function for fission yeast STUbL in suppressing spontaneous and chem...	[ "The failure of cellular DNA repair mechanisms can lead to cancer , neurodegeneration , or premature aging .", "Although much is known about specific DNA repair mechanisms , an understanding of how these processes are critically orchestrated by post-translational modifiers such as SUMO and ubiquitin is in its inf...	2011
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "invertebrates", "medicine and health sciences", "parasite groups", "body fluids", "plasmodium", "parasitic diseases", "animals", "parasitic protozoans", "parasitology", "apicomplexa", "brugia", "protozoans", "molecular biology techniques", "insect vectors", "extraction techniques", "r...	A Novel Xenomonitoring Technique Using Mosquito Excreta/Feces for the Detection of Filarial Parasites and Malaria	journal.pntd.0004641	null	[ [ "Spanning 73 countries and territories and placing an estimated 1 . 39 billion individuals at risk of infection , lymphatic filariasis ( LF ) presents a considerable risk to global health [1] .", "Similarly , with an estimated 198 million malaria infections and 584 , 000 malaria-related deaths in 2013 , t...	[ "Given the continued successes of the world’s lymphatic filariasis ( LF ) elimination programs and the growing successes of many malaria elimination efforts , the necessity of low cost tools and methodologies applicable to long-term disease surveillance is greater than ever before .", "As many countries reach the...	[ "As a non-invasive method of indirectly monitoring insect-borne disease , molecular xenomonitoring ( MX ) , the molecular testing of insects for the presence of a pathogen , can provide important information about disease prevalence without the need for human sampling .", "However , given the successes of tropica...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "helminth infections", "infectious diseases", "schistosomiasis", "medicine and health sciences", "neglected tropical diseases", "tropical diseases", "parasitic diseases" ]	An Immunomics Approach to Schistosome Antigen Discovery: Antibody Signatures of Naturally Resistant and Chronically Infected Individuals from Endemic Areas	journal.ppat.1004033	null	[ [ "Schistosomiasis is a chronic , often debilitating , parasitic disease affecting over 200 million people worldwide and killing at least 300 , 000 people annually [1] .", "The disability adjusted life years ( DALYs ) lost to schistosomiasis are potentially as high as 70 million [2] , [3] .", "Adult flu...	[ "Schistosomiasis is a neglected tropical disease that is responsible for almost 300 , 000 deaths annually .", "Mass drug administration ( MDA ) is used worldwide for the control of schistosomiasis , but chemotherapy fails to prevent reinfection with schistosomes , so MDA alone is not sufficient to eliminate the d...	[ "Schistosomiasis is a neglected tropical disease that kills as many as 300 , 000 people each year .", "Mass drug administration is widely used to control schistosomiasis , but fails to prevent rapid reinfection in endemic areas .", "There is a desperate need for a prophylactic vaccine; however , very few candid...	2014
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "blood cells", "medicine and health sciences", "immune cells", "immune physiology", "viral transmission and infection", "spleen", "immunology", "microbiology", "cytotoxic t cells", "viral load", "research and analysis methods", "specimen preparation and treatment", "staining", "white blood...	Tissue-specific control of latent CMV reactivation by regulatory T cells	journal.ppat.1006507	null	[ [ "The immune system has evolved multiple innate and adaptive strategies to control pathogens[1] .", "Likewise , in order to ensure their persistence , pathogens have developed sophisticated and elaborate mechanisms to avoid the host immune system establishing latent infections that are never cleared from t...	[ "Cytomegalovirus ( CMV ) causes a persistent , lifelong infection .", "CMV persists in a latent state and undergoes intermittent subclinical viral reactivation that is quelled by ongoing T cell responses .", "While T cells are critical to maintain control of infection , the immunological factors that promote CM...	[ "Cytomegalovirus ( CMV ) infection in both mice and humans is normally initially contained by a vigorous adaptive immune response that drives the virus into latency in multiple tissues .", "However , the immunologic mechanisms that control latency are not well understood .", "In this report , we have examined t...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Virulence Factors of Pseudomonas aeruginosa Induce Both the Unfolded Protein and Integrated Stress Responses in Airway Epithelial Cells	journal.ppat.1004946	null	[ [ "The Gram-negative bacterium Pseudomonas aeruginosa is an opportunistic pathogen that increases morbidity and mortality in chronic lung diseases , such as cystic fibrosis ( CF ) and chronic obstructive pulmonary disease ( COPD; GOLD stages III-IV ) ) [1–3] .", "P . aeruginosa often causes chronic infectio...	[ "Pseudomonas aeruginosa infection can be disastrous in chronic lung diseases such as cystic fibrosis and chronic obstructive pulmonary disease .", "Its toxic effects are largely mediated by secreted virulence factors including pyocyanin , elastase and alkaline protease ( AprA ) .", "Efficient functioning of the...	[ "Pseudomonas aeruginosa causes a devastating infection when it affects patients with cystic fibrosis or other chronic lung diseases .", "It often causes chronic infection due to its resistance to antibiotic treatment and its ability to form biofilms in these patients .", "The toxic effects of P . aeruginosa are...	2015
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "biomacromolecule-ligand interactions", "viral vaccines", "macromolecular assemblies", "microbiology", "viral structure", "immunodeficiency viruses", "adaptive immunity", "immunizations", "microbial pathogens", "biology", "biophysics", "viral envelope", "immunity", "virology", "antiviral...	A gp41 MPER-specific Llama VHH Requires a Hydrophobic CDR3 for Neutralization but not for Antigen Recognition	journal.ppat.1003202	null	[ [ "The trimeric HIV-1 envelope glycoprotein ( Env ) , composed of its receptor binding subunit gp120 and the fusion protein gp41 , is the main target for neutralizing antibodies .", "Although recent studies have demonstrated the potential of the human immune system to produce broadly neutralizing antibodies...	[ "The membrane proximal external region ( MPER ) of the HIV-1 glycoprotein gp41 is targeted by the broadly neutralizing antibodies 2F5 and 4E10 .", "To date , no immunization regimen in animals or humans has produced HIV-1 neutralizing MPER-specific antibodies .", "We immunized llamas with gp41-MPER proteoliposo...	[ "Due to the absence of an effective vaccine or cure for acquired immunodeficiency syndrome ( AIDS ) , HIV-1 infections still result in high mortality .", "Two antibodies , 2F5 and 4E10 , previously isolated from HIV-1 infected patients , prevent infections by binding to the MPER of gp41 , a part of the virus that...	2013
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "transfection", "invertebrates", "medicine and health sciences", "transient transfection assay", "membrane potential", "electrophysiology", "cloning", "parasitic diseases", "animals", "physiological processes", "developmental biology", "receptor potentials", "brugia", "molecular biology te...	Identification of Ecdysone Hormone Receptor Agonists as a Therapeutic Approach for Treating Filarial Infections	journal.pntd.0004772	null	[ [ "Diseases caused by the human filarial parasitic nematodes are a significant public health problem faced by developing countries .", "Recent reports estimate that there are over 140 million individuals suffering from human filarial parasites in over 80 countries worldwide .", "Approximately 1 billion ...	[ "A homologue of the ecdysone receptor has previously been identified in human filarial parasites .", "As the ecdysone receptor is not found in vertebrates , it and the regulatory pathways it controls represent attractive potential chemotherapeutic targets .", "Administration of 20-hydroxyecdysone to gerbils inf...	[ "The human filarial parasites are the causative agents of two neglected tropical diseases targeted for elimination by the international community .", "The current elimination programs rely upon the mass distribution of a limited number of drugs , leaving the programs open to failure in the event that resistance d...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "developmental biology/stem cells", "neuroscience/neurodevelopment", "developmental biology/neurodevelopment", "neuroscience/neuronal and glial cell biology", "neuroscience/neuronal signaling mechanisms", "developmental biology/molecular development", "developmental biology/developmental molecular mecha...	Prox1 Regulates the Notch1-Mediated Inhibition of Neurogenesis	journal.pbio.1000565	During development of the spinal cord, Prox1 controls the balance between proliferation and differentiation of neural progenitor cells via suppression of Notch1 gene expression.	[ [ "Notch1 signaling plays an important role in the maintenance of NPCs in the undifferentiated state by inhibiting neuronal differentiation [1]–[3] .", "In the developing nervous system , NPCs initially undergo symmetric divisions to expand the available pool of progenitor cells , while at later stages , du...	[ "Activation of Notch1 signaling in neural progenitor cells ( NPCs ) induces self-renewal and inhibits neurogenesis .", "Upon neuronal differentiation , NPCs overcome this inhibition , express proneural genes to induce Notch ligands , and activate Notch1 in neighboring NPCs .", "The molecular mechanism that coor...	[ "Early during development , neural progenitor cells ( NPCs ) can either proliferate or differentiate into neurons .", "Thus , generation of the correct number of neurons is governed by a tightly regulated balance between proliferation and differentiation , and disruption of this balance can result in severe devel...	2010
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "developmental biology", "cell biology", "chromosome biology", "gene expression", "genetics", "gene regulation", "biology and life sciences", "chromatin" ]	A Discrete Transition Zone Organizes the Topological and Regulatory Autonomy of the Adjacent Tfap2c and Bmp7 Genes	journal.pgen.1004897	null	[ [ "Differential regulation of gene expression transforms shared genomic information into the cell type-specific programs underlying organismal development and homeostasis .", "In vertebrates , it is not uncommon to find gene regulatory elements , in particular enhancers , hundreds of kilobases away from the...	[ "Despite the well-documented role of remote enhancers in controlling developmental gene expression , the mechanisms that allocate enhancers to genes are poorly characterized .", "Here , we investigate the cis-regulatory organization of the locus containing the Tfap2c and Bmp7 genes in vivo , using a series of eng...	[ "The specificity of enhancer-gene interactions is fundamental to the execution of gene regulatory programs underpinning embryonic development and cell differentiation .", "However , our understanding of the mechanisms conferring specificity to enhancers and target gene interactions is limited .", "In this study...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biology" ]	Functional Genomic Analysis of the let-7 Regulatory Network in Caenorhabditis elegans	journal.pgen.1003353	null	[ [ "MicroRNAs ( miRNAs ) are an abundant class of regulatory genes that control many cellular and developmental processes [1] .", "The biogenesis of miRNAs requires multiple steps , beginning with transcription by RNA polymerase II to produce capped and polyadenylated primary transcripts [2] , [3] .", "T...	[ "The let-7 microRNA ( miRNA ) regulates cellular differentiation across many animal species .", "Loss of let-7 activity causes abnormal development in Caenorhabditis elegans and unchecked cellular proliferation in human cells , which contributes to tumorigenesis .", "These defects are due to improper expression...	[ "In the past decade , microRNAs ( miRNAs ) have become recognized as key regulators of gene expression in many biological pathways .", "These small , non-coding RNAs target specific protein-coding genes for repression .", "The specificity is mediated by partial base-pairing interactions between the 22 nucleotid...	2013
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "physics", "stochastic processes", "animal behavior", "mathematics", "statistical mechanics", "ecology", "evolutionary biology", "biology", "probability theory", "behavioral ecology" ]	How Random Is Social Behaviour? Disentangling Social Complexity through the Study of a Wild House Mouse Population	journal.pcbi.1002786	null	[ [ "In a famous passage of his book The Sciences of the Artificial [1] the sociologist Herbert Simon considers the winding , weaving path of an ant as it makes its journey home across the rugged landscape of a wind- and wave-beaten sandy beach .", "He notes that , whilst the homebound ant has a clear destina...	[ "Out of all the complex phenomena displayed in the behaviour of animal groups , many are thought to be emergent properties of rather simple decisions at the individual level .", "Some of these phenomena may also be explained by random processes only .", "Here we investigate to what extent the interaction dynami...	[ "From the synchronised beauty of fish schools to the rigorous hierarchy of ant colonies , animals often display awe-inspiring collective behaviour .", "In recent years , principles of statistical physics have helped to unveil some simple mechanisms behind the emergence of such collective dynamics .", "Among the...	2012
[ "Introduction", "Results and Discussion", "Materials and Methods" ]	[ "medicine", "biochemistry", "genetic mutation", "mutation types", "drug research and development", "drugs and devices", "small molecules", "genetics", "biology", "chemical biology", "drug discovery" ]	A Lack of Premature Termination Codon Read-Through Efficacy of PTC124 (Ataluren) in a Diverse Array of Reporter Assays	journal.pbio.1001593	Numerous nonsense mutation reporter assays fail to reveal read-through activity for the drug PTC124.	[ [ "Nonsense mutations are a type of genetic defect in which an amino acid codon is substituted by a TGA , TAG , or TAA stop codon , thereby interrupting the coding sequence of a protein-encoding gene .", "These mutations represent one major class of premature termination codon mutations ( PTCs ) ; out-of-fr...	[ "The drug molecule PTC124 ( Ataluren ) has been described as a read-through agent , capable of suppressing premature termination codons ( PTCs ) and restoring functional protein production from genes disrupted by nonsense mutations .", "Following the discovery of PTC124 there was some controversy regarding its me...	[ "Ten percent of all single-gene hereditary diseases are caused by nonsense mutations .", "These are alterations in the DNA sequence of a protein-coding gene that cause the ribosome to prematurely finish translating the gene transcript before a full-length , active protein can be produced .", "In 2007 a drug was...	2013
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "sequencing techniques", "medicine and health sciences", "drugs", "population genetics", "alleles", "gene pool", "mutation", "pharmacology", "population biology", "molecular biology techniques", "research and analysis methods", "sequence analysis", "artificial gene amplification and extensio...	Reverse Chemical Genetics: Comprehensive Fitness Profiling Reveals the Spectrum of Drug Target Interactions	journal.pgen.1006275	null	[ [ "Drug resistance is a worldwide health concern that affects all drug classes , including anti-infectives and anti-cancer agents [1–3] .", "Recent reports illustrate that first-line antibiotic treatment failure rates have increased 12% from 1991–2012 [4] .", "Cancer drug resistance has increased , in p...	[ "The emergence and prevalence of drug resistance demands streamlined strategies to identify drug resistant variants in a fast , systematic and cost-effective way .", "Methods commonly used to understand and predict drug resistance rely on limited clinical studies from patients who are refractory to drugs or on la...	[ "One of the most profound outcomes of fast , reliable genome sequencing is the ability to tailor drug therapy to an individual’s genotype .", "This ‘personalized’ or ‘precision medicine’ is the realization of a decades-long effort to maximize drug effect and limit unwanted side effects .", "An undesirable conse...	2016

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