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headings list	keywords list	title stringlengths 20 281	id stringlengths 20 20	toc stringlengths 57 522 ⌀	sections list	abstract list	summary list	year stringclasses 13 values
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "invertebrates", "centrosomes", "rna interference", "metaphase", "cell cycle and cell division", "cell processes", "animals", "dna transcription", "animal models", "mitosis", "drosophila melanogaster", "model organisms", "experimental organism systems", "epigenetics", "centrioles", "ce...	RNAi-mediated depletion of the NSL complex subunits leads to abnormal chromosome segregation and defective centrosome duplication in Drosophila mitosis	journal.pgen.1008371	null	[ [ "The spindle is a microtubule ( MT ) -based highly dynamic molecular machine that mediates chromosome segregation during cell division .", "Spindle formation requires many proteins that specifically bind and/or regulate MT assembly and dynamics , and also some proteins that are associated with the chromat...	[ "The Drosophila Nonspecific Lethal ( NSL ) complex is a major transcriptional regulator of housekeeping genes .", "It contains at least seven subunits that are conserved in the human KANSL complex: Nsl1/Wah ( KANSL1 ) , Dgt1/Nsl2 ( KANSL2 ) , Rcd1/Nsl3 ( KANSL3 ) , Rcd5 ( MCRS1 ) , MBD-R2 ( PHF20 ) , Wds ( WDR5 )...	[ "The Drosophila Nonspecific Lethal ( NSL ) complex is a conserved protein assembly that controls transcription of more than 4 , 000 housekeeping genes .", "We analyzed the mitotic functions of four genes , Rcd1 , Rcd5 , MBD-R2 and wds , encoding NSL subunits .", "Inactivation of these genes by RNA interference ...	2019
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "virology/virion structure, assembly, and egress", "cell biology", "virology", "microbiology", "neuroscience" ]	Assembly of the Murine Leukemia Virus Is Directed towards Sites of Cell–Cell Contact	journal.pbio.1000163	Applying 4D imaging, this study investigates the mechanism by which cell-cell contact enhances retrovirus spreading and demonstrates that viral budding is highly polarized towards sites of cell-cell contact.	[ [ "The ability of retroviruses to utilize and manipulate cell–cell contact for the purpose of efficient transmission contributes to the spread of infection and the progression to diseases such as leukemia and AIDS .", "In vitro , cell-to-cell transmission of the human immunodeficiency virus ( HIV ) is 100–1...	[ "We have investigated the underlying mechanism by which direct cell–cell contact enhances the efficiency of cell-to-cell transmission of retroviruses .", "Applying 4D imaging to a model retrovirus , the murine leukemia virus , we directly monitor and quantify sequential assembly , release , and transmission event...	[ "Retroviruses such as the human immunodeficiency virus are known to spread much more efficiently under conditions of direct cell–cell contact as compared to cell-free conditions .", "How cell–cell contact stimulates virus spreading is poorly understood .", "In this study , we apply four-dimensional imaging ( 3D...	2009
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "han chinese", "demography", "population genetics", "genetic mapping", "ethnicities", "population biology", "tibetan people", "introgression", "comparative genomics", "people and places", "haplotypes", "heredity", "evolutionary processes", "genetics", "population groupings", "biology a...	Evolutionary history of Tibetans inferred from whole-genome sequencing	journal.pgen.1006675	null	[ [ "Adaptation to high altitude is among the most notable examples of natural selection in our species .", "Tibetans exhibit an exceptional capacity to compensate for decreased oxygen availability ( hypoxia ) , UV exposure , cold , and limited food sources as exemplified by continuous habitation at greater t...	[ "The indigenous people of the Tibetan Plateau have been the subject of much recent interest because of their unique genetic adaptations to high altitude .", "Recent studies have demonstrated that the Tibetan EPAS1 haplotype is involved in high altitude-adaptation and originated in an archaic Denisovan-related pop...	[ "The Tibetan population has been residing on high plateau for thousands of years and developed unique adaptation to the local environment .", "To investigate the demographic history of Tibetans and search for possible adaptive genetic variants , we performed whole-genome sequencing of 27 Tibetan individuals .", ...	2017
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "physics", "general physics", "computational neuroscience", "interdisciplinary physics", "biology", "computational biology", "sensory systems" ]	Coordinated Optimization of Visual Cortical Maps (I) Symmetry-based Analysis	journal.pcbi.1002466	null	[ [ "Neurons in the primary visual cortex are selective to a multidimensional set of visual stimulus features , including visual field position , contour orientation , ocular dominance , direction of motion , and spatial frequency [1] , [2] .", "In many mammals , these response properties form spatially compl...	[ "In the primary visual cortex of primates and carnivores , functional architecture can be characterized by maps of various stimulus features such as orientation preference ( OP ) , ocular dominance ( OD ) , and spatial frequency .", "It is a long-standing question in theoretical neuroscience whether the observed ...	[ "Neurons in the visual cortex form spatial representations or maps of several stimulus features .", "How are different spatial representations of visual information coordinated in the brain ?", "In this paper , we study the hypothesis that the coordinated organization of several visual cortical maps can be expl...	2012
[ "Introduction", "Methods", "Results", "Discussion" ]	[]	Inter-Seasonal Influenza is Characterized by Extended Virus Transmission and Persistence	journal.ppat.1004991	null	[ [ "Human influenza virus is characterized by a marked seasonality in temperate regions , where the virus exhibits a distinct annual peak in epidemic activity during the winter months [1] .", "However , in subtropical and tropical regions transmission patterns are often less clearly defined [2] .", "Inde...	[ "The factors that determine the characteristic seasonality of influenza remain enigmatic .", "Current models predict that occurrences of influenza outside the normal surveillance season within a temperate region largely reflect the importation of viruses from the alternate hemisphere or from equatorial regions in...	[ "Human influenza virus commonly causes disease in the winter months of temperate countries , but exhibits more complex patterns in tropical localities .", "Most studies of this complex seasonality have only considered viruses sampled within the “normal” influenza season .", "To help reveal the drivers of influe...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biophysics/transcription and translation", "biophysics/macromolecular assemblies and machines" ]	Complete Structural Model of Escherichia coli RNA Polymerase from a Hybrid Approach	journal.pbio.1000483	A combination of structural approaches yields a complete atomic model of the highly biochemically characterized Escherichia coli RNA polymerase, enabling fuller exploitation of E. coli as a model for understanding transcription.	[ [ "RNA in all cellular organisms is synthesized by a complex molecular machine , the DNA-dependent RNA polymerase ( RNAP ) .", "In bacteria , the catalytically competent core RNAP ( subunit composition α2ββ'ω ) has a molecular mass of ∼400 kDa .", "Evolutionary relationships for each of the bacterial co...	[ "The Escherichia coli transcription system is the best characterized from a biochemical and genetic point of view and has served as a model system .", "Nevertheless , a molecular understanding of the details of E . coli transcription and its regulation , and therefore its full exploitation as a model system , has...	[ "Transcription , or the synthesis of RNA from DNA , is one of the most important processes in the cell .", "The central enzyme of transcription is the DNA-dependent RNA polymerase ( RNAP ) , a large , macromolecular assembly consisting of at least five subunits .", "Historically , much of our fundamental inform...	2010
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine", "gene networks", "animal genetics", "basic cancer research", "cell differentiation", "gene function", "animal models", "oncology", "developmental biology", "caenorhabditis elegans", "model organisms", "molecular development", "biology", "signaling", "genetics", "genetics of...	PTEN Negatively Regulates MAPK Signaling during Caenorhabditis elegans Vulval Development	journal.pgen.1002881	null	[ [ "PTEN ( Phosphatase and TENsin homologue ) is the second-most frequently somatically mutated tumor suppressor gene in human cancer .", "PTEN is often inactivated in glioblastoma , melanoma , prostate and endometrial neoplasia [1] .", "Germline mutations in PTEN are also known to cause a variety of rar...	[ "Vulval development in Caenorhabditis elegans serves as an excellent model to examine the crosstalk between different conserved signaling pathways that are deregulated in human cancer .", "The concerted action of the RAS/MAPK , NOTCH , and WNT pathways determines an invariant pattern of cell fates in three vulval...	[ "The human tumor suppressor PTEN is mutated in many different types of cancer .", "Using the roundworm C . elegans as a model to study how cells communicate during animal development , we discovered a new mechanism by which PTEN inhibits the activity of the oncogenic RAS/MAPK signaling pathway .", "Focusing on ...	2012
[ "Introduction", "Results/Discussion", "Methods" ]	[ "medicine", "urology", "developmental biology", "model organisms", "genetics and genomics", "biology", "genomics", "respiratory medicine", "pulmonology" ]	RAB-Like 2 Has an Essential Role in Male Fertility, Sperm Intra-Flagellar Transport, and Tail Assembly	journal.pgen.1002969	null	[ [ "Infertility affects at least 1 in 20 men of reproductive age [1] and for the majority , the underlying causal mechanism remains unknown .", "This , and the absence of effective male-based contraceptives , stems from a fundamental lack of knowledge of the genes and pathways required to form functional spe...	[ "A significant percentage of young men are infertile and , for the majority , the underlying cause remains unknown .", "Male infertility is , however , frequently associated with defective sperm motility , wherein the sperm tail is a modified flagella/cilia .", "Conversely , a greater understanding of essential...	[ "A greater understanding of the mechanism of male fertility is essential in order to address the medical needs of the 1 in 20 men of reproductive age who are infertile .", "Conversely , there remains a critical need for additional contraceptive options , including those that target male gametes .", "Towards the...	2012
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "cancer genomics", "medicine and health sciences", "breast tumors", "squamous cell lung carcinoma", "genetic networks", "statistics", "carcinomas", "cancers and neoplasms", "basic cancer research", "oncology", "regression analysis", "mathematics", "network analysis", "adenocarcinomas", "...	Pan-cancer association of a centrosome amplification gene expression signature with genomic alterations and clinical outcome	journal.pcbi.1006832	null	[ [ "The centrosome , an organelle composed of two centrioles surrounded by a pericentriolar protein matrix , is the major microtubule-organising centre of animal cells , hence being pivotal for several fundamental cellular processes , including signalling , cell polarity , division and migration [1–4] .", "E...	[ "Centrosome amplification ( CA ) is a common feature of human tumours and a promising target for cancer therapy .", "However , CA’s pan-cancer prevalence , molecular role in tumourigenesis and therapeutic value in the clinical setting are still largely unexplored .", "Here , we used a transcriptomic signature (...	[ "Centrosome amplification , i . e . an increased number of centrosomes—structures that exist inside cells , is a hallmark of cancer cells and therefore an Achilles' heel for the development of innovative therapies that specifically target tumour cells , sparing healthy ones .", "To exploit centrosome amplificatio...	2019
[ "Introduction", "Results", "Discussion" ]	[ "biology", "computational biology" ]	Short Conduction Delays Cause Inhibition Rather than Excitation to Favor Synchrony in Hybrid Neuronal Networks of the Entorhinal Cortex	journal.pcbi.1002306	null	[ [ "Several lines of evidence indicate that synchronous activity in the hippocampal formation is important for learning and memory .", "Coherent activity arises when animals are in states of active locomotion and information acquisition [1] , [2] .", "Disabling coherent theta activity leads to memory imp...	[ "How stable synchrony in neuronal networks is sustained in the presence of conduction delays is an open question .", "The Dynamic Clamp was used to measure phase resetting curves ( PRCs ) for entorhinal cortical cells , and then to construct networks of two such neurons .", "PRCs were in general Type I ( all ad...	[ "Individual oscillators , such as pendulum-based clocks and fireflies , can spontaneously organize into a coherent , synchronized entity with a common frequency .", "Neurons can oscillate under some circumstances , and can synchronize their firing both within and across brain regions .", "Synchronized assemblie...	2012
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "medicine and health sciences", "cost-effectiveness analysis", "economic analysis", "post-exposure prophylaxis", "immunology", "tropical diseases", "geographical locations", "vertebrates", "social sciences", "dogs", "animals", "mammals", "vaccines", "preventive medicine", "rabies", "ne...	Cost-effectiveness of dog rabies vaccination programs in East Africa	journal.pntd.0006490	null	[ [ "Rabies causes an estimated 25 , 000–70 , 000 human deaths annually , with about 90% of those deaths due to dog rabies [1–2] .", "Human rabies can be prevented through prompt post exposure prophylaxis ( PEP ) [3–5]; however , human rabies vaccine and immune globulin , needed for PEP , are frequently unava...	[ "Dog rabies annually causes 24 , 000–70 , 000 deaths globally .", "We built a spreadsheet tool , RabiesEcon , to aid public health officials to estimate the cost-effectiveness of dog rabies vaccination programs in East Africa .", "RabiesEcon uses a mathematical model of dog-dog and dog-human rabies transmission...	[ "Dog rabies causes , globally , approximately 55 , 000 human deaths per year .", "Mass vaccination programs can control dog rabies .", "We built a spreadsheet-based tool , RabiesEcon , to aid public health officials in planning large-scale dog rabies vaccination programs .", "We used RabiesEcon to estimate th...	2018
[ "Introduction", "Results", "Discussion", "Methods" ]	[]	Scalability of Asynchronous Networks Is Limited by One-to-One Mapping between Effective Connectivity and Correlations	journal.pcbi.1004490	null	[ [ "While many aspects of brain dynamics and function remain unexplored , the numbers of neurons and synapses in a given volume are well known , and as such constitute basic parameters that should be taken seriously .", "Despite rapid advances in neural network simulation technology and increased availabilit...	[ "Network models are routinely downscaled compared to nature in terms of numbers of nodes or edges because of a lack of computational resources , often without explicit mention of the limitations this entails .", "While reliable methods have long existed to adjust parameters such that the first-order statistics of...	[ "Neural networks have two basic components: their structural elements ( neurons and synapses ) , and the dynamics of these constituents .", "The so-called effective connectivity combines both components to yield a measure of the actual influence of physical connections .", "Previous work showed effective connec...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "none", "computational biology" ]	Predicting the Receptive Range of Olfactory Receptors	journal.pcbi.0040018	null	[ [ "The mammalian sense of smell is able to detect molecules at levels as low as a few parts per trillion , as well as recognize and discriminate thousands of volatile molecules of diverse structure .", "Smelling begins when airborne odorants traverse the aqueous mucus layer covering the nasal epithelium , a...	[ "Although the family of genes encoding for olfactory receptors was identified more than 15 years ago , the difficulty of functionally expressing these receptors in an heterologous system has , with only some exceptions , rendered the receptive range of given olfactory receptors largely unknown .", "Furthermore , ...	[ "A key goal in biology is to identify specific ligands for specific receptors .", "One example is where the ligand is a drug .", "In turn , in the olfactory system the ligand is the odorant that binds to olfactory receptors .", "There are many olfactory receptor types , and which odorants will activate which ...	2008
[ "Introduction", "Materials and methods", "Results", "Discussion" ]	[ "medicine and health sciences", "body fluids", "nervous system", "african trypanosomiasis", "tropical diseases", "parasitic diseases", "parasitic protozoans", "saliva", "protozoans", "materials science", "neglected tropical diseases", "surfactants", "infectious diseases", "detergents", "...	Using detergent-enhanced LAMP for African trypanosome detection in human cerebrospinal fluid and implications for disease staging	journal.pntd.0007631	null	[ [ "In East Africa , the tsetse fly-transmitted protozoan parasite Trypanosoma brucei rhodesiense causes acute human African trypanosomiasis ( HAT/ sleeping sickness ) [1] .", "Transmitted from animals to man , T . b .", "rhodesiense infection is a zoonosis characterized by relatively high parasite loads...	[ "Where human African trypanosomiasis ( HAT ) patients are seen , failure to microscopically diagnose infections by Trypanosoma brucei gambiense in blood smears and/or cerebrospinal fluid ( CSF ) in the critical early stages of the disease is the single most important factor in treatment failure , a result of delaye...	[ "Human African trypanosomiasis is a fatal disease ( if untreated ) spread by bloodsucking tsetse flies .", "These protozoan parasites first enter the lymph and blood to invade many organ systems ( early stage sleeping sickness ) .", "Weeks to months later , the parasites invade the brain causing a wide variety ...	2019
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	dTULP, the Drosophila melanogaster Homolog of Tubby, Regulates Transient Receptor Potential Channel Localization in Cilia	journal.pgen.1003814	null	[ [ "The auditory system allows animals to communicate and obtain information about their environment .", "The hearing organs transform sound into an electrical signal through a process called mechanotransduction , the conversion of a mechanical force impinging on a cell into an intracellular signal [1] .", ...	[ "Mechanically gated ion channels convert sound into an electrical signal for the sense of hearing .", "In Drosophila melanogaster , several transient receptor potential ( TRP ) channels have been implicated to be involved in this process .", "TRPN ( NompC ) and TRPV ( Inactive ) channels are localized in the di...	[ "Tubby is a member of the Tubby-like protein ( TULP ) family .", "Tubby mutations in mice ( tubby mice ) cause late-onset obesity and neurosensory deficits such as retinal degeneration and hearing loss .", "However , the exact molecular mechanism of Tubby has not been determined .", "Here we show that Drosoph...	2013
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "physics", "biology and life sciences", "physical sciences" ]	A Simulated Intermediate State for Folding and Aggregation Provides Insights into ΔN6 β2-Microglobulin Amyloidogenic Behavior	journal.pcbi.1003606	null	[ [ "β2-microglobulin ( β2m ) is a 99-residue protein with a typical immunoglobulin fold comprising seven anti-parallel β-strands stabilized by a disulfide bridge ( Fig . 1 ) [1] .", "Upon dissociation from the MHC-I heavy chain , human β2m ( Hβ2m ) is catabolised in the kidneys .", "In individuals underg...	[ "A major component of ex vivo amyloid plaques of patients with dialysis-related amyloidosis ( DRA ) is a cleaved variant of β2-microglobulin ( ΔN6 ) lacking the first six N-terminal residues .", "Here we perform a computational study on ΔN6 , which provides clues to understand the amyloidogenicity of the full-len...	[ "Dialysis-related amyloidosis ( DRA ) is a conformational disease that affects individuals undergoing long-term haemodialysis .", "In DRA the progressive accumulation of protein human β2-microglobulin ( Hβ2m ) in the osteoarticular system , followed by its assembly into amyloid fibrils , eventually leads to tissu...	2014
[ "Introduction", "Rationale for developing alternative strategies", "Outlook on alternative strategy development", "Alternative strategies", "Considerations for introducing alternative strategies", "Knowledge base on mosquito biology and behavior", "Acceptability and compliance of alternative methods", ...	[ "invertebrates", "medicine and health sciences", "animals", "wolbachia", "viruses", "review", "infectious disease control", "insect vectors", "bacteria", "infectious diseases", "agrochemicals", "aedes aegypti", "arboviral infections", "disease vectors", "insects", "agriculture", "art...	Alternative strategies for mosquito-borne arbovirus control	journal.pntd.0006822	null	[ [ "International public health workers are challenged by a burden of mosquito-borne arboviral diseases despite best efforts in control programs .", "An estimated 4 billion people live in areas at risk for dengue virus transmission alone [1] .", "Well-documented successes indicate that rigorously applied...	[ "Mosquito-borne viruses—such as Zika , chikungunya , dengue fever , and yellow fever , among others—are of global importance .", "Although vaccine development for prevention of mosquito-borne arbovirus infections has been a focus , mitigation strategies continue to rely on vector control .", "However , vector c...	[ "International public health workers are challenged by the burden of arthropod-borne viral diseases , to include mosquito-borne arboviruses transmitted by Aedes aegypti and A . albopictus due in part to lack of sustainable vector control and insecticide resistance ( IR ) , as well as the inability to scale up and s...	2019
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "gene regulation", "developmental biology", "regulator genes", "organism development", "gene types", "embryos", "cellular structures and organelles", "limb development", "embryology", "limb buds", "gene expression", "organogenesis", "subcellular localization", "hedgehog signaling", "sign...	Gata6-Dependent GLI3 Repressor Function is Essential in Anterior Limb Progenitor Cells for Proper Limb Development	journal.pgen.1006138	null	[ [ "Understanding the developmental mechanisms that regulate progenitor cells to generate organs with specific morphology and function is a central topic in developmental biology .", "The vertebrate limb has been serving as an excellent system for such studies .", "In particular , mesenchymal progenitor ...	[ "Gli3 is a major regulator of Hedgehog signaling during limb development .", "In the anterior mesenchyme , GLI3 is proteolytically processed into GLI3R , a truncated repressor form that inhibits Hedgehog signaling .", "Although numerous studies have identified mechanisms that regulate Gli3 function in vitro , i...	[ "Gli3 is a major regulator of Hedgehog signaling in the limb , where Gli3 counteracts Sonic hedgehog ( Shh ) for patterning and proliferative expansion of limb progenitor cells .", "In the anterior limb mesenchyme , GLI3 is proteolytically processed into GLI3R , a truncated repressor form that inhibits Hedgehog s...	2016
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "medicine and health sciences", "neurogenesis", "cell division analysis", "cell cycle and cell division", "cell processes", "brain", "cloning", "neuroscience", "stem cells", "bioassays and physiological analysis", "molecular biology techniques", "research and analysis methods", "developmenta...	In vivo clonal analysis reveals spatiotemporal regulation of thalamic nucleogenesis	journal.pbio.2005211	null	[ [ "A large portion of the vertebrate brain is organized so that groups of neurons that share similar properties are arranged in aggregates called nuclei .", "Developmental mechanisms underlying the formation of such nuclear brain structures are much less understood compared with the mechanisms that regulate...	[ "The thalamus , a crucial regulator of cortical functions , is composed of many nuclei arranged in a spatially complex pattern .", "Thalamic neurogenesis occurs over a short period during mammalian embryonic development .", "These features have hampered the effort to understand how regionalization , cell divisi...	[ "The thalamus—a brain structure commonly associated with relaying sensory information between cortex and other regions—is organized into many cell clusters called nuclei .", "Each thalamic nucleus is populated by neurons with distinct patterns of gene expression and connections to other brain regions and plays a ...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "cardiovascular disorders/arrhythmias, electrophysiology, and pacing", "physiology/cardiovascular physiology and circulation", "computational biology/systems biology", "cardiovascular disorders/cardiovascular diseases in women" ]	Acute Effects of Sex Steroid Hormones on Susceptibility to Cardiac Arrhythmias: A Simulation Study	journal.pcbi.1000658	null	[ [ "In the past decade , studies have suggested that female gender is an independent risk factor for long-QT ( LQT ) dependent cardiac arrhythmias [1]–[3] .", "Since the differences in QT intervals in males and females appear from the time of puberty [4] , [5] , sex steroid hormone effects on cardiac repolar...	[ "Acute effects of sex steroid hormones likely contribute to the observation that post-pubescent males have shorter QT intervals than females .", "However , the specific role for hormones in modulating cardiac electrophysiological parameters and arrhythmia vulnerability is unclear .", "Here we use a computationa...	[ "It is well known that female gender is an independent risk factor for some types of cardiac arrhythmias .", "However , it has been difficult to determine how much of a role physiological concentrations of circulating sex steroid hormones play in gender linked arrhythmia susceptibility because the cardiac system ...	2010
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biochemistry", "biology", "microbiology", "molecular cell biology", "proteomics" ]	Epstein-Barr Virus-Encoded LMP1 Interacts with FGD4 to Activate Cdc42 and Thereby Promote Migration of Nasopharyngeal Carcinoma Cells	journal.ppat.1002690	null	[ [ "Epstein–Barr virus ( EBV ) is a human γ-herpesvirus that is closely associated with many human malignancies , including nasopharyngeal carcinoma ( NPC ) , Burkitt's lymphoma , T-cell lymphoma , and gastric carcinoma [1] .", "NPC , which is prevalent in Taiwan and southeastern China , is a human squamous ...	[ "Epstein-Barr virus ( EBV ) is closely associated with nasopharyngeal carcinoma ( NPC ) , a human malignancy notorious for its highly metastatic nature .", "Among EBV-encoded genes , latent membrane protein 1 ( LMP1 ) is expressed in most NPC tissues and exerts oncogenicity by engaging multiple signaling pathways...	[ "Epstein-Barr virus ( EBV ) is closely associated with human malignancies , including nasopharyngeal carcinoma ( NPC ) .", "Among EBV-expressed genes , latent membrane protein 1 ( LMP1 ) has been detected in most NPC tissues and has the ability to transform cell growth and drive cell migration , both of which are...	2012
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "biotechnology", "machine learning algorithms", "chemical compounds", "neural networks", "small molecules", "applied mathematics", "electricity", "neuroscience", "organic compounds", "simulation and modeling", "algorithms", "electrostatics", "mathematics", "algebra", "artificial intellig...	Representability of algebraic topology for biomolecules in machine learning based scoring and virtual screening	journal.pcbi.1005929	null	[ [ "Arguably , machine learning has become one of the most important developments in data science and artificial intelligence .", "With its ability to extract features of various levels hierarchically , deep convolutional neural networks ( CNNs ) have made breakthroughs in image processing , video , audio , ...	[ "This work introduces a number of algebraic topology approaches , including multi-component persistent homology , multi-level persistent homology , and electrostatic persistence for the representation , characterization , and description of small molecules and biomolecular complexes .", "In contrast to the conven...	[ "Conventional persistent homology neglects chemical and biological information during the topological abstraction and thus has limited representational power for complex chemical and biological systems .", "In terms of methodological development , we introduce advanced persistent homology approaches for the chara...	2018
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "cardiovascular disorders/hypertension", "genetics and genomics/genetics of disease", "genetics and genomics/complex traits" ]	A Genome-Wide Association Study of Hypertension and Blood Pressure in African Americans	journal.pgen.1000564	null	[ [ "Genome wide association studies ( GWAS ) on large scale population samples have been remarkably successful in uncovering novel susceptibility loci for a wide range of complex human diseases including type 2 diabetes , coronary artery disease , dyslipidemia , breast cancer , obesity-related traits , prostate ...	[ "The evidence for the existence of genetic susceptibility variants for the common form of hypertension ( “essential hypertension” ) remains weak and inconsistent .", "We sought genetic variants underlying blood pressure ( BP ) by conducting a genome-wide association study ( GWAS ) among African Americans , a popu...	[ "Despite intense research , the genetic risk factors for essential hypertension and blood pressure ( BP ) regulation have not been identified with consistency .", "We conducted a genome wide association scan using over 800 , 000 genetic markers in an African American sample of 1 , 017 adults in the Washington , D...	2009
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Nmf9 Encodes a Highly Conserved Protein Important to Neurological Function in Mice and Flies	journal.pgen.1005344	null	[ [ "The biological functions of many protein-coding genes remain unknown , often despite conservation across considerable evolutionary distance .", "Such “orphan” molecules may include genes whose functions affect fitness but not overt phenotypes in experimental settings , genes that affect overt but under-s...	[ "Many protein-coding genes identified by genome sequencing remain without functional annotation or biological context .", "Here we define a novel protein-coding gene , Nmf9 , based on a forward genetic screen for neurological function .", "ENU-induced and genome-edited null mutations in mice produce deficits in...	[ "Genome sequencing projects have identified large numbers of genes that encode proteins of unknown function .", "Many of these genes show strong evolutionary conservation , predicting important and well-conserved functions .", "A fraction of these show strong conservation of core domains but dynamic changes in ...	2015
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "sequencing techniques", "taxonomy", "medicine and health sciences", "pathology and laboratory medicine", "pathogens", "population genetics", "phylogenetics", "data management", "phylogenetic analysis", "molecular biology techniques", "dna", "population biology", "genetic epidemiology", "r...	Bayesian reconstruction of transmission within outbreaks using genomic variants	journal.pcbi.1006117	null	[ [ "Understanding transmission is important for devising effective policies and measures that limit the spread of infectious diseases .", "In recent years , affordable whole genome sequencing has provided unprecedented detail on the relatedness of pathogen samples [1–4] .", "Consequently , accurately inf...	[ "Pathogen genome sequencing can reveal details of transmission histories and is a powerful tool in the fight against infectious disease .", "In particular , within-host pathogen genomic variants identified through heterozygous nucleotide base calls are a potential source of information to identify linked cases an...	[ "We present a new tool to reconstruct transmission events within outbreaks .", "Our approach makes use of pathogen genetic information , notably genetic variants at low frequency within host that are usually discarded , and combines it with epidemiological information of host exposure to infection .", "This lea...	2018
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "infectious diseases/nosocomial and healthcare-associated infections", "microbiology/immunity to infections", "respiratory medicine/respiratory infections", "cell biology/membranes and sorting", "infectious diseases/respiratory infections", "infectious diseases/bacterial infections", "immunology/immunit...	A Pseudomonas aeruginosa Toxin that Hijacks the Host Ubiquitin Proteolytic System	journal.ppat.1001325	null	[ [ "Respiratory infections are the greatest cause of disease worldwide [1] .", "A study by the World Health Organization ( WHO ) determined that the global disease burden of lung infections exceeds that of HIV/AIDS , cancer and heart disease and has since 1990 [1] .", "P . aeruginosa , an opportunistic h...	[ "Pseudomonas aeruginosa ( P . aeruginosa ) is an opportunistic pathogen chronically infecting the lungs of patients with chronic obstructive pulmonary disease ( COPD ) , pneumonia , cystic fibrosis ( CF ) , and bronchiectasis .", "Cif ( PA2934 ) , a bacterial toxin secreted in outer membrane vesicles ( OMV ) by P...	[ "In this manuscript , we present a detailed mechanistic study of how a secreted P . aeruginosa virulence factor disrupts mucociliary clearance in the lung by inactivating a host cell deubiquitinating enzyme ( USP10 ) , thereby facilitating the degradation of the CFTR secretory chloride channel , which reduces mucoc...	2011
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "medicine and health sciences", "breast tumors", "animal models of disease", "cancers and neoplasms", "oncology", "animal models", "histology", "model organisms", "experimental organism systems", "bioassays and physiological analysis", "research and analysis methods", "animal studies", "gene...	Histological subtypes of mouse mammary tumors reveal conserved relationships to human cancers	journal.pgen.1007135	null	[ [ "One of the hallmarks of breast cancer is tumor heterogeneity at both the histological and genomic level .", "The histological type of the tumor refers to the morphological and cytological patterns evident within a tumor .", "There are a large number of special tumor histologies recognized for breast ...	[ "Human breast cancer has been characterized by extensive transcriptional heterogeneity , with dominant patterns reflected in the intrinsic subtypes .", "Mouse models of breast cancer also have heterogeneous transcriptomes and we noted that specific histological subtypes were associated with particular subsets .",...	[ "We developed predictive gene signatures that identify specific histological mouse mammary tumor subtypes with high fidelity to expert pathologist classifications .", "As a result , these signatures are a powerful tool for classification , particularly in cases of intratumor heterogeneity; where confounding resul...	2018
[ "Introduction", "Results/Discussion", "Methods" ]	[ "bioengineering", "systems biology", "developmental biology", "signal transduction", "biological systems engineering", "developmental signaling", "stem cells", "stem cell niche", "biology", "computational biology", "molecular cell biology", "engineering", "signaling in selected disciplines" ...	Model-Based Analysis for Qualitative Data: An Application in Drosophila Germline Stem Cell Regulation	journal.pcbi.1003498	null	[ [ "Optimization algorithms attempt to find a parameter set ( or point , i . e . a value for each uncertain parameter ) that gives the best value for some objective defining model fitness , typically the error between model predictions and data; they are commonly identified as either local or global methods ( Fi...	[ "Discovery in developmental biology is often driven by intuition that relies on the integration of multiple types of data such as fluorescent images , phenotypes , and the outcomes of biochemical assays .", "Mathematical modeling helps elucidate the biological mechanisms at play as the networks become increasingl...	[ "We developed a process to quantitatively fit mathematical models using qualitative data , and applied it in the study of how stem cells are regulated in the fruit fly ovary .", "The available published data we collected are fluorescent images of protein and mRNA expression from genetic experiments .", "Despite...	2014
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "medicine and health sciences", "pathology and laboratory medicine", "pathogens", "geographical locations", "microbiology", "vertebrates", "salmonella typhi", "animals", "mammals", "bacterial diseases", "enterobacteriaceae", "global health", "pharmacology", "united kingdom", "bacteria", ...	Molecular Surveillance Identifies Multiple Transmissions of Typhoid in West Africa	journal.pntd.0004781	null	[ [ "Typhoid fever is a systemic infection caused by the Gram-negative bacterium Salmonella enterica serovar Typhi ( S . Typhi ) that continues to be a serious global health problem and a major cause of morbidity and mortality in low-middle income countries [1] .", "It is estimated that the yearly incidence o...	[ "The burden of typhoid in sub-Saharan African ( SSA ) countries has been difficult to estimate , in part , due to suboptimal laboratory diagnostics .", "However , surveillance blood cultures at two sites in Nigeria have identified typhoid associated with Salmonella enterica serovar Typhi ( S . Typhi ) as an impor...	[ "Typhoid fever , a serious bloodstream infection caused by the bacterium Salmonella Typhi , is a major cause of disease and death around the world .", "There have been limited data on the epidemiology of typhoid in many countries in sub-Saharan African , including Nigeria .", "Recent evidence , however , showed...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "lipoprotein metabolism", "animal genetics", "gene function", "animal models", "drosophila melanogaster", "model organisms", "lipid classes", "lipid metabolism", "tissue distribution", "lipids", "proteins", "lipoproteins", "biology", "biochemistry", "genetics", "apolipoprotein genes", ...	Lipoproteins in Drosophila melanogaster—Assembly, Function, and Influence on Tissue Lipid Composition	journal.pgen.1002828	null	[ [ "Lipoproteins allow the transport of lipids between different organs .", "In humans , perturbed lipoprotein levels correlate with metabolic disease , but to which extent they contribute to tissue pathology is unclear .", "Animals synthesize a huge variety of lipids that form cellular membranes , funct...	[ "Interorgan lipid transport occurs via lipoproteins , and altered lipoprotein levels correlate with metabolic disease .", "However , precisely how lipoproteins affect tissue lipid composition has not been comprehensively analyzed .", "Here , we identify the major lipoproteins of Drosophila melanogaster and use ...	[ "Lipoproteins transport both dietary and endogenously synthesized lipids between different organs .", "Lipoprotein dysfunction is associated with many medical disorders , including cardiovascular disease , but the mechanisms underlying pathogenesis are unclear .", "Simple animal models would be valuable , there...	2012
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "neonatology", "children", "medicine and health sciences", "body fluids", "pathology and laboratory medicine", "maternal health", "vomiting", "pathogens", "tropical diseases", "microbiology", "ebola hemorrhagic fever", "pediatrics", "viruses", "diarrhea", "age groups", "physiological p...	Effects of Mother’s Illness and Breastfeeding on Risk of Ebola Virus Disease in a Cohort of Very Young Children	journal.pntd.0004622	null	[ [ "Young children experience a high case fatality rate from Ebola , but the incidence of Ebola Virus Disease ( EVD ) in children appears to be lower than in adults .", "[1–4] Young children may have limited exposure outside the home , but within the household maintaining hygiene in young children is difficu...	[ "Young children who contract Ebola Virus Disease ( EVD ) have a high case fatality rate , but their sources of infection and the role of breastfeeding are unclear .", "Household members of EVD survivors from the Kerry Town Ebola Treatment Centre in Sierra Leone were interviewed four to 10 months after discharge t...	[ "Our study is the first to quantify sources of infection and describe risk of transmission of Ebola to young children .", "We found that the risk of a child under three developing Ebola disease was low unless their mother had EVD , and that the risk was particularly high if their mother died of EVD .", "But we ...	2016
[ "Introduction", "Results", "Discussion", "Methods" ]	[]	Colour As a Signal for Entraining the Mammalian Circadian Clock	journal.pbio.1002127	Environmental measurements and physiological recordings reveal that mice not only use changes in the intensity of sunlight to entrain their circadian clock, but also employ blue–yellow color discrimination to detect spectral changes associated with dawn and dusk.	[ [ "The ability to predict and adapt to recurring events in the environment is fundamental to survival .", "Organisms across the living world achieve this using endogenous circadian clocks [1–3] .", "However , if such clocks are to fulfil their ethological function they need to be regularly reset to loca...	[ "Twilight is characterised by changes in both quantity ( “irradiance” ) and quality ( “colour” ) of light .", "Animals use the variation in irradiance to adjust their internal circadian clocks , aligning their behaviour and physiology with the solar cycle .", "However , it is currently unknown whether changes i...	[ "Animals use an internal brain clock to keep track of time and adjust their behaviour in anticipation of the coming day or night .", "To be useful , however , this clock must be synchronised to external time .", "Assessing external time is typically thought to rely on measuring large changes in ambient light in...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "virology/host invasion and cell entry", "virology/immunodeficiency viruses", "virology/antivirals, including modes of action and resistance", "virology" ]	Role of Abl Kinase and the Wave2 Signaling Complex in HIV-1 Entry at a Post-Hemifusion Step	journal.ppat.1000956	null	[ [ "HIV-1 enters cells in a pH-independent manner by fusion at the plasma membrane or from within endosomes [1]–[3] .", "HIV-1 entry requires multiple conformational changes in the HIV-1 glycoprotein , and rearrangement of the actin cytoskeleton .", "These events are triggered by binding of the viral env...	[ "Entry of human immunodeficiency virus type 1 ( HIV-1 ) commences with binding of the envelope glycoprotein ( Env ) to the receptor CD4 , and one of two coreceptors , CXCR4 or CCR5 .", "Env-mediated signaling through coreceptor results in Gαq-mediated Rac activation and actin cytoskeleton rearrangements necessary...	[ "Patients infected with HIV-1 are currently treated with highly active antiretroviral therapy ( HAART ) that efficiently suppresses the virus but does not cure the infection .", "HIV-1 envelope activates Rac-mediated actin cytoskeleton rearrangements in the target cell that promote membrane fusion and entry .", ...	2010
[ "Introduction", "Results/Discussion", "Materials and Methods" ]	[]	Conserved Translatome Remodeling in Nematode Species Executing a Shared Developmental Transition	journal.pgen.1003739	null	[ [ "Animals of diverse genera react to unfavorable growth conditions by entering developmentally arrested states known as diapause [1] , [2] .", "Nematodes of the genus Caenorhabditis can enter and exit diapause at several developmental time points , allowing populations to reproduce through boom and bust cy...	[ "Nematodes of the genus Caenorhabditis enter a developmental diapause state after hatching in the absence of food .", "To better understand the relative contributions of distinct regulatory modalities to gene expression changes associated with this developmental transition , we characterized genome-wide changes i...	[ "Working with a set of four related animal species , we have studied a conserved developmental and metabolic transition at the level of protein production and regulation of RNA levels .", "Strikingly , regulatory effects at the level of RNA accumulation and protein synthesis act together to achieve the observed m...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "immunology/immune response", "microbiology/innate immunity", "immunology/innate immunity", "infectious diseases/bacterial infections", "immunology/immunity to infections", "microbiology/medical microbiology", "infectious diseases/antimicrobials and drug resistance" ]	Protein C Inhibitor—A Novel Antimicrobial Agent	journal.ppat.1000698	null	[ [ "Our early response to an invading pathogen relies to a major part on our innate immune system .", "In order to sense and fight an infection , the human host has developed an arsenal of pattern recognition proteins that interact with so-called pathogen associated molecular patterns or PAMPs ( for a review...	[ "Protein C inhibitor ( PCI ) is a heparin-binding serine proteinase inhibitor belonging to the family of serpin proteins .", "Here we describe that PCI exerts broad antimicrobial activity against bacterial pathogens .", "This ability is mediated by the interaction of PCI with lipid membranes , which subsequentl...	[ "The innate immune system is an integral part of our battle against an invading pathogen .", "Antimicrobial peptides and proteins partake in this fight due to their ability to perforate the bacterial cell wall , which eventually will cause the efflux of bacterial cytosolic content and efficient bacterial killing ...	2009
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "invertebrates", "medicine and health sciences", "nervous system", "gene regulation", "regulatory proteins", "blood-brain barrier", "dna-binding proteins", "departures from diploidy", "animals", "animal models", "drosophila melanogaster", "model organisms", "experimental organism systems", ...	Dynamic genome wide expression profiling of Drosophila head development reveals a novel role of Hunchback in retinal glia cell development and blood-brain barrier integrity	journal.pgen.1007180	null	[ [ "The development of complex organs is often accompanied by extensive cell- and tissue rearrangements .", "Initially simple cells undergo profound morphological changes such as extensive cell fusions of muscle precursor cells to form syncytial muscle fibers [1] or the formation of highly polarized neurons ...	[ "Drosophila melanogaster head development represents a valuable process to study the developmental control of various organs , such as the antennae , the dorsal ocelli and the compound eyes from a common precursor , the eye-antennal imaginal disc .", "While the gene regulatory network underlying compound eye deve...	[ "The development of different cell types must be tightly coordinated , and the eye-antennal imaginal discs of Drosophila melanogaster represent an excellent model to study the molecular mechanisms underlying this coordination .", "These imaginal discs contain the anlagen of nearly all adult head structures , such...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine", "infectious diseases", "immunology", "biology" ]	HSV-2 Specifically Down Regulates HLA-C Expression to Render HSV-2-Infected DCs Susceptible to NK Cell Killing	journal.ppat.1003226	null	[ [ "Human Natural killer ( NK ) cells comprise approximately 5–15% of peripheral blood lymphocytes .", "They kill infected or transformed cells and can also contribute to the activation of the adaptive immunity through the secretion of cytokines and chemokines [1] .", "Additionally , NK cells regulates a...	[ "Both NK cells and CTLs kill virus-infected and tumor cells .", "However , the ways by which these killer cells recognize the infected or the tumorigenic cells are different , in fact almost opposite .", "CTLs are activated through the interaction of the TCR with MHC class I proteins .", "In contrast , NK cel...	[ "Approximately 20% of all humans are latently and asymptomatically infected with HSV-2 .", "This suggests that the virus developed mechanisms to avoid immune cell detection; many of which are still unknown .", "Infected cells are killed mainly by two lymphocyte populations; NK cells and CTLs that belong to the ...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "immunology", "microbiology/parasitology", "infectious diseases/protozoal infections", "infectious diseases/tropical and travel-associated diseases", "microbiology/cellular microbiology and pathogenesis" ]	Complement Receptor 1 Is a Sialic Acid-Independent Erythrocyte Receptor of Plasmodium falciparum	journal.ppat.1000968	null	[ [ "The erythrocyte invasion mechanisms of P . falciparum are varied and complex .", "Erythrocytes are rich in surface glycophorins which contain sialic acid .", "Earlier studies demonstrated that invasion of erythrocytes could be inhibited by treatment of erythrocytes with neuraminidase , which removes ...	[ "Plasmodium falciparum is a highly lethal malaria parasite of humans .", "A major portion of its life cycle is dedicated to invading and multiplying inside erythrocytes .", "The molecular mechanisms of erythrocyte invasion are incompletely understood .", "P . falciparum depends heavily on sialic acid present ...	[ "Plasmodium falciparum malaria is a blood parasite that lives for the most part inside red cells .", "It is responsible for the death of 1-2 million people every year .", "The mechanisms by which the parasite invades red cells are complex and not completely understood .", "For many years it has been known tha...	2010
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "genome analysis tools", "genomics", "genetics", "population genetics", "biology", "computational biology", "genetics and genomics" ]	Systematic Detection of Epistatic Interactions Based on Allele Pair Frequencies	journal.pgen.1002463	null	[ [ "The simultaneous perturbation of two epistatically interacting genes leads to a phenotype that is not expected based on the phenotypes of the individual genes .", "Understanding these phenomena is indispensable for explaining multi-factorial traits and diseases [1] .", "In addition , epistatic intera...	[ "Epistatic genetic interactions are key for understanding the genetic contribution to complex traits .", "Epistasis is always defined with respect to some trait such as growth rate or fitness .", "Whereas most existing epistasis screens explicitly test for a trait , it is also possible to implicitly test for fi...	[ "Elucidating non-additive ( epistatic ) interactions between genes is crucial for understanding the molecular mechanisms of complex diseases .", "Even though high-throughput , systematic testing of genetic interactions is possible in simple model organisms , such screens have so far not been successful in mammals...	2012
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "bacteriology", "medicine and health sciences", "body fluids", "pathology and laboratory medicine", "fibrinogen", "pathogens", "microbiology", "staphylococcus aureus", "collagens", "plasmid construction", "dna construction", "molecular biology techniques", "glycoproteins", "bacteria", "b...	Staphylococcus aureus adhesion in endovascular infections is controlled by the ArlRS–MgrA signaling cascade	journal.ppat.1007800	null	[ [ "Staphylococcus aureus , a Gram-positive bacterial pathogen , is a leading cause of infections worldwide .", "The most severe forms are bloodstream infections , such as sepsis , endocarditis , or thrombophlebitis , characterized by their high mortality and frequent disease sequelae [1 , 2] .", "The cr...	[ "Staphylococcus aureus is a leading cause of endovascular infections .", "This bacterial pathogen uses a diverse array of surface adhesins to clump in blood and adhere to vessel walls , leading to endothelial damage , development of intravascular vegetations and secondary infectious foci , and overall disease pro...	[ "Adhesion is central to the success of Staphylococcus aureus as a bacterial pathogen .", "We describe a novel mechanism through which S . aureus alters adhesion to ligands by regulating expression of giant inhibitory surface proteins .", "These giant proteins shield normal surface adhesins , preventing binding ...	2019
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "motor systems", "computational neuroscience", "biology", "computational biology", "neuroscience" ]	A Single-Rate Context-Dependent Learning Process Underlies Rapid Adaptation to Familiar Object Dynamics	journal.pcbi.1002196	null	[ [ "Object manipulation is an essential feature of everyday human behavior [1] .", "It represents a challenge for the motor system because grasping an object changes the relationship between the motor commands and the resulting movement of the arm [2] , [3] , [4] .", "Skillful manipulation thus requires ...	[ "Motor learning has been extensively studied using dynamic ( force-field ) perturbations .", "These induce movement errors that result in adaptive changes to the motor commands .", "Several state-space models have been developed to explain how trial-by-trial errors drive the progressive adaptation observed in s...	[ "Skillful object manipulation is an essential feature of human behavior .", "How humans process and represent information associated with objects is thus a fundamental question in neuroscience .", "Here , we examine the representation of the mechanical properties of objects which define the mapping between the ...	2011
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "plant science", "plant biology", "plant pathology", "biology" ]	A Permeable Cuticle Is Associated with the Release of Reactive Oxygen Species and Induction of Innate Immunity	journal.ppat.1002148	null	[ [ "The cuticle is mainly considered as a constitutive barrier against water loss , irradiation , xenobiotics or pathogens [1] , [2] .", "The structure of this lipid boundary layer covering aerial parts of plants is made of waxes covering and interspersed in cutin , a polymer layer formed by a network of est...	[ "Wounded leaves of Arabidopsis thaliana show transient immunity to Botrytis cinerea , the causal agent of grey mould .", "Using a fluorescent probe , histological staining and a luminol assay , we now show that reactive oxygen species ( ROS ) , including H2O2 and O2− , are produced within minutes after wounding ....	[ "This study provides an explanation for the strong resistance to B . cinerea observed in wounded plants or plants with cuticular defects .", "We have observed that a production of ROS and a permeable cuticle is common to all these situations .", "ROS , that include hydrogen peroxide , are known inducers of resi...	2011
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "molecular biology/post-translational regulation of gene expression", "molecular biology/histone modification", "cell biology/cell growth and division", "virology/effects of virus infection on host gene expression", "molecular biology/translational regulation", "cell biology/gene expression" ]	A Viral microRNA Down-Regulates Multiple Cell Cycle Genes through mRNA 5′UTRs	journal.ppat.1000967	null	[ [ "The recent discovery of a new class of regulatory genes known as microRNAs ( miRNAs ) has resulted in a paradigm shift in gene regulation research .", "miRNAs are small single-stranded RNA species of approximately 20–24 bases in length that regulate gene expression through post transcriptional mechanisms...	[ "Global gene expression data combined with bioinformatic analysis provides strong evidence that mammalian miRNAs mediate repression of gene expression primarily through binding sites within the 3′ untranslated region ( UTR ) .", "Using RNA induced silencing complex immunoprecipitation ( RISC-IP ) techniques we ha...	[ "Regulation of gene expression is as important as the genes themselves in determining the diverse array of living creatures we see in nature .", "Recently , scientists have discovered a whole new level of gene regulation through the actions of small molecules called microRNAs ( miRNAs ) .", "It is currently tho...	2010
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "genome-wide association studies", "medicine", "public health and epidemiology", "statistics", "mathematics", "biostatistics", "genetic epidemiology", "personalized medicine", "epidemiology", "biology", "genetic association studies", "genetics", "human genetics", "genetics of disease", "...	Power and Predictive Accuracy of Polygenic Risk Scores	journal.pgen.1003348	null	[ [ "Although individually significant markers in genome-wide association scans ( GWAS ) explain limited heritability of complex traits , evidence has been accruing that a considerable proportion of phenotypic variation can be explained by the ensemble of markers not achieving significance .", "Thus , while m...	[ "Polygenic scores have recently been used to summarise genetic effects among an ensemble of markers that do not individually achieve significance in a large-scale association study .", "Markers are selected using an initial training sample and used to construct a score in an independent replication sample by form...	[ "Recently there has been much interest in combining multiple genetic markers into a single score for predicting disease risk .", "Even if many of the individual markers have no detected effect , the combined score could be a strong predictor of disease .", "This has allowed researchers to demonstrate that some ...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "infectious diseases/fungal infections", "microbiology/medical microbiology", "infectious diseases/antimicrobials and drug resistance", "microbiology" ]	Hsp90 Governs Echinocandin Resistance in the Pathogenic Yeast Candida albicans via Calcineurin	journal.ppat.1000532	null	[ [ "Candida species have intimate yet perilous connections with their human hosts .", "They are commensals of the human microbiota of the gastrointestinal tract , mucous membranes , and skin .", "They also rank as the most common causative agents of invasive fungal infections and are responsible for a br...	[ "Candida albicans is the leading fungal pathogen of humans , causing life-threatening disease in immunocompromised individuals .", "Treatment of candidiasis is hampered by the limited number of antifungal drugs whose efficacy is compromised by host toxicity , fungistatic activity , and the emergence of drug resis...	[ "Fungal pathogens pose a serious threat to people with compromised immune systems .", "Chief among the opportunistic fungal pathogens is Candida albicans .", "Treatment of C . albicans infections remains challenging because there are very few effective drugs and the pathogen has evolved many strategies to survi...	2009
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "invertebrates", "medicine and health sciences", "onchocerca volvulus", "helminths", "wolves", "vertebrates", "parasitic diseases", "dogs", "mammals", "animals", "onchocerca", "nematode infections", "veterinary diagnostics", "dna", "veterinary science", "veterinary medicine", "bioche...	A real-time PCR tool for the surveillance of zoonotic Onchocerca lupi in dogs, cats and potential vectors	journal.pntd.0006402	null	[ [ "Within the genus Onchocerca ( Spirurida: Onchocercidae ) , Onchocerca volvulus and Onchocerca lupi parasitize humans and carnivores , respectively [1–5] , the latter being a zoonotic agent [6 , 7] .", "While O . volvulus is a well-known parasite of humans transmitted by blackflies ( Simulium spp . ) [8 ,...	[ "The ocular onchocercosis is caused by the zoonotic parasite Onchocerca lupi ( Spirurida: Onchocercidae ) .", "A major hindrance to scientific progress is the absence of a reliable diagnostic test in affected individuals .", "Microscopic examination of skin snip sediments and the identification of adults embedd...	[ "The diagnosis of zoonotic ocular onchocercosis caused by Onchocerca lupi ( Spirurida: Onchocercidae ) is currently based on microscopic examination of skin snip sediments and on the identification of adults embedded in ocular nodules .", "These methods are labour-intensive and require multiple steps to achieve t...	2018
[ "Introduction", "Materials and methods", "Results", "Discussion" ]	[ "medicine and health sciences", "body fluids", "viral transmission and infection", "cell cycle and cell division", "cell processes", "microbiology", "cloning", "physiological processes", "stem cells", "molecular biology techniques", "research and analysis methods", "animal cells", "stem cell...	Clonal dominance and transplantation dynamics in hematopoietic stem cell compartments	journal.pcbi.1005803	null	[ [ "The hematopoietic system has evolved to satisfy the immune , respiratory , and coagulation demands of the host .", "A complex division tree provides both amplification of cell numbers and a variety of differentiated cells with distinct roles in the body [1–3] .", "In a typical adult human ∼1011 termi...	[ "Hematopoietic stem cells in mammals are known to reside mostly in the bone marrow , but also transitively passage in small numbers in the blood .", "Experimental findings have suggested that they exist in a dynamic equilibrium , continuously migrating between these two compartments .", "Here we construct an in...	[ "Clonal hematopoiesis—where mature myeloid cells in the blood deriving from a single stem cell are over-represented—is a major risk factor for overt hematologic malignancies .", "To quantify how likely this phenomena is , we combine existing observations with a novel stochastic model and extensive mathematical an...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "viral entry", "viral transmission and infection", "virology", "subviral particles", "biology", "microbiology", "viral structure", "viral load" ]	Insights into Minor Group Rhinovirus Uncoating: The X-ray Structure of the HRV2 Empty Capsid	journal.ppat.1002473	null	[ [ "A key step in the life cycle of viruses is the delivery of its genome into a compartment of the host cell appropriate for its replication .", "This involves the recognition of specific cell surface receptors by the viral capsid and the passage of the genome across at least one membrane barrier .", "E...	[ "Upon attachment to their respective receptor , human rhinoviruses ( HRVs ) are internalized into the host cell via different pathways but undergo similar structural changes .", "This ultimately results in the delivery of the viral RNA into the cytoplasm for replication .", "To improve our understanding of the ...	[ "Human Rhinoviruses ( HRVs ) , members of the Picornaviridae family , are small non-enveloped viruses possessing an icosahedral capsid that protects the single-stranded RNA genome .", "Although much is known about their binding to cell receptors and their uptake into the host cell , the mechanism by which their g...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "invertebrates", "molecular neuroscience", "animal genetics", "neuroscience", "animals", "gene function", "animal models", "drosophila melanogaster", "model organisms", "molecular genetics", "drosophila", "research and analysis methods", "insects", "arthropoda", "genetics", "biology an...	Drosophila Pheromone-Sensing Neurons Expressing the ppk25 Ion Channel Subunit Stimulate Male Courtship and Female Receptivity	journal.pgen.1004238	null	[ [ "Ever since the identification of the first pheromone , Bombykol , as the sexual attractant of the silkmoth more than fifty years ago [1] , the mechanisms underlying the detection of pheromones and their regulation of animal behavior have been an important area of inquiry .", "The expanding understanding ...	[ "As in many species , gustatory pheromones regulate the mating behavior of Drosophila .", "Recently , several ppk genes , encoding ion channel subunits of the DEG/ENaC family , have been implicated in this process , leading to the identification of gustatory neurons that detect specific pheromones .", "In a sub...	[ "Drosophila mating behaviors serve as an attractive model to understand how external sensory cues are detected and used to generate appropriate behavioral responses .", "Pheromones present on the cuticle of Drosophila have important roles in stimulating male courtship toward females and inhibiting male courtship ...	2014
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "adaptation", "mathematics", "natural selection", "statistics", "statistical methods", "biology", "evolutionary biology", "comparative genomics", "evolutionary processes" ]	Detecting Individual Sites Subject to Episodic Diversifying Selection	journal.pgen.1002764	null	[ [ "Following the introduction of computationally tractable codon-substitution models [1] , [2] nearly two decades ago , there has been sustained interest in using these models to study the past action of natural selection on protein coding genes .", "Positive selection can be inferred whenever the estimated...	[ "The imprint of natural selection on protein coding genes is often difficult to identify because selection is frequently transient or episodic , i . e . it affects only a subset of lineages .", "Existing computational techniques , which are designed to identify sites subject to pervasive selection , may fail to r...	[ "Identifying regions of protein coding genes that have undergone adaptive evolution is important to answering many questions in evolutionary biology and genetics .", "In order to tease out genetic evidence for natural selection , genes from a diverse array of taxa must be analyzed , only a subset of which may hav...	2012
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "microbiology/environmental microbiology", "public health and epidemiology/environmental health", "infectious diseases/neglected tropical diseases", "critical care and emergency medicine/sepsis and multiple organ failure", "public health and epidemiology/infectious diseases", "infectious diseases/bacteria...	The Epidemiology and Clinical Spectrum of Melioidosis: 540 Cases from the 20 Year Darwin Prospective Study	journal.pntd.0000900	null	[ [ "Melioidosis is the clinical disease following infection with the soil and water bacterium Burkholderia pseudomallei [1] , [2] .", "It occurs in humans and a wide variety of animals and is thought to usually follow percutaneous inoculation .", "In addition , inhalation of aerosolized bacteria probably...	[ "Over 20 years , from October 1989 , the Darwin prospective melioidosis study has documented 540 cases from tropical Australia , providing new insights into epidemiology and the clinical spectrum .", "The principal presentation was pneumonia in 278 ( 51% ) , genitourinary infection in 76 ( 14% ) , skin infection ...	[ "Melioidosis is an occupationally and recreationally acquired infection important in Southeast Asia and northern Australia .", "Recently cases have been reported from more diverse locations globally .", "The responsible bacterium , Burkholderia pseudomallei , is considered a potential biothreat agent .", "Ris...	2010
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "medicine and health sciences", "pathology and laboratory medicine", "clinical research design", "tropical diseases", "database searching", "randomized controlled trials", "parasitic diseases", "pediatrics", "research design", "clinical medicine", "signs and symptoms", "neglected tropical dise...	Interventions to treat cutaneous leishmaniasis in children: A systematic review	journal.pntd.0006986	null	[ [ "Cutaneous leishmaniasis is the most common presentation of Leishmaniasis , with global estimates of 0 . 7 to 1 . 2 million cases per year[1] .", "In contexts of peri-domestic and anthroponotic transmission , children represent an important number of cases .", "In 2016 for the Americas , among 48 , 91...	[ "Case management in children with cutaneous leishmaniasis ( CL ) is mainly based on studies performed in adults .", "We aimed to determine the efficacy and harms of interventions to treat CL in children .", "We conducted a systematic review of clinical trials and cohort studies , assessing treatments of CL in c...	[ "Cutaneous leishmaniasis ( CL ) is a parasitic disease that causes chronic , often ulcerated , skin lesions that leave lifelong scars on the face or other visible areas .", "In some regions of the world , children represent a high proportion of cases .", "Treatment options for children are limited , and may req...	2018
[ "Introduction", "Materials and methods", "Results", "Discussion" ]	[ "biotechnology", "alleles", "plant science", "model organisms", "mathematics", "forecasting", "statistics (mathematics)", "experimental organism systems", "plant genomics", "molecular genetics", "plants", "research and analysis methods", "grasses", "mathematical and statistical techniques"...	Incomplete dominance of deleterious alleles contributes substantially to trait variation and heterosis in maize	journal.pgen.1007019	null	[ [ "Understanding the genetic basis of phenotypic variation is critical to many biological endeavors from human health to conservation and agriculture .", "Although most new mutations are likely deleterious [1] , their importance in patterning phenotypic variation is controversial and not well understood [2]...	[ "Deleterious alleles have long been proposed to play an important role in patterning phenotypic variation and are central to commonly held ideas explaining the hybrid vigor observed in the offspring of a cross between two inbred parents .", "We test these ideas using evolutionary measures of sequence conservation...	[ "A key long-term goal of biology is understanding the genetic basis of phenotypic variation .", "Although most new mutations are likely disadvantageous , their prevalence and importance in explaining patterns of phenotypic variation is controversial and not well understood .", "In this study we combine whole ge...	2017
[ "Introduction", "Materials and methods", "Results", "Discussion" ]	[ "invertebrates", "medicine and health sciences", "trypanosoma congolense", "parasitic protozoans", "animals", "glossina", "organisms", "trypanosoma brucei", "protozoans", "trypanosoma vivax", "molecular biology techniques", "tsetse fly", "insect vectors", "research and analysis methods", ...	A single test approach for accurate and sensitive detection and taxonomic characterization of Trypanosomes by comprehensive analysis of internal transcribed spacer 1 amplicons	journal.pntd.0006842	null	[ [ "Human African trypanosomiasis ( HAT ) or sleeping sickness is classified as a neglected tropical disease by WHO , that is endemic in sub-Sahara Africa .", "HAT affects impoverished rural areas of sub-Saharan Africa , where it coexists with animal trypanosomiasis constituting a major health and economic b...	[ "To improve our knowledge on the epidemiological status of African trypanosomiasis , better tools are required to monitor Trypanosome genotypes circulating in both mammalian hosts and tsetse fly vectors .", "This is important in determining the diversity of Trypanosomes and understanding how environmental factors...	[ "Tsetse flies are central actors in the transmission of Trypanosomes to vertebrate hosts .", "Therefore , detection of Trypanosomes in the tsetse flies is important for understanding the epidemiology of African trypanosomiasis as a component of new control or surveillance strategies .", "We have developed a met...	2019
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "taxonomy", "organismal evolution", "medicine and health sciences", "pathology and laboratory medicine", "infectious disease epidemiology", "pathogens", "spatial epidemiology", "microbiology", "epidemiological methods and statistics", "retroviruses", "viruses", "immunodeficiency viruses", "p...	Inference of Transmission Network Structure from HIV Phylogenetic Trees	journal.pcbi.1005316	null	[ [ "Infectious diseases that are directly transmitted spread over contact networks , where each individual host can be represented by a node with a finite set of contacts ( edges ) via which they can transmit the pathogen .", "The structure of these networks is a major determinant of the pathogen transmissio...	[ "Phylogenetic inference is an attractive means to reconstruct transmission histories and epidemics .", "However , there is not a perfect correspondence between transmission history and virus phylogeny .", "Both node height and topological differences may occur , depending on the interaction between within-host ...	[ "Over the past few years , epidemiological models for infectious diseases have incorporated network structure: each individual has a set of contacts to whom they can pass the infection .", "However , collecting data to develop a good representation of the network is very challenging .", "The increasing availabi...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genetics and genomics/animal genetics", "evolutionary biology/sexual behavior", "molecular biology/molecular evolution", "genetics and genomics/gene function", "infectious diseases/epidemiology and control of infectious diseases" ]	Transglutaminase-Mediated Semen Coagulation Controls Sperm Storage in the Malaria Mosquito	journal.pbio.1000272	The mating plug is a key regulator of mosquito fertility.	[ [ "Anopheles gambiae mosquitoes are the principal vectors of human malaria , a disease with devastating consequences for public health and the economic development of disease-endemic countries .", "The creation of new tools to control vector populations is a focal point of intensive efforts to eradicate the...	[ "Insect seminal fluid proteins are powerful modulators of many aspects of female physiology and behaviour including longevity , egg production , sperm storage , and remating .", "The crucial role of these proteins in reproduction makes them promising targets for developing tools aimed at reducing the population s...	[ "Male seminal fluid proteins trigger a wide range of behavioural and physiological changes in females and can have important effects on reproductive success .", "In many animals , seminal fluid is transferred to females as a gelatinous mass termed a mating plug .", "Although many hypotheses have been put forwar...	2009
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "virology", "biology", "microbiology" ]	Fates of Retroviral Core Components during Unrestricted and TRIM5-Restricted Infection	journal.ppat.1003214	null	[ [ "Primates express a range of restriction factors that inhibit retroviral infection , and variation in restriction factors is an important determinant of retroviral tropism [1]–[3] .", "TRIM5α is one such factor [4] , and is a member of the large family of tripartite motif ( TRIM ) proteins that share a co...	[ "TRIM5 proteins can restrict retroviral infection soon after delivery of the viral core into the cytoplasm .", "However , the molecular mechanisms by which TRIM5α inhibits infection have been elusive , in part due to the difficulty of developing and executing biochemical assays that examine this stage of the retr...	[ "The TRIM5 proteins found in primates are inhibitors of retroviral infection that act soon after delivery of the viral core into the cytoplasm .", "It has been difficult to elucidate how TRIM5 proteins work , because techniques that can be applied to this step of the viral life cycle are cumbersome .", "We deve...	2013
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "physiology", "biophysics", "neuroscience" ]	Interaction with Phosphoinositides Confers Adaptation onto the TRPV1 Pain Receptor	journal.pbio.1000046	Ion channels responsible for detection of painful stimuli have properties essential for the adaptation of responsiveness, as occurs in many sensory receptors. This implies that pain sensation is also capable of adaptation at the receptor level.	[ [ "Adaptation is an essential feature of many sensory receptors , allowing them to continuously respond to varying stimuli .", "For example , photoreceptors can adjust their performance to an illumination level varying over orders of magnitude [1] .", "Hair cells can detect bundle deflections <1 nm in t...	[ "Adaptation is a common feature of many sensory systems .", "But its occurrence to pain sensation has remained elusive .", "Here we address the problem at the receptor level and show that the capsaicin ion channel TRPV1 , which mediates nociception at the peripheral nerve terminals , possesses properties essent...	[ "Sensory receptors can adjust their sensitivity to continuously varying stimuli , a process known as adaptation .", "Adaptation has been extensively studied in vision , hearing , and olfactory systems , but whether it also occurs to pain receptors has not been established .", "TRPV1 is an ion channel expressed ...	2009
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "medicine and health sciences", "toxins", "pathology and laboratory medicine", "clinical research design", "tropical diseases", "geographical locations", "vertebrates", "database searching", "animals", "toxic agents", "toxicology", "research design", "signs and symptoms", "reptiles", "ne...	Reviewing evidence of the clinical effectiveness of commercially available antivenoms in sub-Saharan Africa identifies the need for a multi-centre, multi-antivenom clinical trial	journal.pntd.0007551	null	[ [ "More than 100 , 000 people die from snakebite envenoming every year , associating this neglected tropical medical condition with one of the highest burdens of mortality of all neglected tropical diseases ( NTDs ) .", "In sub-Saharan Africa alone , snakebites are estimated to cause between 435 , 000 and 5...	[ "Snakebite envenoming kills more than more than 20 , 000 people in Sub-Saharan Africa every year .", "Poorly regulated markets have been inundated with low-price , low-quality antivenoms .", "This review aimed to systematically collect and analyse the clinical data on all antivenom products now available in mar...	[ "Snakebite envenomation represents one of the most neglected tropical medical conditions worldwide .", "Despite high levels of morbidity and mortality associated with snakebite , its neglected nature has compromised the availability and evaluation of antivenom treatment .", "This review was initiated by Médecin...	2019
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "infectious diseases/tropical and travel-associated diseases", "cardiovascular disorders" ]	Cardiac Alterations in Human African Trypanosomiasis (T.b. gambiense) with Respect to the Disease Stage and Antiparasitic Treatment	journal.pntd.0000383	null	[ [ "Human African Trypanosomiasis ( HAT ) or sleeping sickness evolves in two stages , the first or early ( hemo-lymphatic ) stage and the second or late ( meningo-encephalitic ) stage which is characterized by invasion of the central nervous system ( CNS ) by trypanosomes .", "Neuropsychiatric disturbances ...	[ "In Human African Trypanosomiasis , neurological symptoms dominate and cardiac involvement has been suggested .", "Because of increasing resistance to the available drugs for HAT , new compounds are desperately needed .", "Evaluation of cardiotoxicity is one parameter of drug safety , but without knowledge of t...	[ "In Human African Trypanosomiasis ( HAT ) , neurological symptoms dominate and cardiac involvement has been suggested .", "Because of increasing resistance to the available drugs for HAT , new compounds are desperately needed .", "Evaluation of cardiotoxicity is one parameter of drug safety , but without knowle...	2009
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "keratinocytes", "medicine and health sciences", "dna-binding proteins", "epithelial cells", "dna transcription", "stem cells", "genome analysis", "epigenetics", "mammalian genomics", "chromatin", "genomic libraries", "animal cells", "chromosome biology", "proteins", "gene expression", ...	5C analysis of the Epidermal Differentiation Complex locus reveals distinct chromatin interaction networks between gene-rich and gene-poor TADs in skin epithelial cells	journal.pgen.1006966	null	[ [ "Metazoan development requires the concerted specification of divergent lineages among a genetically homogenous cell population and the tightly controlled , coordinate genesis of cellular structural and functional diversity driven by proper spatial and temporal regulation of transcription .", "Genome topo...	[ "Mammalian genomes contain several dozens of large ( >0 . 5 Mbp ) lineage-specific gene loci harbouring functionally related genes .", "However , spatial chromatin folding , organization of the enhancer-promoter networks and their relevance to Topologically Associating Domains ( TADs ) in these loci remain poorly...	[ "Gene activity programmes in different cell types control development and homeostasis of multi-cellular organisms .", "Spatial genome organization controls gene activity by facilitating or restricting contacts between gene promoters and remote gene enhancers .", "Functionally related co-regulated genes are ofte...	2017
[ "Introduction", "Results", "Discussion", "Material and Methods" ]	[ "genome-wide association studies", "quantitative trait association studies", "genome analysis", "gene expression", "genetics", "gene regulation", "biology and life sciences", "computational biology" ]	Dissecting Dynamic Genetic Variation That Controls Temporal Gene Response in Yeast	journal.pcbi.1003984	null	[ [ "Inherited variation in gene expression is likely to have a major effect on cellular and disease phenotypes , and may allow the underlying DNA polymorphisms ( genetic variants ) to be identified [1] .", "The genetic effect of a particular variant on a certain RNA is the quantitative change in gene express...	[ "Inter-individual variation in regulatory circuits controlling gene expression is a powerful source of functional information .", "The study of associations among genetic variants and gene expression provides important insights about cell circuitry but cannot specify whether and when potential variants dynamicall...	[ "Genetic variation is postulated to play a major role in transcriptional responses to stimulation .", "Such process involves two inter-related dynamic processes: first , the time-dependent changes in gene expression , and second , the time-dependent changes in genetic effects .", "Although the dynamics of gene ...	2014
[ "Introduction", "Methods", "Results", "Discussion" ]	[]	Combining Search, Social Media, and Traditional Data Sources to Improve Influenza Surveillance	journal.pcbi.1004513	null	[ [ "We collected CDC-reported ILI , considered the ground truth for this study , from the ILINet website ( http://gis . cdc . gov/grasp/fluview/fluportaldashboard . html ) .", "We used five independent data sets to develop our ILI weak predictors:", "( a ) near real-time hospital visit records from athen...	[ "We present a machine learning-based methodology capable of providing real-time ( “nowcast” ) and forecast estimates of influenza activity in the US by leveraging data from multiple data sources including: Google searches , Twitter microblogs , nearly real-time hospital visit records , and data from a participatory...	[ "The aggregated activity patterns of Internet users have enabled the detection and tracking of multiple population-wide events such as disease outbreaks , financial markets performance , and preferences in online movie selections .", "As a consequence , a collection of mathematical models aiming at monitoring and...	2015
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "medicine and health sciences", "enzyme-linked immunoassays", "cardiovascular anatomy", "oxygen", "cardiac output", "pulmonology", "arteries", "hypoxia", "pulmonary arteries", "immunologic techniques", "cardiology", "medical hypoxia", "research and analysis methods", "blood vessels", "im...	Preservation of myocardial contractility during acute hypoxia with OMX-CV, a novel oxygen delivery biotherapeutic	journal.pbio.2005924	null	[ [ "Inadequate oxygen ( O2 ) delivery relative to metabolic demand leads to progressive bioenergetic collapse and cellular dysfunction .", "When systemic , this defines the clinical entity of shock , a major cause of morbidity and mortality in both adults and children [1 , 2 , 3 , 4] .", "Rather than a s...	[ "The heart exhibits the highest basal oxygen ( O2 ) consumption per tissue mass of any organ in the body and is uniquely dependent on aerobic metabolism to sustain contractile function .", "During acute hypoxic states , the body responds with a compensatory increase in cardiac output that further increases myocar...	[ "While hemoglobin is the primary oxygen delivery molecule used to maintain tissue oxygenation in metazoans , many organisms have other heme-containing proteins that can bind oxygen and other diatomic gases .", "Here , we tested whether a member of the H-NOX family of heme-containing proteins found in the thermost...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biomacromolecule-ligand interactions", "microbiology", "host-pathogen interaction", "carbohydrates", "animal models", "fungi", "caenorhabditis elegans", "model organisms", "drosophila melanogaster", "protein structure", "mycology", "proteins", "biology", "biophysics", "fungal biochemist...	Plasticity of the β-Trefoil Protein Fold in the Recognition and Control of Invertebrate Predators and Parasites by a Fungal Defence System	journal.ppat.1002706	null	[ [ "Adequate and efficient defence mechanisms to protect an organism's integrity and survival have been essential for the evolution of multicellularity since loss of individual cells may be detrimental for a multicellular organism .", "Any defence mechanism thereby critically relies on the ability to discrim...	[ "Discrimination between self and non-self is a prerequisite for any defence mechanism; in innate defence , this discrimination is often mediated by lectins recognizing non-self carbohydrate structures and so relies on an arsenal of host lectins with different specificities towards target organism carbohydrate struc...	[ "All multicellular organisms have developed mechanisms to defend themselves against predators , parasites and pathogens .", "As a common mechanism , animals , plants and fungi use a large arsenal of carbohydrate-binding proteins ( lectins ) to protect themselves from predation and parasitism .", "The success of...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Live Fast, Die Young: Experimental Evidence of Population Extinction Risk due to Climate Change	journal.pbio.1002281	Warmer climates accelerate the pace of life of lizards and this demographic change leads to a strong decrease in population growth rate that may ultimately result in population extinctions.	[ [ "Over the last decades , consequences of global warming on biodiversity have become obvious [1–3] , with many species likely to be committed to extinction by 2050 [4] .", "Climate warming has already led to changes in species phenology [1] , physiology ( increased metabolic rates [5] ) , morphology ( shri...	[ "Evidence has accumulated in recent decades on the drastic impact of climate change on biodiversity .", "Warming temperatures have induced changes in species physiology , phenology , and have decreased body size .", "Such modifications can impact population dynamics and could lead to changes in life cycle and d...	[ "Ongoing climate change has potentially drastic impacts on biodiversity .", "Because their body temperature depends on their external environment , ectotherm ( “cold-blooded” ) species are thought to be more at risk from warming climates than endotherm ( “warm-blooded” ) species that regulate their temperature in...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "cell death", "molecular probe techniques", "cell processes", "immunoblotting", "vertebrates", "neuroscience", "animals", "animal models", "osteichthyes", "developmental biology", "model organisms", "immunoprecipitation", "neuronal death", "molecular biology techniques", "embryos", "re...	The Machado–Joseph Disease Deubiquitinase Ataxin-3 Regulates the Stability and Apoptotic Function of p53	journal.pbio.2000733	null	[ [ "Spinocerebellar ataxia type 3 ( SCA3 ) , also known as Machado–Joseph disease ( MJD ) , is an autosomal-dominantly inherited ataxia and one of at least nine polyglutamine ( polyQ ) neurodegenerative disorders described so far [1–3] .", "SCA3 is caused by an unstable cytosine-adenine-guanine ( CAG ) trinu...	[ "As a deubiquitinating enzyme ( DUB ) , the physiological substrates of ataxin-3 ( ATX-3 ) remain elusive , which limits our understanding of its normal cellular function and that of pathogenic mechanism of spinocerebellar ataxia type 3 ( SCA3 ) .", "Here , we identify p53 to be a novel substrate of ATX-3 .", "...	[ "Ataxin-3 ( ATX-3 ) is a ubiquitously expressed protein that mutated in a neurodegenerative disease called spinocerebellar ataxia type 3 ( SCA3 ) .", "It contains a polyglutamine ( polyQ ) tract near its C-terminus , the expansion of which is known to be the causative factor for SCA3 .", "It has been known for ...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genome expression analysis", "plant biology", "gene regulation", "population genetics", "quantitative traits", "epistasis", "genome analysis tools", "model organisms", "trait locus analysis", "molecular genetics", "arabidopsis thaliana", "genome complexity", "genetic polymorphism", "plant...	Genomic Analysis of QTLs and Genes Altering Natural Variation in Stochastic Noise	journal.pgen.1002295	null	[ [ "Almost all phenotypes are not fixed within species but instead exhibit significant levels of variation among individuals that is controlled by quantitative genetic loci .", "The study of such quantitative genetic variation has long been fundamental to evolution and ecology and is rapidly becoming a centr...	[ "Quantitative genetic analysis has long been used to study how natural variation of genotype can influence an organism's phenotype .", "While most studies have focused on genetic determinants of phenotypic average , it is rapidly becoming understood that stochastic noise is genetically determined .", "However ,...	[ "Understanding how genetic variation controls phenotypic variation is a fundamental goal of biology in both modern medicine and agriculture .", "Yet , frequently , even a large set of genetic polymorphisms do not fully explain variance of a phenotype within a discrete set of individuals .", "Numerous mechanisti...	2011
[ "Introduction", "Results", "Discussion", "Materials and Methods", "Supporting Information" ]	[ "drosophila", "molecular biology", "genetics and genomics" ]	Drosophila SETDB1 Is Required for Chromosome 4 Silencing	journal.pgen.0030076	null	[ [ "Methylation of conserved lysine residues on histone H3 and H4 tails plays a key role in gene regulation , chromatin structure , and establishment and maintenance of epigenetic memory ( reviewed in [1] ) .", "As proposed by the “histone code” hypothesis [2] , these marks , in association with other modifi...	[ "Histone H3 lysine 9 ( H3K9 ) methylation is associated with gene repression and heterochromatin formation .", "In Drosophila , SU ( VAR ) 3–9 is responsible for H3K9 methylation mainly at pericentric heterochromatin .", "However , the histone methyltransferases responsible for H3K9 methylation at euchromatic s...	[ "DNA is the basic unit carrying genetic information .", "Within the nucleus , DNA is wrapped around an eight-histone complex to form the nucleosome .", "The nucleosomes and other associated proteins assemble to a higher order structure called chromatin .", "The histones are mainly globular , excepted for thei...	2007
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "medicine and health sciences", "body fluids", "melioidosis", "immunology", "bacterial diseases", "chaperone proteins", "bioassays and physiological analysis", "antibody response", "research and analysis methods", "infectious diseases", "proteins", "recombinant proteins", "blood plasma", "...	Rapid and Sensitive Multiplex Detection of Burkholderia pseudomallei-Specific Antibodies in Melioidosis Patients Based on a Protein Microarray Approach	journal.pntd.0004847	null	[ [ "Melioidosis is an often fatal tropical infectious disease caused by the Gram-negative environmental bacterium Burkholderia pseudomallei [1 , 2] .", "The disease is known to be highly endemic in Southeast Asia and northern Australia .", "However , an increasing number of melioidosis case reports or en...	[ "The environmental bacterium Burkholderia pseudomallei causes the infectious disease melioidosis with a high case-fatality rate in tropical and subtropical regions .", "Direct pathogen detection can be difficult , and therefore an indirect serological test which might aid early diagnosis is desirable .", "Howev...	[ "Melioidosis is a potentially fatal infectious disease caused by the Gram-negative environmental bacterium Burkholderia pseudomallei .", "Since the clinical presentations of melioidosis are extremely variable and no specific signs or symptoms exist , early laboratory-based diagnosis is highly desirable to start a...	2016
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "blood cells", "medicine and health sciences", "immune cells", "enzyme-linked immunoassays", "pathology and laboratory medicine", "immune physiology", "pathogens", "immunology", "microbiology", "vertebrates", "animals", "mammals", "retroviruses", "viruses", "immunodeficiency viruses", ...	A recombinant herpesviral vector containing a near-full-length SIVmac239 genome produces SIV particles and elicits immune responses to all nine SIV gene products	journal.ppat.1007143	null	[ [ "There are good reasons for believing that development of an effective preventive vaccine against HIV-1 is going to be a very difficult task [1–3] .", "HIV is able to replicate continuously without relent despite apparently strong humoral and cellular immune responses to the virus .", "The HIV envelop...	[ "The properties of the human immunodeficiency virus ( HIV ) pose serious difficulties for the development of an effective prophylactic vaccine .", "Here we describe the construction and characterization of recombinant ( r ) , replication-competent forms of rhesus monkey rhadinovirus ( RRV ) , a gamma-2 herpesviru...	[ "Given the magnitude and impact of the HIV/AIDS pandemic , development of a safe , effective vaccine against HIV remains a top priority for biomedical research .", "While live-attenuated strains of the simian immunodeficiency virus ( SIV ) have shown promise in monkey studies , concern for safety has limited effo...	2018
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "immunopathology", "immune cells", "t cells", "immunology", "biology", "microbiology", "immune response" ]	Increase in TGF-β Secreting CD4+CD25+ FOXP3+ T Regulatory Cells in Anergic Lepromatous Leprosy Patients	journal.pntd.0002639	null	[ [ "The hall mark of leprosy caused by Mycobacterium leprae is involvement of the skin and peripheral nerves of man .", "Leprosy patients present with varied clinic-pathological manifestations and bacterial load which are influenced by the host immune response .", "Tuberculoid leprosy , both polar ( TT )...	[ "Lepromatous leprosy caused by Mycobacterium leprae is associated with antigen specific T cell unresponsiveness/anergy whose underlying mechanisms are not fully defined .", "We investigated the role of CD25+FOXP3+ regulatory T cells in both skin lesions and M . leprae stimulated PBMC cultures of 28 each of freshl...	[ "Lepromatous leprosy is a generalized infectious disease caused by Mycobacterium leprae with the patients showing T cell mediated unresponsiveness to the pathogen and chronicity of lesions .", "The causation of unresponsiveness and anergy in this form of leprosy is not fully understood .", "The recent discovery...	2014
[ "Introduction", "Materials and methods", "Results", "Discussion" ]	[ "invertebrates", "medicine and health sciences", "animals", "wolbachia", "viruses", "developmental biology", "animal anatomy", "population biology", "insect vectors", "zoology", "bacteria", "population density", "infectious diseases", "aedes aegypti", "life cycles", "arboviral infectio...	How does competition among wild type mosquitoes influence the performance of Aedes aegypti and dissemination of Wolbachia pipientis?	journal.pntd.0005947	null	[ [ "Infectious diseases caused by arboviruses are a growing global health concern .", "Among the disease vectors , mosquitoes from the genus Aedes and mostly important Ae .", "aegypti ( Linnaeus , 1762 ) and Ae .", "albopictus ( Skuse , 1894 ) have a prominent role in transmitting several arboviruses...	[ "Wolbachia has been deployed in several countries to reduce transmission of dengue , Zika and chikungunya viruses .", "During releases , Wolbachia-infected females are likely to lay their eggs in local available breeding sites , which might already be colonized by local Aedes sp .", "mosquitoes .", "Therefore...	[ "Several countries are seeking new vector control tools to reduce the transmission of arboviruses such as dengue , chikungunya and Zika .", "One of these innovative approaches relies on the release of Aedes aegypti mosquitoes infected with the endosymbiont Wolbachia , since this bacterium can block the aforementi...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "infographics", "invertebrates", "gene regulation", "animals", "simulation and modeling", "animal models", "developmental biology", "drosophila melanogaster", "model organisms", "embryos", "drosophila", "research and analysis methods", "embryology", "computer and information sciences", "...	Qualitative Dynamical Modelling Can Formally Explain Mesoderm Specification and Predict Novel Developmental Phenotypes	journal.pcbi.1005073	null	[ [ "Functional genomic approaches ( based on microarrays and next-generation sequencing ) provide a powerful means to decipher the molecular mechanisms underlying the control of development and cell differentiation , as well as deregulations thereof associated with diseases such as cancer .", "Together with ...	[ "Given the complexity of developmental networks , it is often difficult to predict the effect of genetic perturbations , even within coding genes .", "Regulatory factors generally have pleiotropic effects , exhibit partially redundant roles , and regulate highly interconnected pathways with ample cross-talk .", ...	[ "We delineate a logical model encompassing 48 components and 82 regulatory interactions controlling mesoderm specification during Drosophila development , thereby integrating all major genetic processes underlying the formation of four mesodermal tissues .", "The model is based on in vivo genetic data , partly co...	2016
[ "Introduction", "Results", "Discussion", "Methods", "Supporting Information" ]	[ "molecular biology", "arthropods", "eukaryotes", "culex", "evolutionary biology", "animals", "genetics and genomics", "insects" ]	Forty Years of Erratic Insecticide Resistance Evolution in the Mosquito Culex pipiens	journal.pgen.0030205	null	[ [ "Adaptation is often envisioned as a slow and regular improvement , a view embodied by Fisher's geometrical model of adaptation , whereby mutations fix if they bring the current phenotype closer to an optimum [1 , 2] .", "However , the trajectory towards the optimum can take a truly tortuous path [3] , as...	[ "One view of adaptation is that it proceeds by the slow and steady accumulation of beneficial mutations with small effects .", "It is difficult to test this model , since in most cases the genetic basis of adaptation can only be studied a posteriori with traits that have evolved for a long period of time through ...	[ "Adaptation is not always a straightforward process , and often results from natural selection tinkering with available variation .", "We present in this study just such a tortuous natural selection pathway , which allows the mosquito Culex pipiens to resist organophosphorous insecticides .", "In the Montpellie...	2007
[ "Introduction", "Methods", "Results", "Discussion", "Members of the Geosentinel Surveillance Network" ]	[ "infectious diseases/helminth infections", "infectious diseases/tropical and travel-associated diseases", "infectious diseases" ]	Filariasis in Travelers Presenting to the GeoSentinel Surveillance Network	journal.pntd.0000088	null	[ [ "Parasitic diseases are widespread throughout the developing world and are associated with a heavy burden of morbidity and mortality .", "Human filariae , nematodes transmitted by arthropod vectors , are endemic in tropical and subtropical regions of the world .", "With an estimated 80 million people ...	[ "As international travel increases , there is rising exposure to many pathogens not traditionally encountered in the resource-rich countries of the world .", "Filarial infections , a great problem throughout the tropics and subtropics , are relatively rare among travelers even to filaria-endemic regions of the wo...	[ "As international travel increases , there is rising exposure to many pathogens not traditionally encountered in the resource-rich countries of the world .", "The GeoSentinel Surveillance Network , a global network of medicine/travel clinics , was established in 1995 to detect morbidity trends among travelers .",...	2007
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "invertebrates", "gene regulation", "animals", "dna transcription", "animal models", "dna damage", "drosophila melanogaster", "model organisms", "experimental organism systems", "dna", "drosophila", "research and analysis methods", "small interfering rnas", "genome complexity", "gene exp...	Splicing stimulates siRNA formation at Drosophila DNA double-strand breaks	journal.pgen.1006861	null	[ [ "DNA is constantly challenged by mutagenic processes of extrinsic and intrinsic origin .", "Of these damages , DNA double-strand breaks are particularly problematic lesions because they disrupt the continuity of genetic information .", "Their repair can either proceed via end-joining activities or thr...	[ "DNA double-strand breaks trigger the production of locus-derived siRNAs in fruit flies , human cells and plants .", "At least in flies , their biogenesis depends on active transcription running towards the break .", "Since siRNAs derive from a double-stranded RNA precursor , a major question is how broken DNA ...	[ "DNA damage ultimately threatens the integrity of our genome; in addition , it is an impediment for transcription and thus affects cells independently of the mutagenic effects .", "DNA double-strand breaks in transcribed regions can induce the production of corresponding small interfering RNAs , a class of regula...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "skin infections", "dermatology", "infectious diseases", "medicine and health sciences" ]	Selective Chemical Inhibition of agr Quorum Sensing in Staphylococcus aureus Promotes Host Defense with Minimal Impact on Resistance	journal.ppat.1004174	null	[ [ "The global health threat of antibiotic resistant bacterial infections mandates rethinking of how antibiotics are used , how targets for new antibiotics are identified , and how mechanisms for promoting host defense can be enhanced [1] , [2] .", "In this regard , there is much interest in chemical inhibit...	[ "Bacterial signaling systems are prime drug targets for combating the global health threat of antibiotic resistant bacterial infections including those caused by Staphylococcus aureus .", "S . aureus is the primary cause of acute bacterial skin and soft tissue infections ( SSTIs ) and the quorum sensing operon ag...	[ "New approaches are needed to lessen the burden of antibiotic resistant bacterial infections .", "One strategy is to develop therapies that target virulence which rely on host defense elements to clear the bacteria rather than direct antimicrobial killing .", "Quorum sensing is a bacterial signaling mechanism t...	2014
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "phosphorylation", "cell death", "plant anatomy", "cell processes", "microbiology", "fungi", "plant science", "plants", "bacteria", "mapk signaling cascades", "agrobacteria", "plant microbiology", "proteins", "tomatoes", "leaves", "fruits", "yeast", "biochemistry", "signal transd...	The Xanthomonas euvesicatoria type III effector XopAU is an active protein kinase that manipulates plant MAP kinase signaling	journal.ppat.1006880	null	[ [ "Plant immunity against microbial pathogens relies on a complex detection and signaling network [1] .", "A first line of plant immune responses is activated by cell surface-exposed pattern recognition receptors ( PRRs ) that detect broadly conserved pathogen molecules ( pathogen/microbe-associated molecul...	[ "The Gram-negative bacterium Xanthomonas euvesicatoria ( Xe ) is the causal agent of bacterial spot disease of pepper and tomato .", "Xe delivers effector proteins into host cells through the type III secretion system to promote disease .", "Here , we show that the Xe effector XopAU , which is conserved in nume...	[ "Many bacterial pathogens inject effector proteins into their eukaryotic host cells through the type III secretion system to modulate host cellular processes .", "Elucidating the function of bacterial effectors and identification of their host targets is important for understanding the molecular mechanisms of pat...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biology and life sciences" ]	Accumulation of a Threonine Biosynthetic Intermediate Attenuates General Amino Acid Control by Accelerating Degradation of Gcn4 via Pho85 and Cdk8	journal.pgen.1004534	null	[ [ "Cells undergo rapid transcriptional reprogramming in response to environmental changes by mobilizing transcriptional activators and repressors .", "Transcriptional activators function by binding to specific DNA sequences ( UAS elements in yeast ) and recruiting transcriptional cofactor proteins/complexes...	[ "Gcn4 is a master transcriptional regulator of amino acid and vitamin biosynthetic enzymes subject to the general amino acid control ( GAAC ) , whose expression is upregulated in response to amino acid starvation in Saccharomyces cerevisiae .", "We found that accumulation of the threonine pathway intermediate β-a...	[ "Transcriptional activator Gcn4 maintains amino acid homeostasis in budding yeast by inducing multiple amino acid biosynthetic pathways in response to starvation for any amino acid—the general amino acid control .", "Gcn4 abundance is tightly regulated by the interplay between an intricate translational control m...	2014
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "biotechnology", "bioengineering", "systems biology", "biochemical simulations", "biological systems engineering", "synthetic biology", "biology", "computational biology", "molecular biology", "genetics and genomics", "engineering" ]	Combined Model of Intrinsic and Extrinsic Variability for Computational Network Design with Application to Synthetic Biology	journal.pcbi.1002960	null	[ [ "Biological systems are complex , inherently noisy and only partially understood [1]–[5] .", "Systems and synthetic biologists are striving to better understand these systems , as well as to discover generally applicable principles for controlling them in biomedical and biotechnological applications .", ...	[ "Biological systems are inherently variable , with their dynamics influenced by intrinsic and extrinsic sources .", "These systems are often only partially characterized , with large uncertainties about specific sources of extrinsic variability and biochemical properties .", "Moreover , it is not yet well under...	[ "Variability is inherent in biological systems , and in order to understand them , we need to be able to model different sources of variability .", "Systems have evolved to harness and control the variability , and more recently , synthetic biologists are trying to learn how to control variability in engineered b...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "neuroscience/neurodevelopment", "neuroscience/theoretical neuroscience" ]	A Comparative Computer Simulation of Dendritic Morphology	journal.pcbi.1000089	null	[ [ "Dendritic morphology underlies many aspects of nervous system structure and function .", "Dendrites , along with axons , define the connectivity of the brain [1] , [2] , and play a large role in information processing at the single cell level [3] , [4] .", "Many studies have highlighted the importanc...	[ "Computational modeling of neuronal morphology is a powerful tool for understanding developmental processes and structure-function relationships .", "We present a multifaceted approach based on stochastic sampling of morphological measures from digital reconstructions of real cells .", "We examined how dendriti...	[ "Neurons in the brain have a variety of complex arbor shapes that help determine both their interconnectivity and functional roles .", "Molecular biology is beginning to uncover important details on the development of these tree-like structures , but how and why vastly different shapes arise is still largely unkn...	2008
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine and health sciences", "plasmodium vivax", "protozoans", "malarial parasites", "biology and life sciences", "malaria", "protozoan infections", "plasmodium falciparum", "parasitic diseases", "parasitic protozoans", "organisms", "toxoplasmosis" ]	BCKDH: The Missing Link in Apicomplexan Mitochondrial Metabolism Is Required for Full Virulence of Toxoplasma gondii and Plasmodium berghei	journal.ppat.1004263	null	[ [ "The phylum of Apicomplexa comprises a large number of obligate intracellular parasites that infect organisms across the whole animal kingdom .", "Two important members of this phylum , Plasmodium spp .", "and Toxoplasma gondii , are the etiological agents of malaria and toxoplasmosis , respectively ....	[ "While the apicomplexan parasites Plasmodium falciparum and Toxoplasma gondii are thought to primarily depend on glycolysis for ATP synthesis , recent studies have shown that they can fully catabolize glucose in a canonical TCA cycle .", "However , these parasites lack a mitochondrial isoform of pyruvate dehydrog...	[ "The mitochondrial tricarboxylic acid ( TCA ) cycle is one of the core metabolic pathways of eukaryotic cells , which contributes to cellular energy generation and provision of essential intermediates for macromolecule synthesis .", "Apicomplexan parasites possess the complete sets of genes coding for the TCA cyc...	2014
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "blood cells", "flow cytometry", "medicine and health sciences", "immune cells", "nuclear staining", "immunology", "bone marrow cells", "clinical medicine", "cytotoxic t cells", "research and analysis methods", "specimen preparation and treatment", "staining", "white blood cells", "major h...	Murine cytomegalovirus degrades MHC class II to colonize the salivary glands	journal.ppat.1006905	null	[ [ "Herpesviruses establish persistent , productive infections , with high prevalence in most populations and significant disease burdens .", "Vaccine development against Human cytomegalovirus ( HCMV ) is motivated by a high incidence of congenital infection .", "However vaccines to date have not prevent...	[ "Cytomegaloviruses ( CMVs ) persistently and systemically infect the myeloid cells of immunocompetent hosts .", "Persistence implies immune evasion , and CMVs evade CD8+ T cells by inhibiting MHC class I-restricted antigen presentation .", "Myeloid cells can also interact with CD4+ T cells via MHC class II ( MH...	[ "Human cytomegalovirus is the commonest infectious cause of harm to unborn children .", "Vaccines have not stopped it establishing chronic , systemic infections .", "Murine cytomegalovirus ( MCMV ) provides an accessible model to understand why .", "We show that MCMV evades CD4+ T cells via its M78 protein , ...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genome-wide association studies", "cellular stress responses", "molecular cell biology", "cell biology", "genetic screens", "genetics", "gene classes", "molecular genetics", "biology", "genetics of disease", "genetics and genomics" ]	A Genetic Screening Strategy Identifies Novel Regulators of the Proteostasis Network	journal.pgen.1002438	null	[ [ "Protein misfolding is an intrinsic aspect of protein biogenesis that , under optimal conditions , is kept in check by the properties of the proteostasis network ( PN ) , and upon stress , aging , and expression of aggregation-prone proteins causes cellular dysfunction that places the organism at risk for dis...	[ "A hallmark of diseases of protein conformation and aging is the appearance of protein aggregates associated with cellular toxicity .", "We posit that the functional properties of the proteostasis network ( PN ) protect the proteome from misfolding and combat the proteotoxic events leading to cellular pathology ....	[ "A common characteristic of protein conformational diseases is the appearance of protein aggregates associated with late-onset symptoms .", "Here , we have taken an unbiased genetic approach to test the hypothesis that protein aggregation and toxicity are co-linked genetic traits that are regulated by a common pr...	2011
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	The Light Skin Allele of SLC24A5 in South Asians and Europeans Shares Identity by Descent	journal.pgen.1003912	null	[ [ "Human skin color varies widely among and within populations and is a classic example of adaptive evolution .", "Skin pigmentation in humans is largely determined by the quantity and distribution of the pigment melanin , which is packed in melanosomes and then transferred from melanocytes ( melanin-formin...	[ "Skin pigmentation is one of the most variable phenotypic traits in humans .", "A non-synonymous substitution ( rs1426654 ) in the third exon of SLC24A5 accounts for lighter skin in Europeans but not in East Asians .", "A previous genome-wide association study carried out in a heterogeneous sample of UK immigra...	[ "Human skin color is one of the most visible aspects of human diversity .", "The genetic basis of pigmentation in Europeans has been understood to some extent , but our knowledge about South Asians has been restricted to a handful of studies .", "It has been suggested that a single nucleotide difference in SLC2...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "neuroscience" ]	A Novel Molecular Solution for Ultraviolet Light Detection in Caenorhabditis elegans	journal.pbio.0060198	An ultraviolet light receptor drives a robust locomotory response that restores normal levels of movement to paralyzed neuronal signaling mutants. This may helpC. elegans avoid lethal doses of sunlight.	[ [ "An animal's complement of sensory abilities reflects its unique evolutionary and natural history .", "Despite its status as a major model organism , little is known about the natural history of Caenorhabditis elegans .", "Past studies have revealed four major modalities through which C . elegans sens...	[ "For many organisms the ability to transduce light into cellular signals is crucial for survival .", "Light stimulates DNA repair and metabolism changes in bacteria , avoidance responses in single-cell organisms , attraction responses in plants , and both visual and nonvisual perception in animals .", "Despite ...	[ "In all of nature , scientists have discovered only six different mechanisms by which organisms sense light , and only one of these mechanisms can detect ultraviolet light ( the rhodopsins that sense ultraviolet light in non-mammalian vertebrates ) .", "The widely studied model organism Caenorhabditis elegans has...	2008
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "animal genetics", "genetic predisposition", "cancer genetics", "quantitative trait loci", "genetic association studies", "heredity", "gene expression", "genetics", "biology and life sciences", "quantitative traits", "human genetics", "mammalian genetics", "genetics of disease", "genetic l...	A Systems Genetics Approach Identifies CXCL14, ITGAX, and LPCAT2 as Novel Aggressive Prostate Cancer Susceptibility Genes	journal.pgen.1004809	null	[ [ "Prostate cancer is a common disease , and it is estimated that approximately 233 , 000 new cases will be diagnosed in in the United States alone in 2014 [1] .", "However , it typically runs an indolent course , with most men succumbing to unrelated diseases .", "This is reflected in the low prostate ...	[ "Although prostate cancer typically runs an indolent course , a subset of men develop aggressive , fatal forms of this disease .", "We hypothesize that germline variation modulates susceptibility to aggressive prostate cancer .", "The goal of this work is to identify susceptibility genes using the C57BL/6-Tg ( ...	[ "Prostate cancer is a remarkably common disease , and in 2014 it is estimated that it will account for 27% of new cancer cases in men in the US .", "However , less than 13% those diagnosed will succumb to prostate cancer , with most men dying from unrelated causes .", "The tests used to identify men at risk of ...	2014
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "evolutionary ecology", "ecology", "evolutionary biology", "cereals", "crops", "genetics", "population genetics", "biology", "crop diseases", "population ecology", "microbial ecology", "agriculture" ]	Origin, Migration Routes and Worldwide Population Genetic Structure of the Wheat Yellow Rust Pathogen Puccinia striiformis f.sp. tritici	journal.ppat.1003903	null	[ [ "Domestication of ecosystems , climate change and the expanding global trade have accelerated the pace of pathogen emergence and spread [1] , [2] .", "Widely distributed and genetically homogenous crop genotypes are conducive for rapid pathogen emergence and subsequent propagation across large areas .", ...	[ "Analyses of large-scale population structure of pathogens enable the identification of migration patterns , diversity reservoirs or longevity of populations , the understanding of current evolutionary trajectories and the anticipation of future ones .", "This is particularly important for long-distance migrating...	[ "Domestication of ecosystems , climate change and expanding global trade have accelerated the pace of disease emergence , caused by their introduction into new areas with susceptible hosts or the spread of new damaging pathogen genotypes .", "The wheat yellow rust pathogen ( PST ) is a pathogen with recent report...	2014
[ "Introduction", "Results and discussion", "Material and methods" ]	[ "inflammatory diseases", "invertebrates", "rheumatology", "medicine and health sciences", "chemical compounds", "drugs", "diet", "organic compounds", "animals", "purines", "animal models", "fungi", "drosophila melanogaster", "model organisms", "nutrition", "experimental organism system...	A conserved role of the insulin-like signaling pathway in diet-dependent uric acid pathologies in Drosophila melanogaster	journal.pgen.1008318	null	[ [ "Purine homeostasis represents a conserved metabolic pathway that is sustained by multiple enzymes orchestrating de novo synthesis , salvage , and degradation of purine intermediates .", "Urate oxidase , which is conserved across species , catalyzes one of the last steps of purine degradation converting u...	[ "Elevated uric acid ( UA ) is a key risk factor for many disorders , including metabolic syndrome , gout and kidney stones .", "Despite frequent occurrence of these disorders , the genetic pathways influencing UA metabolism and the association with disease remain poorly understood .", "In humans , elevated UA l...	[ "Enzymatic purine degradation in humans ends with uric acid ( UA ) .", "Multiple genetic and dietary factors raise UA levels above the norm , which is called hyperuricemia or hyperuricosuria when detected in the serum or urine , respectively .", "Clinical studies report a correlation between elevated UA and a p...	2019
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "virology/viral replication and gene regulation", "virology", "virology/immune evasion", "virology/effects of virus infection on host gene expression", "virology/host antiviral responses" ]	Rift Valley Fever Virus NSs Protein Promotes Post-Transcriptional Downregulation of Protein Kinase PKR and Inhibits eIF2α Phosphorylation	journal.ppat.1000287	null	[ [ "Rift Valley fever virus ( RVFV ) is a mosquito-borne zoonotic pathogen , which is distributed in sub-Saharan Africa [1] and has also caused large outbreaks in Madagascar [2] , Egypt [3] , [4] , [5] , Saudi Arabia [6] , and Yemen [6] .", "In endemic areas , RVFV naturally circulates among mosquitoes and r...	[ "Rift Valley fever virus ( RVFV ) ( genus Phlebovirus , family Bunyaviridae ) is a negative-stranded RNA virus with a tripartite genome .", "RVFV is transmitted by mosquitoes and causes fever and severe hemorrhagic illness among humans , and fever and high rates of abortions in livestock .", "A nonstructural RV...	[ "The mosquito-borne bunyavirus Rift Valley fever virus ( RVFV ) devastates both humans and domestic animals; it causes abortions in ruminants and complications such as hemorrhage , encephalitis , or retinal vasculitis in humans .", "A major RVFV virulence factor , NSs , disables host cell mRNA synthesis .", "He...	2009
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "developmental biology/organogenesis" ]	Serrano (Sano) Functions with the Planar Cell Polarity Genes to Control Tracheal Tube Length	journal.pgen.1000746	null	[ [ "Multicellular animals employ tubular structures in organs to transport vital fluids and gases that sustain life .", "Examples of organs with prominent tubular architecture include the circulatory system , the lung and kidney in mammals , the secretory and respiratory organs in flies , and the excretory o...	[ "Epithelial tubes are the functional units of many organs , and proper tube geometry is crucial for organ function .", "Here , we characterize serrano ( sano ) , a novel cytoplasmic protein that is apically enriched in several tube-forming epithelia in Drosophila , including the tracheal system .", "Loss of san...	[ "Tubular organ formation is a ubiquitous process required to sustain life in multicellular organisms .", "In this study , we focused on the tracheal system of the fruit fly , Drosophila melanogaster , and identified Serrano ( Sano ) as a novel protein expressed in several embryonic tubular organs , including trac...	2009
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "invertebrates", "computational biology", "geographical locations", "panama", "invertebrate genomics", "animals", "animal models", "north america", "drosophila melanogaster", "model organisms", "experimental organism systems", "genome analysis", "evolutionary adaptation", "drosophila", "...	Genomics of parallel adaptation at two timescales in Drosophila	journal.pgen.1007016	null	[ [ "While parallel phenotypic evolution has long been recognized as one of the strongest pieces of evidence for adaptation [1] , the general repeatability of adaptive evolution in natural populations remains poorly understood .", "In large part this is because only recently has technology been available to f...	[ "Two interesting unanswered questions are the extent to which both the broad patterns and genetic details of adaptive divergence are repeatable across species , and the timescales over which parallel adaptation may be observed .", "Drosophila melanogaster is a key model system for population and evolutionary geno...	[ "Both local adaptation on short timescales and the long-term accumulation of adaptive differences between species have recently been investigated using comparative genomic and population genomic approaches in several species .", "However , the repeatability of adaptive evolution at the genetic level is poorly und...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "cellular stress responses", "chemical compounds", "caulobacter", "enzymes", "cell cycle and cell division", "metabolic processes", "cell processes", "enzymology", "organic compounds", "phosphatases", "prokaryotic models", "dna replication", "proteolysis", "experimental organism systems", ...	A Kinase-Phosphatase Switch Transduces Environmental Information into a Bacterial Cell Cycle Circuit	journal.pgen.1006522	null	[ [ "The bacterial cell cycle has been studied extensively in the past .", "Genetics , biochemistry and more recently , advanced microscopy techniques have provided important insight into the processes of DNA replication , chromosome segregation and cell division , and numerous regulatory mechanisms have been...	[ "The bacterial cell cycle has been extensively studied under standard growth conditions .", "How it is modulated in response to environmental changes remains poorly understood .", "Here , we demonstrate that the freshwater bacterium Caulobacter crescentus blocks cell division and grows to filamentous cells in r...	[ "Free-living bacteria are frequently exposed to various environmental stress conditions .", "To survive under such adverse conditions , cells must induce pathways that prevent and alleviate cellular damages , but they must also adjust their cell cycle to guarantee cellular integrity .", "It has long been observ...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "developmental biology", "plant science", "social and behavioral sciences", "crops", "genetics", "biology", "evolutionary biology", "anthropology", "agriculture" ]	From Many, One: Genetic Control of Prolificacy during Maize Domestication	journal.pgen.1003604	null	[ [ "The “domestication syndrome” of crop plants is a suite of adaptive traits that arose in response to direct and indirect selection pressures during the domestication process [1]–[3] .", "This suite of traits includes an increase seed or fruit size , larger inflorescences , an increase in apical dominance ...	[ "A reduction in number and an increase in size of inflorescences is a common aspect of plant domestication .", "When maize was domesticated from teosinte , the number and arrangement of ears changed dramatically .", "Teosinte has long lateral branches that bear multiple small ears at their nodes and tassels at ...	[ "Crop species underwent profound transformations in morphology during domestication .", "Among crops , maize experienced a more striking change in morphology than other crops .", "Among the changes in maize from its ancestor , teosinte , was a switch from 100 or more small ears per plant in teosinte to just one...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "learning", "medicine and health sciences", "decision making", "nucleus accumbens", "applied mathematics", "brain", "social sciences", "neuroscience", "learning and memory", "simulation and modeling", "algorithms", "synaptic plasticity", "cognitive psychology", "mathematics", "cognition"...	Forgetting in Reinforcement Learning Links Sustained Dopamine Signals to Motivation	journal.pcbi.1005145	null	[ [ "Electrophysiological [1] and fast-scan cyclic voltammetry ( FSCV ) [2 , 3] studies have conventionally shown that dopamine ( DA ) neuronal activity and transmitter release respond to unpredicted but not predicted reward , consistent with the suggestion that DA represents reward-prediction-error ( RPE ) [1 , ...	[ "It has been suggested that dopamine ( DA ) represents reward-prediction-error ( RPE ) defined in reinforcement learning and therefore DA responds to unpredicted but not predicted reward .", "However , recent studies have found DA response sustained towards predictable reward in tasks involving self-paced behavio...	[ "Dopamine ( DA ) has been suggested to have two reward-related roles: ( 1 ) representing reward-prediction-error ( RPE ) , and ( 2 ) providing motivational drive .", "Role ( 1 ) is based on the physiological results that DA responds to unpredicted but not predicted reward , whereas role ( 2 ) is supported by the ...	2016
[ "Introduction", "Materials and methods", "Results", "Discussion" ]	[ "biogeography", "ecology and environmental sciences", "china", "japan", "population genetics", "geographical locations", "genetic mapping", "population biology", "europe", "korea", "geography", "phylogeography", "people and places", "haplotypes", "asia", "heredity", "earth sciences",...	Population structure analysis of the neglected parasite Thelazia callipaeda revealed high genetic diversity in Eastern Asia isolates	journal.pntd.0006165	null	[ [ "The spirurid nematode Thelazia callipaeda ( Spirurida: Thelaziidae ) is the major etiological agent of ocular thelaziosis [1] .", "This worm can parasitize the conjunctival sac of domestic and wild carnivores and humans , causing conjunctivitis , lacrimation and itchiness , and even blindness [2 , 3] .",...	[ "Thelazia callipaeda is the causative agent of thelaziasis in canids , felids and humans .", "However , the population genetic structure regarding this parasite remains unclear .", "In this study , we first explored the genetic variation of 32 T . callipaeda clinical isolates using the following multi-molecular...	[ "Thelazia callipaeda is the causative agent of thelaziasis canids , felids and humans .", "Despite the existing threat of thelaziosis in China , the genetic diversity of T . callipaeda has not been investigated across its wide geographical distribution in China , yet such information may provide insight into the ...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "systems biology", "theoretical biology", "biology", "computational biology", "microbiology", "genetics and genomics" ]	Determining Host Metabolic Limitations on Viral Replication via Integrated Modeling and Experimental Perturbation	journal.pcbi.1002746	null	[ [ "Any virus is necessarily a metabolic product of its host , since viruses lack the macromolecule machinery and small molecule precursors required to replicate .", "This dependence has been underscored by recent screens to determine the host genes required for viral infection in a variety of species .", ...	[ "Viral replication relies on host metabolic machinery and precursors to produce large numbers of progeny - often very rapidly .", "A fundamental example is the infection of Escherichia coli by bacteriophage T7 .", "The resource draw imposed by viral replication represents a significant and complex perturbation ...	[ "Viral infection is a serious problem with relatively few known solutions .", "Much of the complexity of viral infection is contributed by the host's own resources that the virus commandeers .", "Viruses lack the machinery and precursors required to replicate , and thus may be considered metabolic products of t...	2012
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[]	An Epitope-Substituted DNA Vaccine Improves Safety and Immunogenicity against Dengue Virus Type 2	journal.pntd.0003903	null	[ [ "Dengue virus ( DENV ) is a mosquito-borne virus that causes prevalent , global disease .", "It is estimated to cause 390 million infections annually , which lead to a spectrum of clinical syndromes ranging from dengue fever ( DF ) to severe dengue hemorrhagic fever ( DHF ) and dengue shock syndrome ( DSS...	[ "Dengue virus ( DENV ) , a global disease , is divided into four serotypes ( DENV1-4 ) .", "Cross-reactive and non-neutralizing antibodies against envelope ( E ) protein of DENV bind to the Fcγ receptors ( FcγR ) of cells , and thereby exacerbate viral infection by heterologous serotypes via antibody-dependent en...	[ "Dengue virus ( DENV ) infects 390 million humans annually , and is the cause of one of the most important arthropod-borne viral diseases in the world .", "Currently , there are no available licensed vaccines or antiviral drugs for dengue , so development of safe vaccine and effective therapy is urgently needed ....	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "cell death", "cellular stress responses", "cancer genetics", "medicine and health sciences", "rna interference", "cervical cancer", "cancer treatment", "cell processes", "drug dependence", "cancers and neoplasms", "toxicology", "rna stability", "gene function", "oncology", "behavioral p...	tRNA Modifying Enzymes, NSUN2 and METTL1, Determine Sensitivity to 5-Fluorouracil in HeLa Cells	journal.pgen.1004639	null	[ [ "5-Fluorouracil ( 5-FU ) is a pyrimidine analog and is the most widely used chemotherapeutic agent for the treatment of a variety of solid cancers .", "Its mechanism of action has been attributed to the production of cytotoxic metabolites incorporated into RNA and DNA and inhibiting thymidylate synthase ,...	[ "Nonessential tRNA modifications by methyltransferases are evolutionarily conserved and have been reported to stabilize mature tRNA molecules and prevent rapid tRNA decay ( RTD ) .", "The tRNA modifying enzymes , NSUN2 and METTL1 , are mammalian orthologs of yeast Trm4 and Trm8 , which are required for protecting...	[ "The cellular mechanisms for sensing and responding to stress on nucleic acid metabolism or to genotoxic stress are the fundamental and ancient evolutionary biological activities with conserved and diverse biological functions .", "In yeast , hypomodified mature tRNA species are rapidly decayed under heat stress ...	2014

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