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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 and discussion", "Materials and methods" ]	[ "blood cells", "medicine and health sciences", "immune cells", "pathology and laboratory medicine", "engineering and technology", "electronics", "cathodes", "pathogens", "immunology", "electricity", "microbiology", "salmonellosis", "bacterial diseases", "enterobacteriaceae", "electric fi...	Infection-generated electric field in gut epithelium drives bidirectional migration of macrophages	journal.pbio.3000044	Many bacterial pathogens hijack macrophages to spread away from infection sites. This study suggests that macrophages are attracted to the site of infection by a combination of chemotaxis and galvanotaxis; after phagocytosis of bacteria, surface electrical properties of the macrophages change, and galvanotaxis directs ...	[ [ "Common bacterial pathogens such as Salmonella , Shigella , and Yersinia spp .", "invade the gut epithelial barrier , preferentially by targeting the relatively small number of M cells located in the follicle-associated epithelium ( FAE ) [1–3] .", "Disruption of epithelial integrity releases chemokin...	[ "Many bacterial pathogens hijack macrophages to egress from the port of entry to the lymphatic drainage and/or bloodstream , causing dissemination of life-threatening infections .", "However , the underlying mechanisms are not well understood .", "Here , we report that Salmonella infection generates directional...	[ "Bacterial pathogens can invade and survive within macrophages and use them as a vehicle to reach important organs of a human body , resulting in life-threatening infections , but the underlying mechanisms are not well understood .", "Our current understanding is that macrophages are recruited to the infected sit...	2019
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biology", "computational biology", "biophysics" ]	How Cells Integrate Complex Stimuli: The Effect of Feedback from Phosphoinositides and Cell Shape on Cell Polarization and Motility	journal.pcbi.1002402	null	[ [ "In order to address these issues , we have developed a computational model that integrates the signalling biochemistry with actin-based motility in a spatial setting .", "Our main philosophy in constructing the model has been to assemble modules of the signalling repertoire for which there is biological ...	[ "To regulate shape changes , motility and chemotaxis in eukaryotic cells , signal transduction pathways channel extracellular stimuli to the reorganization of the actin cytoskeleton .", "The complexity of such networks makes it difficult to understand the roles of individual components , let alone their interacti...	[ "Single cells , such as amoeba and white blood cells , change shape and move in response to environmental stimuli .", "Their behaviour is a consequence of the intracellular properties balanced by external forces .", "The internal regulation is modulated by several proteins that interact with one another and wit...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biology and life sciences", "plant science" ]	The Secreted Peptide PIP1 Amplifies Immunity through Receptor-Like Kinase 7	journal.ppat.1004331	null	[ [ "Immune signaling in plants is typically initiated when immune-related receptors perceive the presence of pathogen molecules , including so-called “pathogen-associated molecular patterns” ( PAMPs ) and race-specific effectors [1] .", "PAMPs , such as bacterial flagellin and fungal chitin , are recognized ...	[ "In plants , innate immune responses are initiated by plasma membrane-located pattern recognition receptors ( PRRs ) upon recognition of elicitors , including exogenous pathogen-associated molecular patterns ( PAMPs ) and endogenous damage-associated molecular patterns ( DAMPs ) .", "Arabidopsis thaliana produces...	[ "Both animals and plants have evolved mechanisms to trigger innate immunity through perception of exogenous and endogenous molecules .", "In the model plant Arabidopsis thaliana , endogenous molecules such as the peptide elicitor PEP1 activate the immune response by means of cell surface-located receptors .", "...	2014
[ "Introduction", "Results", "Methods", "Discussion" ]	[ "cell physiology", "focal adhesions", "random variables", "covariance", "cell polarity", "simulation and modeling", "developmental biology", "systems science", "mathematics", "molecular development", "cellular structures and organelles", "research and analysis methods", "computer and informa...	Multi-Cell ECM compaction is predictable via superposition of nonlinear cell dynamics linearized in augmented state space	journal.pcbi.1006798	null	[ [ "Cell-induced compaction of fibrous extracellular matrix ( ECM ) is an important mechanism for numerous processes such as wound healing and tissue development [1–3] .", "During wound healing , for example , traction forces exerted by fibroblasts and myofibroblasts result in ECM compaction at the site of i...	[ "Cells interacting through an extracellular matrix ( ECM ) exhibit emergent behaviors resulting from collective intercellular interaction .", "In wound healing and tissue development , characteristic compaction of ECM gel is induced by multiple cells that generate tensions in the ECM fibers and coordinate their a...	[ "Collective behaviors of multiple cells interacting through an ECM are prohibitively complex to predict with a mechanistic computational model due to its highly nonlinear dynamics and high dimensional space .", "We introduce a methodology where nonlinear dynamics of single cells are superposed to predict collecti...	2019
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "molecular cell biology", "molecular biology", "gene expression", "genetics", "epigenetics", "biology", "microbiology", "host-pathogen interaction", "chromatin", "genetics and genomics", "parasitology" ]	Histone H1 Plays a Role in Heterochromatin Formation and VSG Expression Site Silencing in Trypanosoma brucei	journal.ppat.1003010	null	[ [ "The African trypanosome Trypanosoma brucei is a unicellular parasite causing African sleeping sickness , which is transmitted by tsetse flies in sub-Saharan Africa .", "As an extracellular parasite of the mammalian bloodstream , T . brucei has evolved a sophisticated strategy to antigenically vary its ma...	[ "The African sleeping sickness parasite Trypanosoma brucei evades the host immune system through antigenic variation of its variant surface glycoprotein ( VSG ) coat .", "Although the T . brucei genome contains ∼1500 VSGs , only one VSG is expressed at a time from one of about 15 subtelomeric VSG expression sites...	[ "Trypanosoma brucei causes African sleeping sickness , endemic to sub-Saharan Africa .", "Bloodstream form T . brucei is covered with a dense coat of variant surface glycoprotein ( VSG ) .", "Only one VSG is expressed at a time out of a vast repertoire of ∼1500 VSGs .", "The active VSG is transcribed in a tel...	2012
[ "Introduction", "Materials and Methods", "Results/Discussion" ]	[ "erk signaling cascade", "protein kinase signaling cascade", "protein kinase c signaling", "signal transduction", "infectious diseases", "medicine and health sciences", "helminth infections", "cell biology", "biology and life sciences", "ras signaling", "parasitic diseases", "molecular cell bi...	Protein Kinase C and Extracellular Signal-Regulated Kinase Regulate Movement, Attachment, Pairing and Egg Release in Schistosoma mansoni	journal.pntd.0002924	null	[ [ "Protein kinases C ( PKCs ) and extracellular signal-regulated kinases/mitogen-activated protein kinases ( ERKs/MAPKs ) are signalling enzymes that play a critical role in regulating cellular processes , such as gene expression , the cell cycle , growth , development and differentiation , cellular motility , ...	[ "Protein kinases C ( PKCs ) and extracellular signal-regulated kinases ( ERKs ) are evolutionary conserved cell signalling enzymes that coordinate cell function .", "Here we have employed biochemical approaches using ‘smart’ antibodies and functional screening to unravel the importance of these enzymes to Schisto...	[ "Parasitic blood flukes , also called schistosomes , cause human schistosomiasis , a neglected tropical disease and major public health problem in developing countries , especially sub-Saharan Africa .", "Sustainable control of schistosomiasis is difficult , mainly because the complex life cycle of the parasite i...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "developmental biology", "developmental neuroscience", "axon guidance", "biology", "morphogenesis", "neuroscience" ]	MIG-10 Functions with ABI-1 to Mediate the UNC-6 and SLT-1 Axon Guidance Signaling Pathways	journal.pgen.1003054	null	[ [ "Axons navigate to their targets in the developing nervous system by making a series of responses to extracellular guidance cues [1]–[6] .", "Several conserved families of guidance cues have been identified , including the netrins and slits .", "These guidance cues activate receptors on the growth con...	[ "Extracellular guidance cues steer axons towards their targets by eliciting morphological changes in the growth cone .", "A key part of this process is the asymmetric recruitment of the cytoplasmic scaffolding protein MIG-10 ( lamellipodin ) .", "MIG-10 is thought to asymmetrically promote outgrowth by inducing...	[ "To form neural circuits , axons must navigate through the developing nervous system to reach their correct targets .", "Axon navigation is led by the growth cone , a structure at the tip of the growing axon that responds to extracellular guidance cues .", "Many of these guidance cues and their receptors have b...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "plant biology/plant-biotic interactions", "plant biology/plant-environment interactions", "plant biology/plant growth and development", "plant biology/plant biochemistry and physiology", "plant biology/plant genetics and gene expression" ]	Dissection of the Complex Phenotype in Cuticular Mutants of Arabidopsis Reveals a Role of SERRATE as a Mediator	journal.pgen.1000703	null	[ [ "The ability to maintain the barrier properties of the epidermis , which covers the aerial surface of higher plants , is largely due to their outermost cell walls which are impregnated and covered with specialized lipids .", "The fine structure and composition of this complex layer , called the cuticle , ...	[ "Mutations in LACERATA ( LCR ) , FIDDLEHEAD ( FDH ) , and BODYGUARD ( BDG ) cause a complex developmental syndrome that is consistent with an important role for these Arabidopsis genes in cuticle biogenesis .", "The genesis of their pleiotropic phenotypes is , however , poorly understood .", "We provide evidenc...	[ "As the skin of a plant , the epidermis mediates a broad set of protective functions which includes defense against abiotic environmental stresses and pathogens .", "The majority of its barrier capacity is localized to the outermost cell wall , which is covered by a waxy cuticle .", "Several distinct cuticular ...	2009
[ "Introduction", "Results", "Discussion", "Materials & Methods" ]	[]	NADPH Oxidase-Driven Phagocyte Recruitment Controls Candida albicans Filamentous Growth and Prevents Mortality	journal.ppat.1003634	null	[ [ "Candida albicans is a ubiquitous commensal fungus and a clinically important opportunistic pathogen of humans .", "C . albicans is pleomorphic and grows in both yeast and filamentous forms , permitting growth in different environments , tissue invasion , dissemination and immune evasion [1]–[3] .", "...	[ "Candida albicans is a human commensal and clinically important fungal pathogen that grows as both yeast and hyphal forms during human , mouse and zebrafish infection .", "Reactive oxygen species ( ROS ) produced by NADPH oxidases play diverse roles in immunity , including their long-appreciated function as micro...	[ "Over 45 years ago chronic granulomatous disease ( CGD ) was ascribed to a failure of neutrophils to mount a respiratory burst , and it is now known to result from primary genetic deficiencies in the phagocyte NADPH oxidase complex .", "Recent work suggests that reactive oxygen species produced by NADPH oxidases ...	2013
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "cell motility", "medicine and health sciences", "developmental biology", "embryos", "morphogenesis", "cellular structures and organelles", "pattern formation", "digestive system", "embryology", "embryonic pattern formation", "biological tissue", "signaling centers", "head", "chemotaxis", ...	Modeling Edar expression reveals the hidden dynamics of tooth signaling center patterning	journal.pbio.3000064	The generation of patterns during development is generally viewed as a direct process, but this study of mouse tooth development shows how embryonic patterns can be constructed and erased in a very dynamic manner before the correct pattern is achieved.	[ [ "The emergence of ordered patterns in multicellular organisms has been a major field of research in developmental biology , revealing a diversity of pattern formation mechanisms .", "While some patterns appear simultaneously ( e . g . , Drosophila segments , mouse hair ) , others appear sequentially ( e ....	[ "When patterns are set during embryogenesis , it is expected that they are straightly established rather than subsequently modified .", "The patterning of the three mouse molars is , however , far from straight , likely as a result of mouse evolutionary history .", "The first-formed tooth signaling centers , ca...	[ "Organs , such as teeth , that form regular patterns are of particular interest to developmental biologists .", "These patterns are established early in the embryo , and it has generally been thought the organs appear in what is their final position .", "Recent studies that focus on the dynamics of patterning e...	2019
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "aging", "physiological processes", "developmental biology", "organism development", "evolutionary biology", "physiology", "biology", "anatomy and physiology" ]	Variable Pathogenicity Determines Individual Lifespan in Caenorhabditis elegans	journal.pgen.1002047	null	[ [ "A fundamental property of aging in all animals is stochasticity , which refers to the large and unpredictable variability in the lifespan of individuals in a population [1] .", "For example , human lifespan expectancy at birth in modern societies is about 78 years , but there is a large variability in th...	[ "A common property of aging in all animals is that chronologically and genetically identical individuals age at different rates .", "To unveil mechanisms that influence aging variability , we identified markers of remaining lifespan for Caenorhabditis elegans .", "In transgenic lines , we expressed fluorescent ...	[ "One of the long-standing mysteries in aging is that some individuals die early whereas others die late .", "The age at which a specific individual will die is difficult or impossible to predict , and thus a fundamental aspect of aging in all animals is that it is stochastic .", "Aging stochasticity is particul...	2011
[ "Introduction", "Methods", "Results", "Discussion" ]	[]	Social Feedback and the Emergence of Rank in Animal Society	journal.pcbi.1004411	null	[ [ "Individuals from social species must interact with each other to reproduce , find food , and survive .", "Higher-level social structures such as hierarchies emerge when interacting individuals need to manage trade-offs in the costs and benefits of social associations [1 , 2] .", "One of the most impo...	[ "Dominance hierarchies are group-level properties that emerge from the aggression of individuals .", "Although individuals can gain critical benefits from their position in a hierarchy , we do not understand how real-world hierarchies form .", "Nor do we understand what signals and decision-rules individuals us...	[ "An individual’s success depends critically on socially-constructed properties such as rank .", "A detailed study of two independent captive parakeet groups reveals how these properties come into being .", "We show that individuals can use localized patterns in the aggression network to learn the relative ranks...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "parastic protozoans", "signal transduction", "molecular cell biology", "entamoeba histolytica", "parasitology", "protozoology", "biology", "microbiology", "host-pathogen interaction" ]	The Calmodulin-like Calcium Binding Protein EhCaBP3 of Entamoeba histolytica Regulates Phagocytosis and Is Involved in Actin Dynamics	journal.ppat.1003055	null	[ [ "A variety of cell types , such as macrophages and neutrophils and many unicellular eukaryotes have the ability to engulf particles of size greater than 0 . 5 µm through a process called phagocytosis .", "In the former this process has evolved as one of the critical elements of host defence , while in the...	[ "Phagocytosis is required for proliferation and pathogenesis of Entamoeba histolytica and erythrophagocytosis is considered to be a marker of invasive amoebiasis .", "Ca2+ has been found to play a central role in the process of phagocytosis .", "However , the molecular mechanisms and the signalling mediated by ...	[ "Entamoeba histolytica is one of the major causes of morbidity and mortality in developing countries .", "Phagocytosis plays an important role in both survival and virulence and has been used as a virulence marker .", "Inhibition of phagocytosis leads to a defect in cellular proliferation .", "Therefore , the...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biotechnology", "primates", "infectious diseases", "pathology", "virology", "microbiology", "computational biology", "molecular biology", "genetics and genomics", "eubacteria" ]	The Macaque Gut Microbiome in Health, Lentiviral Infection, and Chronic Enterocolitis	journal.ppat.0040020	null	[ [ "The human intestine is home to some 100 trillion microorganisms of at least 400 species .", "The density of bacterial cells in the colon has been estimated at 1011 to 1012 per ml , which makes it one of the most densely populated microbial habitats known [1 , 2] .", "The number of unique genes in the...	[ "The vertebrate gut harbors a vast community of bacterial mutualists , the composition of which is modulated by the host immune system .", "Many gastrointestinal ( GI ) diseases are expected to be associated with disruptions of host-bacterial interactions , but relatively few comprehensive studies have been repor...	[ "Bacterial mutualists within the gastrointestinal tract aid digestion , promote development of the gut immune system , and provide competitive barriers to pathogen invasion .", "The host , in return , provides bacteria with safe housing and food during lean times .", "The composition of the gut microbiota is co...	2008
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "computational biology/systems biology", "computational biology/transcriptional regulation" ]	Circadian Phase Resetting via Single and Multiple Control Targets	journal.pcbi.1000104	null	[ [ "Control theoretic tools have been used to model mRNA transcriptional/translational regulatory feedback mechanisms [1] , to analyze nonlinear phenomena [2] , [3] , and to control complex biological behavior [4] , [5] .", "In our research , we couple systems theoretic tools ( such as sensitivity analysis )...	[ "Circadian entrainment is necessary for rhythmic physiological functions to be appropriately timed over the 24-hour day .", "Disruption of circadian rhythms has been associated with sleep and neuro-behavioral impairments as well as cancer .", "To date , light is widely accepted to be the most powerful circadian...	[ "The robust timing , or phase , of the circadian clock is critical in directing and synchronizing molecular , cellular , and organismal behaviors .", "The clock's failure to maintain precision and adaption is associated with sleeping disorders , depression , and cancer .", "To better study and control the timin...	2008
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "bacteriology", "3' utr", "messenger rna", "microbiology", "untranslated regions", "bacterial genetics", "microbial genetics", "bacteria", "microbial genomics", "bacterial genomics", "gene expression", "mollicutes", "comparative genomics", "biochemistry", "rna", "eukaryota", "nucleic...	In eubacteria, unlike eukaryotes, there is no evidence for selection favouring fail-safe 3’ additional stop codons	journal.pgen.1008386	null	[ [ "Errors throughout transcription , translation , and post-translational modification can , and do , happen all the time [1–5] .", "Whilst an invaluable source of novelty that drives evolution [6] , the majority of these errors are likely deleterious [1–3 , 6–8] .", "Genomes may therefore be under sele...	[ "Errors throughout gene expression are likely deleterious , hence genomes are under selection to ameliorate their consequences .", "Additional stop codons ( ASCs ) are in-frame nonsense ‘codons’ downstream of the primary stop which may be read by translational machinery should the primary stop have been accidenta...	[ "In all organisms , gene expression is error-prone .", "One such error , translational read-through , occurs where the primary stop codon of an expressed gene is missed by the translational machinery .", "Failure to terminate is likely to be costly , hence genomes are under selection to prevent this from happen...	2019
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "taxonomy", "protein interactions", "brassica", "dna-binding proteins", "phylogenetics", "data management", "model organisms", "phylogenetic analysis", "experimental organism systems", "dna", "plants", "homologous recombination", "research and analysis methods", "arabidopsis thaliana", "...	FIGL1 and its novel partner FLIP form a conserved complex that regulates homologous recombination	journal.pgen.1007317	null	[ [ "Homologous recombination ( HR ) is critical for the repair of DNA double-strand breaks ( DSBs ) in both mitotic and meiotic cells [1] .", "Defects in HR repair causes genomic instability , leading to cancer predisposition and various inherited diseases in humans [2] .", "During meiosis , HR promotes ...	[ "Homologous recombination is central to repair DNA double-strand breaks , either accidently arising in mitotic cells or in a programed manner at meiosis .", "Crossovers resulting from the repair of meiotic breaks are essential for proper chromosome segregation and increase genetic diversity of the progeny .", "...	[ "Homologous recombination is a DNA repair mechanism that is essential to preserve the integrity of genetic information and thus to prevent cancer formation .", "Homologous recombination is also used during sexual reproduction to generate genetic diversity in the offspring by shuffling parental chromosomes .", "...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "neuroscience" ]	Converging Intracranial Markers of Conscious Access	journal.pbio.1000061	A neural signature of the conscious perception of words by humans is readable in intracranial electrophysiological recordings, which afford relatively high spatial- and temporal-resolution measurements of neural activity.	[ [ "We adopted a theory-driven approach , trying to test experimentally a set of explicit predictions derived from the global workspace model of conscious access .", "This model , in part inspired from Bernard Baars' theory [30] , proposes that at any given time , many modular cerebral networks are active in...	[ "We compared conscious and nonconscious processing of briefly flashed words using a visual masking procedure while recording intracranial electroencephalogram ( iEEG ) in ten patients .", "Nonconscious processing of masked words was observed in multiple cortical areas , mostly within an early time window ( <300 m...	[ "What is the neural signature of the conscious perception of a visual stimulus ?", "To address this question , we recorded neural activity directly from the brains of human subjects ( who were undergoing neural surgery for medical reasons ) .", "This rare opportunity afforded greater spatial and temporal resolu...	2009
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "emerging infectious diseases", "virology", "biology", "microbiology", "pathogenesis" ]	Cathepsin B & L Are Not Required for Ebola Virus Replication	journal.pntd.0001923	null	[ [ "Members of the family Filoviridae , Ebola virus ( EBOV ) and Marburg virus ( MARV ) , are the causative agents of viral hemorrhagic fever in central Africa and a major public health threat in their endemic areas .", "Worldwide concern relates to the importation of infected individuals and the potential u...	[ "Ebola virus ( EBOV ) , family Filoviridae , emerged in 1976 on the African continent .", "Since then it caused several outbreaks of viral hemorrhagic fever in humans with case fatality rates up to 90% and remains a serious Public Health concern and biothreat pathogen .", "The most pathogenic and best-studied s...	[ "It is currently believed that Ebola virus ( EBOV ) enters cells via macropinocytosis following which , the cysteine proteases cathepsin B and L ( CatB , CatL ) cleave the viral glycoprotein ( GP ) allowing exposure of its core receptor-binding and fusion domain thus facilitating subsequent infection .", "We stud...	2012
[ "Introduction", "Materials and Methods", "Results", "Discussion", "Conclusion" ]	[ "invertebrates", "livestock", "medicine and health sciences", "rift valley fever virus", "immune physiology", "pathology and laboratory medicine", "ruminants", "pathogens", "immunology", "rna extraction", "microbiology", "vertebrates", "animals", "mammals", "viruses", "rna viruses", ...	Rift Valley Fever Virus Circulating among Ruminants, Mosquitoes and Humans in the Central African Republic	journal.pntd.0005082	null	[ [ "Rift Valley fever ( RVF ) is a viral zoonosis that affects mainly animals but is also found in humans .", "It is caused by an RNA virus of the Phlebovirus genus ( Bunyaviridae family ) , the genome consisting of three RNA segments: large , medium , and small [1 , 2] .", "RVFV is transmitted mainly by...	[ "Rift Valley fever virus ( RVFV ) causes a viral zoonosis , with discontinuous epizootics and sporadic epidemics , essentially in East Africa .", "Infection with this virus causes severe illness and abortion in sheep , goats , and cattle as well as other domestic animals .", "Humans can also be exposed through ...	[ "Rift valley fever virus ( RVFV ) is an arthropod-borne virus that causes serious illness in both animals and humans .", "RVFV is transmitted by direct contact with infectious tissues or by the bites of infected mosquito species of the Aedes and Culex genuses .", "Its distribution in tropical forests in central...	2016
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "medicine and health sciences", "pathology and laboratory medicine", "enzymes", "pathogens", "enzymology", "phosphatases", "developmental biology", "regulator genes", "mathematics", "statistics (mathematics)", "gene types", "embryos", "cellular structures and organelles", "embryology", "...	Cell Cycle-Related Kinase (CCRK) regulates ciliogenesis and Hedgehog signaling in mice	journal.pgen.1006912	null	[ [ "In the mammalian embryo , the Hedgehog ( Hh ) signaling pathway controls cell proliferation , cell survival , and tissue patterning ( cell fate specification and differentiation ) in most tissues such as the developing nervous system , skeleton , skin , and internal organs ( reviewed in [1] ) .", "The ro...	[ "The Hedgehog ( Hh ) signaling pathway plays a key role in cell fate specification , proliferation , and survival during mammalian development .", "Cells require a small organelle , the primary cilium , to respond properly to Hh signals and the key regulators of Hh signal transduction exhibit dynamic localization...	[ "The importance of cilia in development and disease has become broadly appreciated in recent years due in part to their roles in signal transduction .", "Despite this attention , crucial aspects of ciliary assembly and function , such as the mechanisms controlling ciliary assembly and the signal transduction even...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "infectious diseases/bacterial infections", "computational biology/systems biology", "computational biology/genomics", "infectious diseases/respiratory infections" ]	Genome-Scale Identification of Legionella pneumophila Effectors Using a Machine Learning Approach	journal.ppat.1000508	null	[ [ "A large number of bacterial pathogens utilize secretion systems for pathogenesis .", "In these systems , a multi-protein complex is used to translocate a repertoire of proteins , termed effectors , into host cells during infection .", "These effector proteins were found to be critical for the pathoge...	[ "A large number of highly pathogenic bacteria utilize secretion systems to translocate effector proteins into host cells .", "Using these effectors , the bacteria subvert host cell processes during infection .", "Legionella pneumophila translocates effectors via the Icm/Dot type-IV secretion system and to date ...	[ "Many pathogenic bacteria exert their function by translocating a set of proteins , termed effectors , into the cytoplasm of their host cell .", "These effectors subvert various host cell processes for the benefit of the bacteria .", "Our goal in this study was to identify novel effectors in a genomic scale , t...	2009
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "biotechnology", "plant anatomy", "rna interference", "gene regulation", "brassica", "viruses", "plant science", "model organisms", "rna viruses", "genetically modified plants", "experimental organism systems", "epigenetics", "molecular biology techniques", "plants", "cellular structures...	RNA decay is an antiviral defense in plants that is counteracted by viral RNA silencing suppressors	journal.ppat.1007228	null	[ [ "Among major infectious pathogens , viruses are the obligate intracellular agents that can infect all types of life forms from bacteria to plants and animals , and exclusively multiply in the host cells .", "The vast majority of known plant viruses are positive-sense single-stranded ( +ss ) RNA viruses th...	[ "Exonuclease-mediated RNA decay in plants is known to be involved primarily in endogenous RNA degradation , and several RNA decay components have been suggested to attenuate RNA silencing possibly through competing for RNA substrates .", "In this paper , we report that overexpression of key cytoplasmic 5’–3’ RNA ...	[ "RNA silencing and RNA decay are two essential pathways that determine the fate of cellular RNA molecules .", "RNA decay has been suggested to compete with RNA silencing for the RNA substrates and thus to suppress RNA silencing in plants .", "In this report , we show that the deficiency of key cytoplasmic 5’–3’...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biology" ]	Targeted Sister Chromatid Cohesion by Sir2	journal.pgen.1002000	null	[ [ "Proper segregation of chromosomes at mitosis and meiosis requires sister chromatid cohesion .", "The process ensures that newly replicated chromatids bi-orient on spindle microtubules such that a single copy of each chromosome transfers to progeny cells .", "Defects in the sister chromatid cohesion p...	[ "The protein complex known as cohesin binds pericentric regions and other sites of eukaryotic genomes to mediate cohesion of sister chromatids .", "In budding yeast Saccharomyces cerevisiae , cohesin also binds silent chromatin , a repressive chromatin structure that functionally resembles heterochromatin of high...	[ "Replication of chromosomes in each cell cycle produces pairs of identical sister chromatids that are held together by a protein complex known as cohesin .", "At mitosis , cohesin is dismantled , permitting segregation of one full set of chromosomes to each daughter cell .", "Cohesin binds at discrete sites alo...	2011
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biotechnology", "plant anatomy", "rna interference", "gene regulation", "viruses", "micrornas", "plant science", "rna viruses", "immunoprecipitation", "genetically modified plants", "epigenetics", "plants", "flowering plants", "genetic engineering", "research and analysis methods", "s...	Distinct Effects of p19 RNA Silencing Suppressor on Small RNA Mediated Pathways in Plants	journal.ppat.1005935	null	[ [ "Viruses are among the most important plant pathogens that cause huge economic losses in many agriculturally important crops worldwide .", "The invasion of the host by viruses deeply alters the physiology of the plants at cellular and tissue levels due to the interaction of the virus with the cellular pat...	[ "RNA silencing is one of the main defense mechanisms employed by plants to fight viruses .", "In change , viruses have evolved silencing suppressor proteins to neutralize antiviral silencing .", "Since the endogenous and antiviral functions of RNA silencing pathway rely on common components , it was suggested t...	[ "To better understand the specific effect of p19 viral suppressor of RNA silencing ( VSR ) on antiviral silencing and endogenous small RNA pathways , we generated a N . benthamiana plant ( p19syn ) capable of sustaining the ectopic expression of the Cymbidium ringspot virus ( CymRSV ) p19 upon infection with a supp...	2016
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "medicine and health sciences", "cardiovascular anatomy", "renal arteries", "fibroblasts", "genetic predisposition", "arteries", "connective tissue cells", "blood vessels", "animal cells", "connective tissue", "biological tissue", "genetic loci", "anatomy", "cell biology", "genetics", ...	PHACTR1 Is a Genetic Susceptibility Locus for Fibromuscular Dysplasia Supporting Its Complex Genetic Pattern of Inheritance	journal.pgen.1006367	null	[ [ "Fibromuscular dysplasia ( FMD ) is a non-atherosclerotic and non-inflammatory vascular disease leading to stenosis , aneurysm , dissection , and/or occlusion of medium-sized arteries , in particular the renal and extracranial cerebrovascular arteries [1–3] .", "FMD predisposes to hypertension , transient...	[ "Fibromuscular dysplasia ( FMD ) is a nonatherosclerotic vascular disease leading to stenosis , dissection and aneurysm affecting mainly the renal and cerebrovascular arteries .", "FMD is often an underdiagnosed cause of hypertension and stroke , has higher prevalence in females ( ~80% ) but its pathophysiology i...	[ "Fibromuscular Dysplasia ( FMD ) is a vascular disease characterized by a succession of occlusions and dilatation of medium-sized arteries ( e . g renal , carotid or coronary arteries ) with important health consequences , mainly resistant hypertension and stroke .", "FMD is an atypical vascular disease because i...	2016
[ "Introduction", "Results", "Discussion", "Methods" ]	[]	Effective Harmonic Potentials: Insights into the Internal Cooperativity and Sequence-Specificity of Protein Dynamics	journal.pcbi.1003209	null	[ [ "Deciphering the motions that underlie many aspects of protein function is a major current challenge in molecular biology , with the potential to generate numerous applications in biomedical research and biotechnology .", "Although molecular dynamics ( MD ) hold a prominent position among computational ap...	[ "The proper biological functioning of proteins often relies on the occurrence of coordinated fluctuations around their native structure , or on their ability to perform wider and sometimes highly elaborated motions .", "Hence , there is considerable interest in the definition of accurate coarse-grained descriptio...	[ "Decades of experimental evidence have underlined the fact that protein structures can hardly be considered as static objects .", "To understand how a protein achieves its biological purpose , it is therefore quite often necessary to unravel the complexity of its dynamical behavior .", "However , the definition...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biochemistry/replication and repair", "genetics and genomics/gene function", "genetics and genomics/chromosome biology" ]	Replication and Recombination Factors Contributing to Recombination-Dependent Bypass of DNA Lesions by Template Switch	journal.pgen.1001205	null	[ [ "Proliferating cells are constantly exposed to DNA damage from both endogenous and exogenous sources .", "These DNA lesions can cause replication fork collapse and cell cycle arrest thereby posing a serious threat to genome integrity .", "To avoid the catastrophic consequences associated with fork dem...	[ "Damage tolerance mechanisms mediating damage-bypass and gap-filling are crucial for genome integrity .", "A major damage tolerance pathway involves recombination and is referred to as template switch .", "Template switch intermediates were visualized by 2D gel electrophoresis in the proximity of replication fo...	[ "Completion of DNA replication is essential for cellular survival .", "Both endogenous processes and exogenous DNA damage can lead to lesions that impede DNA replication or result in an accumulation of DNA gaps .", "Recombination plays an important role in facilitating replication completion under conditions of...	2010
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "medicine", "immune physiology", "clinical research design", "integrative physiology", "dengue", "anatomy and physiology", "immunology", "pediatrics", "critical care team organization", "physiological processes", "hemorrhagic fever with renal syndrome", "fluid management", "neglected tropica...	Dextran Fractional Clearance Studies in Acute Dengue Infection	journal.pntd.0001282	null	[ [ "Dengue infection is increasingly being recognised as a major burden on global health [1] .", "Infection with any of the four viral serotypes may result in asymptomatic infection , or cause a variety of disease manifestations ranging from non-specific fever to a severe syndrome characterised by increased ...	[ "Although increased capillary permeability is the major clinical feature associated with severe dengue infections the mechanisms underlying this phenomenon remain unclear .", "Dextran clearance methodology has been used to investigate the molecular sieving properties of the microvasculature in clinical situations...	[ "Dengue is a potentially serious common viral infection with no specific treatment .", "Plasma leakage from small blood vessels is the major severe problem , but we do not understand how this occurs .", "Techniques using controlled infusions of carbohydrate solutions , combined with careful measurement of the r...	2011
[ "Introduction", "Results", "Discussion", "Material and methods" ]	[ "aspergillus fumigatus", "medicine and health sciences", "protein interactions", "pathology and laboratory medicine", "chemical compounds", "aspergillus", "gene regulation", "pathogens", "regulatory proteins", "microbiology", "dna-binding proteins", "carbohydrates", "organic compounds", "f...	The monothiol glutaredoxin GrxD is essential for sensing iron starvation in Aspergillus fumigatus	journal.pgen.1008379	null	[ [ "Iron is an essential trace element for almost all organisms in all kingdoms of life .", "On the other hand , iron excess is toxic .", "Therefore , to maintain cell homeostasis , the balance between iron uptake and iron consumption has to be tightly regulated .", "Previous studies have shown that ...	[ "Efficient adaptation to iron starvation is an essential virulence determinant of the most common human mold pathogen , Aspergillus fumigatus .", "Here , we demonstrate that the cytosolic monothiol glutaredoxin GrxD plays an essential role in iron sensing in this fungus .", "Our studies revealed that", "( i )...	[ "Aspergillus fumigatus is a ubiquitous saprophytic mold and the major causative pathogen causing life-threatening aspergillosis .", "To improve therapy , there is an urgent need for a better understanding of the fungal physiology .", "We have previously shown that adaptation to iron starvation is an essential v...	2019
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Natural Genetic Transformation Generates a Population of Merodiploids in Streptococcus pneumoniae	journal.pgen.1003819	null	[ [ "Partial duplications of genetic material provide potential for evolution of new traits in all kingdoms of life , with duplicated material able to evolve in the absence of functional selective pressure [1] .", "Such duplications are prevalent in eukaryotes , and were recently shown to be associated with s...	[ "Partial duplication of genetic material is prevalent in eukaryotes and provides potential for evolution of new traits .", "Prokaryotes , which are generally haploid in nature , can evolve new genes by partial chromosome duplication , known as merodiploidy .", "Little is known about merodiploid formation during...	[ "Merodiploids are defined as cells possessing a partial duplication of their genetic material , which potentially allows evolution of new genes .", "Historically , some have been observed in studies of natural genetic transformation .", "Transformation allows the bacteria to take up foreign DNA and incorporate ...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	High Throughput Sequencing Reveals Alterations in the Recombination Signatures with Diminishing Spo11 Activity	journal.pgen.1003932	null	[ [ "An important function of meiosis is to precisely segregate one copy of each chromosome into cells that become gametes .", "This accurate division is accomplished by presenting the meiosis I spindle with homolog pairs that have been linked by crossovers ( COs ) , so that partner chromosomes can segregate ...	[ "Spo11 is the topoisomerase-like enzyme responsible for the induction of the meiosis-specific double strand breaks ( DSBs ) , which initiates the recombination events responsible for proper chromosome segregation .", "Nineteen PCR-induced alleles of SPO11 were identified and characterized genetically and cytologi...	[ "Most eukaryotes depend on the meiotic division to segregate each pair of chromosomes properly into their gametes .", "Chromosome segregation mistakes happening during meiosis are responsible for most miscarriages as well as many diseases such as Down's and Kleinfelter's syndromes in humans .", "Proper chromoso...	2013
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "infectious diseases/epidemiology and control of infectious diseases", "infectious diseases/antimicrobials and drug resistance" ]	On Being the Right Size: The Impact of Population Size and Stochastic Effects on the Evolution of Drug Resistance in Hospitals and the Community	journal.ppat.1001334	null	[ [ "The last decades have shown that the introduction of an antibiotic agent is almost inevitably followed by the spread of resistance mutations that jeopardize the beneficial effect of this agent [1] , [2] .", "Because of this process of bacterial adaptation to antibiotics , maintaining the benefits of anti...	[ "The evolution of drug resistant bacteria is a severe public health problem , both in hospitals and in the community .", "Currently , some countries aim at concentrating highly specialized services in large hospitals in order to improve patient outcomes .", "Emergent resistant strains often originate in health ...	[ "The increasing spread of bacteria , which are resistant to antibiotics , is a serious threat to clinical care .", "Currently , several countries aim at concentrating highly specialized services in large hospitals in order to improve patient outcomes .", "However , empirical studies have shown that resistance l...	2011
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "blood cells", "medicine and health sciences", "immune cells", "immune physiology", "spleen", "immunology", "parasitic diseases", "parasitic protozoans", "clinical medicine", "protozoans", "cytotoxic t cells", "research and analysis methods", "specimen preparation and treatment", "staining...	The Combined Deficiency of Immunoproteasome Subunits Affects Both the Magnitude and Quality of Pathogen- and Genetic Vaccination-Induced CD8+ T Cell Responses to the Human Protozoan Parasite Trypanosoma cruzi	journal.ppat.1005593	null	[ [ "CD8+ T cells are important mediators of pathogen control during intracellular infections .", "Sufficient induction of these cells leads to pathogen elimination [1–8] , whereas weak or exacerbated CD8+ T cell stimulation may lead to pathology [9–17] .", "Therefore , the proper induction of CD8+ T cell...	[ "The β1i , β2i and β5i immunoproteasome subunits have an important role in defining the repertoire of MHC class I-restricted epitopes .", "However , the impact of combined deficiency of the three immunoproteasome subunits in the development of protective immunity to intracellular pathogens has not been investigat...	[ "CD8+ t lymphocytes are cells of the immune system that mediate control of intracellular infections by viruses , prokaryote as well as eukaryote pathogens .", "To confer protection , these lymphocytes need to be elicited by pathogen peptides that are presented in association with MHC class I molecules .", "The ...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Impaired Systemic Tetrahydrobiopterin Bioavailability and Increased Oxidized Biopterins in Pediatric Falciparum Malaria: Association with Disease Severity	journal.ppat.1004655	null	[ [ "Falciparum malaria causes over 600 , 000 deaths worldwide each year , with approximately 560 , 000 fatal cases annually among children in sub-Saharan Africa [1] .", "Coma in malaria , cerebral malaria ( CM ) , portends a grave outcome among children infected with Plasmodium falciparum and , despite advan...	[ "Decreased bioavailability of nitric oxide ( NO ) is a major contributor to the pathophysiology of severe falciparum malaria .", "Tetrahydrobiopterin ( BH4 ) is an enzyme cofactor required for NO synthesis from L-arginine .", "We hypothesized that systemic levels of BH4 would be decreased in children with cereb...	[ "Vascular nitric oxide ( NO ) bioavailability is decreased in severe falciparum malaria and associated with microvascular dysfunction , increased activation of the cells lining blood vessels ( endothelial cells ) and increased parasite biomass .", "Tetrahydrobiopterin ( BH4 ) is an essential cofactor for nitric o...	2015
[ "Introduction", "Results and discussion", "Materials and methods" ]	[ "biogeography", "animal types", "taxonomy", "ecology and environmental sciences", "niger", "domestic animals", "population genetics", "geographical locations", "animals", "genetic mapping", "mutation", "phylogenetics", "data management", "rice", "phylogenetic analysis", "experimental o...	The complex geography of domestication of the African rice Oryza glaberrima	journal.pgen.1007414	null	[ [ "Domestication of crop species represents a key co-evolutionary transition , in which wild plant species were cultivated by humans and eventually gave rise to new species whose propagation were dependent on human action [1–3] .", "The evolutionary origin ( s ) of various crop species have been the subject...	[ "While the domestication history of Asian rice has been extensively studied , details of the evolution of African rice remain elusive .", "The inner Niger delta has been suggested as the center of origin but molecular data to support this hypothesis is lacking .", "Here , we present a comprehensive analysis of ...	[ "For many crops it is not clear how they were domesticated from their wild progenitors .", "Transition from a wild to domesticated state required a series of genetic changes , and studying the evolutionary origin of these domestication-causing mutations are key to understanding the domestication origins of a crop...	2019
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "invertebrates", "animals", "notch signaling", "dna transcription", "animal models", "developmental biology", "drosophila melanogaster", "model organisms", "experimental organism systems", "sequence motif analysis", "morphogenesis", "drosophila", "research and analysis methods", "sequence ...	Lateral inhibition: Two modes of non-autonomous negative autoregulation by neuralized	journal.pgen.1007528	null	[ [ "The specification of discrete cell identities during metazoan development often requires the establishment of disparate genetic programs in adjacent cells .", "The Notch signaling pathway is ideally suited to this task , since it mediates direct cell-cell interactions via contact between transmembrane li...	[ "Developmental patterning involves the progressive subdivision of tissue into different cell types by invoking different genetic programs .", "In particular , cell-cell signaling is a universally deployed means of specifying distinct cell fates in adjacent cells .", "For this mechanism to be effective , it is e...	[ "Much of the process of animal development is concerned with giving cells specific instructions as to what type of cell they are to become—their “fate” .", "Often , it is even necessary to assign very different fates to cells that are adjacent to each other in the tissue .", "In such cases , cell-to-cell signal...	2018
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "biology", "microbiology", "parasitology" ]	Comparative Gene Expression Analysis throughout the Life Cycle of Leishmania braziliensis: Diversity of Expression Profiles among Clinical Isolates	journal.pntd.0001021	null	[ [ "Leishmania are digenic Protozoan parasites endemic worldwide and", "causing a spectrum of diseases in humans collectively referred to as leishmaniasis .", "As part of their life cycle , Leishmania alternate between the", "alimentary tract of the sandfly vector ( where they grow as extracellular f...	[ "Most of the Leishmania genome is reported to be", "constitutively expressed during the life cycle of the parasite , with a few", "regulated genes .", "Inter-species comparative transcriptomics evidenced a low", "number of species-specific differences related to differentially distributed", "genes or the ...	[ "Leishmania is a group of parasites ( Protozoa , Trypanosomatidae )", "responsible for a wide spectrum of clinical forms .", "Among the factors explaining", "this phenotypic polymorphism , parasite features are important contributors .", "One", "approach to identify them consists in characterizing the gen...	2011
[ "Introduction", "Materials and methods", "Results/discussion" ]	[ "blood cells", "medicine and health sciences", "neural networks", "genetic diseases", "neuroscience", "factor analysis", "mathematics", "red blood cells", "statistics (mathematics)", "artificial intelligence", "hemoglobinopathies", "autosomal recessive diseases", "research and analysis metho...	A deep convolutional neural network for classification of red blood cells in sickle cell anemia	journal.pcbi.1005746	null	[ [ "Sickle cell disease ( SCD ) , also known as sickle cell anemia , is a type of inherited RBC disorder associated with abnormal hemoglobin S ( HbS ) [1] .", "When HbS molecules polymerize inside RBCs , due to lack of oxygen , they affect greatly the shape , elasticity , and adhesion properties of RBCs .", ...	[ "Sickle cell disease ( SCD ) is a hematological disorder leading to blood vessel occlusion accompanied by painful episodes and even death .", "Red blood cells ( RBCs ) of SCD patients have diverse shapes that reveal important biomechanical and bio-rheological characteristics , e . g . their density , fragility , ...	[ "There are many hematological disorders in the human circulation involving significant alteration of the shape and size of red blood cells ( RBCs ) , e . g . sickle cell disease ( SCD ) , spherocytosis , diabetes , HIV , etc .", "These morphological alterations reflect subtle multiscale processes taking place at ...	2017
[ "Introduction", "Methods", "Results/Discussion", "Conclusions" ]	[ "computational chemistry", "molecular dynamics", "biology and life sciences", "chemistry", "physical sciences", "computational biology", "biophysics", "biophysical simulations" ]	Pyranose Dehydrogenase Ligand Promiscuity: A Generalized Approach to Simulate Monosaccharide Solvation, Binding, and Product Formation	journal.pcbi.1003995	null	[ [ "Generally , enzymes are perceived as being specific for both their substrates and the reactions they catalyze [1] .", "Deviations from such behavior are often seen as unwanted side effects or even errors in the biological function of the enzyme that come at an additional energetic cost for the organism ....	[ "The flavoenzyme pyranose dehydrogenase ( PDH ) from the litter decomposing fungus Agaricus meleagris oxidizes many different carbohydrates occurring during lignin degradation .", "This promiscuous substrate specificity makes PDH a promising catalyst for bioelectrochemical applications .", "A generalized approa...	[ "Generally , enzymes are perceived as being specific for both their substrates and the reaction they catalyze .", "This standard paradigm started to shift and currently enzyme promiscuity towards various substrates is perceived rather as the rule than the exception .", "Enzyme promiscuity seems to be vital for ...	2014
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "cryptococcus neoformans", "medicine and health sciences", "cryptococcus gattii", "cryptococcus", "pathology and laboratory medicine", "pathogens", "population genetics", "geographical locations", "microbiology", "fungi", "phylogenetic analysis", "molecular biology techniques", "population b...	MLST-Based Population Genetic Analysis in a Global Context Reveals Clonality amongst Cryptococcus neoformans var. grubii VNI Isolates from HIV Patients in Southeastern Brazil	journal.pntd.0005223	null	[ [ "Infection by Cryptococcus species is considered one of the most important disease in patients living with HIV .", "It is estimated that around 624 , 000 deaths occur annually due to cryptococcosis , with most of them occurring in sub-Saharan Africa and Southeast Asia [1 , 2] .", "The infection is mai...	[ "Cryptococcosis is an important fungal infection in immunocompromised individuals , especially those infected with HIV .", "In Brazil , despite the free availability of antiretroviral therapy ( ART ) in the public health system , the mortality rate due to Cryptococcus neoformans meningitis is still high .", "To...	[ "The members of the Cryptococcus neoformans / Cryptococcus gattii species complex are the cause of cryptococcosis , a life-threatening human disease responsible for 624 , 000 deaths annually .", "Infection is acquired through inhalation of dehydrated yeast cells from environmental sources .", "After reaching th...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biology and life sciences", "immunology", "evolutionary biology", "evolutionary immunology", "immune response", "immune system" ]	Caspase-1-Like Regulation of the proPO-System and Role of ppA and Caspase-1-Like Cleaved Peptides from proPO in Innate Immunity	journal.ppat.1004059	null	[ [ "Melanization is the result of the oxidation of mono- and/or diphenols by a redox enzyme , often phenoloxidase , and it is an important reaction in most multicellular organisms , both animals and plants .", "Intruding microorganisms are frequently melanized in invertebrates , and during this process , low...	[ "Invertebrates rely on innate immunity to respond to the entry of foreign microorganisms .", "One of the important innate immune responses in arthropods is the activation of prophenoloxidase ( proPO ) by a proteolytic cascade finalized by the proPO-activating enzyme ( ppA ) , which leads to melanization and the e...	[ "Melanization is an important reaction in most multicellular organisms , both animals and plants .", "The initiation steps of this reaction in invertebrates are catalyzed by the prophenoloxidase ( proPO ) activating system a proteolytic enzyme cascade , which primary function is to recognize cell wall products fr...	2014
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "medicine", "infectious diseases", "diagnostic medicine", "neglected tropical diseases" ]	Actigraphy in Human African Trypanosomiasis as a Tool for Objective Clinical Evaluation and Monitoring: A Pilot Study	journal.pntd.0001525	null	[ [ "Human African trypanosomiasis ( HAT ) , commonly known as sleeping sickness , is caused by subspecies of the protozoan parasite Trypanosoma brucei ( T . b . ) and transmitted by tsetse fly bites in sub-Saharan Africa .", "This disease , which mainly affects rural populations , is one of the most neglecte...	[ "Human African trypanosomiasis ( HAT ) or sleeping sickness leads to a complex neuropsychiatric syndrome with characteristic sleep alterations .", "Current division into a first , hemolymphatic stage and second , meningoencephalitic stage is primarily based on the detection of white blood cells and/or trypanosome...	[ "The clinical picture of the parasitic disease human African trypanosomiasis ( HAT , also called sleeping sickness ) is dominated by sleep alterations .", "We here used actigraphy to evaluate patients affected by the Gambiense form of HAT .", "Actigraphy is based on the use of battery-run , wrist-worn devices s...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "cell biology/cell growth and division", "genetics and genomics/cancer genetics", "developmental biology", "cell biology/cellular death and stress responses" ]	dMyc Functions Downstream of Yorkie to Promote the Supercompetitive Behavior of Hippo Pathway Mutant Cells	journal.pgen.1001140	null	[ [ "Growth regulation requires the fine tuning between the rate of cell death and cell proliferation in developing organs .", "Studies in Drosophila have revealed that somatic cells within a growing epithelium compete with one another for contribution to the adult organ and this phenomenon , known as “cell c...	[ "Genetic analyses in Drosophila epithelia have suggested that the phenomenon of “cell competition” could participate in organ homeostasis .", "It has been speculated that competition between different cell populations within a growing organ might play a role as either tumor promoter or tumor suppressor , dependin...	[ "One of the major challenges of developmental biology and cancer research is to get a better understanding of how different signals regulate proper organ growth and prevent tumor formation .", "Even though there is a strong correlation between tumor progression and Myc family misexpression or Hippo signaling path...	2010
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "blood cells", "phosphorylation", "medicine and health sciences", "immune cells", "pathology and laboratory medicine", "pathogens", "animal models of disease", "immunology", "microbiology", "animal models", "fungi", "model organisms", "experimental organism systems", "kidneys", "fungal p...	Blocking two-component signalling enhances Candida albicans virulence and reveals adaptive mechanisms that counteract sustained SAPK activation	journal.ppat.1006131	null	[ [ "Candida albicans is the leading cause of systemic fungal infections in humans resulting in over 400 , 000 deaths each year in immuno-compromised patients [1] .", "The ability of C . albicans to adapt to host-imposed stresses encountered during infection is an important virulence trait [2] .", "Centra...	[ "The Ypd1 phosphorelay protein is a central constituent of fungal two-component signal transduction pathways .", "Inhibition of Ypd1 in Saccharomyces cerevisiae and Cryptococcus neoformans is lethal due to the sustained activation of the ‘p38-related’ Hog1 stress-activated protein kinase ( SAPK ) .", "As two-co...	[ "As fungi-attributed human deaths are increasing , there is an urgent need to develop new antifungal treatments .", "Two-component related proteins , such as the Ypd1 phosphorelay protein , have been heralded as antifungal targets as they are not found in humans and because inactivation of YPD1 in several differe...	2017
[ "Introduction", "Results", "Discussion", "Material and methods" ]	[ "tumor stem cells", "medicine and health sciences", "reproductive system", "gonads", "nuclear staining", "population genetics", "gene pool", "cell differentiation", "germ cells", "developmental biology", "stem cells", "population biology", "research and analysis methods", "specimen prepara...	SYGL-1 and LST-1 link niche signaling to PUF RNA repression for stem cell maintenance in Caenorhabditis elegans	journal.pgen.1007121	null	[ [ "The balance between stem cell self-renewal and differentiation is pivotal for normal development , adult homeostasis , and regeneration .", "Indeed , aberrant stem cell regulation can cause disease , including human degenerative disorders and cancers [1] .", "Stem cell daughters can exist in a “naïve...	[ "Central questions in regenerative biology include how stem cells are maintained and how they transition from self-renewal to differentiation .", "Germline stem cells ( GSCs ) in Caeno-rhabditis elegans provide a tractable in vivo model to address these questions .", "In this system , Notch signaling and PUF RN...	[ "Stem cells lie at the heart of metazoan development , regeneration , and tissue homeostasis , but the molecular basis of their regulation is poorly understood in their natural context within an animal .", "Here we investigate this problem in the nematode gonad , where germline stem cells are maintained by Notch ...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "microbiology/applied microbiology" ]	Use of Tissue-Specific MicroRNA to Control Pathology of Wild-Type Adenovirus without Attenuation of Its Ability to Kill Cancer Cells	journal.ppat.1000440	null	[ [ "Viruses have a highly successful history as prophylactic vaccines and are also being developed for their intrinsic anticancer activities [1] .", "In both settings the ability to undergo restricted replication is highly desirable .", "Attenuated ( but not killed ) viral strains often represent the mos...	[ "Replicating viruses have broad applications in biomedicine , notably in cancer virotherapy and in the design of attenuated vaccines; however , uncontrolled virus replication in vulnerable tissues can give pathology and often restricts the use of potent strains .", "Increased knowledge of tissue-selective microRN...	[ "Attenuated viruses have found important applications in medicine , including their use as vaccines ( notably for measles , mumps , polio , influenza , and chicken pox ) and their experimental development as selective cancer-killing agents , so-called “virotherapy . ”", "Wild-type versions are often most effectiv...	2009
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "medicine and health sciences", "plagues", "atmospheric science", "geographical locations", "tropical diseases", "vertebrates", "parasitic diseases", "animals", "mammals", "bacterial diseases", "review", "neglected tropical diseases", "infectious disease control", "climate change", "infe...	Rodent-borne diseases and their public health importance in Iran	journal.pntd.0006256	null	[ [ "Rodents are the largest order of living mammals , comprising approximately 42% of global mammalian biodiversity [1 , 2] .", "With almost 2 , 277 known species in 33 families , rodents have nearly a worldwide distribution , being absent only from Antarctica and some isolated islands [2] .", "They are ...	[ "Rodents are reservoirs and hosts for several zoonotic diseases such as plague , leptospirosis , and leishmaniasis .", "Rapid development of industry and agriculture , as well as climate change throughout the globe , has led to change or increase in occurrence of rodent-borne diseases .", "Considering the distr...	[ "This review showed that approximately half of the known rodent-borne diseases have been reported in Iran , half of which were reported both in humans and rodents .", "Most of the diseases were bacterial and parasitic .", "Plague , leishmaniasis , and hymenolepiasis were the most frequent diseases among rodent ...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	An O Antigen Capsule Modulates Bacterial Pathogenesis in Shigella sonnei	journal.ppat.1004749	null	[ [ "Shigellosis , or bacillary dysentery , is an acute human inflammatory disease of the large intestine , characterized by watery diarrhea , fever , abdominal pain , and bloody and mucus stools , caused by Gram-negative Shigella enterobacteria [1] .", "This disease is a major global health concern , respons...	[ "Shigella is the leading cause for dysentery worldwide .", "Together with several virulence factors employed for invasion , the presence and length of the O antigen ( OAg ) of the lipopolysaccharide ( LPS ) plays a key role in pathogenesis .", "S . flexneri 2a has a bimodal OAg chain length distribution regulat...	[ "Shigellosis is a major global health concern .", "Recently , a shift in the dominance of types of Shigella that cause disease has been observed with S . sonnei increasing in prevalence under improved socio-economic conditions leading to a replacement of S . flexneri .", "Most of the knowledge of Shigella disea...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Conditional Cooperativity of Toxin - Antitoxin Regulation Can Mediate Bistability between Growth and Dormancy	journal.pcbi.1003174	null	[ [ "Many bacteria and archaea have multiple Toxin-Antitoxin ( TA ) loci [1] , where the toxin normally inhibits cell growth , while the antitoxin neutralizes the activity of the toxin by forming a tight TA complex .", "One of the known functions of TA loci is to respond to nutritional stress [2] , namely , t...	[ "Many toxin-antitoxin operons are regulated by the toxin/antitoxin ratio by mechanisms collectively coined “conditional cooperativity” .", "Toxin and antitoxin form heteromers with different stoichiometric ratios , and the complex with the intermediate ratio works best as a transcription repressor .", "This all...	[ "The effectiveness of antibiotics on many pathogenic bacteria is compromised by multidrug tolerance .", "This is caused by a small sub-population of bacteria that happen to be in a dormant , non-dividing state when antibiotics are applied and thus are protected from being killed .", "These bacteria are called p...	2013
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "biotechnology", "bioengineering", "systems biology", "biological systems engineering", "biology", "computational biology", "metabolic networks", "genetics and genomics", "engineering" ]	Phenomenological Model for Predicting the Catabolic Potential of an Arbitrary Nutrient	journal.pcbi.1002762	null	[ [ "Our phenomenological model expresses the impact that different carbon sources ( or nutrients ) have on a microbe's ability to grow using only information on the chemical structure of these carbon sources and on the ability of a microbe to catabolize these nutrients .", "Our model is built to reproduce th...	[ "The ability of microbial species to consume compounds found in the environment to generate commercially-valuable products has long been exploited by humanity .", "The untapped , staggering diversity of microbial organisms offers a wealth of potential resources for tackling medical , environmental , and energy ch...	[ "The ability of microbial species to consume compounds found in the environment to generate commercially-valuable products has long been exploited by humanity .", "The vast untapped diversity of microbial species offers a wealth of potential resources .", "However , little is known about most microbial species ...	2012
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "invertebrates", "cell death", "medicine and health sciences", "diabetic endocrinology", "cell processes", "animals", "hormones", "endocrine physiology", "animal models", "oncology", "developmental biology", "drosophila melanogaster", "model organisms", "eyes", "morphogenesis", "drosop...	A Drosophila Model of HPV E6-Induced Malignancy Reveals Essential Roles for Magi and the Insulin Receptor	journal.ppat.1005789	null	[ [ "Cervical cancer is the fourth leading cause of cancer death in women worldwide with ~500 , 000 new cases of cervical cancer annually and ~250 , 000 deaths worldwide .", "The main causative agents of cervical cancer are the high-risk human papillomaviruses ( HPVs ) .", "HPVs can induce hyperproliferat...	[ "Cervical cancer is one of the leading causes of cancer death in women worldwide .", "The causative agents of cervical cancers , high-risk human papillomaviruses ( HPVs ) , cause cancer through the action of two oncoproteins , E6 and E7 .", "The E6 oncoprotein cooperates with an E3 ubiquitin ligase ( UBE3A ) to...	[ "Human papillomaviruses ( HPV ) are the causative agents of cervical cancer , one of the leading causes of cancer death in women worldwide .", "The E6 oncoprotein encoded by HPV has been implicated in the progression of primary tumors to metastatic disease and we have developed a new model in the fruit fly ( Dros...	2016
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "parasite groups", "parasite replication", "plasmodium", "green fluorescent protein", "cloning", "parasitic protozoans", "parasitology", "apicomplexa", "luminescent proteins", "protozoans", "molecular biology techniques", "research and analysis methods", "malarial parasites", "proteins", ...	A mutagenesis screen for essential plastid biogenesis genes in human malaria parasites	journal.pbio.3000136	The apicoplast of the malaria parasite Plasmodium falciparum provides critical metabolites during host cell infection. An unbiased forward genetic screen identifies previously unknown genes required for biogenesis of this organelle, potentially yielding novel antimalarial drug targets.	[ [ "Plasmodium spp .", ", which cause malaria , and related apicomplexan parasites are important human and veterinary pathogens .", "These disease-causing protozoa are highly divergent from well-studied model organisms that are the textbook examples of eukaryotic biology , such that parasite biology ofte...	[ "Endosymbiosis has driven major molecular and cellular innovations .", "Plasmodium spp .", "parasites that cause malaria contain an essential , non-photosynthetic plastid—the apicoplast—which originated from a secondary ( eukaryote–eukaryote ) endosymbiosis .", "To discover organellar pathways with evolutiona...	[ "Plasmodium parasites , which cause malaria , and related apicomplexan parasites evolved from photosynthetic algae that acquired their chloroplast through two successive endosymbioses .", "Although no longer photosynthetic , the apicomplexan plastid—or apicoplast—was retained in these pathogens and provides criti...	2019
[ "Introduction", "Methods", "Models", "Results", "Discussion" ]	[]	Imperfect Bayesian inference in visual perception	journal.pcbi.1006465	null	[ [ "An important function of the visual system is to make inferences about the environment from noisy sensory input .", "It is often claimed that human performance on perceptual inference tasks is optimal or “Bayesian” [1–5] , meaning that subjects supposedly perform as well as theoretically possible given t...	[ "Optimal Bayesian models have been highly successful in describing human performance on perceptual decision-making tasks , such as cue combination and visual search .", "However , recent studies have argued that these models are often overly flexible and therefore lack explanatory power .", "Moreover , there ar...	[ "The main task of perceptual systems is to make truthful inferences about the environment .", "The sensory input to these systems is often astonishingly imprecise , which makes human perception prone to error .", "Nevertheless , numerous studies have reported that humans often perform as accurately as is possib...	2019
[ "Introduction", "Results", "Discussion", "Methods" ]	[]	Vibrissa Self-Motion and Touch Are Reliably Encoded along the Same Somatosensory Pathway from Brainstem through Thalamus	journal.pbio.1002253	Recordings from behaving rats show that information regarding the position of whiskers during "whisking" is encoded along the same neuronal pathway as touch. This contrasts with the separate pathways used for encoding position and touch in the limbs and implies the need for non-linear demodulation of touch with respect...	[ [ "Animals navigate the world around them with actively moving sensory organs [1] .", "This process results in a blend of sensory input from the presence of two underlying sensory signals .", "One input is from the environment or object under study , while the second is from self-generated movement of t...	[ "Active sensing involves the fusion of internally generated motor events with external sensation .", "For rodents , active somatosensation includes scanning the immediate environment with the mystacial vibrissae .", "In doing so , the vibrissae may touch an object at any angle in the whisk cycle .", "The repr...	[ "Animals interrogate the world around them with actively moving sensory organs , resulting in a blend of sensory inputs: one input is from the object under study , while the second is from self-generated movement of the sensor .", "The detection of an object thus depends on the ability of the animal to distinguis...	2015
[ "Introduction", "Results", "Discussion", "Material and methods" ]	[ "invertebrates", "honey bees", "sociology", "social sciences", "animals", "social systems", "animal behavior", "zoology", "animal sociality", "bees", "foraging", "lipids", "hymenoptera", "ants", "behavior", "fats", "gene expression", "insects", "arthropoda", "biochemistry", "...	Vitellogenin-like A–associated shifts in social cue responsiveness regulate behavioral task specialization in an ant	journal.pbio.2005747	null	[ [ "Division of labor—the distribution of work among group members—is a characteristic trait of many social species , including humans , other social mammals , and social insects .", "An important component of division of labor is task specialization , which increases the efficiency in performing a task and ...	[ "Division of labor and task specialization explain the success of human and insect societies .", "Social insect colonies are characterized by division of labor , with workers specializing in brood care early and foraging later in life .", "Theory posits that this task switching requires shifts in responsiveness...	[ "In social insects such as ants and bees , workers specialize in different tasks .", "This specialization is thought to be regulated via response thresholds to task-specific cues , which vary between workers conducting different tasks .", "Whether a worker takes care of the brood , cares for other workers , or ...	2018
[ "Introduction", "Materials and methods", "Results", "Discussion" ]	[ "medicine and health sciences", "atmospheric science", "geographical locations", "tropical diseases", "vertebrates", "parasitic diseases", "animals", "mammals", "seasons", "mathematics", "forecasting", "statistics (mathematics)", "neglected tropical diseases", "infectious disease control",...	Modeling zoonotic cutaneous leishmaniasis incidence in central Tunisia from 2009-2015: Forecasting models using climate variables as predictors	journal.pntd.0005844	null	[ [ "Cutaneous leishmaniasis ( CL ) is a neglected tropical disease widespread in the Middle East , the Mediterranean basin and North Africa [1 , 2] .", "Most of the cases occur in the arid and semi-arid regions [3] .", "The circumstances of the dynamic leishmaniasis disease are often complex and varying ...	[ "Transmission of zoonotic cutaneous leishmaniasis ( ZCL ) depends on the presence , density and distribution of Leishmania major rodent reservoir and the development of these rodents is known to have a significant dependence on environmental and climate factors .", "ZCL in Tunisia is one of the most common forms ...	[ "Zoonotic cutaneous leishmaniasis is a human vector-borne disease caused by the parasite Leishmania major and is well spread in rural areas where human resources in public health and infrastructure are limited .", "The cycle of transmission of the disease is complex because of the impact of climate change .", "...	2017
[ "Introduction", "Results/Discussion", "Materials and Methods" ]	[ "virology/mechanisms of resistance and susceptibility, including host genetics", "virology/new therapies, including antivirals and immunotherapy", "virology/animal models of infection", "virology/antivirals, including modes of action and resistance" ]	Characterization of Oseltamivir-Resistant 2009 H1N1 Pandemic Influenza A Viruses	journal.ppat.1001079	null	[ [ "Since its emergence in early spring of 2009 , 2009 pandemic influenza A ( H1N1 ) viruses have been circulating worldwide [1] .", "Although most infected individuals have exhibited an uncomplicated , mild respiratory disorder , the pathogenicity of this virus is clearly higher than that of seasonal influe...	[ "Influenza viruses resistant to antiviral drugs emerge frequently .", "Not surprisingly , the widespread treatment in many countries of patients infected with 2009 pandemic influenza A ( H1N1 ) viruses with the neuraminidase ( NA ) inhibitors oseltamivir and zanamivir has led to the emergence of pandemic strains ...	[ "Although most of the currently circulating 2009 pandemic influenza A ( H1N1 ) viruses are susceptible to neuraminidase ( NA ) inhibitors ( oseltamivir and zanamivir ) , oseltamivir-resistant mutants have sporadically appeared .", "Yet , the pathogenicity and transmissibility of these oseltamivir-resistant 2009 H...	2010
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biotechnology", "plant anatomy", "chemical compounds", "brassica", "carbohydrates", "organic compounds", "cereal crops", "plant science", "model organisms", "crops", "plant genomics", "chronobiology", "plants", "starches", "arabidopsis thaliana", "research and analysis methods", "gr...	Temporal Shift of Circadian-Mediated Gene Expression and Carbon Fixation Contributes to Biomass Heterosis in Maize Hybrids	journal.pgen.1006197	null	[ [ "A filial F1 hybrid often outperforms inbred parents in growth and fitness , a phenomenon known as heterosis or hybrid vigor .", "Since early twentieth century , heterosis has been applied in breeding and production of maize and many other crops , vegetables , and some animals [1–3] .", "However , the...	[ "Heterosis has been widely used in agriculture , but the molecular mechanism for this remains largely elusive .", "In Arabidopsis hybrids and allopolyploids , increased photosynthetic and metabolic activities are linked to altered expression of circadian clock regulators , including CIRCADIAN CLOCK ASSOCIATED1 ( ...	[ "All corn in the USA is grown as hybrids , which grow more vigorously and produce higher yield than their parents , a phenomenon known as heterosis .", "The molecular basis for heterosis remains elusive .", "Heterosis is predicted to arise from allelic interactions between parental genomes , leading to altered ...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "systems biology", "imaging techniques", "cell biology", "computational techniques", "microscopy", "mathematical and statistical techniques", "biology and life sciences", "computational biology", "biophysics", "research and analysis methods" ]	Depletion of the Chromatin Looping Proteins CTCF and Cohesin Causes Chromatin Compaction: Insight into Chromatin Folding by Polymer Modelling	journal.pcbi.1003877	null	[ [ "Chromosomes are highly folded inside the interphase nucleus .", "Their structure has been extensively studied by light and electron microscopy and more recently by genome-wide mapping of intra- and inter-chromosomal contacts .", "The picture that is emerging is that the chromosomal fibre is packed in...	[ "Folding of the chromosomal fibre in interphase nuclei is an important element in the regulation of gene expression .", "For instance , physical contacts between promoters and enhancers are a key element in cell-type–specific transcription .", "We know remarkably little about the principles that control chromos...	[ "Folding of chromosomes in interphase nuclei of higher eukaryotes is a key element in regulating gene expression .", "The mechanisms that control chromatin folding are largely unknown .", "We have shown earlier that looping is a fundamental aspect of large-scale chromatin structure .", "Two abundant looping p...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "cell death", "invertebrates", "cell processes", "animals", "animal models", "developmental biology", "drosophila melanogaster", "model organisms", "organism development", "stat proteins", "embryos", "morphogenesis", "drosophila", "research and analysis methods", "embryology", "protein...	Drosophila Wnt and STAT Define Apoptosis-Resistant Epithelial Cells for Tissue Regeneration after Irradiation	journal.pbio.1002536	After widespread radiation damage in the developing fruit fly, organs are formed by regeneration from an apoptosis-resistant subpopulation of cells marked by high levels of Wingless and STAT.	[ [ "The ability to regenerate is critical for tissue homeostasis in adult organisms .", "Many tissues such as the gut and the skin suffer constant environmental insults that result in cell death , requiring tissue-specific stem cells to proliferate and compensate for cell loss .", "Two key characteristic...	[ "Drosophila melanogaster larvae irradiated with doses of ionizing radiation ( IR ) that kill about half of the cells in larval imaginal discs still develop into viable adults .", "How surviving cells compensate for IR-induced cell death to produce organs of normal size and appearance remains an active area of inv...	[ "Like other insects , Drosophila larvae have epithelial structures called imaginal discs that will give rise to most of the external adult structures , such as wings , limbs , or antennae; these organ precursors are formed by a single layer of epithelial cells that folds into a sac .", "Imaginal discs manage to r...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "viral immune evasion", "virology", "immunology", "host-pathogen interaction", "biology", "microbiology", "immunomodulation" ]	Cytomegalovirus m154 Hinders CD48 Cell-Surface Expression and Promotes Viral Escape from Host Natural Killer Cell Control	journal.ppat.1004000	null	[ [ "Pathogens have recourse to innumerable tactics for evading host immune surveillance .", "Viruses , and in particular large DNA viruses such as herpesviruses , are endowed with the capacity to encode multiple products committed to altering , during all stages of their life cycle , several functions of the...	[ "Receptors of the signalling lymphocyte-activation molecules ( SLAM ) family are involved in the functional regulation of a variety of immune cells upon engagement through homotypic or heterotypic interactions amongst them .", "Here we show that murine cytomegalovirus ( MCMV ) dampens the surface expression of se...	[ "Cytomegalovirus ( CMV ) has developed diverse tactics to elude the host immune response and guarantee its survival .", "The signalling lymphocyte-activation molecules ( SLAM ) family of receptors encompasses a number of adhesion molecules expressed on the surface of leukocytes that play critical roles in both in...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "heme", "medicine and health sciences", "breast tumors", "oxidative stress", "cancers and neoplasms", "oncology", "physiological processes", "mathematics", "homeostasis", "algebra", "mitochondria", "bioenergetics", "cellular structures and organelles", "polynomials", "proteins", "breas...	Activated Oncogenic Pathway Modifies Iron Network in Breast Epithelial Cells: A Dynamic Modeling Perspective	journal.pcbi.1005352	null	[ [ "This section provides biological background about iron metabolism and its connection to some oncogenic pathways ." ], [ "We describe a discrete dynamic model of the network in Fig 1 , based on an encoding of the regulatory logic for each node through a “logical” update rule .", "This type of mode...	[ "Dysregulation of iron metabolism in cancer is well documented and it has been suggested that there is interdependence between excess iron and increased cancer incidence and progression .", "In an effort to better understand the linkages between iron metabolism and breast cancer , a predictive mathematical model ...	[ "Iron is required for cellular metabolism and growth , but can be toxic due to its ability to cause high oxidative stress and consequently DNA damage .", "To prevent damage , all organisms that require iron have developed mechanisms to tightly control iron levels .", "Dysregulation of iron metabolism is detrime...	2017
[ "Introduction", "Materials and methods", "Results", "Discussion" ]	[ "schistosoma", "invertebrates", "medicine and health sciences", "body fluids", "helminths", "tropical diseases", "dna-binding proteins", "biomarkers", "parasitic diseases", "animals", "urine", "membrane receptor signaling", "neglected tropical diseases", "cell nucleus", "cellular structu...	Quantitative label-free proteomic analysis of human urine to identify novel candidate protein biomarkers for schistosomiasis	journal.pntd.0006045	null	[ [ "Urinary schistosomiasis , caused by the parasite Schistosoma haematobium , is of public health significance in tropical and sub-tropical areas , with an estimated 732 million persons being vulnerable to infection worldwide in well-defined transmission areas [1] .", "In 2008 , 17 . 5 million people were t...	[ "Schistosomiasis is a chronic neglected tropical disease that is characterized by continued inflammatory challenges to the exposed population and it has been established as a possible risk factor in the aetiology of bladder cancer .", "Improved diagnosis of schistosomiasis and its associated pathology is possible...	[ "Schistosomiasis , caused by S . haematobium , causes inflammation in the bladder and is common in tropical areas such as Nigeria .", "Undetected schistosomiasis can lead to inflammation in the bladder which may lead to bladder cancer .", "Diagnosis of bladder cancer in areas with common urinary schistosomiasis...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "evolutionary biology", "genetics and genomics/population genetics" ]	Evidence that Adaptation in Drosophila Is Not Limited by Mutation at Single Sites	journal.pgen.1000924	null	[ [ "The speed of adaptation in eukaryotes is commonly assumed to be limited by the waiting-time for an appropriate adaptive mutation .", "This notion is based on estimates of the population parameter Θ = 4Neμ ( the product of effective population size Ne and per-site mutation rate μ ) derived from levels of ...	[ "Adaptation in eukaryotes is generally assumed to be mutation-limited because of small effective population sizes .", "This view is difficult to reconcile , however , with the observation that adaptation to anthropogenic changes , such as the introduction of pesticides , can occur very rapidly .", "Here we inve...	[ "Adaptation in eukaryotes is often assumed to be limited by the waiting time for adaptive mutations .", "This is because effective population sizes are relatively small , typically on the order of only a few million reproducing individuals or less .", "It should therefore take hundreds or even thousands of gene...	2010
[ "Introduction", "Results", "Discussion", "Materials and Methods", "Supporting Information" ]	[ "biochemistry", "infectious diseases", "microbiology", "eubacteria" ]	Enlightening Energy Parasitism by Analysis of an ATP/ADP Transporter from Chlamydiae	journal.pbio.0050231	This paper explores the functional basis of how the intracellular P. amoebophila manages to effectively exploit the energy pool of its host cell by using the nucleotide transporter PamNTT1.	[ [ "Members of the bacterial orders Rickettsiales and Chlamydiales gained attention because they comprise several human pathogenic species causing severe diseases like typhus , pneumonia , trachoma , or sexually transmitted infections [1 , 2] .", "The obligate intracellular lifestyle of these bacteria depend...	[ "Energy parasitism by ATP/ADP transport proteins is an essential , common feature of intracellular bacteria such as chlamydiae and rickettsiae , which are major pathogens of humans .", "Although several ATP/ADP transport proteins have so far been characterized , some fundamental questions regarding their function...	[ "Diverse members of the bacterial order Chlamydiales cause severe diseases in humans .", "Chlamydiales cannot survive and reproduce outside of host cells , due to the complete loss of several biosynthetic pathways , but rely on specialized transport systems to import the corresponding metabolites from the host ."...	2007
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine", "biology", "microbiology", "molecular cell biology", "toxicology" ]	Preferential Entry of Botulinum Neurotoxin A Hc Domain through Intestinal Crypt Cells and Targeting to Cholinergic Neurons of the Mouse Intestine	journal.ppat.1002583	null	[ [ "Botulinum neurotoxins ( BoNTs ) are responsible for a severe nervous disease in man and animals known as botulism , characterized by skeletal muscle flaccid paralysis and respiratory arrest , resulting from inhibition of acetylcholine ( ACh ) release in peripheral cholinergic nerve terminals .", "BoNTs a...	[ "Botulism , characterized by flaccid paralysis , commonly results from botulinum neurotoxin ( BoNT ) absorption across the epithelial barrier from the digestive tract and then dissemination through the blood circulation to target autonomic and motor nerve terminals .", "The trafficking pathway of BoNT/A passage t...	[ "Botulism is a severe and often fatal disease in man and animals characterized by flaccid paralysis .", "Clostridium botulinum produces a potent neurotoxin ( botulinum neurotoxin ) responsible for all the symptoms of botulism .", "Botulism is most often acquired by ingesting preformed botulinum neurotoxin in co...	2012
[ "Introduction", "Results", "Discussion", "Methods" ]	[]	Predicting Odor Perceptual Similarity from Odor Structure	journal.pcbi.1003184	null	[ [ "One hundred years ago , Alexander Graham Bell asked: “Can you measure the difference between one kind of smell and another . It is very obvious that we have very many different kinds of smells , all the way from the odor of violets and roses up to asafetida . But until you can measure their likenesses and di...	[ "To understand the brain mechanisms of olfaction we must understand the rules that govern the link between odorant structure and odorant perception .", "Natural odors are in fact mixtures made of many molecules , and there is currently no method to look at the molecular structure of such odorant-mixtures and pred...	[ "One hundred years ago , Alexander Graham Bell asked: “Can you measure the difference between one kind of smell and another ? It is very obvious that we have very many different kinds of smells , all the way from the odor of violets and roses up to asafetida . But until you can measure their likenesses and differen...	2013
[ "Introduction", "Methods", "Results", "Discussion" ]	[]	Species-Specific Serological Detection for Schistosomiasis by Serine Protease Inhibitor (SERPIN) in Multiplex Assay	journal.pntd.0004021	null	[ [ "Globally , more than 240 million people are still infected with schistosomiasis [1] .", "Over 90% of the infected people are resident in resource-limited settings in sub-Saharan Africa [2] .", "The next target of the current WHO roadmap for the control and elimination of schistosomiasis is to scale u...	[ "Both Schistosoma mansoni and Schistosoma haematobium cause schistosomiasis in sub-Saharan Africa .", "We assessed the diagnostic value of selected Schistosoma antigens for the development of a multiplex serological immunoassay for sero-epidemiological surveillance .", "Diagnostic ability of recombinant antigen...	[ "More attention is now shifting towards elimination of some of the neglected tropical diseases , including schistosomiasis .", "Efficient diagnostics and surveillance tools are the bedrock of planning , implementation , monitoring and evaluation of such disease interventions .", "We had developed a multiplex im...	2015
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[]	Degradation of Human PDZ-Proteins by Human Alphapapillomaviruses Represents an Evolutionary Adaptation to a Novel Cellular Niche	journal.ppat.1004980	null	[ [ "Papillomaviruses ( PVs ) are a diverse family of dsDNA viruses infecting most , if not all , amniotes .", "Based on nucleotide similarities , PVs are classified into genera identified by Greek letters .", "A genus is further divided into numbered species [1 , 2] .", "Persistent infection with spe...	[ "In order to complete their life cycle , papillomaviruses have evolved to manipulate a plethora of cellular pathways .", "The products of the human Alphapapillomavirus E6 proteins specifically interact with and target PDZ containing proteins for degradation .", "This viral phenotype has been suggested to play a...	[ "It is thought that the ability to degrade PDZ domain containing proteins is a hallmark of oncogenic papillomaviruses .", "However , since papillomaviruses did not evolve to be oncogenic , this hypothesis does not address the evolutionary importance of this phenotype .", "The present manuscript attempts to addr...	2015
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "sequencing techniques", "viral vaccines", "medicine and health sciences", "immune physiology", "pathology and laboratory medicine", "viral transmission and infection", "pathogens", "immunology", "microbiology", "retroviruses", "viruses", "immunodeficiency viruses", "vaccines", "preventive...	Features of Recently Transmitted HIV-1 Clade C Viruses that Impact Antibody Recognition: Implications for Active and Passive Immunization	journal.ppat.1005742	null	[ [ "The development of effective biomedical intervention strategies to prevent HIV-1 infection remains a global priority .", "To support these efforts , two large immunization trials in high incidence , clade C epidemic regions in southern Africa are imminent .", "The first , a Phase 3 efficacy trial usi...	[ "The development of biomedical interventions to reduce acquisition of HIV-1 infection remains a global priority , however their potential effectiveness is challenged by very high HIV-1 envelope diversity .", "Two large prophylactic trials in high incidence , clade C epidemic regions in southern Africa are imminen...	[ "Vaccine and passive immunization prophylactic trials that rely on antibody-mediated protection are planned for HIV-1 clade C epidemic regions of southern Africa , which have amongst the highest HIV-1 incidences globally .", "This includes a phase 2b trial of passively administered monoclonal antibody , VRC01; as...	2016
[ "Introduction", "Results", "Discussion", "Methods" ]	[]	De Novo ORFs in Drosophila Are Important to Organismal Fitness and Evolved Rapidly from Previously Non-coding Sequences	journal.pgen.1003860	null	[ [ "Most new genes arise from the duplication or rearrangement - in whole or in part - of existing genes [1] , [2] .", "These new genes are typically structurally and functionally similar to their progenitors .", "In contrast , protein-coding genes may also evolve de novo from previously non-coding seque...	[ "How non-coding DNA gives rise to new protein-coding genes ( de novo genes ) is not well understood .", "Recent work has revealed the origins and functions of a few de novo genes , but common principles governing the evolution or biological roles of these genes are unknown .", "To better define these principles...	[ "De novo genes are protein-coding genes with no clear homology to previously existing protein-coding genes .", "Since their discovery in Drosophila and other species including humans , their existence has been controversial , with some doubt as to how they would arise , whether they produce proteins , and whether...	2013
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "veterinary diseases", "veterinary epidemiology", "veterinary parasitology", "genetics", "biology", "evolutionary biology", "evolutionary genetics", "veterinary science" ]	A Novel qPCR Assay for the Detection of African Animal Trypanosomosis in Trypanotolerant and Trypanosusceptible Cattle Breeds	journal.pntd.0002345	null	[ [ "Trypanosomiasis affects both humans ( sleeping sickness ) and animals ( nagana ) and occurs in 37 sub-Saharan countries .", "Approximately 60 million people and about 50 million cattle are currently living in risk of infection [1] .", "The International Livestock Research Institute ( ILRI ) has liste...	[ "This study was conducted to", "( i ) determine the prevalence of African Animal Trypanosomosis ( AAT ) in tsetse challenged areas ,", "( ii ) compare conventional with qPCR detection systems and", "( iii ) evaluate the host genetic background and biology as risk factors .", "AAT prevalence studies are ofte...	[ "African Animal Trypanosomosis ( AAT ) is a neglected tropical disease heavily impacting on the poor .", "Sensitive diagnostic tools are needed since actual parasitaemia levels can be very low , particularly in chronically infected or trypanotolerant animals .", "Hence , we present a novel real-time PCR ( qPCR ...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	A Transposable Element within the Non-canonical Telomerase RNA of Arabidopsis thaliana Modulates Telomerase in Response to DNA Damage	journal.pgen.1005281	null	[ [ "The discovery of long noncoding RNA ( lncRNA ) has challenged the prevailing paradigm of protein-mediated regulation of gene expression and cell behavior .", "lncRNAs play essential roles in epigenetic regulation , stem cell biology and signal transduction and are emerging as key targets in human disease...	[ "Long noncoding RNAs ( lncRNAs ) have emerged as critical factors in many biological processes , but little is known about how their regulatory functions evolved .", "One of the best-studied lncRNAs is TER , the essential RNA template for telomerase reverse transcriptase .", "We previously showed that Arabidops...	[ "Telomerase is a highly regulated enzyme whose activity is essential for long-term cellular proliferation .", "In the presence of DNA double-strand breaks ( DSBs ) , telomerase activity must be curtailed to promote faithful DNA repair .", "We previously showed that the flowering plant Arabidopsis thaliana rapid...	2015
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "systems biology", "biochemistry", "signal transduction", "biochemical simulations", "computer and information sciences", "cell biology", "theoretical biology", "network analysis", "synthetic biology", "biology and life sciences", "regulatory networks", "signaling networks", "computational b...	Loads Bias Genetic and Signaling Switches in Synthetic and Natural Systems	journal.pcbi.1003533	null	[ [ "A longstanding question about signal transduction and gene transcription networks is how modular are they .", "Here modularity means relative insulation of small subgraphs or motifs of the main network from each other [1] .", "This question is especially relevant for synthetic biology that aims to bu...	[ "Biological protein interactions networks such as signal transduction or gene transcription networks are often treated as modular , allowing motifs to be analyzed in isolation from the rest of the network .", "Modularity is also a key assumption in synthetic biology , where it is similarly expected that when netw...	[ "Cells rely on complex networks of protein-protein interactions in order to carry out life functions .", "Scientists believe that these networks are organized in a modular fashion; that is they are made up of functionally distinct parts like an electronic circuit .", "Modularity implies that just as we put toge...	2014
[ "Introduction", "Results", "Discussion", "Material and methods" ]	[ "cell binding", "flow cytometry", "cell physiology", "medicine and health sciences", "immune physiology", "pathology and laboratory medicine", "pathogens", "immunology", "microbiology", "retroviruses", "viruses", "immunodeficiency viruses", "rna viruses", "glycoproteins", "antibodies", ...	CD4 occupancy triggers sequential pre-fusion conformational states of the HIV-1 envelope trimer with relevance for broadly neutralizing antibody activity	journal.pbio.3000114	Comprehensive mapping of conformational stages adopted by the HIV‐1 envelope glycoprotein trimer during entry into the cell reveals the preference of broadly neutralizing antibodies for distinct pre-fusion states of the trimer.	[ [ "Human immunodeficiency virus type 1 ( HIV-1 ) envelope glycoprotein ( Env ) trimers , composed of three gp41-gp120 heterodimers , initiate the virus entry process by binding to the primary receptor CD4 via a high-affinity binding site ( referred to as CD4bs ) on gp120 .", "CD4 engagement triggers conform...	[ "During the entry process , the human immunodeficiency virus type 1 ( HIV-1 ) envelope glycoprotein ( Env ) trimer undergoes a sequence of conformational changes triggered by both CD4 and coreceptor engagement .", "Resolving the conformation of these transient entry intermediates has proven challenging .", "Her...	[ "The trimeric human immunodeficiency virus type 1 ( HIV-1 ) envelope glycoprotein ( Env ) mediates HIV-1 entry into its target cells .", "Entry is initiated by sequential triggering of Env upon interaction with its primary receptor CD4 and a coreceptor on target cells .", "The ensuing structural rearrangements ...	2019
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biochemistry", "developmental biology", "base excision repair", "genomic imprinting", "gene expression", "genetics", "biology and life sciences", "dna", "dna repair", "dna modification", "epigenetics", "dna methylation" ]	An AP Endonuclease Functions in Active DNA Demethylation and Gene Imprinting in Arabidopsis	journal.pgen.1004905	null	[ [ "DNA methylation is a stable epigenetic mark that regulates numerous aspects of the genome , including transposon silencing and gene expression [1]–[7] .", "In plants , DNA methylation can occur within CG , CHG , and CHH motifs ( H represents A , T , or C ) .", "Genome-wide mapping of DNA methylation ...	[ "Active DNA demethylation in plants occurs through base excision repair , beginning with removal of methylated cytosine by the ROS1/DME subfamily of 5-methylcytosine DNA glycosylases .", "Active DNA demethylation in animals requires the DNA glycosylase TDG or MBD4 , which functions after oxidation or deamination ...	[ "DNA cytosine methylation ( 5-methylcytosine , 5-meC ) is an important epigenetic mark , and methylation patterns are coordinately controlled by methylation and demethylation reactions during development and reproduction .", "In plants , REPRESSOR OF SILENCING ( ROS1 ) is one of the well characterized 5-meC DNA g...	2015
[ "Introduction", "Model", "Results", "Discussion" ]	[ "neuroscience/theoretical neuroscience", "neuroscience/sensory systems", "computational biology/computational neuroscience" ]	Recognizing Sequences of Sequences	journal.pcbi.1000464	null	[ [ "Many aspects of our sensory environment can be described as dynamic sequences .", "For example , in the auditory domain , speech and music are sequences of sound-waves [1] , [2] , where speech can be described as a sequence of phonemes .", "Similarly , in the visual domain , speaking generates sequen...	[ "The brain's decoding of fast sensory streams is currently impossible to emulate , even approximately , with artificial agents .", "For example , robust speech recognition is relatively easy for humans but exceptionally difficult for artificial speech recognition systems .", "In this paper , we propose that rec...	[ "Despite tremendous advances in neuroscience , we cannot yet build machines that recognize the world as effortlessly as we do .", "One reason might be that there are computational approaches to recognition that have not yet been exploited .", "Here , we demonstrate that the ability to recognize temporal sequenc...	2009
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Using a Sequential Regimen to Eliminate Bacteria at Sublethal Antibiotic Dosages	journal.pbio.1002104	A laboratory treatment model shows that the sequentially alternating use of two antibiotics can be optimized to outperform combination treatments at the equivalent dose.	[ [ "Bacteria have a remarkable capacity to adapt and evolve .", "It is probably unsurprising in retrospect that resistance has developed to every antibiotic in clinical use [1] , with the genes responsible disseminated globally [2 , 3] .", "Antibiotic resistance , therefore , has the potential to become ...	[ "We need to find ways of enhancing the potency of existing antibiotics , and , with this in mind , we begin with an unusual question: how low can antibiotic dosages be and yet bacterial clearance still be observed ?", "Seeking to optimise the simultaneous use of two antibiotics , we use the minimal dose at which ...	[ "So-called “cocktail” treatments are often proposed as a way of enhancing the potency of antibiotics , based on the idea that multiple drugs can synergise when used together as part of a single combined therapy .", "We investigated whether any other multidrug deployment strategies are as effective as—or perhaps e...	2015
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "cell physiology", "biochemistry", "cell biology", "fungal genetics", "genetics", "microbial genetics", "biology and life sciences", "molecular genetics", "molecular cell biology" ]	Enhanced Longevity by Ibuprofen, Conserved in Multiple Species, Occurs in Yeast through Inhibition of Tryptophan Import	journal.pgen.1004860	null	[ [ "Levels of cellular and organismal dysfunction increase dramatically with old age .", "Aging is the greatest risk factor for numerous pathologies , including most forms of cancer , stroke , neurodegenerative disorders , heart disease and diabetes [1] .", "Hence , delaying aging therapeutically promise...	[ "The common non-steroidal anti-inflammatory drug ibuprofen has been associated with a reduced risk of some age-related pathologies .", "However , a general pro-longevity role for ibuprofen and its mechanistic basis remains unclear .", "Here we show that ibuprofen increased the lifespan of Saccharomyces cerevisi...	[ "Aging is the greatest risk factor for many diseases , which together account for the majority of global deaths and healthcare costs .", "Here we show that the common drug ibuprofen increases the lifespan of yeast , worms and flies , indicative of conserved longevity effects .", "In budding yeast , an excellent...	2014
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "medicine and health sciences", "toxins", "pathology and laboratory medicine", "molecular mass", "pichia pastoris", "tropical diseases", "vertebrates", "silver staining", "animals", "toxicology", "toxic agents", "fungi", "reptiles", "neglected tropical diseases", "glycoproteins", "gel ...	Heterologous expression of the antimyotoxic protein DM64 in Pichia pastoris	journal.pntd.0005829	null	[ [ "Accidents involving venomous snakes are medical emergencies that are often neglected in many tropical and subtropical countries [1] .", "Several epidemiological studies have tried to estimate the true burden of snakebite envenoming in the world .", "Overall , they have reported up to 5 million snake ...	[ "Snakebite envenomation is a neglected condition that constitutes a public health problem in tropical and subtropical countries , including Brazil .", "Interestingly , some animals are resistant to snake envenomation due to the presence of inhibitory glycoproteins in their serum that target toxic venom components...	[ "Snakebite envenomation causes medical emergencies that , depending on the species responsible for the bite , involve different organs and tissues .", "Envenomation by snakebite is a worldwide problem , and Brazil presents a high incidence of Bothrops bites .", "Bothrops venoms cause pathological alterations wi...	2017
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "helminth infections", "schistosomiasis", "plant science", "medicine and health sciences", "diagnostic medicine", "epidemiology", "disease surveillance", "plant pathology", "biology and life sciences", "tropical diseases", "neglected tropical diseases", "soil-transmitted helminthiases", "par...	Sensitivity and Specificity of Multiple Kato-Katz Thick Smears and a Circulating Cathodic Antigen Test for Schistosoma mansoni Diagnosis Pre- and Post-repeated-Praziquantel Treatment	journal.pntd.0003139	null	[ [ "Schistosomiasis remains a major public health concern despite praziquantel reaching over 30 million people in endemic areas in 2013 [1] .", "Goals to eliminate schistosomiasis by 2020 have been articulated by the World Health Organization's ( WHO ) ‘Roadmap for Neglected Tropical Disease ( NTD ) Implemen...	[ "Two Kato-Katz thick smears ( Kato-Katzs ) from a single stool are currently recommended for diagnosing Schistosoma mansoni infections to map areas for intervention .", "This ‘gold standard’ has low sensitivity at low infection intensities .", "The urine point-of-care circulating cathodic antigen test ( POC-CCA...	[ "Schistosomiasis is a parasitic disease infecting over 200 million people .", "It remains a major public health concern despite treatment of over 120 million people in sub-Saharan Africa alone .", "Accurate diagnostic methods are essential for monitoring drug efficacy and long-term control program success .", ...	2014
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "systems biology", "computer and information sciences", "network analysis", "biology and life sciences", "metabolic networks", "computerized simulations" ]	Likelihood-Based Gene Annotations for Gap Filling and Quality Assessment in Genome-Scale Metabolic Models	journal.pcbi.1003882	null	[ [ "Genome-scale metabolic models ( GEMs ) integrate available information about metabolism to provide a basis for holistic modeling and prediction of metabolic phenotypes [1] .", "GEMs have been utilized broadly [2] , [3] , [4] , [5] across all three domains of life [6] to accelerate research in such areas ...	[ "Genome-scale metabolic models provide a powerful means to harness information from genomes to deepen biological insights .", "With exponentially increasing sequencing capacity , there is an enormous need for automated reconstruction techniques that can provide more accurate models in a short time frame .", "Cu...	[ "Genome-scale metabolic modeling is a powerful approach that allows one to computationally simulate a variety of metabolic phenotypes .", "However , manually constructing accurate metabolic networks is extremely time intensive and it is thus desirable to have automated computational methods for providing high-qua...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "blood cells", "phosphorylation", "flow cytometry", "innate immune system", "medicine and health sciences", "immune cells", "immune physiology", "cytokines", "immunology", "cloning", "developmental biology", "molecular development", "molecular biology techniques", "cytotoxic t cells", "r...	The Ebola Interferon Inhibiting Domains Attenuate and Dysregulate Cell-Mediated Immune Responses	journal.ppat.1006031	null	[ [ "The 2013–2016 outbreak of Ebola virus ( EBOV ) in West Africa claimed the lives of 11 , 300 people [1] .", "EBOV infections are characterized by ‘immune paralysis’ , the profound immune deficiency resulting in uncontrolled viral replication [2] .", "A characteristic feature of EBOV infections is lymp...	[ "Ebola virus ( EBOV ) infections are characterized by deficient T-lymphocyte responses , T-lymphocyte apoptosis and lymphopenia .", "We previously showed that disabling of interferon-inhibiting domains ( IIDs ) in the VP24 and VP35 proteins effectively unblocks maturation of dendritic cells ( DCs ) and increases ...	[ "The extensive investigation of interferon antagonism mediated by Ebola virus ( EBOV ) over the last 16 years resulted in identification of two interferon inhibiting domains ( IIDs ) located in the VP24 and VP35 proteins of the virus and of multiple mechanisms by which the domains disable the innate immune system a...	2016
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "signal transduction", "molecular cell biology", "membrane receptor signaling", "biology", "biophysics simulations", "biophysics" ]	Structural Investigation of MscL Gating Using Experimental Data and Coarse Grained MD Simulations	journal.pcbi.1002683	null	[ [ "Mechanosensitive ion channels are ubiquitous membrane proteins that enable a cell to respond to deformation forces in the surrounding lipid bilayers or cytoskeleton .", "This process , known as mechanosensation , is thought to have evolved to protect bacterial cells from sudden osmotic shock [1] , [2] ."...	[ "The mechanosensitive channel of large conductance ( MscL ) has become a model system in which to understand mechanosensation , a process involved in osmoregulation and many other physiological functions .", "While a high resolution closed state structure is available , details of the open structure and the gatin...	[ "Cells in biological organisms have to be able to respond to mechanical forces during processes such as touch , hearing , pain sensation and tissue growth .", "One way this is achieved is through mechanosensitive ion channels , membrane embedded proteins that initiate electrical signalling upon tension within the...	2012
[ "Introduction", "Results/Discussion", "Methods" ]	[]	Computer Simulations Imply Forelimb-Dominated Underwater Flight in Plesiosaurs	journal.pcbi.1004605	null	[ [ "Plesiosaurians ( = plesiosaurs ) are an extinct group of highly derived predatory marine reptiles with a global distribution that spans 135 million years from the Early Jurassic to the Late Cretaceous .", "During their long evolutionary history [1] , plesiosaurs maintained a unique body plan with two pai...	[ "Plesiosaurians are an extinct group of highly derived Mesozoic marine reptiles with a global distribution that spans 135 million years from the Early Jurassic to the Late Cretaceous .", "During their long evolutionary history they maintained a unique body plan with two pairs of large wing-like flippers , but the...	[ "Plesiosaurs are an extinct group of Mesozoic marine reptiles with a global distribution that spans 135 million years .", "They maintained a unique body plan with two pairs of large wing-like flippers throughout their long evolutionary history , but how plesiosaurs swam has remained a topic of debate for almost 2...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biochemistry/replication and repair", "molecular biology", "immunology/immunity to infections", "virology/host antiviral responses" ]	Deaminase-Independent Inhibition of Parvoviruses by the APOBEC3A Cytidine Deaminase	journal.ppat.1000439	null	[ [ "Eukaryotes have evolved numerous innate immune defenses against invading pathogens .", "The apolipoprotein B mRNA-editing catalytic polypeptide-like 3 ( APOBEC3 ) proteins comprise a family of seven cytidine deaminases [1]–[4] that may each form distinct intrinsic barriers to endogenous retrotransposons ...	[ "The APOBEC3 proteins form a multigene family of cytidine deaminases with inhibitory activity against viruses and retrotransposons .", "In contrast to APOBEC3G ( A3G ) , APOBEC3A ( A3A ) has no effect on lentiviruses but dramatically inhibits replication of the parvovirus adeno-associated virus ( AAV ) .", "To ...	[ "The APOBEC3 proteins constitute a family of seven cytidine deaminases .", "Cytidine deaminases are editing enzymes able to remove the amine group from cytidine in single-strand DNA ( ssDNA ) and RNA , converting it to uracil .", "APOBEC3 proteins have potent antiviral activity against retroviruses , retrotrans...	2009
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "blood cells", "innate immune system", "medicine and health sciences", "glycosylamines", "immune cells", "immune physiology", "cytokines", "immunology", "parasitic diseases", "nematode infections", "developmental biology", "molecular development", "adenosine", "white blood cells", "anima...	CD39 and immune regulation in a chronic helminth infection: The puzzling case of Mansonella ozzardi	journal.pntd.0006327	null	[ [ "Helminth parasites induce a wide range of mechanisms that downregulate immunity , limiting host’s inflammation-mediated tissue damage and favoring parasites’ persistence in typically asymptomatic carriers [1 , 2] .", "Nearly 40 years ago , T cell proliferation responses to parasite-specific antigens , bu...	[ "Chronic helminth infections typically induce an immunoregulatory environment , with markedly reduced immune responses to both parasite-specific and unrelated bystander antigens .", "Here we tested whether these changes are also observed in human infections with Mansonella ozzardi , a neglected filarial nematode ...	[ "Helminth infections downregulate immunity and reduce host’s inflammatory responses , but the filarial nematode Mansonella ozzardi , which is widely distributed across Latin America , appears to represent an exception to this rule .", "We found similar lymphoproliferative responses to filarial and unrelated antig...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "mycology", "fungi", "adaptation", "natural selection", "speciation", "biology", "evolutionary biology", "hybridization", "microbiology", "evolutionary processes" ]	Genetic Architecture of a Reinforced, Postmating, Reproductive Isolation Barrier between Neurospora Species Indicates Evolution via Natural Selection	journal.pgen.1002204	null	[ [ "The geographical ranges of N . crassa and N . intermedia are broadly overlapping , and individuals of both species can be collected from the same site [15] , [17] , [18] .", "Both species are largely outbreeding , and outbreeding is confirmed by population genetic analysis [19]–[22] .", "Hybrids of t...	[ "A role for natural selection in reinforcing premating barriers is recognized , but selection for reinforcement of postmating barriers remains controversial .", "Organisms lacking evolvable premating barriers can theoretically reinforce postmating isolation , but only under restrictive conditions: parental invest...	[ "Although Darwin believed that natural selection could not drive intersterility between species , it is now well established that there is a role for natural selection in the evolution of premating discrimination that reinforces barriers to hybridization .", "However , natural selection for postmating barriers , ...	2011
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "molecular cell biology", "dna replication", "nucleic acids", "genetics", "molecular genetics", "biology", "dna", "dna repair", "nucleotides", "molecular biology", "genetics and genomics", "gene function" ]	Ixr1 Is Required for the Expression of the Ribonucleotide Reductase Rnr1 and Maintenance of dNTP Pools	journal.pgen.1002061	null	[ [ "Cells experiencing DNA damage or replication blocks activate stress response pathways , or checkpoints , that arrest the cell cycle and facilitate DNA repair .", "In budding yeast , the key checkpoint protein kinases are Mec1 ( homolog of human ATR ) and Rad53 ( homolog of CHK2 and functional homolog of ...	[ "The Saccharomyces cerevisiae Dun1 protein kinase is a downstream target of the conserved Mec1-Rad53 checkpoint pathway .", "Dun1 regulates dNTP pools during an unperturbed cell cycle and after DNA damage by modulating the activity of ribonucleotide reductase ( RNR ) by multiple mechanisms , including phosphoryla...	[ "Dun1 is a non-essential protein kinase important for the maintenance of genome stability in budding yeast .", "Earlier studies found that simultaneous deletion of DUN1 and IXR1 results in lethality , but the reason for this so-called synthetic lethality is not clear .", "Ixr1 is implicated in DNA repair based ...	2011
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "molecular cell biology", "membranes and sorting", "biology" ]	Determinants of GPI-PLC Localisation to the Flagellum and Access to GPI-Anchored Substrates in Trypanosomes	journal.ppat.1003566	null	[ [ "The external cell surface of the mammalian bloodstream form of African trypanosomes is covered with a densely packed protein coat predominantly composed of a single polypeptide species , the variant surface glycoprotein ( VSG ) [1] , [2] .", "The VSG is central to the interaction with the host: it functi...	[ "In Trypanosoma brucei , glycosylphosphatidylinositol phospholipase C ( GPI-PLC ) is a virulence factor that releases variant surface glycoprotein ( VSG ) from dying cells .", "In live cells , GPI-PLC is localised to the plasma membrane where it is concentrated on the flagellar membrane , so activity or access mu...	[ "African trypanosomes are unicellular parasites with a single flagellum that maintain a persistent infection through antigenic variation based on changes in a densely packed cell surface coat of variant surface glycoprotein ( VSG ) .", "The cells also contain an enzyme , GPI-PLC , able to shed the VSG from the ce...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine and health sciences", "crystal structure", "pathology and laboratory medicine", "enzymes", "pathogens", "condensed matter physics", "microbiology", "enzymology", "staphylococcus aureus", "petroleum products", "methicillin-resistant staphylococcus aureus", "antibiotic resistance", "...	Structure and Mechanism of Staphylococcus aureus TarS, the Wall Teichoic Acid β-glycosyltransferase Involved in Methicillin Resistance	journal.ppat.1006067	null	[ [ "Methicillin-Resistant Staphylococcus aureus ( MRSA ) is a leading cause of life-threatening nosocomial infections including pneumonia , bacteremia , and surgical wound infections [1] .", "Due to wide-spread β-lactam antibiotic resistance , the first-line treatment for serious MRSA infections has been van...	[ "In recent years , there has been a growing interest in teichoic acids as targets for antibiotic drug design against major clinical pathogens such as Staphylococcus aureus , reflecting the disquieting increase in antibiotic resistance and the historical success of bacterial cell wall components as drug targets .", ...	[ "Historically , β-lactam class antibiotics such as methicillin have been very successful in the treatment of bacterial infections , effectively destroying bacteria by rupturing their cell walls while posing little harm to the human organism .", "In recent years , however , the alarming emergence of Methicillin Re...	2016
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "guinea", "medicine and health sciences", "ecology and environmental sciences", "tropical diseases", "geographical locations", "uganda", "bacterial diseases", "aquatic environments", "bodies of water", "neglected tropical diseases", "africa", "togo", "infectious diseases", "cholera", "la...	Cholera Incidence and Mortality in Sub-Saharan African Sites during Multi-country Surveillance	journal.pntd.0004679	null	[ [ "Although cholera has disappeared as a public-health problem in developed countries , it remains a major concern in sub-Sahara Africa [1 , 2] .", "From 2007 to 2012 , at least 20 African countries reported more than 100 , 000 cases of cholera ( World Health Organization ( WHO ) weekly epidemiological reco...	[ "Cholera burden in Africa remains unknown , often because of weak national surveillance systems .", "We analyzed data from the African Cholera Surveillance Network ( www . africhol . org ) .", "During June 2011–December 2013 , we conducted enhanced surveillance in seven zones and four outbreak sites in Togo , t...	[ "Cholera burden in Africa remains unknown , often because of weak national surveillance systems .", "Reporting is non-exhaustive for various reasons , such as individual and community fears of stigmatization and economic loss .", "Furthermore , only 3% to 5% of all cases are laboratory confirmed .", "A variet...	2016
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "medicine and health sciences", "pathology and laboratory medicine", "enzymes", "pathogens", "immunology", "enzymology", "plant physiology", "ubiquitin ligases", "plant science", "plant pathology", "ligases", "proteins", "gene expression", "proteasomes", "immune response", "biochemistr...	Proteasome-associated HECT-type ubiquitin ligase activity is required for plant immunity	journal.ppat.1007447	null	[ [ "The ubiquitin-26S proteasome system ( UPS ) plays an essential cellular role in selective degradation of proteins that are short-lived or damaged .", "Degradation of proteins is mediated by an enzymatic cascade in which a small and highly conserved ubiquitin molecule is covalently attached to the substra...	[ "Regulated degradation of proteins by the 26S proteasome plays important roles in maintenance and signalling in eukaryotic cells .", "Proteins are marked for degradation by the action of E3 ligases that site-specifically modify their substrates by adding chains of ubiquitin .", "Innate immune signalling in plan...	[ "Plants are continuously exposed to different disease agents , including bacteria , fungi , oomycetes and chewing or sucking insects .", "To protect themselves plants have evolved a sophisticated multi-layered immune system that depends on the reprogramming of large gene repertoires to prioritize the expression o...	2018
[ "Introduction", "Results", "Discussion", "Methods" ]	[]	Heterogeneous Network Edge Prediction: A Data Integration Approach to Prioritize Disease-Associated Genes	journal.pcbi.1004259	null	[ [ "In the last decade , genome-wide association studies ( GWAS ) have been established as the main strategy to map genetic susceptibility in dozens of complex diseases and phenotypes .", "Despite the success of this approach in mapping variation in thousands of loci to hundreds of complex phenotypes [1–5] ,...	[ "The first decade of Genome Wide Association Studies ( GWAS ) has uncovered a wealth of disease-associated variants .", "Two important derivations will be the translation of this information into a multiscale understanding of pathogenic variants and leveraging existing data to increase the power of existing and f...	[ "For complex human diseases , identifying the genes harboring susceptibility variants has taken on medical importance .", "Disease-associated genes provide clues for elucidating disease etiology , predicting disease risk , and highlighting therapeutic targets .", "Here , we develop a method to predict whether a...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "evolutionary biology", "microbiology/innate immunity" ]	Effective but Costly, Evolved Mechanisms of Defense against a Virulent Opportunistic Pathogen in Drosophila melanogaster	journal.ppat.1000385	null	[ [ "It costs insects to invest in immunity .", "Highly immune Drosophila mate less and produce fewer offspring [1] , [2] , more immune bee colonies are less productive [3] , and crickets with heightened immunity exhibit reduced sexual displays and longevity [4] .", "Recently , it has been shown that reso...	[ "Drosophila harbor substantial genetic variation for antibacterial defense , and investment in immunity is thought to involve a costly trade-off with life history traits , including development , life span , and reproduction .", "To understand the way in which insects invest in fighting bacterial infection , we s...	[ "The fruit fly is commonly used as a model organism to understand the mechanistic nature of the immune response to bacterial pathogens .", "The fly is also commonly used to understand what immunity costs hosts in terms of other traits such as life span and reproductive success .", "Here , we examine these two q...	2009
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine", "neurobiology of disease and regeneration", "neural networks", "neuroscience", "mathematics", "computational neuroscience", "alzheimer disease", "biology", "dementia", "nonlinear dynamics", "central nervous system", "neurological disorders", "neurology", "neurophysiology" ]	Activity Dependent Degeneration Explains Hub Vulnerability in Alzheimer's Disease	journal.pcbi.1002582	null	[ [ "Like many other complex networks , the human brain contains parts that are better connected to the rest than others: ‘hub’ regions .", "Evidence is increasing that a collection of brain hub regions forms a ‘structural core’ or ‘connectivity backbone’ that facilitates cognitive processing [1] , [2] , [3] ...	[ "Brain connectivity studies have revealed that highly connected ‘hub’ regions are particularly vulnerable to Alzheimer pathology: they show marked amyloid-β deposition at an early stage .", "Recently , excessive local neuronal activity has been shown to increase amyloid deposition .", "In this study we use a co...	[ "An intriguing recent observation is that deposition of the amyloid-β protein , one of the hallmarks of Alzheimer's disease , mainly occurs in brain regions that are highly connected to other regions .", "To test the hypothesis that these ‘hub’ regions are more vulnerable due to a higher neuronal activity level ,...	2012
[ "Introduction", "Methods", "Results", "Discussion" ]	[]	Prophylactic TLR9 stimulation reduces brain metastasis through microglia activation	journal.pbio.2006859	null	[ [ "Ten to twenty percent of cancer patients develop brain metastases , commonly as the final stage of cancer progression , with lung and melanoma cancers having the highest incidence ( 40%–50% and 30%–50% , respectively ) [1] .", "Therapies include surgery and radiation; however , both treatments result in ...	[ "Brain metastases are prevalent in various types of cancer and are often terminal , given the low efficacy of available therapies .", "Therefore , preventing them is of utmost clinical relevance , and prophylactic treatments are perhaps the most efficient strategy .", "Here , we show that systemic prophylactic ...	[ "Brain metastases are prevalent and often terminal .", "Thus , reducing their occurrence could markedly improve cancer outcome .", "We show that systemic prophylactic and perioperative administration of a TLR9 agonist , CpG-C , reduced metastatic growth in experimental and spontaneous brain metastasis models , ...	2019
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "medicine", "infectious diseases", "west nile fever", "viral diseases" ]	Dynamics of West Nile Virus Persistence in House Sparrows (Passer domesticus)	journal.pntd.0001860	null	[ [ "West Nile virus ( WNV; Flaviviridae: Flavivirus ) is a relatively new arbovirus in the Western Hemisphere that has been detected each year [1] since its introduction into New York , NY in 1999 .", "West Nile virus is an enveloped , single-stranded RNA virus [2] that is primarily transmitted in an enzooti...	[ "West Nile Virus ( WNV ) is now endemic throughout North America , with annual recurrence dependent upon successful overwintering when cold temperatures drive mosquito vectors into inactivity and halt transmission .", "To investigate whether avian hosts may serve as an overwintering mechanism , groups of eight to...	[ "House Sparrows experimentally infected with West Nile virus [WNV] were necropsied at multiple time points from 3 to 18 weeks post infection ( pi ) .", "The percent of birds with tissues positive for WNV RNA decreased from 100% at 3 wks to 13% at 18 wks pi; infectious virus was recovered from some birds by tissue...	2012
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "medicine", "public health and epidemiology", "science policy and economics", "applied mathematics", "parasitic diseases", "preventive medicine", "mathematics", "cost-benefit analysis", "neglected tropical diseases", "urologic infections", "infectious diseases", "disease ecology", "infectiou...	Projecting the Long-Term Impact of School- or Community-Based Mass-Treatment Interventions for Control of Schistosoma Infection	journal.pntd.0001903	null	[ [ "Schistosomiasis is an environmentally transmitted parasitic disease that results in increased morbidity and mortality among millions of people living in tropical and subtropical regions [1]–[3] .", "Different control initiatives have had success in reducing either the prevalence or the mean intensity of ...	[ "Schistosomiasis remains a significant health burden in many areas of the world .", "Morbidity control , focused on limiting infection intensity through periodic delivery of anti-schistosomal medicines , is the thrust of current World Health Organization guidelines ( 2006 ) for reduction of Schistosoma-related di...	[ "Debate persists about how best to prevent disease caused by Schistosoma parasites .", "Current guidelines focus on suppressing morbidity by limiting average intensity of infection during childhood .", "However , this may not be sufficient to cure infection or prevent reinfection , leaving risk for sub-clinical...	2012

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