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headings list	keywords list	title stringlengths 20 281	id stringlengths 20 20	toc stringlengths 57 522 ⌀	sections list	abstract list	summary list	year stringclasses 13 values
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "3' utr", "nucleases", "gene regulation", "293t cells", "enzymes", "messenger rna", "biological cultures", "microbiology", "dna-binding proteins", "enzymology", "rna stem-loop structure", "virus effects on host gene expression", "untranslated regions", "research and analysis methods", "s...	Nuclease escape elements protect messenger RNA against cleavage by multiple viral endonucleases	journal.ppat.1006593	null	[ [ "A number of viruses restrict host gene expression to reduce competition for resources and dampen immune responses .", "This ‘host shutoff’ phenotype can be triggered through a range of mechanisms that operate at nearly every stage of the gene expression cascade .", "Viruses whose host shutoff strateg...	[ "During lytic Kaposi’s sarcoma-associated herpesvirus ( KSHV ) infection , the viral endonu- clease SOX promotes widespread degradation of cytoplasmic messenger RNA ( mRNA ) .", "However , select mRNAs , including the transcript encoding interleukin-6 ( IL-6 ) , escape SOX-induced cleavage .", "IL-6 escape is m...	[ "The ability of viruses to control the host gene expression environment is crucial to promote viral infection .", "Many viruses express factors that reduce host gene expression through widespread mRNA decay .", "However , some mRNAs escape this fate , like the transcript encoding the immunoregulatory cytokine I...	2017
[ "Results", "Discussion" ]	[ "bacteriology", "biofilms", "cell motility", "swimming", "medicine and health sciences", "cell cycle and cell division", "cell processes", "microbiology", "biological locomotion", "biomechanics", "simulation and modeling", "systems science", "mathematics", "research and analysis methods", ...	Quorum Sensing Desynchronization Leads to Bimodality and Patterned Behaviors	journal.pcbi.1004781	null	[ [ "In order to simulate population scale phenomena , we employed a mix of two methodologies ( a comprehensive set of ODEs simulating batch cultures and a 2D agent based approach , see Model section ) .", "First , ODEs were developed to reflect the trends of Lsr activation seen experimentally in batch cultur...	[ "Quorum Sensing ( QS ) drives coordinated phenotypic outcomes among bacterial populations .", "Its role in mediating infectious disease has led to the elucidation of numerous autoinducers and their corresponding QS signaling pathways .", "Among them , the Lsr ( LuxS-regulated ) QS system is conserved in scores ...	[ "Bacterial behavior is responsive to a multitude of soluble molecular cues .", "Among them are self-secreted autoinducers that control quorum sensing ( QS ) processes .", "While new quorum sensing systems are constantly being discovered , several systems have been well defined in terms of their molecular and ge...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "model organisms", "biology", "neuroscience" ]	Loss of Axonal Mitochondria Promotes Tau-Mediated Neurodegeneration and Alzheimer's Disease–Related Tau Phosphorylation Via PAR-1	journal.pgen.1002918	null	[ [ "Mitochondria are principal mediators of local ATP supply and Ca2+ buffering .", "In neuronal axons , these requirements need to be addressed locally , and the proper distribution of mitochondria is essential for neuronal functions and survival [1] .", "Defects in mitochondrial distribution have been ...	[ "Abnormal phosphorylation and toxicity of a microtubule-associated protein tau are involved in the pathogenesis of Alzheimer's disease ( AD ) ; however , what pathological conditions trigger tau abnormality in AD is not fully understood .", "A reduction in the number of mitochondria in the axon has been implicate...	[ "Abnormal phosphorylation and toxicity of a microtubule-associated protein tau are involved in the pathogenesis of Alzheimer's disease ( AD ) .", "Tau is phosphorylated at multiple sites , and phosphorylation of tau regulates its microtubule binding and physiological functions such as regulation of microtubule st...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine", "research funding", "non-clinical medicine", "science policy", "public health", "research assessment" ]	Nonindustry-Sponsored Preclinical Studies on Statins Yield Greater Efficacy Estimates Than Industry-Sponsored Studies: A Meta-Analysis	journal.pbio.1001770	This study by Lisa Bero and colleagues uses published preclinical statin research to show that nonindustry-funded animal studies yield more efficacious drug results than do industry-funded ones.	[ [ "Preclinical studies are performed to evaluate a drug's efficacy in animal models [1] .", "In addition , the results from animal studies are a critical—and often the only—input to evaluating potential toxicity of drugs before they proceed to human testing .", "Minimizing bias in the design , conduct ,...	[ "Industry-sponsored clinical drug studies are associated with publication of outcomes that favor the sponsor , even when controlling for potential bias in the methods used .", "However , the influence of sponsorship bias has not been examined in preclinical animal studies .", "We performed a meta-analysis of pr...	[ "Industry-sponsored clinical drug studies are associated with publication of outcomes that favor the sponsor , even when controlling for potential bias in the methods used .", "However , the influence of sponsorship bias has not been examined in preclinical animal studies .", "We performed a meta-analysis to id...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "parallel evolution", "organismal evolution", "forms of evolution", "animal evolution", "convergent evolution", "biology", "evolutionary biology", "evolutionary genetics" ]	Parallel Evolution of Auditory Genes for Echolocation in Bats and Toothed Whales	journal.pgen.1002788	null	[ [ "The ability of echolocation using ultrahigh frequency sounds occurs in two groups of bats ( Yangochiroptera and Rhinolophoidea ) and in toothed whales including dolphins [1]–[3] .", "These mammals use this complex bio-sonar system to assist with orientation and feeding [4] , [5] .", "Echolocation by ...	[ "The ability of bats and toothed whales to echolocate is a remarkable case of convergent evolution .", "Previous genetic studies have documented parallel evolution of nucleotide sequences in Prestin and KCNQ4 , both of which are associated with voltage motility during the cochlear amplification of signals .", "...	[ "The convergent origins of laryngeal echolocation in two groups of bats ( Yangochiroptera and Rhinolophoidea ) and toothed whales have long been a focus of interest for biologists .", "We screened three candidate genes—Cdh23 , Pcdh15 , and Otof—involved in different steps in the echolocation system .", "Signals...	2012
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "blood cells", "medicine and health sciences", "immune cells", "body fluids", "immune physiology", "pathology and laboratory medicine", "spleen", "pathogens", "immunology", "microbiology", "cloning", "retroviruses", "viruses", "immunodeficiency viruses", "rna viruses", "cytotoxic t cel...	Collapse of Cytolytic Potential in SIV-Specific CD8+ T Cells Following Acute SIV Infection in Rhesus Macaques	journal.ppat.1006135	null	[ [ "While it is clear that CD8+ T cells are a critical component of the host immune response to human immunodeficiency virus ( HIV ) and simian immunodeficiency virus ( SIV ) control , these cells only rarely fully control virus replication ( i . e . , elite controllers ) [1–3] .", "The reasons why CD8+ T ce...	[ "Poor maintenance of cytotoxic factor expression among HIV-specific CD8+ T cells , in part caused by dysregulated expression of the transcription factor T-bet , is associated with HIV disease progression .", "However , the precise evolution and context in which CD8+ T cell cytotoxic functions become dysregulated ...	[ "The underlying reasons why HIV avoids immune-mediated clearance and establishes chronic infection remain undefined .", "Poor cytotoxic CD8+ T cell ( CTL ) killing functions and localization of CD8+ T cells to critical anatomical sites associated with virus replication and reservoir have been described during chr...	2016
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[]	Exploring the Trypanosoma brucei Hsp83 Potential as a Target for Structure Guided Drug Design	journal.pntd.0002492	null	[ [ "Human African trypanosomiasis ( HAT ) , better known as sleeping sickness is a vector-borne disease present in sub-Saharan Africa , transmitted by Glossina tsetse flies and caused by the protozoan parasite Trypanosoma brucei [1] .", "Two subspecies of this kinetoplastid parasite cause disease in humans a...	[ "Human African trypanosomiasis is a neglected parasitic disease that is fatal if untreated .", "The current drugs available to eliminate the causative agent Trypanosoma brucei have multiple liabilities , including toxicity , increasing problems due to treatment failure and limited efficacy .", "There are two ap...	[ "Sleeping sickness , or human African trypanosomiasis ( HAT ) , is a deadly neglected disease for which new therapeutic options are badly needed .", "Current drugs have several liabilities including toxicity and route of administration limiting their efficacy to combat the disease .", "Our study aimed at valida...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods", "Supporting Information" ]	[ "infectious diseases", "pathology", "immunology", "microbiology", "mus (mouse)", "eubacteria" ]	Analysis of Cells Targeted by Salmonella Type III Secretion In Vivo	journal.ppat.0030196	null	[ [ "The innate and adaptive immune systems of the host present a formidable barrier to infection .", "To overcome the multi-faceted defenses , microbial pathogens have evolved equally complex mechanisms that are only partially understood .", "One of these mechanisms is the type III secretion system ( TTS...	[ "The type III secretion systems ( TTSS ) encoded in Salmonella pathogenicity island-1 and -2 ( SPI-1 and -2 ) are virulence factors required for specific phases of Salmonella infection in animal hosts .", "However , the host cell types targeted by the TTSS have not been determined .", "To investigate this , we ...	[ "Bacteria of the Salmonella genus are important human pathogens and a leading cause of food-borne illness .", "Salmonella species' ability to cause disease relies on the activities of two sophisticated molecular syringes that allow the bacteria to pump proteins into cells that they infect .", "The activities of...	2007
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[]	Pilot Field Trial of the EG95 Vaccine Against Ovine Cystic Echinococcosis in Rio Negro, Argentina: Second Study of Impact	journal.pntd.0004134	null	[ [ "Cystic echinococcosis ( CE ) is a zoonosis present worldwide produced by Echinococcus granulosus ( EG ) .", "As the most common intermediate hosts ( sheep and goats ) that develop cysts in liver and lung [1] [2] , human may be infected and develop cysts in the same organs .", "The dog is the definiti...	[ "Cystic echinococcosis ( CE ) is an important zoonotic disease caused by the cestode parasite Echinococcus granulosus .", "It occurs in many parts of the world where pastoral activities predominate , including the Rio Negro province of Argentina .", "Although CE control activities have been undertaken in the we...	[ "Hydatid disease , otherwise known as cystic echinococcosis ( CE ) , is caused by Echinococcus granulosus .", "The disease is common in many pastoral areas , including parts of the Rio Negro province of Argentina , and is formally recognised by the WHO as a Neglected Tropical Disease .", "We undertook the first...	2015
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "biophysics/transcription and translation", "biophysics/theory and simulation", "computational biology/transcriptional regulation" ]	Effect of Promoter Architecture on the Cell-to-Cell Variability in Gene Expression	journal.pcbi.1001100	null	[ [ "A fundamental property of all living organisms is their ability to gather information about their environment and adjust their internal physiological state in response to environmental conditions .", "This property , shared by all organisms , includes the ability of single-cells to respond to changes in ...	[ "According to recent experimental evidence , promoter architecture , defined by the number , strength and regulatory role of the operators that control transcription , plays a major role in determining the level of cell-to-cell variability in gene expression .", "These quantitative experiments call for a correspo...	[ "Stochastic chemical kinetics provides a framework for modeling gene regulation at the single-cell level .", "Using this framework , we systematically investigate the effect of promoter architecture , that is , the number , quality and position of transcription factor binding sites , on cell-to-cell variability i...	2011
[ "Introduction", "Methods", "Discussion", "Conclusion" ]	[ "medicine and health sciences", "epidemiology of aging", "engineering and technology", "applied mathematics", "simulation and modeling", "algorithms", "electrocardiography", "mathematics", "bioassays and physiological analysis", "cardiology", "research and analysis methods", "arrhythmia", "a...	Novel non-invasive algorithm to identify the origins of re-entry and ectopic foci in the atria from 64-lead ECGs: A computational study	journal.pcbi.1005270	null	[ [ "Atrial tachy-arrhythmias , including atrial fibrillation ( AF ) , atrial tachycardia ( AT ) and flutter ( AFL ) , are the most common cardiac arrhythmias , predisposing to heart attack , stroke and even possible cardiac death [1 , 2] .", "All three are characterised by rapid and irregular electrical acti...	[ "Atrial tachy-arrhytmias , such as atrial fibrillation ( AF ) , are characterised by irregular electrical activity in the atria , generally associated with erratic excitation underlain by re-entrant scroll waves , fibrillatory conduction of multiple wavelets or rapid focal activity .", "Epidemiological studies ha...	[ "Atrial tachy-arrhythmias are associated with irregular excitation waves arising from re-entrant excitation , multiple wavelets or rapid focal activity .", "Identifying the origin of the irregular activity may be vital for diagnosis and treatment of the disorder .", "Where invasive and non-invasive methods prov...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genetics and genomics/gene expression", "molecular biology/transcription initiation and activation", "genetics and genomics/functional genomics" ]	Genome-Wide and Phase-Specific DNA-Binding Rhythms of BMAL1 Control Circadian Output Functions in Mouse Liver	journal.pbio.1000595	Temporal mapping during a circadian day of binding sites for the BMAL1 transcription factor in mouse liver reveals genome-wide daily rhythms in DNA binding and uncovers output functions that are controlled by the circadian oscillator.	[ [ "Circadian clocks provide higher organisms with cell-autonomous and organ-based metronomes that control temporally gated and tissue-specific gene expression or metabolic programs [1]–[4] .", "In the liver , such programs have been implicated in detoxification [5] , glucose homeostasis [6] , [7] , choleste...	[ "The mammalian circadian clock uses interlocked negative feedback loops in which the heterodimeric basic helix-loop-helix transcription factor BMAL1/CLOCK is a master regulator .", "While there is prominent control of liver functions by the circadian clock , the detailed links between circadian regulators and dow...	[ "The circadian clock is a timing system that allows organisms to keep behavioral , physiological , and cellular rhythms in resonance with daily environmental cycles .", "In mammals , such clocks use transcriptional regulatory loops in which the heterodimeric transcription factor BMAL1/CLOCK plays a central role ....	2011
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biology" ]	Visualization and Measurement of ATP Levels in Living Cells Replicating Hepatitis C Virus Genome RNA	journal.ppat.1002561	null	[ [ "Adenosine 5′-triphosphate ( ATP ) is the major energy currency of cells and is involved in a variety of cellular processes , including the virus life cycle , in which ATP-dependent reactions essential for virus multiplication are catalyzed by viral-encoded enzymes or complexes consisting of viral and host-ce...	[ "Adenosine 5′-triphosphate ( ATP ) is the primary energy currency of all living organisms and participates in a variety of cellular processes .", "Although ATP requirements during viral lifecycles have been examined in a number of studies , a method by which ATP production can be monitored in real-time , and by w...	[ "ATP is the major energy currency of living cells .", "Replication of the virus genome is a physiological mechanism that is known to require energy for operations such as the synthesis of DNA or RNA and their unwinding .", "However , it has been difficult to comprehend how the ATP level is regulated inside sing...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "immunology/immune response", "immunology/innate immunity", "immunology", "immunology/immunity to infections", "immunology/leukocyte activation" ]	Role of PKR and Type I IFNs in Viral Control during Primary and Secondary Infection	journal.ppat.1000966	null	[ [ "Innate immunity constitutes the first line of anti-microbial host defense and plays an important role in controlling the spread of pathogens , before the onset of adaptive immunity [1] .", "Innate immunity depends on immune cells such as macrophages , natural killer ( NK ) cells , dendritic cells ( DCs )...	[ "Type I interferons ( IFNs ) are known to mediate viral control , and also promote survival and expansion of virus-specific CD8+ T cells .", "However , it is unclear whether signaling cascades involved in eliciting these diverse cellular effects are also distinct .", "One of the best-characterized anti-viral si...	[ "Type I interferons ( IFNs ) constitute the first line of defense against viral infections , promote antigen presentation by dendritic cells , and play a crucial role in directly stimulating anti-viral T cell responses .", "However , the mechanisms underlying the diverse cellular effects of Type I IFNs are not we...	2010
[ "Introduction", "Results/Discussion", "Materials and Methods" ]	[ "evolutionary biology/microbial evolution and genomics", "microbiology/medical microbiology", "evolutionary biology/evolutionary and comparative genetics" ]	Organised Genome Dynamics in the Escherichia coli Species Results in Highly Diverse Adaptive Paths	journal.pgen.1000344	null	[ [ "Escherichia coli was brought into laboratories almost a century ago to become one of the most important model organisms and by far the best-studied prokaryote .", "Major findings in phage genetics , bacterial conjugation , recombination , genetic regulation and chromosome replication involved the use of ...	[ "The Escherichia coli species represents one of the best-studied model organisms , but also encompasses a variety of commensal and pathogenic strains that diversify by high rates of genetic change .", "We uniformly ( re- ) annotated the genomes of 20 commensal and pathogenic E . coli strains and one strain of E ....	[ "Although abundant knowledge has been accumulated regarding the E . coli laboratory strain K-12 , little is known about the evolutionary trajectories that have driven the high diversity observed among natural isolates of the species , which encompass both commensal and highly virulent intestinal and extraintestinal...	2009
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "neuroscience/neuronal signaling mechanisms", "neuroscience/animal cognition", "neuroscience/cognitive neuroscience" ]	Dynamic Grouping of Hippocampal Neural Activity During Cognitive Control of Two Spatial Frames	journal.pbio.1000403	Hippocampal neurons represent two concurrent streams of spatial information by transiently organizing into subpopulations of coactive neurons and can reflect the most behaviorally relevant information at any given time.	[ [ "At every moment the mammalian brain is confronted with a multitude of sensory stimuli having varying degrees of behavioral relevance and must select from multiple potential responses the ones that are appropriate for the circumstances .", "The ability to coordinate the processing and use of multiple info...	[ "Cognitive control is the ability to coordinate multiple streams of information to prevent confusion and select appropriate behavioral responses , especially when presented with competing alternatives .", "Despite its theoretical and clinical significance , the neural mechanisms of cognitive control are poorly un...	[ "Understanding the world and making optimal decisions requires using the most relevant information while at the same time ignoring irrelevant information , a psychological phenomenon known as “cognitive control . ”", "How the same population of neurons deals with multiple streams of information simultaneously is ...	2010
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "medicine", "infectious diseases", "mosquitoes", "neglected tropical diseases", "viral diseases", "vectors and hosts", "infectious disease modeling", "japanese encephalitis" ]	Ecological Niche Modeling to Estimate the Distribution of Japanese Encephalitis Virus in Asia	journal.pntd.0001678	null	[ [ "Japanese encephalitis virus ( JEV ) , the causative agent of Japanese encephalitis ( JE ) , is an arbovirus that belongs to the family Flaviviridae and is endemic to Southeast and Northeast Asia , the Pacific Islands , and northern Australia ( Figure 1 ) [1] .", "The primary vector of JEV is Culex tritae...	[ "Culex tritaeniorhynchus is the primary vector of Japanese encephalitis virus ( JEV ) , a leading cause of encephalitis in Asia .", "JEV is transmitted in an enzootic cycle involving large wading birds as the reservoirs and swine as amplifying hosts .", "The development of a JEV vaccine reduced the number of JE...	[ "Japanese encephalitis virus ( JEV ) is transmitted predominately by the mosquito , Culex tritaeniorhynchus .", "The primary reservoirs of the virus are wading birds , with swine serving as amplifying hosts .", "Despite the development of a JEV vaccine , people remain unvaccinated in endemic countries and are s...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Functional Interplay between Type I and II Interferons Is Essential to Limit Influenza A Virus-Induced Tissue Inflammation	journal.ppat.1005378	null	[ [ "Influenza A virus ( IAV ) is a leading cause of respiratory infection and an ongoing threat to global health .", "Host clearance of IAV , which infects primarily airway epithelial cells , requires the development of both innate and adaptive immune responses [1 , 2] .", "Interestingly , recent studies...	[ "Host control of influenza A virus ( IAV ) is associated with exuberant pulmonary inflammation characterized by the influx of myeloid cells and production of proinflammatory cytokines including interferons ( IFNs ) .", "It is unclear , however , how the immune system clears the virus without causing lethal immuno...	[ "Influenza A virus ( IAV ) is a leading cause of respiratory infection and induces a strong acute inflammation manifested by the recruitment of monocytes and neutrophils as well as the production of proinflammatory cytokines in infected lungs .", "The interferons ( IFNs ) are strongly induced by IAV and are known...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "animal models", "caenorhabditis elegans", "animal genetics", "model organisms", "gene identification and analysis", "genetics", "gene regulation", "molecular genetics", "biology", "gene expression", "genetics and genomics", "gene function" ]	Genes That Act Downstream of Sensory Neurons to Influence Longevity, Dauer Formation, and Pathogen Responses in Caenorhabditis elegans	journal.pgen.1003133	null	[ [ "Organisms are constantly interacting with their environment .", "Behavioral responses as well as physiological processes such as energy homeostasis , development and immune homeostasis need to be modulated depending on the environmental situation .", "For example , an animal's feeding and development...	[ "The sensory systems of multicellular organisms are designed to provide information about the environment and thus elicit appropriate changes in physiology and behavior .", "In the nematode Caenorhabditis elegans , sensory neurons affect the decision to arrest during development in a diapause state , the dauer la...	[ "The senses provide animals with information about their environment , which affects not only their behavior but also their internal state and physiological outputs .", "How this information is processed is still unclear .", "In this study , we used mutant C . elegans roundworms that had defective sensory neuro...	2012
[ "Introduction", "Results/Discussion", "Methods" ]	[ "biochemistry/molecular evolution", "biochemistry/bioinformatics" ]	An Atlas of the Thioredoxin Fold Class Reveals the Complexity of Function-Enabling Adaptations	journal.pcbi.1000541	null	[ [ "It has been established that protein structures incorporate new variations on an ancestral fold in evolving diverse functions [1] .", "Domains recombine in modular units , are decorated with insertions and extensions of loops and secondary structure elements [2] , and sometimes they drift [3] .", "Ho...	[ "The group of proteins that contain a thioredoxin ( Trx ) fold is huge and diverse .", "Assessment of the variation in catalytic machinery of Trx fold proteins is essential in providing a foundation for understanding their functional diversity and predicting the function of the many uncharacterized members of the...	[ "For any large class of proteins , far more protein sequences are known than can be examined experimentally .", "This is the case with the thioredoxin fold class , a large and diverse collection of proteins , some of which are known to catalyze important steps in metabolism .", "Some others participate in key p...	2009
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "biotechnology", "bioengineering", "biological systems engineering", "computer science", "computer modeling", "biology", "computational biology", "computerized simulations", "engineering" ]	Tension and Robustness in Multitasking Cellular Networks	journal.pcbi.1002491	null	[ [ "Decades of experimental studies have established detailed “wiring diagrams” of diverse cellular networks .", "A striking property of many networks is multitasking – the ability to generate different dynamics according to their operating context ( Figure 1A ) .", "For example , the mitogen-activated p...	[ "Cellular networks multitask by exhibiting distinct , context-dependent dynamics .", "However , network states ( parameters ) that generate a particular dynamic are often sub-optimal for others , defining a source of “tension” between them .", "Though multitasking is pervasive , it is not clear where tension ar...	[ "Multitasking pervades our daily lives .", "For example , the technological devices that we increasingly rely upon are now engineered with such multifunctionality or “integration” in mind .", "Similarly , cellular networks also multitask in that they generate multiple , distinct dynamics according to their oper...	2012
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "ecology and environmental sciences", "population dynamics", "biodiversity", "marine biology", "biogeochemistry", "systems ecology", "theoretical ecology", "population biology", "geochemistry", "computer and information sciences", "ecosystems", "population ecology", "behavioral ecology", "...	Emergent Global Patterns of Ecosystem Structure and Function from a Mechanistic General Ecosystem Model	journal.pbio.1001841	This paper presents the first mathematical model that attempts to represent the biology and behavior of all individual organisms globally, taking us a step closer to holistic ecological and conservation science founded on mechanistic predictions.	[ [ "The pace and scale of anthropogenic environmental change has caused the widespread degradation of ecosystems and the services they provide that ultimately support human life on Earth [1] .", "Understanding and mitigating these impacts necessitates the development of a suite of tools , including policy in...	[ "Anthropogenic activities are causing widespread degradation of ecosystems worldwide , threatening the ecosystem services upon which all human life depends .", "Improved understanding of this degradation is urgently needed to improve avoidance and mitigation measures .", "One tool to assist these efforts is pre...	[ "Ecosystems across the world are being rapidly degraded .", "This threatens their provision of natural goods and services , upon which all life depends .", "To be able to reduce—and one day reverse—this damage , we need to be able to predict the effects of human actions on ecosystems .", "Here , we present th...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "immunotoxicology", "plant science", "immunology", "biology", "microbiology", "molecular cell biology", "toxicology" ]	The Secreted Antifungal Protein Thionin 2.4 in Arabidopsis thaliana Suppresses the Toxicity of a Fungal Fruit Body Lectin from Fusarium graminearum	journal.ppat.1003581	null	[ [ "Plants are exposed to various pathogenic fungi and bacteria .", "As a countermeasure , plants produce antimicrobial chemicals such as phytoalexins [1] , [2] and secretory proteins [2] , [3] that can act as defense mechanisms against phytopathogens .", "Antimicrobial proteins contain a variety of smal...	[ "Plants possess active defense systems and can protect themselves from pathogenic invasion by secretion of a variety of small antimicrobial or antifungal proteins such as thionins .", "The antibacterial and antifungal properties of thionins are derived from their ability to induce open pore formation on cell memb...	[ "Host-pathogen interactions involve a multiplicity of mechanisms that coevolved for successful host resistance to pathogenic invasion or for overcoming host defenses by the pathogen .", "In our study , we focused on antifungal peptides called thionins that plants use for defense against a broad range of phytopath...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine", "bacterial diseases", "infectious diseases", "pulmonology", "gram negative", "cellular stress responses", "molecular cell biology", "chronic obstructive pulmonary diseases", "pediatric pulmonology", "pseudomonas infections", "nosocomial infections", "bacterial pneumonia", "host-p...	X-Box Binding Protein 1 (XBP1s) Is a Critical Determinant of Pseudomonas aeruginosa Homoserine Lactone-Mediated Apoptosis	journal.ppat.1003576	null	[ [ "Pseudomonas aeruginosa is an opportunistic bacterium and infections caused by this pathogen constitute a significant heath-care burden .", "P . aeruginosa is the fourth most-commonly isolated nosocomial pathogen and infections can be fatal , particularly in immuno-compromised subjects such as those with ...	[ "Pseudomonas aeruginosa infections are associated with high mortality rates and occur in diverse conditions including pneumonias , cystic fibrosis and neutropenia .", "Quorum sensing , mediated by small molecules including N- ( 3-oxo-dodecanoyl ) homoserine lactone ( C12 ) , regulates P . aeruginosa growth and vi...	[ "Chronic and acute infections associated with P . aeruginosa constitute a major healthcare burden .", "Antimicrobial approaches are currently used against P . aeruginosa; however , infections are typically refractory to treatment and drug resistant strains have been isolated .", "As such , there is urgent need ...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	A Neural Mechanism for Time-Window Separation Resolves Ambiguity of Adaptive Coding	journal.pbio.1002096	Neuronal data, computational modeling, and behavioral experiments reveal how the conflict between sensory adaptation and sound localization is resolved in the grasshopper auditory system, allowing processing of both absolute and relative sound levels.	[ [ "In many sensory pathways , adaptation serves to adjust neural encoding to the current statistics of the environment and thus enables reliable and invariant representation of relevant aspects within seconds [1–3] .", "In order to achieve this , response normalization has been shown to remove the signal me...	[ "The senses of animals are confronted with changing environments and different contexts .", "Neural adaptation is one important tool to adjust sensitivity to varying intensity ranges .", "For instance , in a quiet night outdoors , our hearing is more sensitive than when we are confronted with the plurality of s...	[ "Smell , vision , hearing—virtually all of our senses adapt their sensitivity to cope with the varying environment .", "Adaptation removes information about absolute stimulus intensity available to the brain , as this information is usually of little relevance for sensory representation .", "For some tasks , ho...	2015
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "developmental biology/embryology", "biochemistry/replication and repair", "genetics and genomics/gene function", "developmental biology/organogenesis", "molecular biology/dna repair" ]	Dual Functions of ASCIZ in the DNA Base Damage Response and Pulmonary Organogenesis	journal.pgen.1001170	null	[ [ "Pathways that maintain genome integrity by responding to spontaneous DNA damage are crucial for normal development and ageing , and act as tumor suppressors to prevent the onset of cancer [1] .", "While DNA damage signaling is rather generic in that structurally diverse lesions eventually lead to activat...	[ "Zn2+-finger proteins comprise one of the largest protein superfamilies with diverse biological functions .", "The ATM substrate Chk2-interacting Zn2+-finger protein ( ASCIZ; also known as ATMIN and ZNF822 ) was originally linked to functions in the DNA base damage response and has also been proposed to be an ess...	[ "ASCIZ is a DNA damage response protein that has been proposed to be a regulator and stabilizing co-factor of the ATM kinase , mutations of which lead to a syndrome involving neurological and immune dysfunctions , tumour predisposition , and X-ray hypersensitivity .", "To study Asciz function in vivo , we have ge...	2010
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biology and life sciences", "computational biology" ]	P-loop Conformation Governed Crizotinib Resistance in G2032R-Mutated ROS1 Tyrosine Kinase: Clues from Free Energy Landscape	journal.pcbi.1003729	null	[ [ "The past decade has witnessed the great benefit of the personalized drug therapy in the treatment of non-small-cell lung cancers ( NSCLC ) [1]–[3] , which was designed to target different drug targets , such as KRAS [4] , EGFR [5] , EML4-ALK [6] , the newly found CD74-ROS1 [7] , [8] , etc .", "Crizotinib...	[ "Tyrosine kinases are regarded as excellent targets for chemical drug therapy of carcinomas .", "However , under strong purifying selection , drug resistance usually occurs in the cancer cells within a short term .", "Many cases of drug resistance have been found to be associated with secondary mutations in dru...	[ "Cancers can eventually confer drug resistance to the continued medication .", "In most cases , mutations occurred in a drug target can attenuate the binding affinity of the drugs .", "Here , we studied the drug resistance mechanisms of the mutations G2032R in the ROS1 tyrosine kinase in fusion-type NSCLC .", ...	2014
[ "Introduction", "Models", "Results/Discussion" ]	[ "genetic polymorphism", "theoretical biology", "natural selection", "population genetics", "biology", "evolutionary biology", "gene flow", "genetic drift", "evolutionary theory" ]	Stability Properties of Underdominance in Finite Subdivided Populations	journal.pcbi.1002260	null	[ [ "With we denote the wildtype allele , whereas represents a transformed ( or mutant ) allele .", "Given a single locus two allele model of diploid organisms , there are three genotypes possible: , , and .", "We set the average allelic fitness of wildtypes ( ) to , the fitness of heterozygote genotype (...	[ "In isolated populations underdominance leads to bistable evolutionary dynamics: below a certain mutant allele frequency the wildtype succeeds .", "Above this point , the potentially underdominant mutant allele fixes .", "In subdivided populations with gene flow there can be stable states with coexistence of wi...	[ "Underdominance is a component of natural evolution: homozygotes – of either wildtypes or mutants – are advantageous .", "This can play a role in speciation and as a method to establish artificial genetic constructs in wild populations .", "The polymorphic state of wildtype and mutant alleles is unstable .", ...	2011
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine", "infectious diseases", "clinical immunology", "immunology", "biology", "microbiology", "molecular cell biology", "hematology" ]	Binding of HIV-1 gp120 to DC-SIGN Promotes ASK-1-Dependent Activation-Induced Apoptosis of Human Dendritic Cells	journal.ppat.1003100	null	[ [ "HIV-1 envelope protein gp120 binds to CD4 and chemokine receptors CCR5 or CXCR4 which are expressed by dendritic cells ( DC ) and which facilitate viral entry into the cells [1] .", "HIV-1 gp120 is also readily shed from the maturing virions [2] and forms immune complexes in the plasma of HIV-infected [H...	[ "During disease progression to AIDS , HIV-1 infected individuals become increasingly immunosuppressed and susceptible to opportunistic infections .", "It has also been demonstrated that multiple subsets of dendritic cells ( DC ) , including DC-SIGN ( + ) cells , become significantly depleted in the blood and lymp...	[ "HIV-1 infected individuals become increasingly immunocompromised and susceptible to opportunistic infection during disease progression , which is associated with significant reduction of the dendritic cell number in the peripheral blood or secondary lymphoid tissues .", "Because dendritic cells are the most powe...	2013
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "blood cells", "sequencing techniques", "medicine and health sciences", "body fluids", "immune cells", "immunology", "cloning", "neuroscience", "learning and memory", "twins", "sequence assembly tools", "developmental biology", "cognition", "genome analysis", "memory", "molecular biolo...	Persisting fetal clonotypes influence the structure and overlap of adult human T cell receptor repertoires	journal.pcbi.1005572	null	[ [ "The adaptive immune system relies on the diversity of T-cell repertoires to protect us from many possible pathogenic threats .", "Each T-cell expresses on its surface many copies of a unique T-cell receptor ( TCR ) , which engages with antigenic peptides—from self or foreign proteins—presented by other c...	[ "The diversity of T-cell receptors recognizing foreign pathogens is generated through a highly stochastic recombination process , making the independent production of the same sequence rare .", "Yet unrelated individuals do share receptors , which together constitute a “public” repertoire of abundant clonotypes ....	[ "The enormous diversity of T-cell receptor ( TCR ) molecules allows our adaptive immune system to recognize and fight infections .", "TCRs are formed through the stochastic rearrangement of DNA .", "By analysing human repertoire sequences of identical twins using a statistical model for TCR formation , we ident...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biology" ]	The miR-35-41 Family of MicroRNAs Regulates RNAi Sensitivity in Caenorhabditis elegans	journal.pgen.1002536	null	[ [ "The ability of double stranded RNA ( dsRNA ) to induce silencing of specific genes was discovered in the nematode Caenorhabditis elegans and dubbed RNA interference ( RNAi ) [1] .", "RNAi was subsequently identified in many organisms , including mammals , providing a powerful experimental tool for inacti...	[ "RNA interference ( RNAi ) utilizes small interfering RNAs ( siRNAs ) to direct silencing of specific genes through transcriptional and post-transcriptional mechanisms .", "The siRNA guides can originate from exogenous ( exo–RNAi ) or natural endogenous ( endo–RNAi ) sources of double-stranded RNA ( dsRNA ) .", ...	[ "RNA interference ( RNAi ) has become a widely used approach for silencing genes of interest .", "This tool is possible because endogenous RNA silencing pathways exist broadly across organisms , including humans , worms , and plants .", "The general RNAi pathway utilizes small ∼21-nucleotide RNAs to target spec...	2012
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "biotechnology", "taxonomy", "brassica", "phylogenetics", "plant science", "model organisms", "data management", "phylogenetic analysis", "experimental organism systems", "plant genomics", "plant pathology", "convergent evolution", "plants", "research and analysis methods", "arabidopsis ...	Parallel evolution of the POQR prolyl oligo peptidase gene conferring plant quantitative disease resistance	journal.pgen.1007143	null	[ [ "Plant pathogens are major threats to biodiversity in natural ecosystems and to food security worldwide .", "Plant disease resistance is mediated by an elaborate multilayered system of defense , sometimes including resistance ( R ) genes conferring complete resistance against a limited number of pathogen ...	[ "Plant pathogens with a broad host range are able to infect plant lineages that diverged over 100 million years ago .", "They exert similar and recurring constraints on the evolution of unrelated plant populations .", "Plants generally respond with quantitative disease resistance ( QDR ) , a form of immunity re...	[ "Plant disease resistance is mediated by molecular components depending on pathogens infection strategy .", "Sclerotinia sclerotiorum is a devastating plant pathogenic fungus notorious for its ability to infect a wide variety of plant species by rapidly triggering cell death .", "Plant exhibit a response design...	2017
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "parasite groups", "markov models", "plasmodium", "split-decomposition method", "parasitology", "multiple alignment calculation", "apicomplexa", "mathematics", "sequence motif analysis", "research and analysis methods", "sequence analysis", "sequence alignment", "bioinformatics", "proteins...	Improving pairwise comparison of protein sequences with domain co-occurrence	journal.pcbi.1005889	null	[ [ "Proteins are macromolecules essential for the structuring and functioning of living cells .", "Proteins generally have different functional regions which are conserved along evolution [1] and are commonly termed as “functional motifs” or “domains” .", "Domains/motifs are found in different proteins a...	[ "Comparing and aligning protein sequences is an essential task in bioinformatics .", "More specifically , local alignment tools like BLAST are widely used for identifying conserved protein sub-sequences , which likely correspond to protein domains or functional motifs .", "However , to limit the number of false...	[ "Deciphering the functions of the different proteins of an organism constitutes a first step toward the understanding of its biology .", "Because they provide strong clues regarding protein functions , domains occupy a key position among the relevant annotations that can be assigned to a protein .", "Protein do...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "infectious diseases", "immunology/immune response", "immunology", "infectious diseases/respiratory infections", "infectious diseases/bacterial infections", "immunology/immunity to infections" ]	Differentiation, Distribution and γδ T Cell-Driven Regulation of IL-22-Producing T Cells in Tuberculosis	journal.ppat.1000789	null	[ [ "IL-22 is a member of IL-10 cytokine family and primarily produced by Th17 T cells [1] .", "IL-22 signals though its heterodimer receptor comprised of IL-22R1 and IL-10R2 [2] , with the IL-22 binding effect dictated by IL-22R1 that are expressed mainly on skin and mucosal epithelial cells such as digestiv...	[ "Differentiation , distribution and immune regulation of human IL-22-producing T cells in infections remain unknown .", "Here , we demonstrated in a nonhuman primate model that M . tuberculosis infection resulted in apparent increases in numbers of T cells capable of producing IL-22 de novo without in vitro Ag st...	[ "TB remains one of the leading causes of morbidity and mortality among infectious diseases worldwide .", "Protective immunity against TB in humans remains poorly characterized , although the importance of CD4 T cells is well described in HIV-related TB .", "Similarly , little is known about the role of newly-de...	2010
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "biotechnology", "plant anatomy", "medicine and health sciences", "brassica", "electrophysiology", "plant physiology", "neuroscience", "fungi", "plant science", "rice", "ion channels", "model organisms", "genetically modified plants", "experimental organism systems", "plant pathology", ...	The fungal pathogen Magnaporthe oryzae suppresses innate immunity by modulating a host potassium channel	journal.ppat.1006878	null	[ [ "Potassium ( K+ ) plays important roles in many fundamental processes in plants , including enzyme activation , cellular homeostasis , membrane transport , osmoregulation and immunoreaction [1 , 2] .", "The uptake and translocation of K+ in plants relies on a number of K+ channels and transporters .", ...	[ "Potassium ( K+ ) is required by plants for growth and development , and also contributes to immunity against pathogens .", "However , it has not been established whether pathogens modulate host K+ signaling pathways to enhance virulence and subvert host immunity .", "Here , we show that the effector protein Av...	[ "Plant nutritional status can greatly influence plant immunity in response to pathogen invasion .", "Rice blast , a devastating rice disease caused by the hemibiotrophic fungus Magnaporthe oryzae , causes a significant reduction in yield and affects food security .", "In this study , we demonstrate that the M ....	2018
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "infectious diseases/neglected tropical diseases" ]	Geographical Variation in the Response of Visceral Leishmaniasis to Paromomycin in East Africa: A Multicentre, Open-Label, Randomized Trial	journal.pntd.0000709	null	[ [ "Visceral leishmaniasis ( VL ) is among the most neglected and serious tropical diseases [1] , [2] .", "The disease is caused by protozoal parasites of the genus Leishmania transmitted to humans by bites of female sandflies .", "The incubation period varies from 2 to 6 months .", "The most promine...	[ "Visceral leishmaniasis ( VL ) is a major health problem in developing countries .", "The untreated disease is fatal , available treatment is expensive and often toxic , and drug resistance is increasing .", "Improved treatment options are needed .", "Paromomycin was shown to be an efficacious first-line trea...	[ "Visceral leishmaniasis ( VL ) is a fatal parasitic disease with 500 , 000 new cases each year according to WHO estimates .", "New and better treatment options are urgently needed in disease endemic areas due to the long courses , toxicity and development of resistance to current treatments .", "Recently , the ...	2010
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "biomacromolecule-ligand interactions", "agrochemicals", "protein folding", "crop diseases", "biology", "biophysics", "agriculture" ]	Dimerization of VirD2 Binding Protein Is Essential for Agrobacterium Induced Tumor Formation in Plants	journal.ppat.1003948	null	[ [ "The Type IV Secretion System ( T4SS ) has an unmatched versatility among the seven different secretion systems known in bacteria .", "T4SS can translocate not only proteins but also DNA to phylogenetically diverse taxa , including many bacterial species and various eukaryotic cells , as well as import an...	[ "The Type IV Secretion System ( T4SS ) is the only bacterial secretion system known to translocate both DNA and protein substrates .", "The VirB/D4 system from Agrobacterium tumefaciens is a typical T4SS .", "It facilitates the bacteria to translocate the VirD2-T-DNA complex to the host cell cytoplasm .", "In...	[ "Agrobacterium tumefaciens causes crown gall disease ( tumors ) in agriculturally important plant species .", "It initiates infection through its Ti plasmid , which integrates a portion of its own DNA ( T-DNA ) into that of the host genome .", "The T-DNA is bound to VirD2 relaxase , and this complex is required...	2014
[ "Introduction", "Methods", "Results/Discussion" ]	[ "taxonomy", "medicine and health sciences", "pathology and laboratory medicine", "pathogens", "histoplasmosis", "population genetics", "microbiology", "vertebrates", "animals", "mammals", "animal phylogenetics", "organisms", "phylogenetics", "data management", "phylogenetic analysis", ...	Worldwide Phylogenetic Distributions and Population Dynamics of the Genus Histoplasma	journal.pntd.0004732	null	[ [ "Histoplasma capsulatum sensu lato are dimorphic fungal species found in a filamentous form in the environment as saprobiotic-geophilic microorganisms [1] .", "These species encompass a globally distributed complex of fungi , which are mainly found in nitrogen/phosphate-enriched soils associated with bird...	[ "Histoplasma capsulatum comprises a worldwide complex of saprobiotic fungi mainly found in nitrogen/phosphate ( often bird guano ) enriched soils .", "The microconidia of Histoplasma species may be inhaled by mammalian hosts , and is followed by a rapid conversion to yeast that can persist in host tissues causing...	[ "Histoplasmosis is a potentially severe fungal disease of mammals caused by Histoplasma capsulatum .", "The highest incidence of the disease is reported on the American continent , and approximately 30% of HIV and histoplasmosis co-infections are fatal .", "Previous studies have suggested at least 7 phylogeneti...	2016
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "public and occupational health", "helminth infections", "infectious diseases", "medicine and health sciences", "trichuriasis", "global health", "neglected tropical diseases", "hookworm diseases", "tropical diseases", "soil-transmitted helminthiases", "ascariasis", "parasitic diseases", "ped...	Effects of a Post-Deworming Health Hygiene Education Intervention on Absenteeism in School-Age Children of the Peruvian Amazon	journal.pntd.0003007	null	[ [ "Soil-transmitted helminth ( STH ) infections are the world's most important cluster of neglected tropical diseases and cause significant morbidity in school-age children ( i . e . children aged between 5 and 14 years ) [1] .", "It has recently been estimated that the intestinal parasites Ascaris lumbrico...	[ "Soil-transmitted helminth ( STH ) infections are a leading cause of disability and disease burden in school-age children of worm-endemic regions .", "Their effect on school absenteeism , however , remains unclear .", "The World Health Organization currently recommends delivering mass deworming and health hygie...	[ "Soil-transmitted helminths ( STHs ) are intestinal parasites that infect over 2 billion people in the world .", "Children infected with STHs often experience growth delays and perform poorly in school .", "However , the specific effects of STH infections on school absenteeism in children are not well understoo...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods", "Supporting Information" ]	[ "infectious diseases", "microbiology", "evolutionary biology", "genetics and genomics", "eubacteria" ]	Being Pathogenic, Plastic, and Sexual while Living with a Nearly Minimal Bacterial Genome	journal.pgen.0030075	null	[ [ "Organisms belonging to the Mycoplasma genus ( class Mollicutes ) are commonly described as the simplest and smallest self-replicating bacteria because of their total lack of cell wall , the paucity of their metabolic pathways , and the small size of their genome [1 , 2] .", "In the 1980s , they were show...	[ "Mycoplasmas are commonly described as the simplest self-replicating organisms , whose evolution was mainly characterized by genome downsizing with a proposed evolutionary scenario similar to that of obligate intracellular bacteria such as insect endosymbionts .", "Thus far , analysis of mycoplasma genomes indica...	[ "Mycoplasmas are cell wall–lacking prokaryotes that evolved from ancestors common to Gram-positive bacteria by way of massive losses of genetic material .", "With their minimal genome , mycoplasmas are considered to be the simplest free-living organisms , yet several species are successful pathogens of man and an...	2007
[ "Introduction", "Results", "Discussion", "Materials and Methods", "Supporting Information" ]	[ "biochemistry" ]	Selective Ligand Recognition by a Diversity-Generating Retroelement Variable Protein	journal.pbio.0060131	Although the massively variable protein Mtd of theBordetella bacteriophage diversity-generating retroelement recognizes ligands in a different manner from antigen receptors of the immune system, general principles underlying anticipatory recognition are strikingly conserved.	[ [ "The vertebrate adaptive immune response long has been considered unique among biological systems in having the capacity to recognize novel ligands in an anticipatory fashion [1] .", "Such anticipatory recognition depends on antigen receptors that accommodate massive sequence variation in their ligand bin...	[ "Diversity-generating retroelements ( DGRs ) recognize novel ligands through massive protein sequence variation , a property shared uniquely with the adaptive immune response .", "Little is known about how recognition is achieved by DGR variable proteins .", "Here , we present the structure of the Bordetella ba...	[ "The immune system long has been considered unique in its capacity to recognize alien molecules .", "This anticipatory recognition depends on a repertoire of receptors—antibodies and T cell receptors—with binding sites capable of accommodating trillions of different amino acid sequence combinations .", "A simil...	2008
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "immune cells", "immunity", "t cells", "immunity to infections", "immunology", "immune tolerance", "biology", "immune response" ]	Infection of Adult Thymus with Murine Retrovirus Induces Virus-Specific Central Tolerance That Prevents Functional Memory CD8+ T Cell Differentiation	journal.ppat.1003937	null	[ [ "Antigen-specific CD8+ T cell populations are a major component that eliminate cells infected with intracellular pathogens .", "After infections that are cleared acutely , antigen-specific CD8+ T cells can differentiate into functionally competent memory CD8+ T cells , and can persist for a long time in t...	[ "In chronic viral infections , persistent antigen presentation causes progressive exhaustion of virus-specific CD8+ T cells .", "It has become clear , however , that virus-specific naïve CD8+ T cells newly generated from the thymus can be primed with persisting antigens .", "In the setting of low antigen densit...	[ "During thymocyte development , cells that recognize self-antigens are specifically deleted by the process known as negative selection .", "However , some pathogens disseminate to the thymus , and can induce foreign antigen presentation within this organ , resulting in potentially harmful clonal deletion of patho...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "bacteriology", "biology", "evolutionary biology", "microbiology", "bacterial evolution", "evolutionary genetics", "bacterial pathogens", "host-pathogen interaction" ]	Age of the Association between Helicobacter pylori and Man	journal.ppat.1002693	null	[ [ "The Gram-negative bacterium Helicobacter pylori infects the stomachs of at least 50% of all humans , causing gastric inflammation in all infected individuals , gastric or duodenal ulcers in 10–15% and gastric carcinoma or lymphoma of the mucosa-associated lymphoid tissue in ∼1% [1] .", "H . pylori infect...	[ "When modern humans left Africa ca .", "60 , 000 years ago ( 60 kya ) , they were already infected with Helicobacter pylori , and these bacteria have subsequently diversified in parallel with their human hosts .", "But how long were humans infected by H . pylori prior to the out-of-Africa event ?", "Did this ...	[ "We previously showed that the population history of H . pylori may be used as a marker for human migrations , including the demonstration that humans carried H . pylori out of Africa 60 , 000 years ago during their recent global expansions .", "But how long were humans infected by H . pylori prior to the out-of-...	2012
[ "Introduction", "Results and discussion", "Materials and methods" ]	[ "medicine and health sciences", "diagnostic radiology", "engineering and technology", "vertebrates", "neuroscience", "animals", "mammals", "animal signaling and communication", "animal behavior", "tongue", "remote sensing", "audio equipment", "zoology", "neuroimaging", "fruit bats", "d...	Tongue-driven sonar beam steering by a lingual-echolocating fruit bat	journal.pbio.2003148	null	[ [ "Adaptive sampling is a universal principle of animal sensing that has recently gained popularity in engineering practices [1] .", "By selectively gathering information pertinent to behavioral goals , animals are able to efficiently parse and process information in complex environments [2 , 3] .", "Ec...	[ "Animals enhance sensory acquisition from a specific direction by movements of head , ears , or eyes .", "As active sensing animals , echolocating bats also aim their directional sonar beam to selectively “illuminate” a confined volume of space , facilitating efficient information processing by reducing echo inte...	[ "It is well known that animals move their eyes , ears , and heads towards stimuli of interest to selectively gather information in complex environments .", "Interestingly , lingual-echolocating fruit bats , which generate sonar signals for object localization by clicking their tongues , can rapidly switch the dir...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biochemistry", "rna", "cellular structures", "subcellular organelles", "rna transport", "nucleic acids", "protein translation", "gene expression", "genetics", "cell nucleus", "biology", "molecular cell biology" ]	RanBP2/Nup358 Potentiates the Translation of a Subset of mRNAs Encoding Secretory Proteins	journal.pbio.1001545	After nuclear export, mRNAs encoding secretory proteins interact with RanBP2/Nup358 on the cytoplasmic face of the nuclear pore, a step that is required for the efficient translation of these mRNAs.	[ [ "In eukaryotic cells , mRNA synthesis and processing occur in the nucleus while the translation of mRNA into protein is restricted to the cytoplasm .", "Although these various mRNA metabolic steps take place in distinct compartments , these events are biochemically coupled [1] , [2] .", "For example ,...	[ "In higher eukaryotes , most mRNAs that encode secreted or membrane-bound proteins contain elements that promote an alternative mRNA nuclear export ( ALREX ) pathway .", "Here we report that ALREX-promoting elements also potentiate translation in the presence of upstream nuclear factors .", "These RNA elements ...	[ "About one-fifth of the protein-coding genes in the human genome code for secreted and/or membrane-bound proteins .", "In the nucleus these genes are transcribed into messenger RNAs ( mRNAs ) , which are then exported to the cytoplasm .", "These mRNAs are then transported to the surface of the endoplasmic retic...	2013
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "neuroscience/behavioral neuroscience", "neuroscience/theoretical neuroscience" ]	A Common Cortical Circuit Mechanism for Perceptual Categorical Discrimination and Veridical Judgment	journal.pcbi.1000253	null	[ [ "Perceptual judgments involve detection , identification and discrimination of objects", "in a sensory scene [1] , [2] .", "Given an ambiguous visual motion pattern , for", "instance , a subject may be asked to detect whether a net motion direction is present", "or absent [3] , to identify the...	[ "Perception involves two types of decisions about the sensory world:", "identification of stimulus features as analog quantities , or discrimination of", "the same stimulus features among a set of discrete alternatives .", "Veridical", "judgment and categorical discrimination have traditionally been concept...	[ "In daily life , we constantly face two types of perceptual decisions: to identify", "an object feature ( what is the speed of that car ? ) or to discriminate the same", "feature among two or more possible categories ( is that car going faster than the", "speed limit ?", ") .", "These decision processes a...	2008
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "antimicrobials", "invertebrates", "innate immune system", "medicine and health sciences", "viral transmission and infection", "immune activation", "immunology", "microbiology", "animals", "viral vectors", "emerging infectious diseases", "infectious diseases", "epidemiology", "insects", ...	Complement-Related Proteins Control the Flavivirus Infection of Aedes aegypti by Inducing Antimicrobial Peptides	journal.ppat.1004027	null	[ [ "Animals have evolved multiple immune systems to eradicate pathogenic viruses .", "The innate immune response plays a crucial antiviral role in the early stage of infection .", "Immune responses are initiated based on the recognition of viral components , including viral surface glycoproteins and gene...	[ "The complement system functions during the early phase of infection and directly mediates pathogen elimination .", "The recent identification of complement-like factors in arthropods indicates that this system shares common ancestry in vertebrates and invertebrates as an immune defense mechanism .", "Thioester...	[ "Hosts are equipped with sophisticated machineries for detecting and eliminating invading viruses before they cause significant physiological damage .", "Unlike mammals which have both innate and adaptive immune systems , insects rely solely on the innate immune system to limit viral infection .", "Mosquitoes a...	2014
[ "Introduction", "Results", "Discussion", "Conclusion", "Methods" ]	[ "invertebrates", "medicine and health sciences", "population genetics", "geographical locations", "malawi", "animals", "genetic mapping", "population biology", "insect vectors", "africa", "agrochemicals", "epidemiology", "disease vectors", "insects", "genetic loci", "agriculture", "a...	Genomic Footprints of Selective Sweeps from Metabolic Resistance to Pyrethroids in African Malaria Vectors Are Driven by Scale up of Insecticide-Based Vector Control	journal.pgen.1006539	null	[ [ "Scaling up of malaria prevention and treatment has averted over 660 million cases of malaria since 2000 [1] .", "The vast majority of this reduction has come from mosquito control with pyrethroid insecticide-based interventions , primarily the use of long lasting insecticide-treated bednets ( LLINs ) and...	[ "Insecticide resistance in mosquito populations threatens recent successes in malaria prevention .", "Elucidating patterns of genetic structure in malaria vectors to predict the speed and direction of the spread of resistance is essential to get ahead of the ‘resistance curve’ and to avert a public health catastr...	[ "Malaria control currently relies heavily on insecticide-based vector control interventions .", "Unfortunately , resistance to insecticides threatens the continued effectiveness of these measures .", "Metabolic resistance , caused by increased detoxification of insecticides , presents the greatest threat to vec...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods", "Supporting Information" ]	[ "oncology", "viruses", "cell biology", "virology", "mus (mouse)", "animals", "mammals" ]	EBV Latent Membrane Protein 1 Activates Akt, NFκB, and Stat3 in B Cell Lymphomas	journal.ppat.0030166	null	[ [ "Epstein-Barr virus ( EBV ) is a ubiquitous γ-herpesvirus that infects humans predominantly at an early age with greater than 90% of the adult population infected with EBV [1] .", "EBV is linked to the development of both B lymphocyte and epithelial cell malignancies , including Burkitt lymphoma , Hodgkin...	[ "Latent membrane protein 1 ( LMP1 ) is the major oncoprotein of Epstein-Barr virus ( EBV ) .", "In transgenic mice , LMP1 promotes increased lymphoma development by 12 mo of age .", "This study reveals that lymphoma develops in B-1a lymphocytes , a population that is associated with transformation in older mice...	[ "Epstein-Barr virus ( EBV ) is linked to the development of multiple cancers , including post-transplant lymphoma , Hodgkin disease , and nasopharyngeal carcinoma .", "Latent membrane protein 1 ( LMP1 ) is expressed in many EBV-associated cancers and is responsible for most of the altered cellular growth properti...	2007
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "embryology", "developmental biology", "mutation", "animal genetics", "molecular development", "gene expression", "genetics", "biology and life sciences", "morphogenesis", "pattern formation", "gene function" ]	Sp6 and Sp8 Transcription Factors Control AER Formation and Dorsal-Ventral Patterning in Limb Development	journal.pgen.1004468	null	[ [ "The apical ectodermal ridge ( AER ) , a specialized thickened epithelium at the distal edge of the developing limb bud , is a major signaling center for limb development ( for a review , see [1] ) .", "The AER , through the production of several members of the Fibroblast growth factor ( Fgf ) family , co...	[ "The formation and maintenance of the apical ectodermal ridge ( AER ) is critical for the outgrowth and patterning of the vertebrate limb .", "The induction of the AER is a complex process that relies on integrated interactions among the Fgf , Wnt , and Bmp signaling pathways that operate within the ectoderm and ...	[ "In this report we examined the functional roles of Sp6 and Sp8 during limb development using compound loss-of-function mutants .", "Sp6 and Sp8 , two members of the Sp gene family , are expressed in the limb bud ectoderm and function downstream of WNT/βcatenin signaling for Fgf8 induction .", "The analysis of ...	2014
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "biology and life sciences", "viral disease diagnosis", "microbiology", "virology" ]	Comparison of Biotinylated Monoclonal and Polyclonal Antibodies in an Evaluation of a Direct Rapid Immunohistochemical Test for the Routine Diagnosis of Rabies in Southern Africa	journal.pntd.0003189	null	[ [ "Rabies is a neglected zoonosis that is responsible for the death of tens of thousands of people per annum [1] .", "The majority of human rabies deaths are associated with canine rabies in resource-limited countries .", "Rabies is caused by multiple lyssaviruses ( Genus: Lyssavirus , Family: Rhabdovir...	[ "The major etiological agent of rabies , rabies virus ( RABV ) , accounts for tens of thousands of human deaths per annum .", "The majority of these deaths are associated with rabies cycles in dogs in resource-limited countries of Africa and Asia .", "Although routine rabies diagnosis plays an integral role in ...	[ "Rabies is a neglected disease that primarily affects poor rural communities of the developing world .", "Lack of surveillance , related to limited diagnostic capabilities , contributes to the underestimation of the burden of this disease .", "Here we report an evaluation of the direct immunohistochemical test ...	2014
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "computational biology/molecular dynamics", "computer science/applications", "biochemistry/membrane proteins and energy transduction" ]	Functional Rotation of the Transporter AcrB: Insights into Drug Extrusion from Simulations	journal.pcbi.1000806	null	[ [ "The acquisition of multidrug resistance ( MDR ) by bacteria , both in hospitals and in the community , has become one of the most serious impediments to improved healthcare [1]–[6] .", "Unfortunately , MDR is not restricted to antimicrobials , being common to antimalarials , herbicides , and anticancer a...	[ "The tripartite complex AcrAB-TolC is the major efflux system in Escherichia coli .", "It extrudes a wide spectrum of noxious compounds out of the bacterium , including many antibiotics .", "Its active part , the homotrimeric transporter AcrB , is responsible for the selective binding of substrates and energy t...	[ "In nature , bacteria have to resist several toxic threats to be able to survive , from bile acids in intestines up to antibiotics .", "The Escherichia coli bacterium , which usually is a commensal inhabitant of human intestines , can also acquire pathogenic properties which would harm the human body .", "To di...	2010
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "immunology", "biology", "microbiology" ]	A Role for the Chemokine RANTES in Regulating CD8 T Cell Responses during Chronic Viral Infection	journal.ppat.1002098	null	[ [ "During many chronic infections , virus spreads rapidly from the site of initial infection to distal tissues .", "T cells , on the other hand , must first become activated in the LNs and spleen and then gain the ability to migrate to infected organs .", "Chemokines play a key role in orchestrating all...	[ "RANTES ( CCL5 ) is a chemokine expressed by many hematopoietic and non-hematopoietic cell types that plays an important role in homing and migration of effector and memory T cells during acute infections .", "The RANTES receptor , CCR5 , is a major target of anti-HIV drugs based on blocking viral entry .", "Ho...	[ "Chemokines are small proteins that attract cells and play complex roles in coordinating immune responses .", "RANTES is one such chemokine that attracts many different cell types .", "The receptor for RANTES , CCR5 , is also a coreceptor for HIV and drugs blocking the RANTES∶CCR5 pathway are in clinical use to...	2011
[ "Introduction", "Results/Discussion", "Materials and Methods" ]	[ "biochemistry/biocatalysis", "biochemistry/protein folding", "biochemistry/biomacromolecule-ligand interactions", "infectious diseases/bacterial infections", "chemical biology/macromolecular chemistry", "infectious diseases/antimicrobials and drug resistance" ]	Unique Structure and Stability of HmuY, a Novel Heme-Binding Protein of Porphyromonas gingivalis	journal.ppat.1000419	null	[ [ "Periodontitis causes chronic inflammation of the gums and it affects", "10–15% of adults worldwide , potentially leading to tissue", "destruction and tooth loss , and Porphyromonas gingivalis is its", "main etiological agent [1] , [2] .", "In addition , P . gingivalis , an", "anaerobic bl...	[ "Infection , survival , and proliferation of pathogenic bacteria in humans depend on", "their capacity to impair host responses and acquire nutrients in a hostile", "environment .", "Among such nutrients is heme , a co-factor for oxygen storage ,", "electron transport , photosynthesis , and redox biochemist...	[ "Pathogenic bacteria cause infection in humans as found in periodontitis , which is", "a chronic inflammation of the gums caused by Porphyromonas", "gingivalis .", "As part of the infective process , bacteria must acquire", "nutrients to survive and multiply at the infection site , and among such", "nutri...	2009
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "medicine and health sciences", "chemical compounds", "carbohydrates", "galactose", "organic compounds", "chromatids", "surgical and invasive medical procedures", "fungi", "model organisms", "experimental organism systems", "dna", "gene conversion", "homologous recombination", "saccharomyc...	DNA strand-exchange patterns associated with double-strand break-induced and spontaneous mitotic crossovers in Saccharomyces cerevisiae	journal.pgen.1007302	null	[ [ "DNA is constantly assaulted by endogenous damaging agents and maintenance of its integrity is essential for the stable inheritance of genetic material .", "Double-strand breaks ( DSBs ) , which disrupt both DNA strands , are especially toxic lesions whose repair can result in local sequence changes as we...	[ "Mitotic recombination can result in loss of heterozygosity and chromosomal rearrangements that shape genome structure and initiate human disease .", "Engineered double-strand breaks ( DSBs ) are a potent initiator of recombination , but whether spontaneous events initiate with the breakage of one or both DNA str...	[ "Chromosome breakage during mitosis is a threat to genome stability , and duplex integrity can be restored through the process of homologous recombination .", "Although double-strand breaks ( DSBs ) are a potent initiator of mitotic recombination , their role in the initiation of spontaneous events is less clear ...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "molecular cell biology", "cell biology", "biology and life sciences", "developmental biology" ]	Rabconnectin-3a Regulates Vesicle Endocytosis and Canonical Wnt Signaling in Zebrafish Neural Crest Migration	journal.pbio.1001852	A novel role for Rabconnectin-3a in endosome maturation regulates Wnt signaling, migration, and fate specification in zebrafish neural crest cells.	[ [ "The epithelial-mesenchymal transition ( EMT ) is characterized by loss of epithelial cell adhesion , dynamic expression and subcellular localization of cell–cell adhesion molecules , and increased cell motility [1] .", "EMT is a hallmark of cancer metastasis [2] and of many cell populations during embryo...	[ "Cell migration requires dynamic regulation of cell–cell signaling and cell adhesion .", "Both of these processes involve endocytosis , lysosomal degradation , and recycling of ligand–receptor complexes and cell adhesion molecules from the plasma membrane .", "Neural crest ( NC ) cells in vertebrates are highly...	[ "The neural crest is a highly migratory population of embryonic cells , which requires Wnt signaling at several stages to promote migration and cell fate decisions .", "Intracellular trafficking of Wnt receptors and associated proteins can affect the timing and intensity of Wnt signaling .", "An obvious questio...	2014
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "mosquitoes", "entomology", "viral transmission and infection", "vector biology", "virology", "emerging viral diseases", "biology", "microbiology", "zoology", "viral vectors" ]	Aedes (Stegomyia) albopictus (Skuse): A Potential Vector of Zika Virus in Singapore	journal.pntd.0002348	null	[ [ "The Asian tiger mosquito , Aedes ( Stegomyia ) albopictus ( Skuse ) , is considered a vector or potential vector of several pathogens of human and veterinary importance .", "Viral isolation and vector competence studies have shown that this mosquito is an efficient vector of more than 20 arboviruses [1] ...	[ "Zika virus ( ZIKV ) is a little known arbovirus until it caused a major outbreak in the Pacific Island of Yap in 2007 .", "Although the virus has a wide geographic distribution , most of the known vectors are sylvatic Aedes mosquitoes from Africa where the virus was first isolated .", "Presently , Ae .", "ae...	[ "The prominence of Ae .", "albopictus as a major vector came to light during the global pandemic of chikungunya .", "The continual global expansion of Ae .", "albopictus coupled with data from competence studies that show its ability to transmit more than 20 arboviruses has fuelled growing concerns that this ...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "virology/virion structure, assembly, and egress", "infectious diseases/viral infections", "biochemistry/cell signaling and trafficking structures", "cell biology/cytoskeleton" ]	Vaccinia Protein F12 Has Structural Similarity to Kinesin Light Chain and Contains a Motor Binding Motif Required for Virion Export	journal.ppat.1000785	null	[ [ "Vaccinia virus ( VACV ) is a large DNA virus that replicates in the cytoplasm [1] and produces morphologically distinct virions that have different roles in virus dissemination [2] , [3] .", "Virus replication occurs in cytoplasmic factories and starts with the formation of membrane crescents , composed ...	[ "Vaccinia virus ( VACV ) uses microtubules for export of virions to the cell surface and this process requires the viral protein F12 .", "Here we show that F12 has structural similarity to kinesin light chain ( KLC ) , a subunit of the kinesin-1 motor that binds cargo .", "F12 and KLC share similar size , pI , ...	[ "Vaccinia virus ( VACV ) , the vaccine used to eradicate smallpox , exploits the host cell motor kinesin-1 to export virus particles to the cell surface .", "We demonstrate that the VACV F12 protein has structural similarity with kinesin light chain ( KLC ) and facilitates viral transport using a kinesin binding ...	2010
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "mutation", "deletion mutation", "point mutation", "medicine and health sciences", "genomics", "anatomy", "nonsense mutation", "genome analysis", "human genetics", "genetics", "biology and life sciences", "renal system", "kidneys", "computational biology", "somatic mutation" ]	Whole Exome Sequencing Identifies TSC1/TSC2 Biallelic Loss as the Primary and Sufficient Driver Event for Renal Angiomyolipoma Development	journal.pgen.1006242	null	[ [ "Renal angiomyolipoma is a pathologically benign mesenchymal kidney tumor , characterized by vascular , smooth muscle , and adipocyte elements [1 , 2] .", "Angiomyolipomas are rare in the general population ( autopsy prevalence about 1 in 1 , 000 [3] ) but are seen in > 70% adults with Tuberous Sclerosis ...	[ "Renal angiomyolipoma is a kidney tumor in the perivascular epithelioid ( PEComa ) family that is common in patients with Tuberous Sclerosis Complex ( TSC ) and Lymphangioleiomyomatosis ( LAM ) but occurs rarely sporadically .", "Though histologically benign , renal angiomyolipoma can cause life-threatening hemor...	[ "We performed comprehensive genome analysis of a kidney tumor called angiomyolipoma .", "These tumors are known to develop in most individuals who have Tuberous Sclerosis Complex ( TSC ) and those who have sporadic lymphangioleiomyomatosis ( LAM ) , and are seen rarely in the general population .", "In these an...	2016
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "cell processes", "cloning", "neuroscience", "dyneins", "molecular motors", "molecular cloning", "altmetrics", "nerve fibers", "mitochondria", "molecular biology techniques", "bioenergetics", "cellular structures and organelles", "motor proteins", "research and analysis methods", "animal...	A transient helix in the disordered region of dynein light intermediate chain links the motor to structurally diverse adaptors for cargo transport	journal.pbio.3000100	A highly conserved mechanism links the microtubule minus end–directed motor dynein to structurally diverse cargo adaptors through its light intermediate chain; this interaction is crucial for dynein function in vivo.	[ [ "Microtubule-based cargo transport and force production are critical for a wide range of cellular and developmental processes .", "In animal cells , the 1 . 4-MDa complex cytoplasmic dynein 1 ( dynein ) is the major molecular motor with motility directed toward microtubule minus ends .", "Dynein-drive...	[ "All animal cells use the motor cytoplasmic dynein 1 ( dynein ) to transport diverse cargo toward microtubule minus ends and to organize and position microtubule arrays such as the mitotic spindle .", "Cargo-specific adaptors engage with dynein to recruit and activate the motor , but the molecular mechanisms rema...	[ "The large size and complex organization of animal cells make the correct and efficient distribution of intracellular content a challenge .", "The solution is to use motor proteins , which harness energy from ATP hydrolysis to walk along actin filaments or microtubules , for directional transport of cargo .", "...	2019
[ "Introduction", "Results", "Materials and methods" ]	[ "bacteriology", "antimicrobials", "medicine and health sciences", "pathology and laboratory medicine", "intracellular pathogens", "viral transmission and infection", "pathogens", "plasmids", "drugs", "microbiology", "nucleotides", "antibiotics", "genetic elements", "bacterial genetics", ...	Selective advantages favour high genomic AT-contents in intracellular elements	journal.pgen.1007778	null	[ [ "Bacterial genomes exhibit a considerable amount of variation in their nucleotide composition ( G+C versus A+T ) , ranging from less than 13% to more than 75% GC [1 , 2] .", "Despite intense efforts during the past decades , the selective pressures determining the evolution and maintenance of this variati...	[ "Extrachromosomal genetic elements such as bacterial endosymbionts and plasmids generally exhibit AT-contents that are increased relative to their hosts’ DNA .", "The AT-bias of endosymbiotic genomes is commonly explained by neutral evolutionary processes such as a mutational bias towards increased A+T .", "Her...	[ "Genomes of endosymbiotic bacteria are commonly more AT-rich than the ones of their free-living relatives .", "Interestingly , genomes of other intracellular elements like plasmids or bacteriophages also tend to be richer in AT than the genomes of their hosts .", "The AT-bias of endosymbiotic genomes is commonl...	2019
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "cell biology/membranes and sorting", "neurological disorders/prion diseases", "biochemistry/protein folding" ]	Selective Processing and Metabolism of Disease-Causing Mutant Prion Proteins	journal.ppat.1000479	null	[ [ "Several diseases are caused by mutations that generate aberrant proteins with adverse cytotoxic consequences [1] .", "Analysis of the biosynthesis , maturation , processing , trafficking and metabolism of the aberrant protein generated in these diseases is instrumental in identifying the mechanisms under...	[ "Prion diseases are fatal neurodegenerative disorders caused by aberrant metabolism of the cellular prion protein ( PrPC ) .", "In genetic forms of these diseases , mutations in the globular C-terminal domain are hypothesized to favor the spontaneous generation of misfolded PrP conformers ( including the transmis...	[ "Prion diseases are transmissible fatal neurodegenerative diseases caused by aberrant metabolism of the cellular prion protein ( PrPC ) .", "The transmissible agent is PrPSc , a misfolded version ( conformer ) of PrP capable of converting PrPC into PrPSc .", "PrPSc can be generated de novo in inherited prion di...	2009
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "bacteriology", "genomics", "biology", "computational biology", "microbiology" ]	Immune Subversion and Quorum-Sensing Shape the Variation in Infectious Dose among Bacterial Pathogens	journal.ppat.1002503	null	[ [ "Bacteria are a significant part of the human body , often establishing commensal or mutualistic interactions with it [1] .", "Yet , some species , or some strains within species , have a significant negative impact on the host while exploiting its resources .", "Such antagonistic associations lead to...	[ "Many studies have been devoted to understand the mechanisms used by pathogenic bacteria to exploit human hosts .", "These mechanisms are very diverse in the detail , but share commonalities whose quantification should enlighten the evolution of virulence from both a molecular and an ecological perspective .", ...	[ "Every pathogen is unique and uses distinctive combinations of specific mechanisms to exploit the human host .", "Yet , several common themes in the ways pathogens use these mechanisms can be found among distantly related bacteria .", "The understanding of these common themes provides useful concepts and uncove...	2012
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "action potentials", "medicine and health sciences", "neural networks", "engineering and technology", "signal processing", "membrane potential", "signaling networks", "electrophysiology", "neuroscience", "signal filtering", "network analysis", "computational neuroscience", "coding mechanisms...	Computational Account of Spontaneous Activity as a Signature of Predictive Coding	journal.pcbi.1005355	null	[ [ "A growing amount of experimental evidence suggests a complex interaction between stimulus-driven and spontaneous activity [1–3] .", "In sensory cortices of awake behaving animals , neural activity is present both during periods when the neural population is driven by sensory stimuli , as well as in absen...	[ "Spontaneous activity is commonly observed in a variety of cortical states .", "Experimental evidence suggested that neural assemblies undergo slow oscillations with Up ad Down states even when the network is isolated from the rest of the brain .", "Here we show that these spontaneous events can be generated by...	[ "Spontaneous bursts of activity , commonly observed in the brain , can be understood in terms of error-correcting computation within a neural network .", "Bursts arise automatically in a network that is inefficiently correcting its internal representation ." ]	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "cryptococcosis", "medicine", "infectious diseases", "infectious diseases of the nervous system", "immune cells", "respiratory infections", "clinical immunology", "immunity", "nk cells", "immune defense", "immunology", "fungal diseases", "biology", "lower respiratory tract infections", "...	An Acidic Microenvironment Increases NK Cell Killing of Cryptococcus neoformans and Cryptococcus gattii by Enhancing Perforin Degranulation	journal.ppat.1003439	null	[ [ "The yeast , Cryptococcus causes potentially life threatening pneumonia and meningitis .", "While C . neoformans causes infections more commonly in immunosuppressed individuals such as those with AIDS or hematologic malignancies [1] , the tropical fungus C . gattii has recently emerged on Vancouver Island...	[ "Cryptococcus gattii and Cryptococcus neoformans are encapsulated yeasts that can produce a solid tumor-like mass or cryptococcoma .", "Analogous to malignant tumors , the microenvironment deep within a cryptococcoma is acidic , which presents unique challenges to host defense .", "Analogous to malignant cells ...	[ "Immune responses that protect from infection must occur in a variety of unique and potentially hostile environments .", "Within these environments , acidosis causes profound affects on protective responses .", "Low pH can occur in focal tumor-like infections , such as in a cryptococcoma produced by the fungal ...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Genomic Location of the Major Ribosomal Protein Gene Locus Determines Vibrio cholerae Global Growth and Infectivity	journal.pgen.1005156	null	[ [ "The bacterial genome consists of a DNA molecule which is compacted 1000-fold to occupy about 15% of the cell volume [1] .", "The genome is precisely organized within such a limited cellular space to ensure that DNA replication , segregation and gene expression are well orchestrated [1–3] .", "Bioinfo...	[ "The effects on cell physiology of gene order within the bacterial chromosome are poorly understood .", "In silico approaches have shown that genes involved in transcription and translation processes , in particular ribosomal protein ( RP ) genes , localize near the replication origin ( oriC ) in fast-growing bac...	[ "Increasing evidence indicates that nucleoid spatiotemporal organization is crucial for bacterial physiology since these microorganism lack compartmentalized nucleus .", "However , it is still unclear how gene order within the chromosome can influence cell physiology .", "Here , by systematically relocating rib...	2015
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "invertebrates", "medicine and health sciences", "body fluids", "pathology and laboratory medicine", "viral transmission and infection", "pathogens", "vector-borne diseases", "microbiology", "saliva", "animals", "viral vectors", "viruses", "rna viruses", "insect vectors", "infectious dis...	Estimating the effects of variation in viremia on mosquito susceptibility, infectiousness, and R0 of Zika in Aedes aegypti	journal.pntd.0006733	null	[ [ "Although discovered in 1947 [1] , Zika virus ( ZIKV ) has recently become a public health concern due to its rapid spread and newly identified teratogenic effects [2] .", "Shortly after isolation from a rhesus macaque in Uganda , the virus caused several mild infections in humans [3 , 4] .", "ZIKV in...	[ "Zika virus ( ZIKV ) is an arbovirus primarily transmitted by Aedes mosquitoes .", "Like most viral infections , ZIKV viremia varies over several orders of magnitude , with unknown consequences for transmission .", "To determine the effect of viral concentration on ZIKV transmission risk , we exposed field-deri...	[ "The number of people at risk for contracting Zika virus ( ZIKV ) is difficult to estimate accurately because most infected hosts are asymptomatic and the relationship between variation in host viremia and transmission to local mosquitoes is unclear .", "Controlling ZIKV transmission remains a major challenge due...	2018
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[]	A Shift from Cellular to Humoral Responses Contributes to Innate Immune Memory in the Vector Snail Biomphalaria glabrata	journal.ppat.1005361	null	[ [ "The environment of an invertebrate is filled with complex and changing populations of microorganisms , including potential pathogens .", "This engenders selective pressures comparable to those experienced by Gnathostomes [1] , and means that invertebrates should possess sophisticated immune systems capab...	[ "Discoveries made over the past ten years have provided evidence that invertebrate antiparasitic responses may be primed in a sustainable manner , leading to the failure of a secondary encounter with the same pathogen .", "This phenomenon called “immune priming” or \"innate immune memory\" was mainly phenomenolog...	[ "Schistosomiasis is the second most widespread tropical parasitic disease after malaria .", "It is caused by flatworms of the genus Schistosoma .", "Its life cycle is complex and requires certain freshwater snail species as the intermediate host .", "Given the limited options for treating S . mansoni infectio...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "meiosis", "animal genetics", "genetic mutation", "chromosome structure and function", "gene function", "animal models", "telomeres", "model organisms", "molecular genetics", "chromatin", "chromosome biology", "biology", "mouse", "cell biology", "heredity", "genetics", "genomics", ...	Conditional Inactivation of the DNA Damage Response Gene Hus1 in Mouse Testis Reveals Separable Roles for Components of the RAD9-RAD1-HUS1 Complex in Meiotic Chromosome Maintenance	journal.pgen.1003320	null	[ [ "The requirement for effective genome maintenance is particularly notable in germ cells , which must transmit high quality DNA to future generations .", "Therefore , germ cells must employ DNA damage response mechanisms that are at least as stringent as those present in somatic cells .", "Meiosis , wh...	[ "The RAD9-RAD1-HUS1 ( 9-1-1 ) complex is a heterotrimeric PCNA-like clamp that responds to DNA damage in somatic cells by promoting DNA repair as well as ATR-dependent DNA damage checkpoint signaling .", "In yeast , worms , and flies , the 9-1-1 complex is also required for meiotic checkpoint function and efficie...	[ "Meiosis is a specialized cell division process in which germ cells undergo two cell divisions to produce haploid progeny .", "Two processes , genetic recombination and chromosome pairing/synapsis , are critical for successful meiosis and the production of gametes with high chromosomal integrity .", "The RAD9-R...	2013
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "oncology", "medicine", "infectious diseases", "gastroenterology and hepatology", "biology", "microbiology", "molecular cell biology" ]	Caveolin-1 Protects B6129 Mice against Helicobacter pylori Gastritis	journal.ppat.1003251	null	[ [ "Helicobacter pylori ( H . pylori ) is a Gram-negative bacterium which colonizes stomachs of approx .", "50% of the world's population and increases the risk for development of chronic gastritis , peptic ulcer disease , gastric mucosa-associated lymphoid tissue ( MALT ) lymphoma , mucosal atrophy and gast...	[ "Caveolin-1 ( Cav1 ) is a scaffold protein and pathogen receptor in the mucosa of the gastrointestinal tract .", "Chronic infection of gastric epithelial cells by Helicobacter pylori ( H . pylori ) is a major risk factor for human gastric cancer ( GC ) where Cav1 is frequently down-regulated .", "However , the ...	[ "Infection with the bacterium Helicobacter pylori ( H . pylori ) mainly affects children in the developing countries who are at risk to progress to gastric cancer ( GC ) as adults after many years of persistent infection , especially with strains which are positive for the oncogenic virulence factor CagA .", "Era...	2013
[ "Introduction", "Materials and methods", "Results", "Discussion" ]	[ "medicine and health sciences", "ecology and environmental sciences", "pathology and laboratory medicine", "togaviruses", "chikungunya infection", "viral transmission and infection", "muscle tissue", "chemical compounds", "gene regulation", "pathogens", "atmospheric science", "cell processes",...	Macropinocytosis dependent entry of Chikungunya virus into human muscle cells	journal.pntd.0007610	null	[ [ "Chikungunya virus ( CHIKV ) is an arthropod-borne virus belonging to genus Alphavirus and family Togaviridae .", "CHIKV is most commonly transmitted by Aedes ( Ae . ) mosquitoes .", "First isolated in 1952 in Tanzania , CHIKV transmission begins with infection of female mosquitoes via a viremic blood...	[ "Chikungunya virus ( CHIKV ) is a re-emerging arbovirus known to cause chronic myalgia and arthralgia with high morbidity .", "CHIKV is now considered endemic in many countries across Asia and Africa .", "In this study , the susceptibility of various human , mammalian and mosquito cell lines to CHIKV infection ...	[ "This study revealed the differences in susceptibility of various human , mammalian and mosquito cell lines to CHIKV infection .", "CHIKV infection was found to be cell-type dependent and virus-strain specific .", "Additionally , two human muscle cell lines , SJCRH30 ( rhabdomyosarcoma cell line ) and HSMM ( hu...	2019
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "taxonomy", "oomycetes", "chemical compounds", "microbiology", "nitrates", "phylogenetics", "data management", "fungi", "phylogenetic analysis", "research and analysis methods", "sequence analysis", "computer and information sciences", "sequence alignment", "bioinformatics", "proteins", ...	Reticulate evolution in eukaryotes: Origin and evolution of the nitrate assimilation pathway	journal.pgen.1007986	null	[ [ "One of the most significant advances in evolution was the realization that lineages , either genes or genomes , can also evolve through interchanging genetic material , this leading to reticulate evolutionary patterns [1 , 2] .", "Reticulate evolution , and in particular horizontal gene transfer ( HGT ) ...	[ "Genes and genomes can evolve through interchanging genetic material , this leading to reticular evolutionary patterns .", "However , the importance of reticulate evolution in eukaryotes , and in particular of horizontal gene transfer ( HGT ) , remains controversial .", "Given that metabolic pathways with taxon...	[ "One of the most relevant findings in evolution was that lineages , either genes or genomes , can evolve through interchanging genetic material .", "For example , exon shuffling can lead to genes with complete novel functions , and genomes can acquire novel functionalities by means of horizontal gene transfer ( H...	2019
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "invertebrates", "medicine and health sciences", "pig models", "population genetics", "tropical diseases", "computational biology", "parasitic diseases", "animals", "invertebrate genomics", "animal models", "model organisms", "ectoparasitic infections", "sexually transmitted diseases", "ge...	Mitochondrial Genome Sequence of the Scabies Mite Provides Insight into the Genetic Diversity of Individual Scabies Infections	journal.pntd.0004384	null	[ [ "The scabies mite is an ectoparasitic arachnid that causes an itchy skin infection , known as scabies .", "Each year around 300 million people worldwide are affected by scabies [1] .", "Scabies is responsible for a significant disease burden in affected populations through its obligate parasitic lifec...	[ "The scabies mite , Sarcoptes scabiei , is an obligate parasite of the skin that infects humans and other animal species , causing scabies , a contagious disease characterized by extreme itching .", "Scabies infections are a major health problem , particularly in remote Indigenous communities in Australia , where...	[ "The scabies mite is a skin parasite that infects humans and other animal species , causing scabies , a contagious disease characterized by extreme itching .", "Scabies infections are a major health problem in developing countries and in indigenous Australian populations , where scabies is associated with pyoderm...	2016
[ "Introduction", "Material and Methods", "Results", "Discussion" ]	[]	Cell-Based Multi-Parametric Model of Cleft Progression during Submandibular Salivary Gland Branching Morphogenesis	journal.pcbi.1003319	null	[ [ "Branching morphogenesis is a specific type of tissue morphogenesis that is a crucial developmental process occurring in several organs , such as the mammary glands , lungs , kidney , and salivary glands to maximize epithelial surface area for secretion or absorption of fluids and gases [1] .", "The proce...	[ "Cleft formation during submandibular salivary gland branching morphogenesis is the critical step initiating the growth and development of the complex adult organ .", "Previous experimental studies indicated requirements for several epithelial cellular processes , such as proliferation , migration , cell-cell adh...	[ "Branching morphogenesis is a complex and dynamic embryonic process that creates the structure of many adult organs , including the salivary gland .", "During this process , many cellular changes occur in the epithelial cells , including changes in cell-cell adhesions , cell-extracellular matrix ( matrix ) adhesi...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genetics and genomics", "developmental biology", "neuroscience/sensory systems" ]	A Novel zf-MYND Protein, CHB-3, Mediates Guanylyl Cyclase Localization to Sensory Cilia and Controls Body Size of Caenorhabditis elegans	journal.pgen.1001211	null	[ [ "Cilia are highly conserved microtubule-based hair-like organelles , which are specialized subcellular compartments where a number of transmembrane receptors and channels are localized [1] .", "Through these molecules in cilia , environmental signals are transmitted to the cytoplasm and nucleus .", "F...	[ "Cilia are important sensory organelles , which are thought to be essential regulators of numerous signaling pathways .", "In Caenorhabditis elegans , defects in sensory cilium formation result in a small-body phenotype , suggesting the role of sensory cilia in body size determination .", "Previous analyses sug...	[ "Caenorhabditis elegans is a 1–2 mm long nematode .", "Its body size is controlled by sensory inputs; some mutants with defects in sensory perception grow into small size ( 20%–30% decrease in body volume ) , although the animals seem to feed normally .", "The EGL-4 cGMP-dependent protein kinase and the GCY-12 ...	2010
[ "Introduction", "Methods", "Results", "Discussion" ]	[]	Elimination and Eradication of Neglected Tropical Diseases with Mass Drug Administrations: A Survey of Experts	journal.pntd.0002562	null	[ [ "The most prevalent neglected tropical diseases ( NTDs ) , including lymphatic filariasis ( LF ) , onchocerciasis , schistosomiasis , soil-transmitted helminths ( STHs ) , and trachoma , are routinely treated with periodic mass drug administrations ( MDAs ) [1] , [2] .", "Repeated mass drug treatments may...	[ "Lymphatic filariasis , onchocerciasis , schistosomiasis , soil-transmitted helminths , and trachoma are the five most prevalent neglected tropical diseases in the world , and each is frequently treated with mass drug administrations .", "We performed a survey of neglected tropical diseases experts to elicit thei...	[ "Mass drug administrations are used for each of the five most common neglected tropical diseases: lymphatic filariasis , onchocerciasis , schistosomiasis , soil-transmitted helminths , and trachoma .", "Three of these infections—lymphatic filariasis , onchocerciasis , and trachoma—are officially targeted for elim...	2013
[ "Introduction", "Methods", "Results", "Discussion" ]	[]	Medical Student Knowledge of Neglected Tropical Diseases in Peru: A Cross-Sectional Study	journal.pntd.0004197	null	[ [ "The concept of neglected tropical diseases ( NTD ) is a set of disabling conditions that are the most common chronic infections in the poorest people [1 , 2] .", "These conditions are typically prevalent in low-income communities in rural or pre-urban areas that lack of sanitation and access to health ca...	[ "In developing countries , education to health-care professionals is a cornerstone in the battle against neglected tropical diseases ( NTD ) .", "Studies evaluating the level of knowledge of medical students in clinical and socio-demographic aspects of NTD are lacking .", "Therefore , a cross-sectional study wa...	[ "Since the promulgation of the United Nations Millennium Development Goals in 2000 and the posterior creation of the WHO’s Department of Control of Neglected Tropical Diseases five years later; encouraging progress in the diagnosis , treatment and prevention of these infectious diseases has been made .", "However...	2015
[ "Introduction", "Methods", "Results", "Discussion", "Conclusion" ]	[ "public health and epidemiology/epidemiology" ]	Risk Factors for Buruli Ulcer: A Case Control Study in Cameroon	journal.pntd.0000101	null	[ [ "Buruli ulcer ( BU ) is an infectious disease involving the skin , caused by Mycobacterium ulcerans , characterized by a painless nodule , papule , plaque or edema , evolving into a painless ulcer with undermined edges , often leading to disabling sequelae [1] .", "BU has been reported from 30 countries i...	[ "Buruli ulcer is an infectious disease involving the skin , caused by Mycobacterium ulcerans .", "This disease is associated with areas where the water is slow-flowing or stagnant .", "However , the exact mechanism of transmission of the bacillus and the development of the disease through human activities is un...	[ "Buruli ulcer ( BU ) is a neglected tropical infectious disease caused by Mycobacterium ulcerans .", "While BU is associated with areas where the water is slow-flowing or stagnant , the exact mechanism of transmission of the bacillus is unknown , impairing efficient control programs .", "Two hypotheses are prop...	2007
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "neuroscience/cognitive neuroscience", "neuroscience/sensory systems", "computational biology/computational neuroscience", "neuroscience/experimental psychology", "neuroscience/theoretical neuroscience" ]	Probability Matching as a Computational Strategy Used in Perception	journal.pcbi.1000871	null	[ [ "Human performance in perceptual tasks is often benchmarked by optimal strategies .", "An optimal strategy is one that performs best with respect to its objectives or maximizes expected reward or equivalently , minimizes a cost function [1] , [2] .", "Previous studies have investigated whether perform...	[ "The question of which strategy is employed in human decision making has been studied extensively in the context of cognitive tasks; however , this question has not been investigated systematically in the context of perceptual tasks .", "The goal of this study was to gain insight into the decision-making strategy...	[ "For any task , the utility function specifies the goal to be achieved .", "For example , in taking a multiple-choice test , the utility is the total number of correct answers .", "An optimal decision strategy for a task is one that maximizes the utility .", "Because the utility functions and decision strateg...	2010
[ "Introduction", "Methods", "Results", "Discussion" ]	[]	Validation of Recombinant Salivary Protein PpSP32 as a Suitable Marker of Human Exposure to Phlebotomus papatasi, the Vector of Leishmania major in Tunisia	journal.pntd.0003991	null	[ [ "Leishmaniasis affects millions of people worldwide .", "It is a heterogeneous group of diseases caused by Leishmania parasites .", "Zoonotic cutaneous leishmaniasis ( ZCL ) is the most prevalent form in North Africa and is widespread in Central Tunisia .", "With an annual incidence of ~5 , 000 ca...	[ "During a blood meal , female sand flies , vectors of Leishmania parasites , inject saliva into the host skin .", "Sand fly saliva is composed of a large variety of components that exert different pharmacological activities facilitating the acquisition of blood by the insect .", "Importantly , proteins present ...	[ "Leishmaniasis results from an infection by Leishmania parasites that are transmitted through the bites of infected sand flies .", "This disease affects millions of people worldwide .", "Zoonotic cutaneous leishmaniasis is widespread in Central Tunisia and constitutes an actual public health problem .", "Leis...	2015
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "cell death", "medicine and health sciences", "cancer treatment", "cell processes", "biological cultures", "cancers and neoplasms", "basic cancer research", "epithelial cells", "oncology", "animal models", "model organisms", "experimental organism systems", "cell cultures", "chromatophores...	The RhoJ-BAD signaling network: An Achilles’ heel for BRAF mutant melanomas	journal.pgen.1006913	null	[ [ "Oncogenes regulate cellular homeostasis in normal cells , and when mutated induce secondary physiological changes that stress cellular capacity for survival [1 , 2] .", "Paradoxically , oncogenes drive the uncontrolled growth of tumor cells [3] and represent some of the most effective cancer therapeutic ...	[ "Genes and pathways that allow cells to cope with oncogene-induced stress represent selective cancer therapeutic targets that remain largely undiscovered .", "In this study , we identify a RhoJ signaling pathway that is a selective therapeutic target for BRAF mutant cells .", "RhoJ deletion in BRAF mutant melan...	[ "BRAFV600E is the most common mutation in human melanomas , and kinase inhibitors that block BRAFV600E signaling can rapidly induce tumor regression but only modestly improve melanoma long-term survival .", "In this study , we identify a novel therapeutic vulnerability for BRAF mutant melanoma tumors .", "Targe...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "physiological processes", "computational neuroscience", "physiology", "sleep", "biology and life sciences", "computational biology", "neuroscience" ]	Synchronization of Isolated Downstates (K-Complexes) May Be Caused by Cortically-Induced Disruption of Thalamic Spindling	journal.pcbi.1003855	null	[ [ "The EEG during deep non-rapid eye movement sleep ( NREM stage N3 ) is dominated by very large slow oscillations ( SO ) at ∼1 Hz .", "Intracellular recordings show that the SO represents alternating ‘upstates’ when neural activity is comparable to waking , and ‘downstates’ when most pyramidal ( PY ) and i...	[ "Sleep spindles and K-complexes ( KCs ) define stage 2 NREM sleep ( N2 ) in humans .", "We recently showed that KCs are isolated downstates characterized by widespread cortical silence .", "We demonstrate here that KCs can be quasi-synchronous across scalp EEG and across much of the cortex using electrocorticog...	[ "EEG in the most common stage of human sleep is dominated by K-complexes ( KCs ) and sleep spindles ( bursts of 10–14 Hz oscillations ) occupying the thalamus and cortex .", "Recently , we discovered that KCs are brief moments when the cortex becomes almost completely silent .", "Here , using recordings directl...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Ly6C- Monocytes Regulate Parasite-Induced Liver Inflammation by Inducing the Differentiation of Pathogenic Ly6C+ Monocytes into Macrophages	journal.ppat.1004873	null	[ [ "Hosts can develop two different strategies to control pathogen infections , resistance and tolerance .", "During resistance , the host reduces the pathogen burden by activating and recruiting immune cells to the site of infection that mount a pro-inflammatory immune response .", "Tolerance refers to ...	[ "Monocytes consist of two well-defined subsets , the Ly6C+ and Ly6C– monocytes .", "Both CD11b+ myeloid cells populations have been proposed to infiltrate tissues during inflammation .", "While infiltration of Ly6C+ monocytes is an established pathogenic factor during hepatic inflammation , the role of Ly6C– mo...	[ "The liver is not only a central organ for efficient metabolism of nutrients and for toxin clearance , but also for immune surveillance , including elimination of intravascular infections .", "However , excess of nutrients like fat or of toxins like alcohol and certain medications , as well as infections can trig...	2015
[ "Introduction", "Materials and methods", "Results", "Discussion" ]	[ "dengue virus", "viral vaccines", "medicine and health sciences", "immune physiology", "enzyme-linked immunoassays", "pathology and laboratory medicine", "pathogens", "immunology", "microbiology", "viruses", "vaccines", "preventive medicine", "immunologic adjuvants", "rna viruses", "infe...	Zika virus-like particle (VLP) based vaccine	journal.pntd.0005608	null	[ [ "Zika fever results from an infection with the Zika virus ( ZIKV ) , which is transmitted to humans by the bite of an infected Aedes mosquito ( primarily A . aegypti ) .", "Zika virus was isolated for the first time from a Rhesus monkey in the Zika Forest in Uganda in 1947 and later from humans in Africa ...	[ "The newly emerged mosquito-borne Zika virus poses a major public challenge due to its ability to cause significant birth defects and neurological disorders .", "The impact of sexual transmission is unclear but raises further concerns about virus dissemination .", "No specific treatment or vaccine is currently ...	[ "Zika is an emerging mosquito-borne infection for which vaccines or specific treatments are not available to combat and control its rapid dissemination and deleterious effects .", "This work describes a novel strategy for the development of a virus-like particle ( VLP ) based Zika vaccine and shows its effectiven...	2017
[ "Introduction", "Results", "Discussion", "Material and Methods" ]	[ "medicine and health sciences", "vesicles", "crystal structure", "biomineralization", "condensed matter physics", "operons", "light microscopy", "physiological processes", "crystals", "microscopy", "materials science", "dna", "crystallography", "cellular structures and organelles", "mate...	Genetic and Ultrastructural Analysis Reveals the Key Players and Initial Steps of Bacterial Magnetosome Membrane Biogenesis	journal.pgen.1006101	null	[ [ "Although many prokaryotes are currently known to form intracytoplasmic membranes ( ICM ) , the underlying mechanisms of ICM formation are still widely unexplored [1 , 2] .", "One of the most sophisticated model systems to study the biogenesis of prokaryotic ICM and organelles are bacterial magnetosomes ,...	[ "Magnetosomes of magnetotactic bacteria contain well-ordered nanocrystals for magnetic navigation and have recently emerged as the most sophisticated model system to study the formation of membrane bounded organelles in prokaryotes .", "Magnetosome biosynthesis is thought to begin with the formation of a dedicate...	[ "One of the most intriguing examples for membrane-bounded prokaryotic organelles are magnetosomes which consist of well-ordered chains of perfectly shaped magnetic nanocrystals that in many aquatic bacteria serve as geomagnetic field sensors to direct their swimming towards microoxic zones at the bottom of natural ...	2016
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "learning", "cognitive neurology", "medicine and health sciences", "diagnostic radiology", "functional magnetic resonance imaging", "engineering and technology", "signal processing", "social sciences", "neuroscience", "learning and memory", "signal filtering", "magnetic resonance imaging", "...	Self-regulation strategy, feedback timing and hemodynamic properties modulate learning in a simulated fMRI neurofeedback environment	journal.pcbi.1005681	null	[ [ "Neuroimaging studies often find correlations between behaviors and recorded neural activation .", "To test whether these relationships are causal , neuroscientists must find a way to manipulate the underlying neural structure and observe whether the associated behavior is affected .", "In human neuro...	[ "Direct manipulation of brain activity can be used to investigate causal brain-behavior relationships .", "Current noninvasive neural stimulation techniques are too coarse to manipulate behaviors that correlate with fine-grained spatial patterns recorded by fMRI .", "However , these activity patterns can be man...	[ "By repeatedly stimulating fine-grained patterns of neural activity , it is possible to manipulate behaviors associated with these patterns .", "While millimeter-scale patterns cannot yet be targeted with noninvasive brain stimulation , some people can learn to self-stimulate these activity patterns if they recei...	2017
[ "Introduction", "Results", "Discussion" ]	[ "cell binding", "cell physiology", "leukemias", "chemical characterization", "medicine and health sciences", "gene regulation", "regulatory proteins", "dna-binding proteins", "cancers and neoplasms", "dna transcription", "oncology", "hematologic cancers and related disorders", "mutation", ...	PAX5 is part of a functional transcription factor network targeted in lymphoid leukemia	journal.pgen.1008280	null	[ [ "It is becoming increasingly clear that transcription factors essential for normal B-cell development are frequently mutated in B-lineage Acute Lymphoblastic Leukemia ( B-ALL ) [1] .", "One of the most common targets for genetic alterations in B-ALL is the transcription factor PAX5 targeted both by transl...	[ "One of the most frequently mutated proteins in human B-lineage leukemia is the transcription factor PAX5 .", "These mutations often result in partial rather than complete loss of function of the transcription factor .", "While the functional dose of PAX5 has a clear connection to human malignancy , there is li...	[ "The use of modern high throughput DNA-sequencing has dramatically increased our ability to identify genetic alterations associated with cancer .", "However , while the mutations per se are rather easily identified , our understanding of how these mutations impact cellular functions and drive malignant transforma...	2019
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genetics and genomics/comparative genomics", "genetics and genomics/chromosome biology", "genetics and genomics/genetics of disease", "genetics and genomics", "genetics and genomics/cancer genetics" ]	Post-Replication Repair Suppresses Duplication-Mediated Genome Instability	journal.pgen.1000933	null	[ [ "Post-replication repair ( PRR ) was first identified in bacteria as a pathway for the repair of single-stranded gaps in DNA produced during the replication of DNA that had been damaged by exposure to ultraviolet light resulting in replication blocking lesions [1] , [2] .", "PRR was also identified in the...	[ "RAD6 is known to suppress duplication-mediated gross chromosomal rearrangements ( GCRs ) but not single-copy sequence mediated GCRs .", "Here , we found that the RAD6- and RAD18-dependent post-replication repair ( PRR ) and the RAD5- , MMS2- , UBC13-dependent error-free PRR branch acted in concert with the repli...	[ "Genome instability is a hallmark of many cancers and underlies many inherited disorders that cause a predisposition to cancer .", "The human genome has many different types of duplicated sequences that can lead to genome instability by recombination-mediated pathways .", "We previously discovered that duplicat...	2010
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "neuroscience/behavioral neuroscience", "neuroscience/cognitive neuroscience", "neuroscience/sensory systems", "neuroscience/motor systems", "mathematics/statistics", "neuroscience/experimental psychology" ]	Grasping Objects with Environmentally Induced Position Uncertainty	journal.pcbi.1000538	null	[ [ "Optimal sensorimotor control models actions as decisions that maximize the desirableness of outcomes , where the desirableness is captured by an expected cost or utility to each action sequence .", "These models provide explanations for many aspects of our ability to compensate for uncertainty [1]–[3] ."...	[ "Due to noisy motor commands and imprecise and ambiguous sensory information , there is often substantial uncertainty about the relative location between our body and objects in the environment .", "Little is known about how well people manage and compensate for this uncertainty in purposive movement tasks like g...	[ "Optimal sensorimotor control models actions as decisions that maximize the desirableness of outcomes , where the desirableness is captured by an expected cost or utility to each action sequence .", "These models provide explanations for many aspects of our ability to compensate for uncertainty , but they have no...	2009
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "connectomics", "behavioral neuroscience", "neuroanatomy", "biology", "neuroscience", "learning and memory", "neuroimaging", "animal cognition" ]	Identification of a Functional Connectome for Long-Term Fear Memory in Mice	journal.pcbi.1002853	null	[ [ "Long-term memories are thought to be represented by changes in the strength of connections among neurons in the brain [1] , [2] .", "While much is understood about the molecular , cellular and structural changes that contribute to the changes in connection strength between neurons [3] , [4] , [5] , it ha...	[ "Long-term memories are thought to depend upon the coordinated activation of a broad network of cortical and subcortical brain regions .", "However , the distributed nature of this representation has made it challenging to define the neural elements of the memory trace , and lesion and electrophysiological approa...	[ "Memory retrieval is thought to involve the coordinated activation of multiple regions of the brain , rather than localized activity in a specific region .", "In order to visualize networks of brain regions activated by recall of a fear memory in mice , we quantified expression of an activity-regulated gene ( c-f...	2013
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "biology" ]	Improving the Cost-Effectiveness of Visual Devices for the Control of Riverine Tsetse Flies, the Major Vectors of Human African Trypanosomiasis	journal.pntd.0001257	null	[ [ "African sleeping sickness or Human African Trypanosomiasis ( HAT ) is endemic to 36 countries in sub-Saharan Africa covering 9 million km2 with 60 million of the 400 million inhabitants at risk of the disease .", "Africa has emerged from a recent sleeping sickness epidemic .", "In 1997 about 450 , 00...	[ "Control of the Riverine ( Palpalis ) group of tsetse flies is normally achieved with stationary artificial devices such as traps or insecticide-treated targets .", "The efficiency of biconical traps ( the standard control device ) , 1×1 m black targets and small 25×25 cm targets with flanking nets was compared u...	[ "Sleeping Sickness ( Human African Trypanosomiasis ) is a serious threat to health and development in sub-Saharan Africa .", "Currently there are no vaccines or prophylactic drugs available to prevent contraction of the disease .", "Consequently vector control is the only method of disease prevention .", "In ...	2011
[ "Introduction", "Materials and methods", "Results and discussion" ]	[ "death rates", "invertebrates", "medicine and health sciences", "ixodes", "pathology and laboratory medicine", "demography", "pathogens", "geographical locations", "microbiology", "rickettsia", "animals", "developmental biology", "nymphs", "ticks", "infectious disease control", "bacter...	Transmission dynamics and control of Rickettsia rickettsii in populations of Hydrochoerus hydrochaeris and Amblyomma sculptum	journal.pntd.0005613	null	[ [ "Rickettsia rickettsii is the etiological agent of the Brazilian spotted fever ( BSF ) , the deadliest spotted fever in the world .", "This infection is partially pathogenic to Amblyomma sculptum ticks , main vectors of the R . rickettsii in South America [1 , 2] , generating a drop in the infection rate ...	[ "Brazilian Spotted Fever ( BSF ) , caused by the bacterium Rickettsia rickettsii , is the tick-borne disease that generates the largest number of human deaths in the world .", "In Brazil , the current increase of BSF human cases has been associated with the presence and expansion of capybaras Hydrochoerus hydroch...	[ "A stochastic model for the spread of R . rickettsii among the Amblyomma sculptum tick vector and the Hydrochoerus hydrochaeris , amplifier host , was formulated .", "We found that the introduction of a single infected capybara , with at least one infected attached tick , is enough to trigger the disease in a non...	2017
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "livestock", "medicine and health sciences", "ruminants", "infectious disease epidemiology", "tropical diseases", "geographical locations", "vertebrates", "census", "animals", "mammals", "bacterial diseases", "research design", "farms", "flooding", "neglected tropical diseases", "fiji"...	Human Leptospirosis Infection in Fiji: An Eco-epidemiological Approach to Identifying Risk Factors and Environmental Drivers for Transmission	journal.pntd.0004405	null	[ [ "Leptospirosis is an emerging infectious disease worldwide , with particularly high incidence reported in the Pacific Islands [1 , 2] .", "Humans are infected through direct contact with infected animals , or through contact with water or soil that has been contaminated by urine of infected animals .", ...	[ "Leptospirosis is an important zoonotic disease in the Pacific Islands .", "In Fiji , two successive cyclones and severe flooding in 2012 resulted in outbreaks with 576 reported cases and 7% case-fatality .", "We conducted a cross-sectional seroprevalence study and used an eco-epidemiological approach to charac...	[ "Leptospirosis is a bacterial infection transmitted from animals to humans , and many outbreaks are associated with flooding .", "Globally , leptospirosis is responsible for at least a million cases of severe illness each year , and many deaths .", "The bacteria are excreted in the urine of infected animals; hu...	2016
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "medicine", "infectious diseases", "geography", "public health and epidemiology", "social and behavioral sciences", "diagnostic medicine", "epidemiology", "global health", "public health" ]	Population Structure of Staphylococcus aureus from Remote African Babongo Pygmies	journal.pntd.0001150	null	[ [ "Methicillin-resistant Staphylococcus aureus ( MRSA ) has emerged as a community-acquired pathogen in many countries throughout the world ( community-acquired MRSA , CA-MRSA ) .", "CA-MRSA mostly causes skin or soft-tissue infections as well as deep-seated infections such as necrotizing pneumonia .", ...	[ "Pandemic community-acquired methicillin-resistant Staphylococcus aureus isolates ( CA-MRSA ) predominantly encode the Panton-Valentine leukocidin ( PVL ) , which can be associated with severe infections .", "Reports from non-indigenous Sub-Saharan African populations revealed a high prevalence of PVL-positive is...	[ "Staphylococcus aureus is a bacterium that colonizes humans worldwide .", "The anterior nares are its main ecological niche .", "Carriers of S . aureus are at a higher risk of developing invasive infections .", "Few reports indicated a different clonal structure and profile of virulence factors in S . aureus ...	2011
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "molecular neuroscience", "developmental neuroscience", "peripheral nervous system", "biology", "neuroscience", "neurophysiology" ]	Uncoupling of Molecular Maturation from Peripheral Target Innervation in Nociceptors Expressing a Chimeric TrkA/TrkC Receptor	journal.pgen.1004081	null	[ [ "Sensory neurons of the dorsal root ganglia ( DRG ) represent a powerful model for studying neuronal survival , fate determination and neuronal circuit assembly during development .", "Indeed , after initial fate specification , these neurons establish connections with neurons in the spinal cord and with ...	[ "Neurotrophins and their receptors control a number of cellular processes , such as survival , gene expression and axonal growth , by activating multiple signalling pathways in peripheral neurons .", "Whether each of these pathways controls a distinct developmental process remains unknown .", "Here we describe ...	[ "Sensory neurons located in dorsal root ganglia are critical for perception of various stimuli by transmitting information from their peripheral targets to the spinal cord .", "During embryonic development , distinct populations of sensory neurons are defined based on expression of neurotrophin receptors Trks .",...	2014
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "public and occupational health", "infectious diseases", "helminth infections", "medicine and health sciences", "filariasis", "disease eradication", "global health", "neglected tropical diseases", "lymphatic filariasis", "tropical diseases", "infectious disease control", "loiasis", "onchocer...	Repurposed Automated Handheld Counter as a Point-of-Care Tool to Identify Individuals ‘At Risk’ of Serious Post-Ivermectin Encephalopathy	journal.pntd.0003180	null	[ [ "Among the many parasitic helminth infections , the diseases caused by Loa loa , Wuchereria bancrofti and Onchocerca volvulus infections are major public health and socio-economic problems in many countries in West and Central Africa .", "Commonly , individuals harboring microfilariae ( mf ) of W . bancro...	[ "Administration of ivermectin ( IVM ) as part of mass drug administration ( MDA ) campaigns for onchocerciasis and/or lymphatic filariasis ( LF ) has been suspended in areas co-endemic for Loa loa due to severe post-treatment adverse events ( SAEs ) associated with high-burden of infection ( >30 , 000 mf/ml ) .", ...	[ "Mass drug administration ( MDA ) efforts with ivermectin-based regimens for onchocerciasis and for lymphatic filariasis in Africa have been suspended in certain areas that are co-endemic for Loa loa infection .", "This is due to the serious adverse events ( encephalopathy and death ) that can develop following i...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	The Yeast GSK-3 Homologue Mck1 Is a Key Controller of Quiescence Entry and Chronological Lifespan	journal.pgen.1005282	null	[ [ "Research into the biology of aging in different model organisms has identified several signaling pathways affecting lifespan .", "Among them , the partially conserved insulin/IGF-1 signaling pathway and the conserved TOR pathway regulate lifespan in organisms from insects to mammals [1–2] .", "Multip...	[ "Upon starvation for glucose or any other core nutrient , yeast cells exit from the mitotic cell cycle and acquire a set of G0-specific characteristics to ensure long-term survival .", "It is not well understood whether or how cell cycle progression is coordinated with the acquisition of different G0-related feat...	[ "The vast majority of eukaryotic cells exist in a non-proliferating state known as G0 .", "However , how cells transit into , and survive during , the G0 state is poorly understood .", "Dysregulation of the G0 state leads to age-related diseases such as Alzheimer’s or cancers .", "We have revealed that the ye...	2015
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "livestock", "medicine and health sciences", "immune physiology", "enzyme-linked immunoassays", "ruminants", "immunology", "vertebrates", "animals", "mammals", "cereal crops", "marsupials", "rice", "model organisms", "crops", "antibodies", "immunologic techniques", "plants", "fruit...	Epidemiology of Emergent Madariaga Encephalitis in a Region with Endemic Venezuelan Equine Encephalitis: Initial Host Studies and Human Cross-Sectional Study in Darien, Panama	journal.pntd.0004554	null	[ [ "Madariaga ( MADV ) and Venezuelan equine encephalitis viruses ( VEEV ) are mosquito-borne , single-stranded positive sense RNA viruses ( family Togaviridae , genus Alphavirus ) .", "Both circulate nearly throughout the Americas .", "In Central and South America , VEEV gives rise to a spectrum of dise...	[ "Neurotropic arboviral infections are an important cause of encephalitis .", "A zoonotic , vector-borne alphavirus , Madariaga virus ( MADV; formerly known as South American eastern equine encephalitis virus ) , caused its first documented human outbreak in 2010 in Darien , Panama , where the genetically similar ...	[ "Arthropod-borne viruses are important causes of encephalitis .", "In 2010 , the first documented human outbreak of the mosquito-borne , zoonotic Madariaga virus ( MADV ) occurred in the Darien region of Panama .", "Neither its epidemiology nor its transmission cycle is understood .", "In this study , the aut...	2016
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "medicine and health sciences", "chemical compounds", "electricity", "immunology", "variant genotypes", "population genetics", "organic compounds", "genetic mapping", "clinical medicine", "electrostatics", "amino acid substitution", "gastroenterology and hepatology", "biliary disorders", "...	Amino acid residues in five separate HLA genes can explain most of the known associations between the MHC and primary biliary cholangitis	journal.pgen.1007833	null	[ [ "Primary Biliary Cholangitis ( PBC; formerly known as Primary Biliary Cirrhosis ) is a rare cholestatic liver disease characterized by progressive auto-immune destruction of intrahepatic bile ducts resulting in cholangitis , liver fibrosis and , eventually , cirrhosis .", "Candidate gene studies have cons...	[ "Primary Biliary Cholangitis ( PBC ) is a chronic autoimmune liver disease characterised by progressive destruction of intrahepatic bile ducts .", "The strongest genetic association is with HLA-DQA1*04:01 , but at least three additional independent HLA haplotypes contribute to susceptibility .", "We used dense ...	[ "Primary Biliary Cholangitis ( PBC ) is a chronic autoimmune liver disease that exhibits strong genetic associations , especially with variants in the human leukocyte antigen ( HLA ) gene region .", "Here we use dense single nucleotide polymorphism ( SNP ) data from the largest PBC study to date ( 2861 cases , 85...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Intra-Tumour Signalling Entropy Determines Clinical Outcome in Breast and Lung Cancer	journal.pcbi.1004115	null	[ [ "Over recent years considerable evidence has arisen supporting the hypothesis that some cancers are hierarchically organised , akin to the organisation of healthy cells , with a small population of Cancer Stem Cells ( CSCs ) driving a heterogeneous , hierarchical structure [1 , 2] .", "The abundance of CS...	[ "The cancer stem cell hypothesis , that a small population of tumour cells are responsible for tumorigenesis and cancer progression , is becoming widely accepted and recent evidence has suggested a prognostic and predictive role for such cells .", "Intra-tumour heterogeneity , the diversity of the cancer cell pop...	[ "The Cancer Stem Cell ( CSC ) hypothesis , the idea that a small population of tumour cells have the capacity to seed and grow the tumour , and intra-tumour heterogeneity , the diversity of the cancer cell population within the tumour of an individual patient , have long been considered the basis of potential progn...	2015

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