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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" ]	[ "ecology", "computational biology", "evolutionary biology" ]	Amazonian Amphibian Diversity Is Primarily Derived from Late Miocene Andean Lineages	journal.pbio.1000056	Phylogenetic analysis and ancestral range modeling of the poison-frog clade (Dendrobatidae) indicates that Amazonian species richness derives from repeated dispersals from adjacent regions, especially the Andes.	[ [ "Tropical regions contain more than half of biological diversity on just 7% of the Earth's surface [1 , 2] .", "Differences in biodiversity between tropical and temperate regions have been attributed to contrasting speciation and extinction rates [3] .", "Within the Neotropical realm , the Amazon Basi...	[ "The Neotropics contains half of remaining rainforests and Earth's largest reservoir of amphibian biodiversity .", "However , determinants of Neotropical biodiversity ( i . e . , vicariance , dispersals , extinctions , and radiations ) earlier than the Quaternary are largely unstudied .", "Using a novel method ...	[ "The Neotropics , which includes South and Central America , contains half of remaining rainforests and the largest reservoir of amphibian diversity .", "Why there are so many species in certain areas and how such diversity arose before the Quaternary ( i . e . , more that 1 . 8 million years ago [MYA] ) are larg...	2009
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "humoral immunity", "medicine", "immune cells", "cytokines", "immunity to infections", "immunology", "microbiology", "host-pathogen interaction", "parasitic diseases", "helminth infection", "animal models", "adaptive immunity", "model organisms", "immune defense", "neglected tropical dis...	Early Peritoneal Immune Response during Echinococcus granulosus Establishment Displays a Biphasic Behavior	journal.pntd.0001293	null	[ [ "Helminths are metazoan parasites currently infecting a quarter of the world population [1] .", "The high prevalence of helminthiasis reflects one outstanding feature of parasite infections: chronicity .", "This fact could be read into helminths having special skills to adapt to defense mechanisms tri...	[ "Cystic echinococcosis is a worldwide distributed helminth zoonosis caused by the larval stage of Echinococcus granulosus .", "Human secondary cystic echinococcosis is caused by dissemination of protoscoleces after accidental rupture of fertile cysts and is due to protoscoleces ability to develop into new metaces...	[ "Cystic echinococcosis is a zoonotic disease caused by the larval stage of the cestode Echinococcus granulosus and shows a cosmopolitan distribution with a worldwide prevalence of roughly 6 million infected people .", "Human cystic echinococcosis can develop in two types of infection .", "Primary infection occu...	2011
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "messenger rna", "simulation and modeling", "genome analysis", "molecular biology techniques", "cellular structures and organelles", "genetic footprinting", "research and analysis methods", "genomics", "gene expression", "molecular biology", "ribosomes", "biochemistry", "genetic fingerprinti...	The extent of ribosome queuing in budding yeast	journal.pcbi.1005951	null	[ [ "Understanding the dynamics of protein translation is a fundamental question in biology , and has been extensively studied using experimental and computational methods in recent years [1 , 2] .", "During translation , multiple ribosomes may translate the same mRNA .", "The density of ribosomal traffic...	[ "Ribosome queuing is a fundamental phenomenon suggested to be related to topics such as genome evolution , synthetic biology , gene expression regulation , intracellular biophysics , and more .", "However , this phenomenon hasn't been quantified yet at a genomic level .", "Nevertheless , methodologies for study...	[ "During translation , multiple ribosomes may translate the same mRNA .", "The density of ribosomal traffic across the transcript poses several open questions , such as how often a ribosome’s path is blocked by a second ribosome , do queues of multiple ribosomes typically form on mRNAs and what is their effect on ...	2018
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "ellipses", "statistics", "random variables", "geometry", "covariance", "simulation and modeling", "interpolation", "regression analysis", "mathematics", "artificial intelligence", "research and analysis methods", "statistical distributions", "computer and information sciences", "mathemati...	Prepaid parameter estimation without likelihoods	journal.pcbi.1007181	null	[ [ "Models without an analytical likelihood are increasingly used in various disciplines , such as genetics [1] , ecology [2 , 3] , economics [4 , 5] and neuroscience [6] .", "For such models , parameter estimation is a major challenge for which a variety of solutions have been proposed [2 , 1 , 7] .", "...	[ "In various fields , statistical models of interest are analytically intractable and inference is usually performed using a simulation-based method .", "However elegant these methods are , they are often painstakingly slow and convergence is difficult to assess .", "As a result , statistical inference is greatl...	[ "Interesting nonlinear models are often analytically intractable .", "As a result , statistical inference has to rely on massive , time-intensive , simulations .", "The main idea of our method is to avoid the redundancy of similar computations that typically occur when different researchers independently fit th...	2019
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "invertebrates", "parasite groups", "medicine and health sciences", "pathology and laboratory medicine", "immunology", "tropical diseases", "parasitic diseases", "animals", "parasitic protozoans", "parasitology", "vaccines", "preventive medicine", "apicomplexa", "protozoans", "vaccinatio...	Probability of Transmission of Malaria from Mosquito to Human Is Regulated by Mosquito Parasite Density in Naïve and Vaccinated Hosts	journal.ppat.1006108	null	[ [ "Mosquito-to-human malaria transmission occurs when sporozoites from the salivary gland of the mosquito are injected into the skin during blood-feeding .", "Parasites then pass to the liver where they replicate , each sporozoite yielding many thousands of merozoites which go on to cause patent infection ....	[ "Over a century since Ronald Ross discovered that malaria is caused by the bite of an infectious mosquito it is still unclear how the number of parasites injected influences disease transmission .", "Currently it is assumed that all mosquitoes with salivary gland sporozoites are equally infectious irrespective of...	[ "Malaria is transmitted to humans by the bite of an infectious mosquito though it is unclear whether a mosquito with a high number of parasites is more infectious than one with only a few .", "Here we show that the greater the number of parasites within the salivary gland of the mosquito following blood-feeding t...	2017
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "medicine", "computer science", "social and behavioral sciences", "mathematics", "chemistry", "biology", "engineering" ]	How Entorhinal Grid Cells May Learn Multiple Spatial Scales from a Dorsoventral Gradient of Cell Response Rates in a Self-organizing Map	journal.pcbi.1002648	null	[ [ "Navigating the world requires the brain to learn and maintain memory of spatial positions within various environments .", "Place cells in the hippocampal areas CA1 and CA3 demonstrate a neural code for position in large spaces that higher mammals inhabit [1] and thereby play a critical role in spatial na...	[ "Place cells in the hippocampus of higher mammals are critical for spatial navigation .", "Recent modeling clarifies how this may be achieved by how grid cells in the medial entorhinal cortex ( MEC ) input to place cells .", "Grid cells exhibit hexagonal grid firing patterns across space in multiple spatial sca...	[ "Spatial navigation is a critical competence of all higher mammals , and place cells in the hippocampus represent the large spaces in which they navigate .", "Recent modeling clarifies how this may occur via interactions between grid cells in the medial entorhinal cortex ( MEC ) and place cells .", "Grid cells ...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "functional genomics", "genetic mutation", "genome evolution", "genome scans", "neutral theory", "population genetics", "genome sequencing", "mutation", "genome analysis tools", "genome databases", "mutation types", "mutation databases", "genetic polymorphism", "biology", "genetics", "...	A Comprehensive Map of Mobile Element Insertion Polymorphisms in Humans	journal.pgen.1002236	null	[ [ "Retrotransposons are endogenous genomic sequences that copy and paste into locations throughout host genomes [1]–[3] .", "Most mobile elements annotated in the human reference genome are remnants of ancient retrotransposition events and are no longer capable of active retrotransposition .", "However ...	[ "As a consequence of the accumulation of insertion events over evolutionary time , mobile elements now comprise nearly half of the human genome .", "The Alu , L1 , and SVA mobile element families are still duplicating , generating variation between individual genomes .", "Mobile element insertions ( MEI ) have ...	[ "We embarked on this study to explore the 1000 Genomes Project ( 1000GP ) pilot dataset as a substrate for Mobile Element Insertion ( MEI ) discovery and analysis .", "MEI is already well known as a significant component of genetic variation in the human population .", "However the full extent and effects of ME...	2011
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "computational biology/literature analysis", "genetics and genomics/genomics", "oncology", "genetics and genomics/functional genomics", "genetics and genomics/genome projects", "computational biology/genomics", "genetics and genomics", "genetics and genomics/bioinformatics" ]	U87MG Decoded: The Genomic Sequence of a Cytogenetically Aberrant Human Cancer Cell Line	journal.pgen.1000832	null	[ [ "Grade IV glioma , also called glioblastoma multiforme ( GBM ) , is the most common primary malignant brain tumor with about 16 , 000 new diagnoses each year in the United States .", "While the number of cases is relatively small , comprising only 1 . 35% of primary malignant cancers in the US [1] , GBMs ...	[ "U87MG is a commonly studied grade IV glioma cell line that has been analyzed in at least 1 , 700 publications over four decades .", "In order to comprehensively characterize the genome of this cell line and to serve as a model of broad cancer genome sequencing , we have generated greater than 30× genomic sequenc...	[ "Glioblastoma has a particularly dismal prognosis with median survival time of less than fifteen months .", "Here , we describe the broad genome sequencing of U87MG , a commonly used and thus well-studied glioblastoma cell line .", "One of the major features of the U87MG genome is the large number of chromosoma...	2010
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "medicine and health sciences", "pathology and laboratory medicine", "pathogens", "tropical diseases", "rna extraction", "microbiology", "vertebrates", "animals", "mammals", "dogs", "viruses", "rabies", "rna viruses", "neglected tropical diseases", "molecular biology techniques", "geno...	Validation of a Rapid Rabies Diagnostic Tool for Field Surveillance in Developing Countries	journal.pntd.0005010	null	[ [ "Rabies is a viral zoonotic encephalomyelitis transmitted to humans after exposure to infected mammals , mainly dogs , through bites , scratches or licks on damaged skin or mucous membranes .", "This disease still continues to represent a public health concern worldwide , with an estimate of 60 , 000 huma...	[ "One root cause of the neglect of rabies is the lack of adequate diagnostic tests in the context of low income countries .", "A rapid , performance friendly and low cost method to detect rabies virus ( RABV ) in brain samples will contribute positively to surveillance and consequently to accurate data reporting ,...	[ "The high fatality and burden of rabies stands in contrast to the very low performance of laboratory-based surveillance in resource-challenged countries .", "The absence of reliable human and animal rabies incidence data ultimately result in neglect of disease prevention and control and the perpetuation of RABV t...	2016
[ "Introduction", "Materials and methods", "Results", "Discussion" ]	[ "transfer rna", "chromosome structure and function", "centromeres", "telomeres", "fungi", "model organisms", "non-coding rna", "materials science", "experimental organism systems", "epigenetics", "macromolecules", "structural genomics", "chromatin", "materials by structure", "saccharomyc...	Spatial organization of the budding yeast genome in the cell nucleus and identification of specific chromatin interactions from multi-chromosome constrained chromatin model	journal.pcbi.1005658	null	[ [ "Understanding the spatial organization of the genome in the cell nucleus is essential to gain insight into important nuclear activities such as repair , recombination , and replication of DNA , as well as the control of the transcriptional status of genes [1 , 2] .", "The overall organization of genome h...	[ "Nuclear landmarks and biochemical factors play important roles in the organization of the yeast genome .", "The interaction pattern of budding yeast as measured from genome-wide 3C studies are largely recapitulated by model polymer genomes subject to landmark constraints .", "However , the origin of inter-chro...	[ "The architecture of the cell nucleus and the spatial organization of the genome are important in determining nuclear functions .", "Single-cell imaging techniques and chromosome conformation capture ( 3C ) based methods have provided a wealth of information on the spatial organization of chromosomes .", "Here ...	2017
[ "Introduction", "Methods", "Results", "Discussion" ]	[]	Impact of a Dengue Outbreak Experience in the Preventive Perceptions of the Community from a Temperate Region: Madeira Island, Portugal	journal.pntd.0003395	null	[ [ "Most of the 2011 worldwide major causes of death ( MCD ) , rely on behaviour changes for their prevention [1] .", "Increasing physical activity , fruits/vegetables intake , hand-washing , use of condoms , and decreasing not only fat , salt and sugar intake but also smoking habits , are crucial in the con...	[ "The ability to effectively modify behaviours is increasingly relevant to attain and maintain a good health status .", "Current behaviour-change models and theories present two main approaches for ( healthier ) decision-making: one analytical/logical , and one experiential/emotional/intuitive .", "Therefore , t...	[ "Since there is no vaccine or treatment available for dengue fever , its prevention relies on community participation .", "Residents are asked to remove from their houses and gardens all receptacles where mosquitoes can breed .", "Exploring the public perception regarding dengue prevention is crucial for detect...	2015
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "infectious diseases/neglected tropical diseases" ]	Using Recombinant Proteins from Lutzomyia longipalpis Saliva to Estimate Human Vector Exposure in Visceral Leishmaniasis Endemic Areas	journal.pntd.0000649	null	[ [ "The Leishmaniasis is a widely distributed disease , caused by Leishmania protozoans and transmitted by sand fly vectors .", "Infected sand flies inject parasites when attempting to take a blood meal .", "In this process , vector saliva is inoculated together with Leishmania into the host skin .", ...	[ "Leishmania is transmitted by female sand flies and deposited together with saliva , which contains a vast repertoire of pharmacologically active molecules that contribute to the establishment of the infection .", "The exposure to vector saliva induces an immune response against its components that can be used as...	[ "During the blood meal , female sand flies ( insects that transmit the parasite Leishmania ) inject saliva containing a large variety of molecules with different pharmacological activities that facilitate the acquisition of blood .", "These molecules can induce the production of anti-saliva antibodies , which can...	2010
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "infectious diseases/hiv infection and aids", "immunology/immunity to infections", "immunology/innate immunity" ]	Lysis of Endogenously Infected CD4+ T Cell Blasts by rIL-2 Activated Autologous Natural Killer Cells from HIV-Infected Viremic Individuals	journal.ppat.1000101	null	[ [ "Natural killer ( NK ) cells are important effectors of innate immune responses and are capable of providing cellular immunity against tumor-transformed and virally-infected cells , without prior antigen sensitization [1] , [2] .", "Among the several NK cell effector-functions , spontaneous killing of non...	[ "Understanding the cellular mechanisms that ensure an appropriate innate immune response against viral pathogens is an important challenge of biomedical research .", "In vitro studies have shown that natural killer ( NK ) cells purified from healthy donors can kill heterologous cell lines or autologous CD4+ T cel...	[ "Natural killer ( NK ) cells represent an important line of defense against viral infections .", "In vitro studies with exogenously infected CD4+ T cell blasts from healthy donors have demonstrated that NK cells can kill autologous HIV-1-infected target cells .", "However , the ability of NK cells from HIV-1-in...	2008
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	The TgsGP Gene Is Essential for Resistance to Human Serum in Trypanosoma brucei gambiense	journal.ppat.1003686	null	[ [ "Throughout their evolution in sub-Saharan Africa , humans have been under assault by a range of different pathogens .", "One defining challenge is that posed by African trypanosomes , a species complex of blood-borne protozoan parasites transmitted by tsetse flies [1] .", "The principle pathogenic sp...	[ "Trypanosoma brucei gambiense causes 97% of all cases of African sleeping sickness , a fatal disease of sub-Saharan Africa .", "Most species of trypanosome , such as T . b .", "brucei , are unable to infect humans due to the trypanolytic serum protein apolipoprotein-L1 ( APOL1 ) delivered via two trypanosome ly...	[ "Trypanosoma brucei gambiense causes 97% of all cases of African sleeping sickness , a fatal disease of sub-Saharan Africa .", "Most species of trypanosome , such as T . b .", "brucei , are unable to infect humans due to trypanolytic factors in human serum .", "Understanding how T . b .", "gambiense overcom...	2013
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "plant biology/plant-biotic interactions", "plant biology/plant cell biology", "virology/host invasion and cell entry" ]	ANK, a Host Cytoplasmic Receptor for the Tobacco mosaic virus Cell-to-Cell Movement Protein, Facilitates Intercellular Transport through Plasmodesmata	journal.ppat.1001201	null	[ [ "Plasmodesma ( PD ) is a cell-wall spanning channel that interconnects plant cells and is unique for plants .", "This structure is characterized by a neck-like constriction at its each end , is lined by the plasma membrane , and is traversed by a strand of appressed endoplasmic reticulum , providing endom...	[ "Plasmodesma ( PD ) is a channel structure that spans the cell wall and provides symplastic connection between adjacent cells .", "Various macromolecules are known to be transported through PD in a highly regulated manner , and plant viruses utilize their movement proteins ( MPs ) to gate the PD to spread cell-to...	[ "During infection , plant viruses utilize their cell-to-cell movement proteins ( MPs ) to gate plant intercellular connections , the plasmodesmata ( PD ) , and spread between the host cells .", "The mechanism by which MPs facilitate their cell-to-cell translocation remains elusive .", "We have identified a toba...	2010
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "immunology/cellular microbiology and pathogenesis", "immunology/immune response", "immunology/immunity to infections", "immunology/innate immunity", "microbiology/innate immunity", "microbiology/cellular microbiology and pathogenesis" ]	RIG-I, MDA5 and TLR3 Synergistically Play an Important Role in Restriction of Dengue Virus Infection	journal.pntd.0000926	null	[ [ "Pathogen associated molecular patterns ( PAMP ) trigger innate immunity against pathogens and this response represents the first line of defense against various microorganisms [1] .", "Double strand RNA ( dsRNA ) , a viral replication intermediate , is sensed by cytoplasmic RNA helicases retinoic acid-in...	[ "Dengue virus ( DV ) infection is one of the most common mosquito-borne viral diseases in the world .", "The innate immune system is important for the early detection of virus and for mounting a cascade of defense measures which include the production of type 1 interferon ( IFN ) .", "Hence , a thorough underst...	[ "Dengue fever , dengue haemmorhagic fever and dengue shock syndrome , which are caused by dengue virus infection , are a major public health problem in many parts of the world , especially South East Asia .", "The investigation of host cell transcriptional changes in response to virus infection using DNA microarr...	2011
[ "Introduction", "Results", "Discussion", "Models" ]	[ "cellular stress responses", "classical mechanics", "cell cycle and cell division", "cell processes", "biological cultures", "radii", "mechanical stress", "geometry", "simulation and modeling", "mathematics", "research and analysis methods", "compression", "cell lines", "glucans", "physi...	Quantitative cell-based model predicts mechanical stress response of growing tumor spheroids over various growth conditions and cell lines	journal.pcbi.1006273	null	[ [ "Mechanotransduction is the mechanism by which cells transform an external mechanical stimulus into internal signals .", "It emerges in many cellular processes , such as embryonic development and tumor growth [1] .", "Cell growth in a confined environment such as provided by the stroma and surrounding...	[ "Model simulations indicate that the response of growing cell populations on mechanical stress follows the same functional relationship and is predictable over different cell lines and growth conditions despite experimental response curves look largely different .", "We develop a hybrid model strategy in which ce...	[ "The effect of mechanical resistance on the growth of tumor cells remains today largely unquantified .", "We studied data from two different experimental setups that monitor the growth of tumor cells under mechanical compression .", "The existing data in the first experiment examined growing CT26 cells in an el...	2019
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "blood cells", "cell motility", "medicine and health sciences", "immune cells", "immune physiology", "pathology and laboratory medicine", "spleen", "pathogens", "immunology", "cell-mediated immunity", "microbiology", "orthomyxoviruses", "viruses", "developmental biology", "rna viruses", ...	ADAMTS5 Is a Critical Regulator of Virus-Specific T Cell Immunity	journal.pbio.1002580	The extracellular matrix enzyme ADAMTS5 enhances the clearance of viruses by facilitating migration of T lymphocytes to the periphery following influenza virus infection.	[ [ "Influenza A virus infection is responsible for substantial global morbidity and mortality ( >500 , 000 deaths each year [1] ) and largely afflicts high-risk groups , including the very young and elderly .", "There are currently two countermeasures employed to control influenza virus infection: vaccines a...	[ "The extracellular matrix ( ECM ) provides physical scaffolding for cellular constituents and initiates biochemical and biomechanical cues that are required for physiological activity of living tissues .", "The ECM enzyme ADAMTS5 , a member of the ADAMTS ( A Disintegrin-like and Metalloproteinase with Thrombospon...	[ "Movement of immune cells is critical for effective clearance of pathogens .", "The response to influenza virus infection requires immune cell trafficking between the lung , mediastinal lymph node and other peripheral lymphoid organs such as the spleen .", "We set out to assess the contribution of a specific ex...	2016
[ "Introduction", "Results and Discussion", "Materials and Methods" ]	[ "anaphase", "micronuclei", "molecular probe techniques", "cell cycle and cell division", "cell processes", "microbiology", "vertebrates", "animals", "lampreys", "developmental biology", "epigenetics", "molecular biology techniques", "embryos", "chromatin", "research and analysis methods"...	Cellular and Molecular Features of Developmentally Programmed Genome Rearrangement in a Vertebrate (Sea Lamprey: Petromyzon marinus)	journal.pgen.1006103	null	[ [ "The sea lamprey ( Petromyzon marinus ) represents one of the few vertebrate species known to undergo large-scale programmatic elimination of genomic DNA over the course of its normal development [1–4] .", "Programmed genome rearrangements ( PGRs ) result in the reproducible loss of ~20% of the genome fro...	[ "The sea lamprey ( Petromyzon marinus ) represents one of the few vertebrate species known to undergo large-scale programmatic elimination of genomic DNA over the course of its normal development .", "Programmed genome rearrangements ( PGRs ) result in the reproducible loss of ~20% of the genome from somatic cell...	[ "Lampreys possess a fascinating genome biology wherein large portions of the genome , including large numbers of genes , are programmatically deleted during development .", "The lamprey therefore represents a uniquely informative system with respect to several broad areas of biology , including genome stability/r...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "evolutionary biology", "genetics", "biology and life sciences", "genomics" ]	Speciation and Introgression between Mimulus nasutus and Mimulus guttatus	journal.pgen.1004410	null	[ [ "While speciation is often depicted as a simple event in which a single species splits into two , there is increasing evidence that this process is often more complex .", "In particular , speciation reflects a tension among divergence , the assortment of ancestral variation , ecological interactions and i...	[ "Mimulus guttatus and M . nasutus are an evolutionary and ecological model sister species pair differentiated by ecology , mating system , and partial reproductive isolation .", "Despite extensive research on this system , the history of divergence and differentiation in this sister pair is unclear .", "We pres...	[ "While speciation is often depicted as a simple population split , in many cases it is likely more complex .", "Recently , whole genome sequencing and computational methods to interpret patterns of genomic variation have facilitated the inference of complex speciation histories .", "We present and analyze genom...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "ecology", "evolutionary biology", "plants", "insects" ]	Linkage Rules for Plant–Pollinator Networks: Trait Complementarity or Exploitation Barriers?	journal.pbio.0050031	The topology of plant-pollinator networks can be explained by relatively simple rules incorporating both "complementarity" and "barrier" traits, thus providing insights into the possible evolutionary and ecological processes driving the pattern.	[ [ "Generalisation is a widespread feature of plant–pollinator interactions [1] , and there is a growing interest in the study of complete communities of interacting plants and flower-visiting insects [2 , 3] .", "The topology of plant–pollinator qualitative networks ( networks that simply consider whether s...	[ "Recent attempts to examine the biological processes responsible for the general characteristics of mutualistic networks focus on two types of explanations: nonmatching biological attributes of species that prevent the occurrence of certain interactions ( “forbidden links” ) , arising from trait complementarity in ...	[ "Whether they are antagonistic—as between predator and prey—or beneficial—as between pollinator and flower , interactions among all the key species in an ecosystem follow regular patterns .", "Connectivity ( the proportion of possible interactions that are actually realised ) , for instance , decreases with netwo...	2007
[ "Introduction", "Results", "Discussion" ]	[ "systems biology", "molecular genetics", "biology", "genomics", "evolutionary biology", "computational biology" ]	New Universal Rules of Eukaryotic Translation Initiation Fidelity	journal.pcbi.1003136	null	[ [ "Gene translation is the central cellular process of sequence decoding to produce a protein .", "This process occurs in every organism and consumes most of the cellular energy [1]–[3] , thus it has important ramifications to every biomedical field [3]–[9] .", "Translation consists of three stages: ini...	[ "The accepted model of eukaryotic translation initiation begins with the scanning of the transcript by the pre-initiation complex from the 5′end until an ATG codon with a specific nucleotide ( nt ) context surrounding it is recognized ( Kozak rule ) .", "According to this model , ATG codons upstream to the beginn...	[ "Gene translation is an important step of the intra-cellular protein synthesis , which is a central process in all living organisms .", "Thus , understanding how translation efficiency is encoded in transcripts has ramifications to every biomedical discipline .", "The aim of the current study is to decipher the...	2013
[ "Introduction", "Materials and methods", "Results", "Discussion" ]	[ "medicine and health sciences", "maternal health", "obstetrics and gynecology", "tropical diseases", "vertebrates", "parasitic diseases", "dogs", "parasitic protozoans", "animals", "mammals", "protozoans", "veterinary diagnostics", "leishmania", "women's health", "pregnancy", "neglecte...	Maternal Leishmania infantum infection status has significant impact on leishmaniasis in offspring	journal.pntd.0007058	null	[ [ "Leishmaniosis is a disease caused by the obligate intracellular protozoan parasite Leishmania infantum [1–3] .", "Visceral Leishmaniasis ( VL ) can also be caused by Leishmania donovani which causes anthroponotic human visceral leishmaniasis in many countries including areas of Asia and Africa [4 , 5] ."...	[ "Visceral Leishmaniasis is a deadly disease caused by Leishmania infantum , endemic in more than 98 countries across the globe .", "Although the most common means of transmission is via a sand fly vector , there is growing evidence that vertical transmission may be critical for maintaining L . infantum infection ...	[ "Canine leishmaniosis ( CanL ) is a deadly disease caused by Leishmania infantum parasite , it is found in animal populations , including people , in more than 98 countries across the globe .", "CanL was first identified within the US in hunting dogs 1980 and then again in 1999 when a large outbreak in a kennel i...	2019
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genetics and genomics" ]	Epigenomic Consequences of Immortalized Plant Cell Suspension Culture	journal.pbio.0060302	Immortalized plant cells undergo epigenomic changes, reminiscent of immortalized animal cell lines and cancer cells, accompanied by shifts in small RNA classes, implicating a role for the RNAi machinery in regulating the epigenome.	[ [ "More than half a century has passed since the concept and practice of plant cell culture was first introduced [1] .", "Unlike most animal cells , plant cells can change from one differentiated state , representing a committed developmental program , to a completely different one via a transition through ...	[ "Plant cells grown in culture exhibit genetic and epigenetic instability .", "Using a combination of chromatin immunoprecipitation and DNA methylation profiling on tiling microarrays , we have mapped the location and abundance of histone and DNA modifications in a continuously proliferating , dedifferentiated cel...	[ "Cultured plant cells are genetically and epigenetically unstable .", "We investigated the epigenomic consequences of long-term plant cell culture and found that some genes show an increase in DNA methylation , reminiscent of immortalized animal cell lines and cancer cells .", "By contrast , in the heterochroma...	2008
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "medicine", "bacterial diseases", "infectious diseases", "public health and epidemiology", "cholera", "epidemiology", "infectious disease epidemiology", "neglected tropical diseases", "spatial epidemiology", "infectious disease control", "infectious disease modeling" ]	Urban Cholera Transmission Hotspots and Their Implications for Reactive Vaccination: Evidence from Bissau City, Guinea Bissau	journal.pntd.0001901	null	[ [ "With the introduction of inexpensive , easy to administer , and effective oral vaccines against cholera , vaccination in response to an epidemic ( reactive vaccination ) may be an effective supplement to conventional control measures .", "Two safe and internationally licensed oral cholera vaccines are cu...	[ "Use of cholera vaccines in response to epidemics ( reactive vaccination ) may provide an effective supplement to traditional control measures .", "In Haiti , reactive vaccination was considered but , until recently , rejected in part due to limited global supply of vaccine .", "Using Bissau City , Guinea-Bissa...	[ "Cholera remains a major public health threat , causing 3–5 million cases and 100 , 000–120 , 000 deaths each year .", "In 2010 , data on vaccine performance and the changing epidemiology of cholera prompted the WHO's Strategic Advisory Group to recommend that reactive vaccination be considered in specific areas ...	2012
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "blood cells", "medicine and health sciences", "immune cells", "immune physiology", "spleen", "antigen-presenting cells", "immunology", "cytotoxic t cells", "antibodies", "research and analysis methods", "specimen preparation and treatment", "staining", "immune system proteins", "white blo...	Cross-priming induces immunodomination in the presence of viral MHC class I inhibition	journal.ppat.1006883	null	[ [ "Strategies to leverage strong cytotoxic CD8+ T cells ( CTL ) responses to viral infections are of particular interest as CTLs play essential roles in controlling viral infections [1–5] .", "Before gaining effector functions , virus-specific CTL precursors must be primed by antigen presenting cells ( APCs...	[ "Viruses have evolved mechanisms of MHCI inhibition in order to evade recognition by cytotoxic CD8+ T cells ( CTLs ) , which is well-illustrated by our prior studies on cowpox virus ( CPXV ) that encodes potent MHCI inhibitors .", "Deletion of CPXV viral MHCI inhibitors markedly attenuated in vivo infection due t...	[ "The use of vaccinia virus ( VACV ) to eradicate smallpox is the arguably the most successful demonstration of vaccination .", "The VACV vaccine also provides cross-protection against related zoonotic orthopoxviruses , including monkey poxvirus ( MXPV ) and CPXV , which circulate between various animal hosts and ...	2018
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "blood cells", "sequencing techniques", "organismal evolution", "viral vaccines", "medicine and health sciences", "pathology and laboratory medicine", "population genetics", "immunology", "microbiology", "immunodeficiency viruses", "microbial evolution", "molecular biology techniques", "hiv ...	Genotypic and Functional Impact of HIV-1 Adaptation to Its Host Population during the North American Epidemic	journal.pgen.1004295	null	[ [ "Escape from Human Leukocyte Antigen ( HLA ) class I-restricted CD8+ T-lymphocytes ( CTL ) in Human Immunodeficiency Virus Type 1 ( HIV ) occurs along mutational pathways that are broadly reproducible based on the HLA alleles expressed by the host [1]–[4] .", "The opposite phenomenon ( that is , reversion...	[ "HLA-restricted immune escape mutations that persist following HIV transmission could gradually spread through the viral population , thereby compromising host antiviral immunity as the epidemic progresses .", "To assess the extent and phenotypic impact of this phenomenon in an immunogenetically diverse populatio...	[ "Upon HIV transmission , many – though not all – immune escape mutations selected in the previous host will revert to the consensus residue .", "The persistence of certain escape mutations following transmission has led to concerns that these could gradually accumulate in circulating HIV sequences over time , the...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biotechnology", "invertebrates", "protein interactions", "caenorhabditis", "gene regulation", "animals", "animal models", "developmental biology", "caenorhabditis elegans", "micrornas", "model organisms", "immunoprecipitation", "genetic engineering", "research and analysis methods", "ge...	GW182-Free microRNA Silencing Complex Controls Post-transcriptional Gene Expression during Caenorhabditis elegans Embryogenesis	journal.pgen.1006484	null	[ [ "MiRNAs are highly conserved small non-coding RNAs that orchestrate gene expression in a broad range of developmental processes .", "The production of miRNA implicates a successive two-step processing involving two RNase III enzymes , Drosha and Dicer , which cleave the primary and precursor miRNA molecul...	[ "MicroRNAs and Argonaute form the microRNA induced silencing complex or miRISC that recruits GW182 , causing mRNA degradation and/or translational repression .", "Despite the clear conservation and molecular significance , it is unknown if miRISC-GW182 interaction is essential for gene silencing during animal dev...	[ "Animal cells possess different small RNA species capable of precisely controlling the gene expression .", "Among them , microRNAs form a silencing complex with an Argonaute protein ( known as miRISC ) that abrogates protein production by targeting specific messenger RNAs .", "While there is a consensus that mi...	2016
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "invertebrates", "medicine and health sciences", "cell cycle and cell division", "cell processes", "animals", "animal models", "developmental biology", "drosophila melanogaster", "model organisms", "experimental organism systems", "eyes", "synthesis phase", "morphogenesis", "drosophila", ...	An alternatively spliced form affecting the Marked Box domain of Drosophila E2F1 is required for proper cell cycle regulation	journal.pgen.1007204	null	[ [ "The E2F family of transcription factors was first cloned as a cellular factor that binds to the Early E2 region of the adenovirus genome [1] .", "Since its discovery , families of E2F transcription factors have been identified in metazoans ranging from nematodes to mammals [2] .", "One of the importa...	[ "Across metazoans , cell cycle progression is regulated by E2F family transcription factors that can function as either transcriptional activators or repressors .", "For decades , the Drosophila E2F family has been viewed as a streamlined RB/E2F network , consisting of one activator ( dE2F1 ) and one repressor ( ...	[ "The Drosophila E2F1 ( dE2F1 ) protein has been studied as one of the principal regulators of cell cycle control in both mitotic cells and cells undergoing a variant cell cycle called the endocycle .", "dE2F1 is the sole “activator” E2F of the highly streamlined Drosophila RB/E2F network .", "However , there ha...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Corp Regulates P53 in Drosophila melanogaster via a Negative Feedback Loop	journal.pgen.1005400	null	[ [ "When cells encounter damage to their DNA in the form of DSBs , DNA damage response ( DDR ) pathways are triggered .", "The ensuing signaling cascades result in cell cycle arrest , induction of DNA repair genes , and in some cases , apoptosis .", "It is generally thought that , if damage cannot be rep...	[ "The tumor suppressor P53 is a critical mediator of the apoptotic response to DNA double-strand breaks through the transcriptional activation of pro-apoptotic genes .", "This mechanism is evolutionarily conserved from mammals to lower invertebrates , including Drosophila melanogaster .", "P53 also transcription...	[ "Organisms have exquisitely sensitive mechanisms to detect and respond to DNA damage .", "If DNA damage in a cell can be repaired , then that cell may resume its normal function .", "In multi-cellular organisms , if a cell cannot repair DNA damage it usually undergoes programmed cell death .", "This prevents ...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Ultra-Sensitive Sequencing Reveals an Age-Related Increase in Somatic Mitochondrial Mutations That Are Inconsistent with Oxidative Damage	journal.pgen.1003794	null	[ [ "Mitochondria are the primary source of energy for cells .", "Owing to their evolutionary history , these organelles harbor a small , independently replicated genome ( mtDNA ) .", "Human mtDNA encodes two rRNA genes , 13 protein coding genes that are essential components of the electron transport chai...	[ "Mitochondrial DNA ( mtDNA ) is believed to be highly vulnerable to age-associated damage and mutagenesis by reactive oxygen species ( ROS ) .", "However , somatic mtDNA mutations have historically been difficult to study because of technical limitations in accurately quantifying rare mtDNA mutations .", "We ha...	[ "Owing to their evolutionary history , mitochondria harbor independently replicating genomes .", "Failure to faithfully transmit the genetic information of mtDNA during replication can lead to the production of dysfunctional electron transport proteins and a subsequent decline in energy production .", "Cellular...	2013
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "infectious diseases/helminth infections", "public health and epidemiology/infectious diseases", "microbiology/parasitology", "infectious diseases/neglected tropical diseases" ]	A New PCR-Based Approach Indicates the Range of Clonorchis sinensis Now Extends to Central Thailand	journal.pntd.0000367	null	[ [ "It is estimated that approximately 17 million people are currently infected with fish-borne trematodes worldwide [1] .", "In Asia , Opisthorchis viverrini is known to occur in Thailand , Laos , Cambodia and southern Vietnam and Clonorchis sinensis in Korea , China , Taiwan and northern Vietnam [2] , [3] ...	[ "Differentiation of the fish-borne trematodes belonging to the Opisthorchiidae , Heterophyidae and Lecithodendriidae is important from a clinical and epidemiological perspective , yet it is impossible to do using conventional coprological techniques , as the eggs are morphologically similar .", "Epidemiological i...	[ "It is estimated that approximately 17 million people are currently infected with fish-borne flukes worldwide .", "The fish-borne liver flukes Opisthrochis viverrini and Clonorchis sinensis cause hepatic and biliary disease in humans .", "The minute intestinal flukes are widely distributed in southeast Asia and...	2009
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "computer and information sciences", "cognition", "neural networks", "computational neuroscience", "biology and life sciences", "computational biology", "cognitive science", "neuroscience", "learning and memory", "animal cognition" ]	Continuous Attractor Network Model for Conjunctive Position-by-Velocity Tuning of Grid Cells	journal.pcbi.1003558	null	[ [ "Responses of grid cells recorded in medial entorhinal cortex ( MEC ) provide accurate population codes for the positions in an environment [1] , and could result from path-integration mechanism [2] .", "Attractor network models of MEC spatial representations have been proposed , based on two foundations ...	[ "The spatial responses of many of the cells recorded in layer II of rodent medial entorhinal cortex ( MEC ) show a triangular grid pattern , which appears to provide an accurate population code for animal spatial position .", "In layer III , V and VI of the rat MEC , grid cells are also selective to head-directio...	[ "How do animals self-localize when they explore the environments with variable velocities ?", "One mechanism is dead reckoning or path-integration .", "Recent experiments on rodents show that such computation may be performed by grid cells in medial entorhinal cortex .", "Each grid cell fires strongly when th...	2014
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "dimers (chemical physics)", "fluorescence imaging", "medicine and health sciences", "pathology and laboratory medicine", "cell cycle and cell division", "pathogens", "cell processes", "vibrio", "microbiology", "vibrio cholerae", "dna", "translocations", "bacteria", "bacterial pathogens", ...	Fast growth conditions uncouple the final stages of chromosome segregation and cell division in Escherichia coli	journal.pgen.1006702	null	[ [ "DNA synthesis , chromosome segregation and cell division must be coordinated to ensure the stable inheritance of the genetic material during proliferation .", "In eukaryotes , this is achieved by coupling the assembly and activity of the cell division apparatus to the assembly and activity of the mitotic...	[ "Homologous recombination between the circular chromosomes of bacteria can generate chromosome dimers .", "They are resolved by a recombination event at a specific site in the replication terminus of chromosomes , dif , by dedicated tyrosine recombinases .", "The reaction is under the control of a cell division...	[ "DNA synthesis , chromosome segregation and cell division must be coordinated to ensure the stable inheritance of the genetic material during proliferation .", "In eukaryotes , this is achieved by their temporal separation and the existence of checkpoint mechanisms that delay certain steps until others are comple...	2017
[ "Introduction", "Results", "Discussion", "Material and methods" ]	[ "control theory", "medicine and health sciences", "fish", "swimming", "engineering and technology", "membrane potential", "vertebrates", "electrophysiology", "social sciences", "neuroscience", "animals", "biological locomotion", "motor neurons", "control engineering", "animal anatomy", ...	A theory of how active behavior stabilises neural activity: Neural gain modulation by closed-loop environmental feedback	journal.pcbi.1005926	null	[ [ "Neural response are strongly sensitive to behavioural state .", "The onset of movement such as running and whisking is coincident with prominent modulations in neural activity in sensory areas [1–3] .", "The rodent whisker system has become a key model system within which to investigate these changes...	[ "During active behaviours like running , swimming , whisking or sniffing , motor actions shape sensory input and sensory percepts guide future motor commands .", "Ongoing cycles of sensory and motor processing constitute a closed-loop feedback system which is central to motor control and , it has been argued , fo...	[ "Animals actively exploring or interacting with their surroundings must process a cyclical flow of information from the environment through sensory receptors , the central nervous system , the musculoskeletal system and back to the environment .", "This closed-loop sensorimotor system is essential for an animal's...	2018
[ "Introduction", "Results/Discussion", "Methods" ]	[]	Regulation of the Boundaries of Accessible Chromatin	journal.pgen.1003778	null	[ [ "Open chromatin provides access to a wide spectrum of DNA binding proteins for genetic regulation processes such as transcription , repair , recombination , and replication .", "In this regard , open chromatin profiling has been widely used to identify the location of regulatory regions , including promot...	[ "Regulatory regions maintain nucleosome-depleted , open chromatin status but simultaneously require the presence of nucleosomes for specific histone modifications .", "It remains unclear how these can be achieved for proper regulatory function .", "Here we demonstrate that nucleosomes positioned within accessib...	[ "Open chromatin formation and regulation are intimately coupled with nucleosome remodelling and modification .", "Regulatory regions such as promoters and enhancers maintain nucleosome-free , open chromatin states whilst at the same time the presence of nucleosomes is required for specific histone modifications ....	2013
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "chemistry/organic chemistry", "infectious diseases/neglected tropical diseases", "pharmacology/drug development", "biochemistry/biomacromolecule-ligand interactions", "infectious diseases/protozoal infections", "biochemistry/small molecule chemistry", "biochemistry/drug discovery" ]	In Vitro and In Vivo Studies of the Trypanocidal Properties of WRR-483 against Trypanosoma cruzi	journal.pntd.0000825	null	[ [ "American trypanosomiasis , or Chagas' disease , is the third largest parasitic disease burden in the world , and largest in the Western hemisphere .", "[1] The disease is endemic in Central and South America , and approximately 16 million people are currently afflicted .", "Patients with Chagas' dise...	[ "Cruzain , the major cysteine protease of Trypanosoma cruzi , is an essential enzyme for the parasite life cycle and has been validated as a viable target to treat Chagas' disease .", "As a proof-of-concept , K11777 , a potent inhibitor of cruzain , was found to effectively eliminate T . cruzi infection and is cu...	[ "Current drugs for Chagas' disease , caused by Trypanosoma cruzi infection , are limited in efficacy and are severely toxic .", "Hence the development of novel chemotherapeutic agents targeting T . cruzi infections is an important undertaking .", "In recent years , there has been considerable interest in cruzai...	2010
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "action potentials", "medicine and health sciences", "optogenetics", "membrane potential", "electrophysiology", "neuroscience", "ganglion cells", "brain mapping", "bioassays and physiological analysis", "neuronal dendrites", "research and analysis methods", "animal cells", "biophysics", "n...	Neuronal gain modulability is determined by dendritic morphology: A computational optogenetic study	journal.pcbi.1006027	null	[ [ "Neuronal gain modulation occurs when the sensitivity of a neuron to one input is controlled by a second input .", "Its role in neuronal computation has been the subject of much investigation [1–4] , and its dysfunction has been implicated in a range of disorders from attention deficit disorders , through...	[ "The mechanisms by which the gain of the neuronal input-output function may be modulated have been the subject of much investigation .", "However , little is known of the role of dendrites in neuronal gain control .", "New optogenetic experimental paradigms based on spatial profiles or patterns of light stimula...	[ "New experimental techniques based on optogenetics allow neuronal activity to be manipulated with a high degree of spatial and temporal precision .", "This opens up new prospects for testing computational models of neuronal function , including questions such as the role of dendrites in neuronal gain control .", ...	2018
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "parasitology", "biology and life sciences", "immunology" ]	Unravelling Human Trypanotolerance: IL8 is Associated with Infection Control whereas IL10 and TNFα Are Associated with Subsequent Disease Development	journal.ppat.1004469	null	[ [ "Human African trypanosomiasis ( HAT ) , or sleeping sickness , caused by Trypanosoma brucei gambiense ( T . b . gambiense ) is classically described as a chronic infection characterized by an early hemolymphatic stage ( stage", "1 ) associated with nonspecific symptoms such as intermittent fevers and hea...	[ "In West Africa , Trypanosoma brucei gambiense , causing human African trypanosomiasis ( HAT ) , is associated with a great diversity of infection outcomes .", "In addition to patients who can be diagnosed in the early hemolymphatic phase ( stage 1 ) or meningoencephalitic phase ( stage 2 ) , a number of individu...	[ "Whereas immunological mechanisms involved in the control of trypanosome infections have been extensively studied in animal models , knowledge of how Trypanosoma brucei gambiense interacts with its human hosts lags far behind .", "In this study we measured cytokine levels in sleeping sickness patients and individ...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biotechnology", "genome evolution", "plant biology", "population genetics", "ploidy", "crop genetics", "genetic maps", "algorithms", "genome sequencing", "genome analysis tools", "plant science", "linkage maps", "plant genomics", "sequence analysis", "genome complexity", "plant geneti...	Switchgrass Genomic Diversity, Ploidy, and Evolution: Novel Insights from a Network-Based SNP Discovery Protocol	journal.pgen.1003215	null	[ [ "In the past decade , switchgrass ( Panicum virgatum L . ) has been targeted as a prime candidate energy crop .", "As a C4 grass , switchgrass has high biomass production with minimal field-based inputs .", "Its adaptability allows it to be grown productively in large areas of the USA , including marg...	[ "Switchgrass ( Panicum virgatum L . ) is a perennial grass that has been designated as an herbaceous model biofuel crop for the United States of America .", "To facilitate accelerated breeding programs of switchgrass , we developed both an association panel and linkage populations for genome-wide association stud...	[ "Recent advances in sequencing technologies have enabled large-scale surveys of genetic diversity in model species with a wholly or partly sequenced reference genome .", "However , thousands of key species , which are essential for food , health , energy , and ecology , do not have reference genomes .", "To acc...	2013
[ "Introduction", "Methods", "Results", "Discussion" ]	[]	Does High-Dose Antimicrobial Chemotherapy Prevent the Evolution of Resistance?	journal.pcbi.1004689	null	[ [ "Antimicrobial resistance is one of greatest challenges faced by modern medicine .", "There is a widely held view that the evolutionary emergence of drug resistance is best slowed by using high doses of drugs to eliminate pathogens as early and quickly as possible .", "This view , first expounded by E...	[ "High-dose chemotherapy has long been advocated as a means of controlling drug resistance in infectious diseases but recent empirical studies have begun to challenge this view .", "We develop a very general framework for modeling and understanding resistance emergence based on principles from evolutionary biology...	[ "The evolution of antimicrobial resistant pathogens threatens much of modern medicine .", "For over one hundred years , the advice has been to ‘hit hard’ , in the belief that high doses of antimicrobials best contain resistance evolution .", "We argue that nothing in evolutionary theory supports this as a good ...	2016
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "medicine and health sciences", "diagnostic radiology", "functional magnetic resonance imaging", "neural networks", "signaling networks", "neuroscience", "magnetic resonance imaging", "brain morphometry", "cognitive neuroscience", "brain mapping", "network analysis", "neuroimaging", "researc...	Structure-Function Network Mapping and Its Assessment via Persistent Homology	journal.pcbi.1005325	null	[ [ "The last decade has witnessed considerable progress towards understanding how the brain structural connections constrain and enable brain functional networks and the resulting behavior [1–3] .", "Structural connectivity ( SC ) refers to the ‘hard-wired’ white matter anatomic connections between brain are...	[ "Understanding the relationship between brain structure and function is a fundamental problem in network neuroscience .", "This work deals with the general method of structure-function mapping at the whole-brain level .", "We formulate the problem as a topological mapping of structure-function connectivity via ...	[ "One of the major challenges in neuroscience is to understand how brain structure is related to function .", "In this work , we present a whole-brain method to quantify the structure-function relationship .", "Our data-driven approach allows the inferred functional connectivity matrix to be represented as a wei...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biochemistry", "infectious diseases", "in vitro", "immunology", "eukaryotes", "molecular biology" ]	Hemoglobin Is a Co-Factor of Human Trypanosome Lytic Factor	journal.ppat.0030129	null	[ [ "African trypanosomes are blood parasites of mammals in sub-Saharan Africa that cause chronic wasting diseases in both humans and domestic animals [1] .", "The three subspecies of Trypanosoma brucei are defined by their host range , geographical distribution , and course of disease [1–3] .", "Trypanos...	[ "Trypanosome lytic factor ( TLF ) is a high-density lipoprotein ( HDL ) subclass providing innate protection to humans against infection by the protozoan parasite Trypanosoma brucei brucei .", "Two primate-specific plasma proteins , haptoglobin-related protein ( Hpr ) and apolipoprotein L-1 ( ApoL-1 ) , have been...	[ "African trypanosomes are parasites that can infect a wide range of mammals , including domestic animals and humans .", "Several hundred thousand humans are infected with African sleeping sickness , but this number would be much higher if not for a natural defense molecule found in human blood .", "The trypanos...	2007
[ "Introduction", "Methods", "Results/Discussion" ]	[ "taxonomy", "medicine and health sciences", "pathology and laboratory medicine", "burkholderia pseudomallei", "pathogens", "melioidosis", "burkholderia infection", "geographical locations", "microbiology", "bacterial diseases", "phylogenetics", "data management", "phylogenetic analysis", "...	Identification of Burkholderia thailandensis with novel genotypes in the soil of central Sierra Leone	journal.pntd.0007402	null	[ [ "The Gram-negative environmental bacterium Burkholderia pseudomallei is the etiological agent of melioidosis , an emerging but neglected infectious disease .", "Disease presentations vary from abscess formation to fulminant sepsis [1] .", "Melioidosis has a mortality up to 50% in low resource settings...	[ "The soil-dwelling bacillus Burkholderia pseudomallei is the etiological-agent of the neglected and life-threatening emerging infection melioidosis .", "The distribution of B . pseudomallei in West Africa is unknown .", "In the present study we aimed to determine whether B . pseudomallei and B . thailandensis a...	[ "The environmental bacterium Burkholderia pseudomallei is the cause of melioidosis , an often-fatal but neglected infection prevalent across tropical areas .", "B . thailandensis is a member of the B . pseudomallei complex , rarely causes disease in humans and is considered a-virulent .", "Modelling studies hav...	2019
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "blood serum", "animal diseases", "medicine and health sciences", "body fluids", "foot and mouth disease", "microbiology", "precursor cells", "vertebrates", "animals", "mammals", "viruses", "animal models", "rna viruses", "experimental organism systems", "sequence motif analysis", "zoo...	Identification of a short, highly conserved, motif required for picornavirus capsid precursor processing at distal sites	journal.ppat.1007509	null	[ [ "Picornaviruses comprise a large family of non-enveloped RNA viruses that includes important human and animal pathogens .", "Examples include poliovirus ( PV ) ( genus: Enterovirus ) , hepatitis A virus ( Hepatovirus ) , encephalomyocarditis virus ( Cardiovirus ) and foot-and-mouth disease virus ( FMDV ) ...	[ "Many picornaviruses cause important diseases in humans and other animals including poliovirus , rhinoviruses ( causing the common cold ) and foot-and-mouth disease virus ( FMDV ) .", "These small , non-enveloped viruses comprise a positive-stranded RNA genome ( ca . 7–9 kb ) enclosed within a protein shell compo...	[ "The picornavirus family includes clinically important human and animal pathogens , for example: poliovirus , rhinovirus ( causing the common cold ) and foot-and-mouth disease virus ( FMDV ) that infects cloven-hoofed animals .", "Picornaviruses contain a positive-sense RNA genome surrounded by a protein shell , ...	2019
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "invertebrates", "children", "medicine and health sciences", "pruritus", "onchocerca volvulus", "pathology and laboratory medicine", "helminths", "tropical diseases", "geographical locations", "social sciences", "parasitic diseases", "animals", "onchocerca", "neuroscience", "age groups",...	Onchocerca volvulus infection in Tihama region - west of Yemen: Continuing transmission in ivermectin-targeted endemic foci and unveiled endemicity in districts with previously unknown status	journal.pntd.0006329	null	[ [ "Onchocerciasis is a neglected tropical disease of the skin and eyes caused by the filarial nematode Onchocerca volvulus and transmitted by the bites of infected Simulium blackflies .", "It is endemic in 31 countries in sub-Saharan Africa and in some foci in Latin America and Yemen , with approximately 18...	[ "Onchocerciasis in Yemen is one of the most neglected diseases , where baseline estimates of onchocerciasis and monitoring of the impact of ivermectin regularly administered to the affected individuals on its transmission are lacking .", "Therefore , this study aimed to determine the anti-Ov16 IgG4 seroprevalence...	[ "Onchocerciasis is endemic in certain foci in the western governorates of Yemen .", "Monitoring the impact of the regular ivermectin administration to affected individuals on the transmission status and providing baseline onchocerciasis estimates in endemic areas are crucial for planning effective elimination str...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "neuroscience/cognitive neuroscience", "neuroscience/theoretical neuroscience", "neuroscience/sensory systems", "physiology/sensory systems", "computational biology/computational neuroscience", "physiology/morphogenesis and cell biology", "computational biology/systems biology" ]	Neocortical Axon Arbors Trade-off Material and Conduction Delay Conservation	journal.pcbi.1000711	null	[ [ "Brains , like electronic networks , face a hard design problem: how to pack very many , yet highly interconnected , discrete computing devices within the least possible space while simultaneously preserving efficient communication [1] .", "Neocortex , for example , is densely packed and composed mostly o...	[ "The brain contains a complex network of axons rapidly communicating information between billions of synaptically connected neurons .", "The morphology of individual axons , therefore , defines the course of information flow within the brain .", "More than a century ago , Ramón y Cajal proposed that conservatio...	[ "Within the grey matter of cerebral cortex is a complex network formed by a dense tangle of individual branching axons mostly of cortical origin .", "Yet remarkably when presented with a barrage of complex , noisy sensory stimuli this convoluted network architecture computes accurately and rapidly .", "How does...	2010
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "infectious diseases/hiv infection and aids", "microbiology/microbial evolution and genomics", "ecology/evolutionary ecology" ]	Molecular Ecology and Natural History of Simian Foamy Virus Infection in Wild-Living Chimpanzees	journal.ppat.1000097	null	[ [ "Foamy viruses ( also termed spumaviruses ) are complex retroviruses that naturally infect numerous mammal species , including primates , felines , bovines and equines , but not humans [1]–[4] .", "Simian foamy viruses ( SFVs ) have been identified in a wide variety of primates , including prosimians , Ne...	[ "Identifying microbial pathogens with zoonotic potential in wild-living primates can be important to human health , as evidenced by human immunodeficiency viruses types 1 and 2 ( HIV-1 and HIV-2 ) and Ebola virus .", "Simian foamy viruses ( SFVs ) are ancient retroviruses that infect Old and New World monkeys and...	[ "Cross-species transmissions of infectious agents from primates to humans have led to major disease outbreaks , with AIDS representing a particularly serious example .", "It has recently been shown that humans who hunt primates frequently acquire simian foamy virus ( SFV ) infections .", "Thus , these viruses h...	2008
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "medicine and health sciences", "pathology and laboratory medicine", "intracellular pathogens", "pathogens", "tropical diseases", "microbiology", "bacterial diseases", "population modeling", "neglected tropical diseases", "bacterial pathogens", "neuropathy", "infectious diseases", "mycobacte...	IL-10 and NOS2 Modulate Antigen-Specific Reactivity and Nerve Infiltration by T Cells in Experimental Leprosy	journal.pntd.0003149	null	[ [ "Leprosy is a neglected tropical disease that is still diagnosed in >200 , 000 new patients every year [1] .", "Its clinical spectrum is associated with a diverse and often dynamic immune response ranging from strong cell mediated immunity ( CMI ) at one end to complete anergy toward Mycobacterium leprae ...	[ "Although immunopathology dictates clinical outcome in leprosy , the dynamics of early and chronic infection are poorly defined .", "In the tuberculoid region of the spectrum , Mycobacterium leprae growth is restricted yet a severe granulomatous lesion can occur .", "The evolution and maintenance of chronic inf...	[ "Despite effective antimicrobial therapy , 30–50% of leprosy patients develop immunological complications called leprosy reactions before , during or even years after being cured .", "Leprosy reactions are a major risk for neuritis that leads to peripheral nerve damage , disfigurement and disability .", "Unfort...	2014
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "infectious diseases/neglected tropical diseases", "pediatrics and child health", "public health and epidemiology/global health", "public health and epidemiology/infectious diseases", "infectious diseases/skin infections" ]	Community Management of Endemic Scabies in Remote Aboriginal Communities of Northern Australia: Low Treatment Uptake and High Ongoing Acquisition	journal.pntd.0000444	null	[ [ "Skin infections are a significant cause of morbidity in disadvantaged settings around the world [1] , [2] .", "Scabies and pyoderma are endemic in many Aboriginal communities in northern Australia .", "These conditions cause local morbidity and contribute substantially to clinic workload and costs [3...	[ "Scabies and skin infections are endemic in many Australian Aboriginal communities .", "There is limited evidence for effective models of scabies treatment in high prevalence settings .", "We aimed to assess the level of treatment uptake amongst clinically diagnosed scabies cases and amongst their household con...	[ "Like many impoverished areas around the world , Aboriginal communities in Australia experience an unacceptably high burden of scabies , skin infections , and secondary complications .", "Young children are most at risk .", "Our study investigated scabies in a remote setting with very high rates of skin disease...	2009
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "biophysics/transcription and translation", "molecular biology/transcription initiation and activation", "computational biology/transcriptional regulation" ]	Model of Transcriptional Activation by MarA in Escherichia coli	journal.pcbi.1000614	null	[ [ "Transcription factors control cellular protein production by binding to DNA and changing the frequency with which mRNA transcripts are produced .", "There are hundreds of transcription factors in Escherichia coli and while most of these target only a small number of genes , there are several that regulat...	[ "The AraC family transcription factor MarA activates ∼40 genes ( the marA/soxS/rob regulon ) of the Escherichia coli chromosome resulting in different levels of resistance to a wide array of antibiotics and to superoxides .", "Activation of marA/soxS/rob regulon promoters occurs in a well-defined order with respe...	[ "When environmental conditions change , cell survival can depend on sudden production of proteins that are normally in low demand .", "Protein production is controlled by transcription factors which bind to DNA near genes and either increase or decrease RNA production .", "Many puzzles remain concerning the way...	2009
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Manipulation of the Xanthophyll Cycle Increases Plant Susceptibility to Sclerotinia sclerotiorum	journal.ppat.1004878	null	[ [ "Chloroplasts are not only the factory for photosynthesis , but are also involved in various types of plant-pathogen interactions [1–3] .", "Indeed , the process of photosynthesis is functionally linked to plant immunity by providing energy , reducing equivalents and carbon skeletons [4–9] as well as prod...	[ "The xanthophyll cycle is involved in dissipating excess light energy to protect the photosynthetic apparatus in a process commonly assessed from non-photochemical quenching ( NPQ ) of chlorophyll fluorescence .", "Here , it is shown that the xanthophyll cycle is modulated by the necrotrophic pathogen Sclerotinia...	[ "In recent years , the role of the chloroplast in the defense against microbes has been intensively investigated and is of high interest to both plant-microbe interaction and photosynthesis research .", "The xanthophyll cycle is well known to be involved in dissipating excess light energy to protect the photosynt...	2015
[ "Introduction", "Methods", "Results", "Discussion" ]	[]	Complete Protection against Pneumonic and Bubonic Plague after a Single Oral Vaccination	journal.pntd.0004162	null	[ [ "Plague has been one of the deadliest bacterial infections in human history , causing millions of deaths during three major historical pandemics and leaving an indelible mark engraved in human's collective memory .", "In addition to ancient foci of the disease in Asia and Africa , the last pandemic ( plag...	[ "No efficient vaccine against plague is currently available .", "We previously showed that a genetically attenuated Yersinia pseudotuberculosis producing the Yersinia pestis F1 antigen was an efficient live oral vaccine against pneumonic plague .", "This candidate vaccine however failed to confer full protectio...	[ "Yersinia pestis , the agent of plague , is among the deadliest infectious agents affecting humans .", "Injected in the skin by infected fleas , Y . pestis causes bubonic plague , which occasionally evolves into the very lethal and contagious pneumonic plague .", "Y . pestis is also a dangerous potential biowea...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "cellular neuroscience", "computational neuroscience", "single neuron function", "biology", "neuroscience" ]	Effective Stimuli for Constructing Reliable Neuron Models	journal.pcbi.1002133	null	[ [ "Ever since the seminal study of Hodgkin and Huxley [1] on the biophysical basis of the squid giant axon action potential , conductance-based models ( CBMs ) have provided a critical connection between the microscopic level of membrane ion channels and the macroscopic level of signal flow in neuronal circuits...	[ "The rich dynamical nature of neurons poses major conceptual and technical challenges for unraveling their nonlinear membrane properties .", "Traditionally , various current waveforms have been injected at the soma to probe neuron dynamics , but the rationale for selecting specific stimuli has never been rigorous...	[ "Neurons perform complicated non-linear transformations on their input before producing their output - a train of action potentials .", "This input-output transformation is shaped by the specific composition of ion channels , out of the many possible types , that are embedded in the neuron's membrane .", "Exper...	2011
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "chemical compounds", "organic compounds", "age groups", "developmental biology", "adults", "steroids", "lipid signaling", "lipids", "chemistry", "people and places", "biochemistry", "signal transduction", "organic chemistry", "cell biology", "genetic screens", "gene identification and...	Steroid Hormone Signaling Is Essential for Pheromone Production and Oenocyte Survival	journal.pgen.1006126	null	[ [ "Pheromones , chemical communication signals , profoundly influence the behavior of many organisms [1 , 2] .", "For example , the choice to mate or fight in Drosophila melanogaster is largely dictated by pheromones [3] .", "In Lepidoptera , a subtle shift of sex pheromone composition alters mate recog...	[ "Many of the lipids found on the cuticles of insects function as pheromones and communicate information about age , sex , and reproductive status .", "In Drosophila , the composition of the information-rich lipid profile is dynamic and changes over the lifetime of an individual .", "However , the molecular basi...	[ "Pheromones are used by many animals to control social behaviors such as mate choice and kin recognition .", "The pheromone profile of insects is dynamic and can change depending on environmental , physiological , and social conditions .", "While many genes responsible for the biosynthesis of insect pheromones ...	2016
[ "Introduction", "Materials and methods", "Results", "Discussion" ]	[ "invertebrates", "ecology and environmental sciences", "medicine and health sciences", "onchocerca volvulus", "rivers", "helminths", "keratitis", "tropical diseases", "geographical locations", "parasitic diseases", "animals", "onchocerca", "aquatic environments", "bodies of water", "negl...	Onchocerca volvulus infection and serological prevalence, ocular onchocerciasis and parasite transmission in northern and central Togo after decades of Simulium damnosum s.l. vector control and mass drug administration of ivermectin	journal.pntd.0006312	null	[ [ "In large parts of Africa , onchocerciasis has been controlled as a public health problem by the Onchocerciasis Control Programme in West Africa ( OCP ) and the African Programme for Onchocerciasis Control ( APOC ) by mass drug administration ( MDA ) of ivermectin , and this intervention has been applied for ...	[ "Mass drug administration ( MDA ) of ivermectin has become the main intervention to control onchocerciasis or “river blindness” .", "In Togo , after many years of MDA , Onchocerca volvulus infection has declined dramatically , and elimination appears achievable , but in certain river basins the current situation ...	[ "Mass drug administration ( MDA ) with ivermectin has become the main tool in the efforts to control and eliminate onchocerciasis ( “river blindness” ) .", "In some areas , and after many years of MDA , levels of Onchocerca volvulus infection ( the causative parasite ) have declined greatly , and elimination appe...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "transfection", "medicine and health sciences", "pathology and laboratory medicine", "gene regulation", "pathogens", "microbiology", "light microscopy", "immunoprecipitation", "microscopy", "signalosomes", "confocal microscopy", "molecular biology techniques", "bacterial pathogens", "resea...	ER Adaptor SCAP Translocates and Recruits IRF3 to Perinuclear Microsome Induced by Cytosolic Microbial DNAs	journal.ppat.1005462	null	[ [ "Microbial infections represent an ever-present threat to host homeostasis and survival .", "The extracellular and intracellular microbes are dynamically and rapidly sensed by specific Pattern Recognition Receptors ( PRRs ) , including TLRs , NLRs and RLRs [1–3] .", "Upon recognition of the conserved ...	[ "Stimulator of interferon genes ( STING , also known as MITA , ERIS or MPYS ) induces the activation of TBK1 kinase and IRF3 transcription factor , upon sensing of microbial DNAs .", "How IRF3 is recruited onto the STING signalosome remains unknown .", "We report here that silencing of the ER adaptor SCAP marke...	[ "The stimulator of interferon genes ( STING/MITA/ERIS/MPYS ) is characterized as the converging point of the cytosolic DNAs-triggered innate immune signaling , and its function has been well documented in mediating the production of type I interferon and other pro-inflammatory cytokines .", "It remains intriguing...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "cellular stress responses", "genetic mutation", "microbiology", "gene function", "aspergillus nidulans", "eukaryotic cells", "model organisms", "cell growth", "molecular genetics", "gene expression", "biology", "systems biology", "biochemistry", "cell biology", "genetics", "yeast and ...	Control of Multicellular Development by the Physically Interacting Deneddylases DEN1/DenA and COP9 Signalosome	journal.pgen.1003275	null	[ [ "Conjugation and deconjugation of target proteins with ubiquitin ( Ub ) and related proteins is an important posttranslational regulatory principle to control the stability , activity or location of modified substrates .", "The neuronal precursor cell expressed developmentally down-regulated gene 8 ( Nedd...	[ "Deneddylases remove the ubiquitin-like protein Nedd8 from modified proteins .", "An increased deneddylase activity has been associated with various human cancers .", "In contrast , we show here that a mutant strain of the model fungus Aspergillus nidulans deficient in two deneddylases is viable but can only gr...	[ "The family of small ubiquitin-like ( Ubl ) proteins plays a major role in the control of stability , activity , or localization of modified target proteins in a eukaryotic cell .", "Lysine side chains are modified by covalent Ubl attachment , and this process can be reversed by specific proteases .", "Nedd8 is...	2013
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "innate immune system", "medicine and health sciences", "immune physiology", "cytokines", "pathology and laboratory medicine", "respiratory infections", "influenza", "immunology", "pulmonology", "animal models", "developmental biology", "model organisms", "signs and symptoms", "inflammasom...	Delayed oseltamivir plus sirolimus treatment attenuates H1N1 virus-induced severe lung injury correlated with repressed NLRP3 inflammasome activation and inflammatory cell infiltration	journal.ppat.1007428	null	[ [ "Influenza A virus ( IAV ) infection represents a leading threat to global public health .", "New estimates have indicated that up to approximately 645 , 000 influenza-associated respiratory deaths occur annually [1] .", "Our previous clinical data showed that critically ill patients infected with inf...	[ "Severe influenza A virus infection causes high mortality and morbidity worldwide due to delayed antiviral treatment and inducing overwhelming immune responses , which contribute to immunopathological lung injury .", "Sirolimus , an inhibitor of mammalian target of rapamycin ( mTOR ) , was effective in improving ...	[ "The severity and lethality of influenza A virus infection are frequently aggravated by virus-induced tissue destruction and overwhelming immune responses .", "Combined therapy with antiviral medications and immunomodulators , which not only inhibit viral replication , but also reduce the damaging consequences of...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods", "Supporting Information" ]	[ "developmental biology", "infectious diseases", "cell biology", "yeast and fungi", "microbiology", "evolutionary biology", "molecular biology", "genetics and genomics" ]	αADα Hybrids of Cryptococcus neoformans: Evidence of Same-Sex Mating in Nature and Hybrid Fitness	journal.pgen.0030186	null	[ [ "The level of genetic variation within a species is correlated with evolutionary potential [1] .", "Hybridization can provide genetic variation within and between populations by yielding progeny more fit in novel or changing environments , and both intra- and interspecies hybridization are a driving force...	[ "Cryptococcus neoformans is a ubiquitous human fungal pathogen that causes meningoencephalitis in predominantly immunocompromised hosts .", "The fungus is typically haploid , and sexual reproduction involves two individuals with opposite mating types/sexes , α and a .", "However , the overwhelming predominance ...	[ "Cryptococcus neoformans is a major cause of fungal meningitis , predominantly in immunocompromised individuals .", "This fungus has two mating types/sexes , a and α , and mating typically requires two individuals with opposite mating types .", "It is mysterious why the α mating type is overwhelmingly predomina...	2007
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "action potentials", "medicine and health sciences", "nervous system", "membrane potential", "brain", "electrophysiology", "light", "neuroscience", "electromagnetic radiation", "nerve fibers", "interneurons", "neuronal dendrites", "animal cells", "axons", "light pulses", "amygdala", ...	Differential excitatory control of 2 parallel basket cell networks in amygdala microcircuits	journal.pbio.2001421	null	[ [ "Gamma-aminobutyric acid ( GABA ) ergic basket and axo-axonic cells ( AACs ) targeting the perisomatic region of cortical principal neurons ( PNs ) are in a key position to effectively control the firing of their postsynaptic partners [1 , 2] .", "Consequently , perisomatic inhibitory interneurons are ess...	[ "Information processing in neural networks depends on the connectivity among excitatory and inhibitory neurons .", "The presence of parallel , distinctly controlled local circuits within a cortical network may ensure an effective and dynamic regulation of microcircuit function .", "By applying a combination of ...	[ "The perisomatic region of neurons refers collectively to the membrane surface of the cell body or soma , proximal dendrites , and axon initial segment .", "This is a unique functional domain in which the activity of a neuron can be controlled in the most effective manner .", "In the cerebral cortex , the peris...	2017
[ "Introduction", "Results", "Discussion", "Materials and methods", "Availability" ]	[ "crystal structure", "markov models", "engineering and technology", "synthetic biology", "condensed matter physics", "synthetic bioengineering", "mathematics", "protein structure", "sequence motif analysis", "macromolecular design", "crystallography", "research and analysis methods", "bioeng...	Rosetta FunFolDes – A general framework for the computational design of functional proteins	journal.pcbi.1006623	null	[ [ "Proteins are one of the main functional building blocks of the cell .", "The ability to create novel proteins outside of the natural realm has opened the path towards innovative achievements , such as new pathways [1] , cellular functions [2] , and therapeutic leads [3–5] .", "Computational protein d...	[ "The robust computational design of functional proteins has the potential to deeply impact translational research and broaden our understanding of the determinants of protein function and stability .", "The low success rates of computational design protocols and the extensive in vitro optimization often required ...	[ "The ability to use computational tools to manipulate the structure and function of proteins has the potential to impact many facets of fundamental and translational science .", "Due to our limited understanding of the principles that govern protein function and structure , the computational design of functional ...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "gene expression", "genetics", "epigenetics", "biology", "chromatin", "histone modification" ]	Single Cell Visualization of Yeast Gene Expression Shows Correlation of Epigenetic Switching between Multiple Heterochromatic Regions through Multiple Generations	journal.pbio.1001601	A single-cell method allows the assessment of relationships between the dynamic epigenetic behavior of yeast heterochromatin boundaries over multiple generations.	[ [ "The silencing domain in Saccharomyces cerevisiae comprises the homothallic mating-type loci HMR and HML , telomeres , and the rDNA locus .", "Repression of gene expression in HMR , HML , and telomere regions is achieved via binding of a protein complex that includes Sir2p , Sir3p , and Sir4p , whereas re...	[ "Differences in gene expression between individual cells can be mediated by epigenetic regulation; thus , methods that enable detailed analyses of single cells are crucial to understanding this phenomenon .", "In this study , genomic silencing regions of Saccharomyces cerevisiae that are subject to epigenetic reg...	[ "Although eukaryotic gene repression usually acts on individual genes , cells can also repress larger chromosomal regions via the establishment of a high order chromatin structure called heterochromatin .", "Once initiated , heterochromatin spreads until halted by a boundary , and in this study we focus on how th...	2013
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "schistosoma", "invertebrates", "medicine and health sciences", "surface water", "education", "helminths", "sociology", "tropical diseases", "geographical locations", "social sciences", "parasitic diseases", "animals", "health care", "data mining", "neglected tropical diseases", "sanit...	Improving spatial prediction of Schistosoma haematobium prevalence in southern Ghana through new remote sensors and local water access profiles	journal.pntd.0006517	null	[ [ "Schistosomiasis is an important parasitic disease that affects more than 250 million people [1] .", "Expressed in years lived with disability ( YLDs ) , the impact of schistosomiasis is comparable to that of malaria ( 2 . 9 versus 3 . 2 million YLDs ) [2] .", "Schistosomiasis is a disease of poverty ...	[ "Schistosomiasis is a water-related neglected tropical disease .", "In many endemic low- and middle-income countries , insufficient surveillance and reporting lead to poor characterization of the demographic and geographic distribution of schistosomiasis cases .", "Hence , modeling is relied upon to predict are...	[ "Schistosomiasis is a water-related neglected tropical disease that disproportionately affects school-aged children in poor communities of low- and middle-income countries .", "Schistosomiasis transmission risk is affected by environmental , socioeconomic , and behavioral factors , including water , sanitation , ...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biotechnology", "systems biology", "environmental biotechnology", "microbial evolution", "gene expression", "genetics", "synthetic biology", "biology", "microbiology", "gene networks", "molecular biology", "genetics and genomics" ]	Increasing Signal Specificity of the TOL Network of Pseudomonas putida mt-2 by Rewiring the Connectivity of the Master Regulator XylR	journal.pgen.1002963	null	[ [ "The mechanisms that bacteria use to transduce external stimuli into specific responses rely on connected transcriptional factors that shape circuit-like input/output devices [1] .", "Such networks are comprised of interacting molecular components and can adopt different topologies [2] .", "The respon...	[ "Prokaryotic transcription factors ( TFs ) that bind small xenobiotic molecules ( e . g . , TFs that drive genes that respond to environmental pollutants ) often display a promiscuous effector profile for analogs of the bona fide chemical signals .", "XylR , the master TF for expression of the m-xylene biodegrada...	[ "It is generally taken for granted that promoters regulated by transcriptional factors ( TFs ) that respond to small molecules control their specificity to given effectors by tightening or relaxing the intrinsic dual interaction between the TF and the particular inducer .", "One such promoter is Pu , which drives...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genetics and genomics/gene function", "genetics and genomics/plant genetics and gene expression", "genetics and genomics/gene expression" ]	Arabidopsis CaM Binding Protein CBP60g Contributes to MAMP-Induced SA Accumulation and Is Involved in Disease Resistance against Pseudomonas syringae	journal.ppat.1000301	null	[ [ "Plant innate immunity is multi-layered and tightly regulated by a complex signaling network [1] .", "Defense against biotrophic or hemibiotrophic bacterial pathogens can be thought of as consisting of two branches: the broad and nonspecific defenses triggered by the perception of microbe- or pathogen-ass...	[ "Salicylic acid ( SA ) -induced defense responses are important factors during effector triggered immunity and microbe-associated molecular pattern ( MAMP ) -induced immunity in plants .", "This article presents evidence that a member of the Arabidopsis CBP60 gene family , CBP60g , contributes to MAMP-triggered S...	[ "Plants respond to attack by microbial pathogens through activation of a battery of defense responses .", "This activation is controlled by a complex signaling network .", "Disease resistance depends on rapid activation of plant defense responses .", "Improved understanding of the signaling network may lead t...	2009
[ "Introduction", "Results", "Discussion", "Methods" ]	[]	A global map of the protein shape universe	journal.pcbi.1006969	null	[ [ "Proteins are the primary workers in a living cell , involved in transportation , catalysis , signaling , energy production , and many other processes .", "Classification of protein structures provides fundamental information for our understanding of the principles that govern and determine protein struct...	[ "Proteins are involved in almost all functions in a living cell , and functions of proteins are realized by their tertiary structures .", "Obtaining a global perspective of the variety and distribution of protein structures lays a foundation for our understanding of the building principle of protein structures ."...	[ "Proteins are the major molecules involved in almost all cellular processes .", "In this work , we present a novel mapping of protein shapes that represents the variety and the similarities of 3D shapes of proteins and their assemblies .", "This mapping provides various novel insights into protein shapes includ...	2019
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "g1 phase", "classical mechanics", "engineering and technology", "cell cycle and cell division", "lasers", "cell processes", "g2 phase", "mechanical energy", "molecular motors", "actin motors", "stem cells", "microscopy", "optical equipment", "motor proteins", "research and analysis meth...	Elasticity-based boosting of neuroepithelial nucleokinesis via indirect energy transfer from mother to daughter	journal.pbio.2004426	null	[ [ "Formation of large brains such as the mammalian cerebral cortex depends on continuous and efficient cell production by neural progenitor cells ( NPCs ) [1 , 2 , 3] .", "NPCs are elongated , spanning a developing brain wall ( up to 300 μm thick in mice ) , and divide at the apical surface [4 , 5 , 6 , 7 ,...	[ "Neural progenitor cells ( NPCs ) , which are apicobasally elongated and densely packed in the developing brain , systematically move their nuclei/somata in a cell cycle–dependent manner , called interkinetic nuclear migration ( IKNM ) : apical during G2 and basal during G1 .", "Although intracellular molecular m...	[ "The development of large brain structures , such as the mammalian cerebral cortex , depends on the continuous and efficient production of cells by neural progenitor cells .", "Neural progenitor cells are elongated and span the developing brain wall .", "The nuclei and bodies of these cells move cyclically betw...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Auxin Response Factor SlARF2 Is an Essential Component of the Regulatory Mechanism Controlling Fruit Ripening in Tomato	journal.pgen.1005649	null	[ [ "Fruit ripening is a complex , genetically programmed process that is associated with dramatic metabolic and textural transformations including color change , fruit softening , sugar accumulation and production of flavor and aroma compounds [1–3] .", "The ripening process ultimately leads to fruit witheri...	[ "Ethylene is the main regulator of climacteric fruit ripening , by contrast the putative role of other phytohormones in this process remains poorly understood .", "The present study brings auxin signaling components into the mechanism regulating tomato fruit ripening through the functional characterization of Aux...	[ "The plant hormone ethylene is regarded as the major regulator of fruit ripening but the putative role of other hormones remains elusive .", "Auxin Response Factors ( ARFs ) are transcriptional regulators modulating the expression of auxin-response genes shown recently to play a primary role in regulating fruit s...	2015
[ "Introduction", "Materials and Methods", "Results and Discussion" ]	[ "immunology/immunomodulation", "infectious diseases/neglected tropical diseases", "dermatology/skin infections", "infectious diseases/skin infections", "microbiology/parasitology", "infectious diseases/protozoal infections" ]	Systemic FasL and TRAIL Neutralisation Reduce Leishmaniasis Induced Skin Ulceration	journal.pntd.0000844	null	[ [ "Leishmaniasis is a group of parasitic diseases associated with heterogeneous clinical manifestations .", "Symptoms range from lethal disease with overwhelming infection of the bone-marrow , spleen and liver to localised self-healing ulcers of the skin .", "Leishmania aethiopica is the main causative ...	[ "Cutaneous leishmaniasis ( CL ) is caused by Leishmania infection of dermal macrophages and is associated with chronic inflammation of the skin .", "L . aethiopica infection displays two clinical manifestations , firstly ulcerative disease , correlated to a relatively low parasite load in the skin , and secondly ...	[ "Cutaneous leishmaniases are associated with parasite-induced inflammatory lesions of the skin .", "The degree of clinical pathology is not associated with parasitic burden; on the contrary , ulcerative lesions are associated with low infectious load , and non-ulcerative lesions are associated with an abundant pa...	2010
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "animal types", "animal genetics", "genetic mutation", "gene function", "animal models", "histology", "model organisms", "molecular genetics", "veterinary science", "gene splicing", "membranes and sorting", "biology", "veterinary pathology", "autosomal recessive", "congenital hereditary ...	Altered Splicing of the BIN1 Muscle-Specific Exon in Humans and Dogs with Highly Progressive Centronuclear Myopathy	journal.pgen.1003430	null	[ [ "Amphiphysin 2 is one of the key factors in muscular membrane remodeling .", "The gene , BIN1 , has recently been associated with two different muscle disorders: centronuclear myopathy ( CNM , MIM #255200 ) [1] and myotonic dystrophy ( DM , MIM #160900 and #602668 ) [2] .", "However , the muscle-speci...	[ "Amphiphysin 2 , encoded by BIN1 , is a key factor for membrane sensing and remodelling in different cell types .", "Homozygous BIN1 mutations in ubiquitously expressed exons are associated with autosomal recessive centronuclear myopathy ( CNM ) , a mildly progressive muscle disorder typically showing abnormal nu...	[ "The intracellular organization of muscle fibers relies on a complex membrane system important for muscle structural organization , maintenance , contraction , and resistance to stress .", "Amphiphysin 2 , encoded by BIN1 , plays a central role in membrane sensing and remodelling and is involved in intracellular ...	2013
[ "Introduction", "Results", "Discussion", "Methods" ]	[]	Hedging Your Bets: Intermediate Movements as Optimal Behavior in the Context of an Incomplete Decision	journal.pcbi.1004171	null	[ [ "In the reaction time before a movement is initiated , two distinct processes are thought to occur: first , the exact goals of the movement must be decided upon and , second , the actions that will achieve the chosen goal must be selected and/or prepared [1] .", "Decisions about high-level movement goals ...	[ "Existing theories of movement planning suggest that it takes time to select and prepare the actions required to achieve a given goal .", "These theories often appeal to circumstances where planning apparently goes awry .", "For instance , if reaction times are forced to be very low , movement trajectories are ...	[ "Two critical processes need to occur before a movement can be made: identification of the goal of the movement and selection and preparation of the motor commands that will be sent to muscles to generate the movement—in other words , what movement to make , and how to make it .", "It has long been thought that p...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "influenza", "medicine", "infectious diseases", "viral diseases" ]	Prolonged Influenza Virus Shedding and Emergence of Antiviral Resistance in Immunocompromised Patients and Ferrets	journal.ppat.1003343	null	[ [ "During the first 12 months of the 2009 influenza A/H1N1 virus ( pH1N1 ) pandemic an estimated 284 , 000 patients died and hospitalization rates were considerably higher than for seasonal influenza [1] .", "Although many severe cases were observed in otherwise healthy patients under 50 years of age , most...	[ "Immunocompromised individuals tend to suffer from influenza longer with more serious complications than otherwise healthy patients .", "Little is known about the impact of prolonged infection and the efficacy of antiviral therapy in these patients .", "Among all 189 influenza A virus infected immunocompromised...	[ "Immunocompromised patients , such as transplant recipients on immune suppressive therapy , are a substantial and gradually expanding patient group .", "Upon influenza virus infection , these patients clear the virus less efficiently and are more likely to develop severe pneumonia than immunocompetent individuals...	2013
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "medicine and health sciences", "pathology and laboratory medicine", "brain damage", "enzymes", "enzymology", "toxicology", "animal models", "microscopy", "experimental organism systems", "mitochondria", "bioenergetics", "cellular structures and organelles", "research and analysis methods", ...	TDP-43 induces mitochondrial damage and activates the mitochondrial unfolded protein response	journal.pgen.1007947	null	[ [ "TDP-43 proteinopathy is characterized by the presence of TDP-43 immunoreactive inclusion bodies in the affected tissues .", "Clinically , TDP-43 proteinopathy manifests as a spectrum of different neurodegenerative diseases , ranging from dementia ( especially fronto-temporal lobar degeneration , FTLD ) a...	[ "Mutations in or dys-regulation of the TDP-43 gene have been associated with TDP-43 proteinopathy , a spectrum of neurodegenerative diseases including Frontotemporal Lobar Degeneration ( FTLD ) and Amyotrophic Lateral Sclerosis ( ALS ) .", "The underlying molecular and cellular defects , however , remain unclear ...	[ "TDP-43 proteinopathy is a group of fatal neurological diseases .", "Here , we report a systematic examination of the role of mitochondrial damage in TDP-43 proteinopathy using patient brain tissues , as well as cellular and animal models .", "Our data show that TDP-43 induces severe mitochondrial damage , acco...	2019
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "blood cells", "medicine and health sciences", "immune cells", "antiviral therapy", "immunology", "liver diseases", "preventive medicine", "infectious hepatitis", "hepatitis", "gastroenterology and hepatology", "cytotoxic t cells", "vaccination and immunization", "research and analysis metho...	Interferon Alpha Induces Sustained Changes in NK Cell Responsiveness to Hepatitis B Viral Load Suppression In Vivo	journal.ppat.1005788	null	[ [ "Chronic Hepatitis B ( CHB ) related cirrhosis and hepatocellular carcinoma ( HCC ) account for approximately 600 , 000 deaths per year [1] .", "Current treatments for Hepatitis B virus ( HBV ) include Pegylated Interferon-Alpha ( PegIFNα ) and nuleos ( t ) ide analogues ( NUCs ) .", "Although PegIFNα...	[ "NK cells are important antiviral effectors , highly enriched in the liver , with the potential to regulate immunopathogenesis in persistent viral infections .", "Here we examined whether changes in the NK pool are induced when patients with eAg-positive CHB are ‘primed’ with PegIFNα and importantly , whether the...	[ "Current therapies for CHB are limited in achieving HBsAg decline and loss leading to a cure .", "Although PegIFNα may be used , the majority of patients progress to NUC therapy due to treatment failure .", "PegIFNα and NUCs used in isolation act differentially on the immune response; PegIFNα induces NK cell ac...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "diabetes and endocrinology/bone and mineral metabolism", "cell biology/extra-cellular matrix", "biochemistry/protein folding", "cell biology/developmental molecular mechanisms" ]	Severe Osteogenesis Imperfecta in Cyclophilin B–Deficient Mice	journal.pgen.1000750	null	[ [ "OI is an inherited disorder of collagen , affecting one in 12 , 000 newborns [1] , [2] .", "Point mutations in the type I collagen genes COL1A1 or COL1A2 are responsible for the majority of cases , which are typically autosomal dominant .", "The severity of symptoms of OI is highly heterogeneous , ra...	[ "Osteogenesis Imperfecta ( OI ) is a human syndrome characterized by exquisitely fragile bones due to osteoporosis .", "The majority of autosomal dominant OI cases result from point or splice site mutations in the type I collagen genes , which are thought to lead to aberrant osteoid within developing bones .", ...	[ "Osteogenesis Imperfecta ( OI ) , also known as “brittle bone disease , ” is an inherited condition with multiple defects in collagen-containing structures , including the bones , skin , and other connective tissues .", "Patients with OI suffer from short stature , scoliosis , thin skin , hearing loss , and , mos...	2009
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "mycology", "fungi", "rna processing", "genetic screens", "medical microbiology", "gene identification and analysis", "gene expression", "genetics", "gene regulation", "molecular genetics", "gene splicing", "biology", "microbiology", "microbial pathogens", "rna stability" ]	Introns Regulate Gene Expression in Cryptococcus neoformans in a Pab2p Dependent Pathway	journal.pgen.1003686	null	[ [ "Introns , discovered in 1977 , are genomic sequences that are removed from the corresponding RNA transcripts of genes [1] .", "First considered just as elements to be removed for correct gene expression , it has since become obvious that they participate in many aspects of gene regulation .", "Actual...	[ "Most Cryptococccus neoformans genes are interrupted by introns , and alternative splicing occurs very often .", "In this study , we examined the influence of introns on C . neoformans gene expression .", "For most tested genes , elimination of introns greatly reduces mRNA accumulation .", "Strikingly , the n...	[ "Cryptococcus neoformans is a major human pathogen responsible for deadly infection in immunocompromised patients .", "The analysis of its genome previously revealed that most of its genes are interrupted by introns .", "Here , we demonstrate that introns modulate gene expression in a cumulative manner .", "W...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Knowledge-Based Analysis for Detecting Key Signaling Events from Time-Series Phosphoproteomics Data	journal.pcbi.1004403	null	[ [ "Cell signaling controls various aspects of basic cellular processes including homeostasis , proliferation , survival , and cell fate decisions , and defects in mechanisms underlying these processes are associated with a wide range of diseases [1–3] .", "Protein post-translational modifications ( PTMs ) ,...	[ "Cell signaling underlies transcription/epigenetic control of a vast majority of cell-fate decisions .", "A key goal in cell signaling studies is to identify the set of kinases that underlie key signaling events .", "In a typical phosphoproteomics study , phosphorylation sites ( substrates ) of active kinases a...	[ "A key goal in cell signaling studies is to identify the set of kinases that underlie key signaling events .", "Mass spectrometry-based technologies have emerged as a powerful tool to profile proteome-wide phosphorylation events in vivo at a single amino acid resolution with high precision .", "However , develo...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genetics and genomics/gene discovery", "biotechnology/plant biotechnology", "cell biology/cell growth and division", "genetics and genomics/gene function", "genetics and genomics/plant genomes and evolution" ]	The CYCLIN-A CYCA1;2/TAM Is Required for the Meiosis I to Meiosis II Transition and Cooperates with OSD1 for the Prophase to First Meiotic Division Transition	journal.pgen.1000989	null	[ [ "Meiosis is a central feature in the reproductive program of all sexually reproducing eukaryotes .", "The process of meiosis involves two rounds of chromosome segregation that follow a single round of chromosome duplication leading to the production of haploid gametes .", "Meiosis differs from mitosis...	[ "Meiosis halves the chromosome number because its two divisions follow a single round of DNA replication .", "This process involves two cell transitions , the transition from prophase to the first meiotic division ( meiosis I ) and the unique meiosis I to meiosis II transition .", "We show here that the A-type ...	[ "In the life cycle of sexual organisms , a specialized cell division—meiosis—reduces the number of chromosomes from two sets ( 2n , diploid ) to one set ( n , haploid ) , while fertilization restores the original chromosome number .", "Meiosis reduces ploidy because it consists of two divisions following a single...	2010
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "learning", "medicine and health sciences", "engineering and technology", "signal processing", "limbs (anatomy)", "social sciences", "neuroscience", "learning and memory", "noise reduction", "regression analysis", "cognitive psychology", "mathematics", "human performance", "statistics (mat...	Neuromotor Noise Is Malleable by Amplifying Perceived Errors	journal.pcbi.1005044	null	[ [ "A hallmark of human movement is its variability , recognized in the phrase “repetition without repetition” [1] .", "Even the world champion in dart throwing does not hit the bull’s eye every time—in fact , it is this remaining randomness that creates the thrill in championships .", "This variability ...	[ "Variability in motor performance results from the interplay of error correction and neuromotor noise .", "This study examined whether visual amplification of error , previously shown to improve performance , affects not only error correction , but also neuromotor noise , typically regarded as inaccessible to int...	[ "It is widely recognized that neuromotor noise limits human motor performance , generating errors and variability even in highly skilled performers .", "Arising from many spatiotemporal scales within the physiological system , the intrinsic noise component is commonly assumed to be invariant by most computational...	2016
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "phosphorylation", "yeast two-hybrid assays", "protein interactions", "chemical compounds", "threonine", "organic compounds", "protein interaction assays", "amino acids", "molecular biology techniques", "gel electrophoresis", "bacteria", "research and analysis methods", "electrophoretic tech...	Mycobacterium tuberculosis universal stress protein Rv2623 interacts with the putative ATP binding cassette (ABC) transporter Rv1747 to regulate mycobacterial growth	journal.ppat.1006515	null	[ [ "Mycobacterium tuberculosis , the causative agent of tuberculosis ( TB ) , remains a global public health problem , causing , in 2015 alone , over 10 . 4 million new cases and 1 . 8 million deaths worldwide [1] .", "M . tuberculosis is able to establish an asymptomatic latent infection that can later reac...	[ "We have previously shown that the Mycobacterium tuberculosis universal stress protein Rv2623 regulates mycobacterial growth and may be required for the establishment of tuberculous persistence .", "Here , yeast two-hybrid and affinity chromatography experiments have demonstrated that Rv2623 interacts with one of...	[ "Mycobacterium tuberculosis remains a significant public health burden worldwide .", "The tubercle bacillus can establish a clinically silent latent infection in the host , which can subsequently reactivate to cause diseases , resulting in transmission of the pathogen .", "We have previously shown that the M . ...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biochemistry", "molecular cell biology", "nucleic acids", "genetics", "dna", "biology", "dna repair", "molecular genetics", "population genetics", "molecular biology", "genetics and genomics" ]	RecX Facilitates Homologous Recombination by Modulating RecA Activities	journal.pgen.1003126	null	[ [ "The bacterial RecA recombinase ( homologue to human RAD51 and DMC1 ) , arranged as higher-order oligomers assembled on tracts of single-stranded ( ss ) DNA , is involved in the DNA strand exchange reaction to warrant genome integrity by recombinational repair ( RR ) , and genetic diversity by genetic recombi...	[ "The Bacillus subtilis recH342 strain , which decreases interspecies recombination without significantly affecting the frequency of transformation with homogamic DNA , carried a point mutation in the putative recX ( yfhG ) gene , and the mutation was renamed as recX342 .", "We show that RecX ( 264 residues long )...	[ "This study describes mechanisms employed by the bacterium Bacillus subtilis to survive DNA damages by recombinational repair ( RR ) and to provide genetic variation via genetic recombination ( GR ) .", "At the center of homologous recombination ( HR ) is the recombinase RecA , which forms RecA·ssDNA filaments to...	2012
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "genome-wide association studies", "medicine and health sciences", "sociology", "social sciences", "epidemiological methods and statistics", "coronary heart disease", "mathematics", "statistics (mathematics)", "genome analysis", "research and analysis methods", "cardiology", "statistical distr...	Identifying systematic heterogeneity patterns in genetic association meta-analysis studies	journal.pgen.1006755	null	[ [ "The common disease—common variant ( CD-CV ) hypothesis has been confirmed by the discovery of thousands of robustly associated loci for a wide variety of complex diseases and quantitative inherited traits [1] .", "The genetic effects conferred by common susceptibility loci tend to be small ( per-allele d...	[ "Progress in mapping loci associated with common complex diseases or quantitative inherited traits has been expedited by large-scale meta-analyses combining information across multiple studies , assembled through collaborative networks of researchers .", "Participating studies will usually have been independently...	[ "Meta-analysis of genome-wide association studies ( GWAS ) is a valuable tool for the discovery of genes that protect or predispose individuals to common complex diseases .", "It can though be hampered by excessive heterogeneity among its participating studies .", "To date , the impact of heterogeneity is asses...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biology", "microbiology", "molecular cell biology" ]	The Pore-Forming Toxin Listeriolysin O Mediates a Novel Entry Pathway of L. monocytogenes into Human Hepatocytes	journal.ppat.1002356	null	[ [ "Despite the diversity of virulence factors promoting host cell invasion , only two major mechanisms of entry have been observed [1]–[3] .", "First , invasins on the bacterial cell surface bind to host cell receptors to activate complex signaling cascades that orchestrate the internalization of the bacter...	[ "Intracellular pathogens have evolved diverse strategies to invade and survive within host cells .", "Among the most studied facultative intracellular pathogens , Listeria monocytogenes is known to express two invasins-InlA and InlB-that induce bacterial internalization into nonphagocytic cells .", "The pore-fo...	[ "Listeria monocytogenes is responsible for the severe foodborne disease listeriosis .", "During pathogenesis , invasion of nonphagocytic cells by L . monocytogenes is crucial for crossing the host epithelial barriers and colonization of multiple organs including the liver .", "In this study , we investigated th...	2011
[ "Introduction", "Results", "Discussion", "Methods" ]	[]	The siRNA Non-seed Region and Its Target Sequences Are Auxiliary Determinants of Off-Target Effects	journal.pcbi.1004656	null	[ [ "RNA interference ( RNAi ) is a highly regulated , evolutionarily conserved mechanism of post-transcriptional gene regulation .", "Small interfering RNAs ( siRNAs ) , the intermediate utilised by this pathway , are 19 base pair ( bp ) long double stranded RNAs ( dsRNAs ) , with 2 nucleotide ( nt ) 3’ over...	[ "RNA interference ( RNAi ) is a powerful tool for post-transcriptional gene silencing .", "However , the siRNA guide strand may bind unintended off-target transcripts via partial sequence complementarity by a mechanism closely mirroring micro RNA ( miRNA ) silencing .", "To better understand these off-target ef...	[ "Small interfering RNAs ( siRNAs ) are double stranded RNA molecules designed to perfectly match the sequence of a target gene and silence its expression .", "The function is exerted through the RNA interference ( RNAi ) pathway and has revolutionised biological research due to its ease-of-use and high potency ."...	2015
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "invertebrates", "rna interference", "chemical compounds", "aliphatic amino acids", "caenorhabditis", "organic compounds", "animals", "animal models", "caenorhabditis elegans", "model organisms", "serine", "experimental organism systems", "amino acids", "epigenetics", "research and analy...	Glycine promotes longevity in Caenorhabditis elegans in a methionine cycle-dependent fashion	journal.pgen.1007633	null	[ [ "Aging is characterized by a progressive deterioration of the functional capacity of tissues and organs .", "Pioneering studies in the nematode C . elegans have identified longevity-associated genes and provided us with great insights into the plasticity of aging [1–3] .", "In the last few decades , g...	[ "The deregulation of metabolism is a hallmark of aging .", "As such , changes in the expression of metabolic genes and the profiles of amino acid levels are features associated with aging animals .", "We previously reported that the levels of most amino acids decline with age in Caenorhabditis elegans ( C . ele...	[ "There is a growing number of studies showing that amino acids function as signal metabolites that influence aging and health .", "Although contemporary -OMICs studies have uncovered various associations between metabolite levels and aging , in many cases the directionality of the relationships is unclear .", "...	2019
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "developmental biology/cell differentiation", "neuroscience/neurodevelopment", "developmental biology/neurodevelopment", "developmental biology/developmental molecular mechanisms", "cell biology/gene expression" ]	The Gene Regulatory Cascade Linking Proneural Specification with Differentiation in Drosophila Sensory Neurons	journal.pbio.1000568	Temporal expression profiling of sensory precursor cells reveals how the atonal proneural transcription factor regulates a specialized neuronal differentiation pathway.	[ [ "Once an embryonic cell is committed to a particular fate , it is likely that a precisely ordered progression of gene expression is required to coordinate the complex cell biological events that eventually lead to its terminal differentiation .", "Determining how this progression is regulated is an import...	[ "In neurogenesis , neural cell fate specification is generally triggered by proneural transcription factors .", "Whilst the role of proneural factors in fate specification is well studied , the link between neural specification and the cellular pathways that ultimately must be activated to construct specialised n...	[ "Early during development , cells differentiate and take on specialized forms and functions .", "This requires the activation of specific genes for different cellular pathways .", "Our study addresses how this activation is regulated in the developing Drosophila nervous system .", "In this model , it is well ...	2011
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biochemistry", "virology", "biology", "microbiology", "metabolism" ]	Divergent Effects of Human Cytomegalovirus and Herpes Simplex Virus-1 on Cellular Metabolism	journal.ppat.1002124	null	[ [ "Herpesviruses are large , enveloped , double-stranded DNA viruses , capable of both lytic infection and life-long latency in mammalian hosts [1] .", "They are major causes of human disease .", "A majority of adults are infected with herpes simplex virus 1 ( HSV-1 ) and/or human cytomegalovirus ( HCMV...	[ "Viruses rely on the metabolic network of the host cell to provide energy and macromolecular precursors to fuel viral replication .", "Here we used mass spectrometry to examine the impact of two related herpesviruses , human cytomegalovirus ( HCMV ) and herpes simplex virus type-1 ( HSV-1 ) , on the metabolism of...	[ "Enveloped viruses draw on cellular machinery and materials to generate copies of their genome , structural proteins , and membrane .", "These biosynthetic processes use the host metabolic network to provide energy and small-molecule precursors .", "We have investigated how two important enveloped viruses , hum...	2011
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "infectious diseases" ]	Response to Treatment in a Prospective Cohort of Patients with Large Ulcerated Lesions Suspected to Be Buruli Ulcer (Mycobacterium ulcerans Disease)	journal.pntd.0000736	null	[ [ "Mycobacterium ulcerans disease , commonly called “Buruli ulcer” ( BU ) , is a neglected and emergent tropical disease [1] , [2] , with Africa being the most affected continent [3] .", "For many years , management of the disease relied mainly on surgical procedures [4] , [5] , [6] .", "Other treatment...	[ "The World Health Organization ( WHO ) advises treatment of Mycobacterium ulcerans disease , also called “Buruli ulcer” ( BU ) , with a combination of the antibiotics rifampicin and streptomycin ( R+S ) , whether followed by surgery or not .", "In endemic areas , a clinical case definition is recommended .", "W...	[ "Buruli ulcer ( BU ) disease , a neglected devastating infection caused by Mycobacterium ulcerans , has a huge impact because of the massive necrotizing , disfiguring ulcers that may result if not treated .", "Therapeutic options are surgery , antibiotics or combinations of both .", "Since 2004 , the World Heal...	2010
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "invertebrates", "cell death", "medicine and health sciences", "pathology and laboratory medicine", "gene regulation", "cell processes", "neuroscience", "animals", "invertebrate genomics", "toxicology", "animal models", "dna damage", "toxicity", "drosophila melanogaster", "model organism...	Retrotransposon activation contributes to neurodegeneration in a Drosophila TDP-43 model of ALS	journal.pgen.1006635	null	[ [ "RTEs are “genomic parasites”–“selfish” genetic elements that are coded within our genomes and that replicate themselves via an RNA intermediate .", "After transcription , an RTE-encoded reverse transcriptase generates a cDNA copy , and this cDNA is inserted into a new genomic location at the site of doub...	[ "Amyotrophic lateral sclerosis ( ALS ) and frontotemporal lobar degeneration ( FTLD ) are two incurable neurodegenerative disorders that exist on a symptomological spectrum and share both genetic underpinnings and pathophysiological hallmarks .", "Functional abnormality of TAR DNA-binding protein 43 ( TDP-43 ) , ...	[ "Functional abnormality of TAR DNA-binding protein 43 ( TDP-43 ) , an aggregation-prone RNA and DNA binding protein , is observed in the vast majority of both familial and sporadic ALS cases and in ~40% of FTLD cases , and mutations in TDP-43 are causal in a subset of familial ALS cases .", "Although cytoplasmic ...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "viral vaccines", "medicine and health sciences", "pathology and laboratory medicine", "pathogens", "immunology", "microbiology", "retroviruses", "vaccines", "viruses", "vaccination and immunization", "medical microbiology", "microbial pathogens", "attenuated vaccines", "virology", "vira...	Protective Efficacy of Centralized and Polyvalent Envelope Immunogens in an Attenuated Equine Lentivirus Vaccine	journal.ppat.1004610	null	[ [ "The scientific community has aggressively sought after the development of a universal HIV vaccine that can prevail over the extraordinary levels of antigenic diversity in the fight against HIV and AIDS .", "The considerable extent of genomic variation found between isolates and within clades , and to a l...	[ "Lentiviral Envelope ( Env ) antigenic variation and related immune evasion present major hurdles to effective vaccine development .", "Centralized Env immunogens that minimize the genetic distance between vaccine proteins and circulating viral isolates are an area of increasing study in HIV vaccinology .", "To...	[ "Our best effort for containment of the global HIV epidemic is the development of a broadly protective vaccine .", "Current research has focused on vaccines that can generate a protective immune response against numerous strains of the virus .", "For this reason , vaccines with centralized HIV genes as immunoge...	2015
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "ecology and environmental sciences", "theoretical biology", "ecology", "theoretical ecology", "biology and life sciences" ]	Determining Individual Variation in Growth and Its Implication for Life-History and Population Processes Using the Empirical Bayes Method	journal.pcbi.1003828	null	[ [ "A better understanding of growth will always be an important problem in biology .", "Somatic growth is one the most important life-history traits across taxa , since survival , sexual maturity , reproductive success , movement and migration are frequently related to growth and body size [1] .", "Vari...	[ "The differences in demographic and life-history processes between organisms living in the same population have important consequences for ecological and evolutionary dynamics .", "Modern statistical and computational methods allow the investigation of individual and shared ( among homogeneous groups ) determinan...	[ "Somatic growth is a crucial determinant of ecological and evolutionary dynamics , since larger organisms often have higher survival and reproductive success .", "Size may be the result of intrinsic ( i . e . genetic ) , environmental ( temperature , food ) , and social ( competition with conspecifics ) factors a...	2014
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "medicine and health sciences", "breast tumors", "reproductive system", "maternal health", "obstetrics and gynecology", "cancers and neoplasms", "cell differentiation", "hormones", "epithelial cells", "oncology", "developmental biology", "women's health", "pregnancy", "animal cells", "ge...	Deletion of Cdkn1b in ACI rats leads to increased proliferation and pregnancy-associated changes in the mammary gland due to perturbed systemic endocrine environment	journal.pgen.1008002	null	[ [ "Emerging data indicate that breast epithelial stem cells and progenitors are the normal cells-of-origin of breast carcinomas and factors that influence breast cancer risk ( e . g . , reproductive and hereditary factors ) may alter the number and/or properties of these cells [1] .", "Besides germline muta...	[ "Mammary epithelial progenitors are the normal cell-of-origin of breast cancer .", "We previously defined a population of p27+ quiescent hormone-responsive progenitor cells in the normal human breast whose frequency associates with breast cancer risk .", "Here , we describe that deletion of the Cdkn1b gene enco...	[ "The frequency and proliferation of tissue-specific stem and progenitor cells is associated with the risk of malignancy .", "Thus , regulators of the pool size and proliferation of progenitor cells determine cancer risk .", "p27 is a key regulator of cellular proliferation and is required for the terminal diffe...	2019
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genetics and genomics/epigenetics", "genetics and genomics/plant genetics and gene expression" ]	Global Analysis of Genetic, Epigenetic and Transcriptional Polymorphisms in Arabidopsis thaliana Using Whole Genome Tiling Arrays	journal.pgen.1000032	null	[ [ "Epigenetic modification has a profound effect on genome activity .", "In eukaryotes , DNA methylation of cytosine residues is a common phenomenon [1] that serves as a mechanism to suppress mobile elements [2] , [3] and other nuclear processes such as transcription and recombination [4] .", "Globally ...	[ "Whole genome tiling arrays provide a high resolution platform for profiling of genetic , epigenetic , and gene expression polymorphisms .", "In this study we surveyed natural genomic variation in cytosine methylation among Arabidopsis thaliana wild accessions Columbia ( Col ) and Vancouver ( Van ) by comparing h...	[ "The functional expression of DNA sequence depends on the chromatin status .", "Epigenetic marks at specific loci could affect local chromatin accessibility , thus affect the gene activity of that loci .", "We applied an enzyme methylome approach to globally detect one type of epigenetic mark , cytosine methyla...	2008
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Modularity of Protein Folds as a Tool for Template-Free Modeling of Structures	journal.pcbi.1004419	null	[ [ "The revolution in DNA sequencing technologies over the last decade has resulted in an enormous , and ever growing , number of gene sequences , which is doubling every ~18 months [1–3] .", "At the same time , the number of experimentally determined protein structures has increasingly lagged behind due to ...	[ "Predicting the three-dimensional structure of proteins from their amino acid sequences remains a challenging problem in molecular biology .", "While the current structural coverage of proteins is almost exclusively provided by template-based techniques , the modeling of the rest of the protein sequences increasi...	[ "Each protein folds into a unique three-dimensional structure that enables it to carry out its biological function .", "Knowledge of the atomic details of protein structures is therefore a key to understanding their function .", "Advances in high throughput experimental technologies have lead to an exponential ...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine", "biology" ]	The BTB-zinc Finger Transcription Factor Abrupt Acts as an Epithelial Oncogene in Drosophila melanogaster through Maintaining a Progenitor-like Cell State	journal.pgen.1003627	null	[ [ "Cancer cells with significant tumour-propagating potential are increasingly referred to as cancer stem cells .", "Whilst this refers to the potential of these cells to regenerate the tumour in both in vivo and in vitro assays , it also alludes to the possibility that these cells may have either hijacked ...	[ "The capacity of tumour cells to maintain continual overgrowth potential has been linked to the commandeering of normal self-renewal pathways .", "Using an epithelial cancer model in Drosophila melanogaster , we carried out an overexpression screen for oncogenes capable of cooperating with the loss of the epithel...	[ "Cancer is a multigenic process , involving cooperative interactions between oncogenes or tumour suppressors .", "In this study , in a genetic screen in the vinegar fly , Drosophila melanogaster , for genes that cooperate with a mutation in the cell polarity ( shape ) regulator , scribbled ( scrib ) , we identify...	2013
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "interaction networks", "genetic networks", "protein interactions", "statistics", "applied mathematics", "protein interaction networks", "simulation and modeling", "algorithms", "mathematics", "forecasting", "network analysis", "genome analysis", "research and analysis methods", "computer ...	Disease gene prediction for molecularly uncharacterized diseases	journal.pcbi.1007078	null	[ [ "High throughput sequencing and screening techniques have led to an increasing accumulation of genomic data .", "Despite this growth , the mechanisms of action through which genomic variants drive disease development are not fully understood .", "As genomic alleles and malignant mutations are continuo...	[ "Network medicine approaches have been largely successful at increasing our knowledge of molecularly characterized diseases .", "Given a set of disease genes associated with a disease , neighbourhood-based methods and random walkers exploit the interactome allowing the prediction of further genes for that disease...	[ "The elucidation of the genetic causes of diseases is central to understanding the mechanisms of action of a pathology and the development of treatments .", "Disease gene prediction methods streamline the discovery of the molecular basis for a disease by prioritizing genes for experimental validation .", "Altho...	2019
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genome-wide association studies", "genetics", "epigenetics", "biology", "human genetics", "genetics and genomics" ]	Epigenome-Wide Scans Identify Differentially Methylated Regions for Age and Age-Related Phenotypes in a Healthy Ageing Population	journal.pgen.1002629	null	[ [ "DNA methylation is an epigenetic mechanism that plays an important role in gene expression regulation , development , and disease .", "Increasing evidence points to the distinct contributions of genetic [1] , [2] , [3] , [4] , [5] , environmental [6] , [7] , [8] , and stochastic factors to DNA methylatio...	[ "Age-related changes in DNA methylation have been implicated in cellular senescence and longevity , yet the causes and functional consequences of these variants remain unclear .", "To elucidate the role of age-related epigenetic changes in healthy ageing and potential longevity , we tested for association between...	[ "Epigenetic patterns vary during healthy ageing and development .", "Age-related DNA methylation changes have been implicated in cellular senescence and longevity , yet the causes and functional consequences of these variants remain unclear .", "To understand the biological mechanisms involved in potential long...	2012
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "medicine", "veterinary science", "biology" ]	Leptospira Interrogans Induces Fibrosis in the Mouse Kidney through Inos-Dependent, TLR- and NLR-Independent Signaling Pathways	journal.pntd.0002664	null	[ [ "Leptospira interrogans ( L . interrogans ) are spirochetal bacteria responsible for a worldwide reemerging zoonosis [1] .", "Rodents asymptomatically carry the bacteria in their kidneys and excrete them in the urine , contaminating the environment .", "Humans become infected from contaminated ponds ,...	[ "Leptospira ( L . ) interrogans are bacteria responsible for a worldwide reemerging zoonosis .", "Rodents carry L . interrogans asymptomatically in their kidneys and excrete bacteria in the urine , contaminating the environment .", "Humans get infected through skin contact and develop a mild or severe leptospir...	[ "Leptospirosis is a bacterial disease transmitted by asymptomatic rodents to humans .", "The symptoms may be mild , or severe with kidney failure .", "Renal fibrosis , occurring during inflammatory situations , is characterized by the pathological accumulation of extra-cellular matrix components and can comprom...	2014
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[]	Generation of a Novel Bacteriophage Library Displaying scFv Antibody Fragments from the Natural Buffalo Host to Identify Antigens from Adult Schistosoma japonicum for Diagnostic Development	journal.pntd.0004280	null	[ [ "Schistosomiasis is one of the most insidious of all the tropical parasitic infections and threatens the health of hundreds of millions of people worldwide [1] .", "The last 20 years has seen remarkable progress in disease control through the use of praziquantel ( PZQ ) , but this drug does not protect ag...	[ "The development of effective diagnostic tools will be essential in the continuing fight to reduce schistosome infection; however , the diagnostic tests available to date are generally laborious and difficult to implement in current parasite control strategies .", "We generated a series of single-chain antibody F...	[ "Mass drug administration using the highly effective drug praziquantel ( PZQ ) is currently the method of choice to combat schistosomiasis .", "However , this treatment regime has limitations; in particular , it does not prevent re-infection and sporadic parasite resistance against PZQ is a continuing threat .", ...	2015

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