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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" ]	[ "genetics", "developmental biology", "biology" ]	The RNA-binding Proteins FMR1, Rasputin and Caprin Act Together with the UBA Protein Lingerer to Restrict Tissue Growth in Drosophila melanogaster	journal.pgen.1003598	null	[ [ "Understanding how cells and organs control their growth is a major endeavor in developmental biology .", "In Drosophila melanogaster and in mammalian systems , genetic studies have revealed a tight regulation mainly at two different layers .", "Whereas the Hippo and the Insulin receptor signal transd...	[ "Appropriate expression of growth-regulatory genes is essential to ensure normal animal development and to prevent diseases like cancer .", "Gene regulation at the levels of transcription and translational initiation mediated by the Hippo and Insulin signaling pathways and by the TORC1 complex , respectively , ha...	[ "Animal growth is orchestrated by controlled expression of growth-regulatory factors .", "This regulation is achieved at different molecular levels like transcription , translation initiation , and translational regulation .", "Whereas transcriptional control and translation initiation of growth components have...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine and health sciences", "microtubules", "cell processes", "neurites", "neuroscience", "fibroblasts", "animal models", "developmental biology", "model organisms", "connective tissue cells", "embryos", "cellular structures and organelles", "neuronal dendrites", "cytoskeleton", "res...	Phosphatidylserine Ameliorates Neurodegenerative Symptoms and Enhances Axonal Transport in a Mouse Model of Familial Dysautonomia	journal.pgen.1006486	null	[ [ "Familial Dysautonomia ( FD ) is an autosomal recessive congenital neuropathy that occurs almost exclusively in the Ashkenazi Jewish population with a remarkably high carrier frequency ranging from 1 in 18 ( in those of Polish descent ) to 1 in 32 [1] .", "Individuals with FD suffer from a variety of symp...	[ "Familial Dysautonomia ( FD ) is a neurodegenerative disease in which aberrant tissue-specific splicing of IKBKAP exon 20 leads to reduction of IKAP protein levels in neuronal tissues .", "Here we generated a conditional knockout ( CKO ) mouse in which exon 20 of IKBKAP is deleted in the nervous system .", "The...	[ "We create a novel FD mouse model , in which exon 20 of IKBKAP was deleted in the nervous system , to study the role of IKAP in the neurodegeneration process .", "The lack of IKBKAP exon 20 impaired retrograde nerve growth factor ( NGF ) transport and axonal outgrowth .", "Reduction of IKAP levels resulted in e...	2016
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "invertebrates", "innate immune system", "medicine and health sciences", "emerging viral diseases", "immunology", "microbiology", "animals", "epidemiology", "disease vectors", "insects", "immune response", "immune system", "arthropoda", "mosquitoes", "immunity", "virology", "vector b...	Dicer-2-Dependent Activation of Culex Vago Occurs via the TRAF-Rel2 Signaling Pathway	journal.pntd.0002823	null	[ [ "Hematophagous insects ( mosquitoes , sand flies and midges ) serve as vectors of many important viral diseases of humans and livestock .", "Arthropod-borne viruses are endemic or seasonally epidemic through most regions of the world , accounting for inestimable numbers of human infections , significant r...	[ "Despite their importance as vectors of human and livestock diseases , relatively little is known about innate antiviral immune pathways in mosquitoes and other insects .", "Previous work has shown that Culex Vago ( CxVago ) , which is induced and secreted from West Nile virus ( WNV ) -infected mosquito cells , a...	[ "Viruses like West Nile , dengue and Japanese encephalitis are responsible for large number of human and livestock diseases worldwide .", "These viruses , transmitted by female mosquitoes via saliva during blood-feeding , elicit an immune response in these mosquitoes .", "The details of this immune response are...	2014
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "cell death", "medicine and health sciences", "autophagic cell death", "pathology and laboratory medicine", "293t cells", "pathogens", "cell processes", "biological cultures", "microbiology", "vertebrates", "orthomyxoviruses", "animals", "viruses", "virus effects on host gene expression", ...	Dysregulation of M segment gene expression contributes to influenza A virus host restriction	journal.ppat.1007892	null	[ [ "Influenza A virus ( IAV ) epidemics and pandemics result in widespread and often severe disease [1–3] , as well as considerable societal economic costs [4] .", "IAV lineages endemic in humans are ultimately derived from those circulating in wild waterfowl .", "Sporadic transmission of IAV from avian ...	[ "The M segment of the 2009 pandemic influenza A virus ( IAV ) has been implicated in its emergence into human populations .", "To elucidate the genetic contributions of the M segment to host adaptation , and the underlying mechanisms , we examined a panel of isogenic viruses that carry avian- or human-derived M s...	[ "Influenza A virus ( IAV ) pandemics arise when a virus adapted to a non-human host overcomes species barriers to successfully infect humans and sustain human-to-human transmission .", "To gauge the adaptive potential and therefore pandemic risk posed by a particular IAV , it is critical to understand the mechani...	2019
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "computational biology/signaling networks", "computational biology/transcriptional regulation", "computational biology/systems biology", "computational biology" ]	Network Inference Algorithms Elucidate Nrf2 Regulation of Mouse Lung Oxidative Stress	journal.pcbi.1000166	null	[ [ "Sustained elevated levels of reactive oxygen species ( ROS ) have been associated with the etiology of a vast range of pathological conditions .", "These include a variety of neurodegenerative diseases , cardiovascular diseases , cancer , diabetes mellitus , rheumatoid arthritis , and obstructive sleep a...	[ "A variety of cardiovascular , neurological , and neoplastic conditions have been associated with oxidative stress , i . e . , conditions under which levels of reactive oxygen species ( ROS ) are elevated over significant periods .", "Nuclear factor erythroid 2-related factor ( Nrf2 ) regulates the transcription ...	[ "A variety of conditions including certain cancers and heart diseases , diabetes mellitus , and rheumatoid arthritis have been associated with the generation of high levels of highly reactive molecular species under conditions known as “oxidative stress . ”", "A number of protein molecules have been identified as...	2008
[ "Introduction", "Models and methods", "Results", "Discussion" ]	[ "biogeography", "organismal evolution", "ecology and environmental sciences", "classical mechanics", "fluid mechanics", "population genetics", "variant genotypes", "microbiology", "genetic mapping", "mutation", "microbial evolution", "dna", "population biology", "geography", "fluid dynam...	Recombination and mutational robustness in neutral fitness landscapes	journal.pcbi.1006884	null	[ [ "The reshuffling of genetic material by recombination is a ubiquitous part of the evolutionary process across the entire range of organismal complexity .", "Starting with viruses as the simplest evolving entities , recombination occurs largely at random during the coinfection of a cell by more than one vi...	[ "Mutational robustness quantifies the effect of random mutations on fitness .", "When mutational robustness is high , most mutations do not change fitness or have only a minor effect on it .", "From the point of view of fitness landscapes , robust genotypes form neutral networks of almost equal fitness .", "U...	[ "Two long-standing and seemingly unrelated puzzles in evolutionary biology concern the ubiquity of sexual reproduction and the robustness of organisms against genetic perturbations .", "Using a theoretical approach based on the concept of a fitness landscape , in this article we argue that the two phenomena may i...	2019
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "molecular cell biology", "cell division", "cell biology", "chromosome biology", "nucleic acids", "dna", "biology", "genomics", "molecular biology", "genetics and genomics" ]	Nondisjunction of a Single Chromosome Leads to Breakage and Activation of DNA Damage Checkpoint in G2	journal.pgen.1002509	null	[ [ "Chromosomes lagging or bridging during anaphase are believed to be one of the main sporadic causes of cytokinesis failure , which leads to tetraploid cells with multicentrosomes , a hallmark of early tumourigenesis [1] , [2] .", "Conversely , if these anaphase bridges break apart , chromosomes could ente...	[ "The resolution of chromosomes during anaphase is a key step in mitosis .", "Failure to disjoin chromatids compromises the fidelity of chromosome inheritance and generates aneuploidy and chromosome rearrangements , conditions linked to cancer development .", "Inactivation of topoisomerase II , condensin , or se...	[ "When cells divide they must segregate copies of their chromosomes to each of their daughters .", "A particular harmful situation arises when those copies are glued to each other ( i . e . , nondisjunction ) at the moment of division .", "Previously , it has been possible to genetically favour this scenario , y...	2012
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "animal models", "systems biology", "developmental biology", "drosophila melanogaster", "model organisms", "gene expression", "genetics", "biology", "computational biology", "gene networks", "pattern formation", "genetics and genomics" ]	Efficient Reverse-Engineering of a Developmental Gene Regulatory Network	journal.pcbi.1002589	null	[ [ "Elucidating the regulatory structure and dynamics of gene networks is a major objective in biology .", "The inference of regulatory networks from gene expression data is known as reverse engineering [1]–[7] .", "It is being widely and successfully applied , from microbes to animals ( see , for exampl...	[ "Understanding the complex regulatory networks underlying development and evolution of multi-cellular organisms is a major problem in biology .", "Computational models can be used as tools to extract the regulatory structure and dynamics of such networks from gene expression data .", "This approach is called re...	[ "To better understand multi-cellular organisms we need a better and more systematic understanding of the complex regulatory networks that govern their development and evolution .", "However , this problem is far from trivial .", "Regulatory networks involve many factors interacting in a non-linear manner , whic...	2012
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "gene function", "plant science", "plant growth and development", "gene expression", "genetics", "plant biology", "epigenetics", "biology", "genetics and genomics", "histone modification" ]	A Companion Cell–Dominant and Developmentally Regulated H3K4 Demethylase Controls Flowering Time in Arabidopsis via the Repression of FLC Expression	journal.pgen.1002664	null	[ [ "DNA is packaged as chromatin in eukaryotic cells .", "Nucleosomes , which consist of an octamer of four histones wrapped around 146 base pairs of DNA , are the fundamental unit of chromatin [1] .", "The flexible N-terminal tails of histones , which protrude from the nucleosome core particle , are sub...	[ "Flowering time relies on the integration of intrinsic developmental cues and environmental signals .", "FLC and its downstream target FT are key players in the floral transition in Arabidopsis .", "Here , we characterized the expression pattern and function of JMJ18 , a novel JmjC domain-containing histone H3K...	[ "Flowering is an important developmental transition during plant life cycle and the key process for production of the next generation .", "Flowering time is controlled by both intrinsic developmental and environmental signals .", "FLC and its target FT work as repressor and activator , respectively , to regulat...	2012
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "invertebrates", "medicine and health sciences", "neural networks", "nervous system", "caenorhabditis", "electrophysiology", "neuroscience", "animals", "motor neurons", "animal models", "caenorhabditis elegans", "model organisms", "brain mapping", "interneurons", "research and analysis m...	Vulnerability-Based Critical Neurons, Synapses, and Pathways in the Caenorhabditis elegans Connectome	journal.pcbi.1005084	null	[ [ "Understanding the fundamental architectural design of nervous systems will provide insights into nervous system function and how mental illness arises from its dysfunction .", "The design derives from a trade-off between physical wiring costs and functional complexity [1–4] .", "Nervous systems media...	[ "Determining the fundamental architectural design of complex nervous systems will lead to significant medical and technological advances .", "Yet it remains unclear how nervous systems evolved highly efficient networks with near optimal sharing of pathways that yet produce multiple distinct behaviors to reach the...	[ "One of the most important scientific aims is to uncover the functional design principles of nervous systems .", "To reach this aim , it is useful to examine a complex nervous system that is both well specified and highly tractable , making the nematode roundworm Caenorhabditis elegans an attractive model system ...	2016
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "gene regulation", "brassica", "dna-binding proteins", "cereal crops", "rice", "model organisms", "experimental organism systems", "genetic elements", "crops", "plants", "flowering plants", "research and analysis methods", "arabidopsis thaliana", "grasses", "crop science", "proteins", ...	Transcriptional and Post-transcriptional Mechanisms Limit Heading Date 1 (Hd1) Function to Adapt Rice to High Latitudes	journal.pgen.1006530	null	[ [ "Rice ( Oryza sativa L . ) was originally domesticated ~8000 years ago in tropical Asia .", "Archeological remains and genome re-sequencing indicated southern China as the region of first cultivation , despite the debate regarding the domestication dynamics is still open [1–3] .", "Although of tropica...	[ "Rice flowering is controlled by changes in the photoperiod that promote the transition to the reproductive phase as days become shorter .", "Natural genetic variation for flowering time has been largely documented and has been instrumental to define the genetics of the photoperiodic pathway , as well as providin...	[ "Many plant species flower in response to changes in day length and can be categorized depending on their requirements for long or short days .", "Rice has tropical origins and normally flowers in response to shortening days .", "However , artificial selection operated by ancient farmers or modern breeders adap...	2017
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[]	Sensitive Detection of Viral Transcripts in Human Tumor Transcriptomes	journal.pcbi.1003228	null	[ [ "To date , pathogenic agents are known to be causally related to 20% of human cancer cases [1] and significantly affect the global health burden of this disease [2] .", "The majority of these agents comprise oncogenic viruses such as human papilloma virus ( HPV ) , Epstein-Barr virus ( EBV ) , hepatitis B...	[ "In excess of % of human cancer incidents have a viral cofactor .", "Epidemiological studies of idiopathic human cancers indicate that additional tumor viruses remain to be discovered .", "Recent advances in sequencing technology have enabled systematic screenings of human tumor transcriptomes for viral transcr...	[ "Many human cancers are caused by infections with tumor viruses and identification of these pathogens is considered a critical contribution to cancer prevention .", "Deep sequencing enables us to systematically investigate viral nucleotide signatures in order to either verify or exclude the existence of viruses i...	2013
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "schistosoma", "invertebrates", "schistosoma mansoni", "digestion", "medicine and health sciences", "rna interference", "chemical compounds", "helminths", "enzymes", "enzymology", "animals", "organic compounds", "physiological processes", "cysteine proteases", "amino acids", "epigeneti...	Cysteine and Aspartyl Proteases Contribute to Protein Digestion in the Gut of Freshwater Planaria	journal.pntd.0004893	null	[ [ "The family Platyhelminthes contains an estimated 25 , 000 species , including the free-living planaria Schmidtea mediterranea .", "This freshwater flatworm has been an experimental model for over a century due to its regenerative capacity .", "Worms can fully regenerate missing body tissues from frag...	[ "Proteases perform numerous vital functions in flatworms , many of which are likely to be conserved throughout the phylum Platyhelminthes .", "Within this phylum are several parasitic worms that are often poorly characterized due to their complex life-cycles and lack of responsiveness to genetic manipulation .", ...	[ "Certain parasitic flatworms pose serious threats to human health .", "Understanding more about the biology of flatworms can lead to new and better drug targets .", "However , due to the complex life cycles of parasitic flatworms , it has been suggested that a non-parasitic flatworm , Schmidtea mediterranea , b...	2016
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[]	Spatio-temporal Use of Oral Rabies Vaccines in Fox Rabies Elimination Programmes in Europe	journal.pntd.0003953	null	[ [ "Elimination of infectious diseases from wildlife populations is a major challenge .", "Thus , until a few decades ago , elimination of wildlife-mediated rabies from Europe was considered wishful thinking .", "This paralleled the results of early conventional control measures aimed at stopping the exp...	[ "In Europe , the elimination of wildlife rabies using oral rabies vaccination [ORV] of foxes for more than 30 years has been a success story .", "Since a comprehensive review on the scope of the different oral rabies vaccine baits distributed across Europe has not been available yet , we evaluated the use of diff...	[ "Oral rabies vaccination [ORV] is the pre-eminent example of successful vaccination of wildlife populations which has resulted in virtual elimination of fox-mediated rabies from large parts of Western and Central Europe .", "This achievement is unprecedented in history .", "Attractive species-specific baits , e...	2015
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "invertebrates", "medicine and health sciences", "ecology and environmental sciences", "rna interference", "caenorhabditis", "diet", "neuroscience", "animals", "animal models", "caenorhabditis elegans", "model organisms", "nutrition", "experimental organism systems", "epigenetics", "mapk...	A novel gene-diet pair modulates C. elegans aging	journal.pgen.1007608	null	[ [ "Animals dwell in a complex ecosystem where they interact with a host of other organisms; some of them may alter their life history traits .", "For example , the nematode Caenorhabditis elegans is found in decaying moist vegetation that is co-inhabited by different types of bacteria that they feed on .", ...	[ "Diet profoundly affects metabolism and incidences of age-related diseases .", "Animals adapt their physiology to different food-types , modulating complex life-history traits like aging .", "The molecular mechanisms linking adaptive capacity to diet with aging are less known .", "We identify FLR-4 kinase as ...	[ "For animals living in the wild , being able to utilize a wide range of diet is evolutionarily advantageous as they can survive even when their optimal diet is depleted .", "Since diet is known to influence the rate of aging , animals seem to have evolved intricate mechanisms to maintain homeostasis and normal li...	2018
[ "Introduction", "Materials and methods", "Results", "Discussion" ]	[ "antimicrobials", "cell walls", "cell death", "medicine and health sciences", "pathology and laboratory medicine", "pathogens", "drugs", "cell processes", "microbiology", "pseudomonas aeruginosa", "antibiotic resistance", "developmental biology", "antibiotics", "pharmacology", "microbial...	Mathematical modelling of the antibiotic-induced morphological transition of Pseudomonas aeruginosa	journal.pcbi.1006012	null	[ [ "Antimicrobial resistance ( AMR ) is now acknowledged as an urgent global health threat and the severity of the situation was highlighted by the World Health Organization 2014 report that discusses the increasing incidence of resistance-induced health problems in every region of the world [1] .", "A “post...	[ "Here we formulate a mechanistic mathematical model to describe the growth dynamics of P . aeruginosa in the presence of the β-lactam antibiotic meropenem .", "The model is mechanistic in the sense that carrying capacity is taken into account through the dynamics of nutrient availability rather than via logistic ...	[ "Antimicrobial resistance is an urgent global health threat and it is critical that we formulate alternative treatment strategies to combat bacterial infections .", "To do this we must understand how bacteria respond to currently used antibiotics .", "Pseudomonas aeruginosa is the leading cause of death among c...	2018
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "phosphorylation", "medicine and health sciences", "pathology and laboratory medicine", "enzymes", "pathogens", "microbiology", "enzymology", "viral structure", "hepatitis b virus", "phosphatases", "serine proteases", "viruses", "rna structure", "proteins", "medical microbiology", "mic...	Hepatitis B virus core protein phosphorylation: Identification of the SRPK1 target sites and impact of their occupancy on RNA binding and capsid structure	journal.ppat.1007488	null	[ [ "Chronic infection with hepatitis B virus ( HBV ) puts more than 250 million people at a greatly increased risk to develop terminal liver disease [1] .", "HBV , the prototypic hepadnavirus , is a small enveloped virus that replicates its 3 kb DNA genome through capsid-internal reverse transcription of a p...	[ "Hepatitis B virus ( HBV ) replicates its 3 kb DNA genome through capsid-internal reverse transcription , initiated by assembly of 120 core protein ( HBc ) dimers around a complex of viral pregenomic ( pg ) RNA and polymerase .", "Following synthesis of relaxed circular ( RC ) DNA capsids can be enveloped and sec...	[ "The liver-pathogenic hepatitis B virus ( HBV ) is a small enveloped DNA virus that replicates through reverse transcription of a pregenomic ( pg ) RNA .", "This requires specific encapsidation of pgRNA and viral polymerase into a shell of 240 core protein ( HBc ) subunits .", "Capsid-internal formation of rela...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "immunity", "virology", "viral classification", "immunology", "biology", "microbiology" ]	Enhancement of Chemokine Function as an Immunomodulatory Strategy Employed by Human Herpesviruses	journal.ppat.1002497	null	[ [ "Herpes simplex virus type 1 and 2 ( HSV-1 and HSV-2 , respectively ) and varizella zoster virus ( VZV ) are the three human members of the Alphaherpesvirinae subfamily , which establish latency in the sensory ganglia of the peripheral nervous system .", "Both HSV-1 and -2 are highly prevalent viruses wit...	[ "Herpes simplex virus ( HSV ) types 1 and 2 are highly prevalent human neurotropic pathogens that cause a variety of diseases , including lethal encephalitis .", "The relationship between HSV and the host immune system is one of the main determinants of the infection outcome .", "Chemokines play relevant roles ...	[ "Chemokines are chemotactic cytokines that direct the flux of leukocytes to the site of injury and infection , playing a relevant role in the antiviral response .", "An uncontrolled , unorganized chemokine response is beneath the onset and maintenance of several immunopathologies .", "During millions of years o...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "cell biology/membranes and sorting", "virology/host invasion and cell entry" ]	A Spatio-Temporal Analysis of Matrix Protein and Nucleocapsid Trafficking during Vesicular Stomatitis Virus Uncoating	journal.ppat.1000994	null	[ [ "The entry of enveloped viruses that utilize the clathrin-dependent endocytic pathway involves attachment of virus to the cell surface and uptake of virions in coated vesicles that are transported to early or late endosomes .", "When virions reach a compartment in which the lumen has the appropriate pH th...	[ "To study VSV entry and the fate of incoming matrix ( M ) protein during virus uncoating we used recombinant viruses encoding M proteins with a C-terminal tetracysteine tag that could be fluorescently labeled using biarsenical ( Lumio ) compounds .", "We found that uncoating occurs early in the endocytic pathway ...	[ "Vesicular stomatitis virus ( VSV ) is a prototypic enveloped virus that enters cells following endocytosis and a low pH-dependent membrane fusion event between the viral and endosomal membrane .", "To initiate a productive infection the viral nucleocapsid must dissociate from the matrix ( M ) protein , which und...	2010
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "tuberculosis", "macrophage", "coronin", "ezrin-binding protein 50", "microbiology", "nitric oxide synthase" ]	Mechanism of Inducible Nitric Oxide Synthase Exclusion from Mycobacterial Phagosomes	journal.ppat.0030186	null	[ [ "Approximately one-third of the world's population is asymptomatically infected with Mycobacterium tuberculosis .", "This represents the reservoir leading to 8 million cases of active disease and 2 million deaths annually from tuberculosis .", "Being an intracellular pathogen , M . tuberculosis is abl...	[ "Mycobacterium tuberculosis is sensitive to nitric oxide generated by inducible nitric oxide synthase ( iNOS ) .", "Consequently , to ensure its survival in macrophages , M . tuberculosis inhibits iNOS recruitment to its phagosome by an unknown mechanism .", "Here we report the mechanism underlying this process...	[ "Mycobacterium tuberculosis infects one third of the world's population , with the majority of infected individuals being asymptomatic while running a lifetime risk of developing active disease .", "The key to the success of M . tuberculosis as a recalcitrant human pathogen is its ability to parasitize macrophage...	2007
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "reverse transcriptase-polymerase chain reaction", "dengue virus", "medicine and health sciences", "pathology and laboratory medicine", "pathogens", "geographical locations", "tropical diseases", "microbiology", "social sciences", "health care", "viruses", "rna viruses", "neglected tropical ...	Trends in dengue research in the Philippines: A systematic review	journal.pntd.0007280	null	[ [ "Dengue is a mosquito-borne , acute febrile illness that is an important public health problem in tropical countries .", "In the early 1950’s , the disease was described in the Philippines as hemorrhagic fever or infectious acute thrombocytopenic purpura [1 , 2] .", "Dengue continues to cause consider...	[ "Dengue is an important public health problem in the Philippines .", "We sought to describe the trends in dengue research in the country .", "We searched four databases and identified published studies on dengue research in the Philippines during the past 60 years .", "We reviewed 135 eligible studies , of wh...	[ "Dengue is a disease caused by four separate but related viruses transmitted by mosquitos .", "In this systematic review , we aimed to describe dengue research in the Philippines , where the disease is of great concern , to better understand the types of dengue research and the main findings and important gaps ."...	2019
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "cell binding", "blood cells", "cell physiology", "t helper cells", "medicine and health sciences", "immune cells", "gene regulation", "regulatory proteins", "immunology", "dna-binding proteins", "gastroenterology and hepatology", "transcription factors", "sequence motif analysis", "resear...	Genetic variants alter T-bet binding and gene expression in mucosal inflammatory disease	journal.pgen.1006587	null	[ [ "The differentiation of naïve CD4+ T cells into distinct T helper cell ( Th ) lineages is essential for adaptive immunity .", "The original paradigm of interferon-gamma ( IFN-γ ) producing T-helper 1 ( Th1 ) , and type-2 ( Interleukin 4 , 5 , and 13 ) cytokine producing Th2 cells has expanded to include b...	[ "The polarization of CD4+ T cells into distinct T helper cell lineages is essential for protective immunity against infection , but aberrant T cell polarization can cause autoimmunity .", "The transcription factor T-bet ( TBX21 ) specifies the Th1 lineage and represses alternative T cell fates .", "Genome-wide ...	[ "Research to date has identified many genetic variants that are more common in people with a particular disease .", "However , in conditions that reflect multiple genetic and environmental factors , it is difficult to know with certainty if and why any particular genetic variant is causative and the mechanism tha...	2017
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "chemical characterization", "medicine and health sciences", "chemical compounds", "cancers and neoplasms", "organic compounds", "oncology", "basic amino acids", "amino acids", "sequence motif analysis", "chemical synthesis", "research and analysis methods", "sequence analysis", "peptide syn...	Deciphering HLA-I motifs across HLA peptidomes improves neo-antigen predictions and identifies allostery regulating HLA specificity	journal.pcbi.1005725	null	[ [ "HLA-I molecules play a central role in defence mechanisms against pathogens and immune recognition of cancer cells .", "Their main functionality is to bind short peptides ( mainly 9- to 12-mers ) coming from degradation products of endogenous or viral proteins .", "The peptides are cleaved in the pro...	[ "The precise identification of Human Leukocyte Antigen class I ( HLA-I ) binding motifs plays a central role in our ability to understand and predict ( neo- ) antigen presentation in infectious diseases and cancer .", "Here , by exploiting co-occurrence of HLA-I alleles across ten newly generated as well as forty...	[ "Predicting the differences between cancer and normal cells that are visible to the immune system is of central importance for cancer immunotherapy .", "Here we introduce a novel computational framework to harness the wealth of data from in-depth HLA peptidomics studies , including ten novel high quality ( <1% FD...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "infectious diseases/protozoal infections", "infectious diseases/tropical and travel-associated diseases", "cell biology/cell signaling" ]	Activation of Akt Signaling Reduces the Prevalence and Intensity of Malaria Parasite Infection and Lifespan in Anopheles stephensi Mosquitoes	journal.ppat.1001003	null	[ [ "Malaria is one of the world's most severe public health concerns , killing nearly one million people annually [1] .", "The disease is caused by infection with parasites of the genus Plasmodium that are transmitted by female anopheline mosquitoes .", "Shortly after an infective bloodmeal is consumed b...	[ "Malaria ( Plasmodium spp . ) kills nearly one million people annually and this number will likely increase as drug and insecticide resistance reduces the effectiveness of current control strategies .", "The most important human malaria parasite , Plasmodium falciparum , undergoes a complex developmental cycle in...	[ "For malaria transmission to occur , a mosquito must ingest and harbor the parasites for approximately two weeks while the parasites complete multiple developmental stages .", "Until development is complete and the malaria parasites invade the mosquito salivary glands , transmission to another host cannot occur ....	2010
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genetics and genomics/disease models", "neurological disorders/neuro-ophthalmology and neuro-otology", "ophthalmology/glaucoma", "cell biology/cell signaling" ]	Mutations in Zebrafish lrp2 Result in Adult-Onset Ocular Pathogenesis That Models Myopia and Other Risk Factors for Glaucoma	journal.pgen.1001310	null	[ [ "The multi-factorial nature of many ocular diseases poses a major challenge in understanding their molecular etiology and in engineering animal models to study mechanisms of pathology .", "Macular degeneration , myopia , and glaucoma are examples of prevalent and disruptive complex ocular diseases .", ...	[ "The glaucomas comprise a genetically complex group of retinal neuropathies that typically occur late in life and are characterized by progressive pathology of the optic nerve head and degeneration of retinal ganglion cells .", "In addition to age and family history , other significant risk factors for glaucoma i...	[ "Complex genetic inheritance , including variable penetrance and severity , underlies many common eye diseases .", "In this study , we present analysis of a zebrafish mutant , bugeye , which shows complex inheritance of multiple ocular phenotypes that are known risk factors for glaucoma , including high myopia , ...	2011
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biochemistry", "streptococci", "proteins", "biology", "microbiology", "biophysics", "bacterial pathogens", "defense proteins", "gram positive" ]	D-Alanylation of Lipoteichoic Acids Confers Resistance to Cationic Peptides in Group B Streptococcus by Increasing the Cell Wall Density	journal.ppat.1002891	null	[ [ "The innate immune system of almost all living organisms produce cationic antimicrobial peptides ( CAMPs ) to protect against bacterial invaders .", "CAMPs are gene-encoded peptides that differ in their primary amino acid sequences [1] , [2] but most native CAMPs share a well-defined α-helix or β-strand s...	[ "Cationic antimicrobial peptides ( CAMPs ) serve as the first line of defense of the innate immune system against invading microbial pathogens .", "Gram-positive bacteria can resist CAMPs by modifying their anionic teichoic acids ( TAs ) with D-alanine , but the exact mechanism of resistance is not fully understo...	[ "Cationic antimicrobial peptides ( CAMPs ) represent important evolutionarily conserved elements of innate immunity and their killing mechanism involves bacterial cell wall permeation .", "As a result , gram-positive bacteria can resist CAMPs by modifying their anionic teichoic acids ( TAs ) following incorporati...	2012
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "antimicrobials", "medicine and health sciences", "body fluids", "gene regulation", "cell cycle and cell division", "drugs", "cell processes", "tropical diseases", "microbiology", "antifungals", "parasitic diseases", "notch signaling", "neglected tropical diseases", "pharmacology", "cell...	Transcriptional blood signatures for active and amphotericin B treated visceral leishmaniasis in India	journal.pntd.0007673	null	[ [ "Visceral leishmaniasis ( VL ) , also known as kala-azar , is a potentially fatal disease caused by obligate intracellular parasites of the Leishmania donovani complex .", "VL is a serious public health problem in indigenous and rural populations in India , causing high morbidity and mortality , as well a...	[ "Amphotericin B provides improved therapy for visceral leishmaniasis ( VL ) caused by Leishmania donovani , with single dose liposomal-encapsulated Ambisome providing the best cure rates .", "The VL elimination program aims to reduce the incidence rate in the Indian subcontinent to <1/10 , 000 population/year .",...	[ "Visceral leishmaniasis ( VL ) , also known as kala-azar , is a potentially fatal disease caused by intracellular parasites of the Leishmania donovani complex .", "VL is a serious public health problem in rural India , causing high morbidity and mortality , as well as major costs to local and national health budg...	2019
[ "Introduction", "Results/Discussion", "Materials and Methods" ]	[ "genetics and genomics/microbial evolution and genomics", "evolutionary biology/microbial evolution and genomics", "genetics and genomics/comparative genomics", "evolutionary biology/evolutionary and comparative genetics", "microbiology/microbial evolution and genomics", "genetics and genomics/bioinformat...	Comparative ICE Genomics: Insights into the Evolution of the SXT/R391 Family of ICEs	journal.pgen.1000786	null	[ [ "There are three types of self-transmissible mobile genetic elements: plasmids , bacteriophages and integrative conjugative elements ( ICEs ) .", "All three classes of elements enable horizontal transmission of genetic information and all have had major impacts on bacterial evolution [1]–[4] .", "ICEs...	[ "Integrating and conjugative elements ( ICEs ) are one of the three principal types of self-transmissible mobile genetic elements in bacteria .", "ICEs , like plasmids , transfer via conjugation; but unlike plasmids and similar to many phages , these elements integrate into and replicate along with the host chrom...	[ "Integrative and conjugative elements ( ICEs ) are a class of mobile genetic elements that are key mediators of horizontal gene flow in bacteria .", "These elements integrate into the host chromosome , yet are able to excise and transfer via conjugation .", "Our understanding of ICE evolution is rudimentary .",...	2009
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	In Vivo Analysis of Lrig Genes Reveals Redundant and Independent Functions in the Inner Ear	journal.pgen.1003824	null	[ [ "Protein-protein interactions are critical for diverse and complex biological functions throughout the animal kingdom , including nervous system development , cell adhesion and signaling , tissue morphogenesis , the immune response and human disease [1]–[4] .", "This functional diversity is accomplished b...	[ "Lrig proteins are conserved transmembrane proteins that modulate a variety of signaling pathways from worm to humans .", "In mammals , there are three family members – Lrig1 , Lrig2 , and Lrig3 – that are defined by closely related extracellular domains with a similar arrangement of leucine rich repeats and immu...	[ "The mammalian genome encodes three Lrig family members - Lrig1 , Lrig2 , and Lrig3 .", "Lrig proteins share a characteristic extracellular domain that can bind to a variety of signaling receptors , but the three family members show little homology in the cytoplasmic domain .", "Lrig1 is a tumor suppressor gene...	2013
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "dengue virus", "medicine and health sciences", "microbial mutation", "immune physiology", "protein interactions", "pathology and laboratory medicine", "statistics", "pathogens", "immunology", "microbiology", "viruses", "multivariate analysis", "mathematics", "rna viruses", "antibodies",...	Molecular basis of dengue virus serotype 2 morphological switch from 29°C to 37°C	journal.ppat.1007996	null	[ [ "Dengue virus ( DENV ) infects ~400 million people annually around the world especially in the tropical and sub-tropical regions [1 , 2] .", "It causes diseases ranging from mild dengue fever to severe dengue hemorrhagic fever ( DHF ) and dengue shock syndrome ( DSS ) .", "DENV is a flavivirus , and i...	[ "The ability of DENV2 to display different morphologies ( hence different antigenic properties ) complicates vaccine and therapeutics development .", "Previous studies showed most strains of laboratory adapted DENV2 particles changed from smooth to “bumpy” surfaced morphology when the temperature is switched from...	[ "DENV2 particles have been shown to change their morphologies ( compact smooth to loose bumpy surfaced ) when temperature is switched from 28°C to 37°C .", "We used two DENV2 viruses both belonging to the same strain designation but with a different passage history—one of which exhibited the smooth surfaced morph...	2019
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "cell motility", "actin filaments", "molecular motors", "actin motors", "motor proteins", "dynamic actin filaments", "contractile proteins", "actins", "proteins", "biophysics", "physics", "biochemistry", "cytoskeletal proteins", "biochemical simulations", "cell biology", "myosins", "...	Emergent mechanics of actomyosin drive punctuated contractions and shape network morphology in the cell cortex	journal.pcbi.1006344	null	[ [ "Dynamic actomyosin networks play a critical role in development by providing motive forces for cell shape change and morphogenesis , and by establishing tissue mechanical properties [1–3] .", "For instance , actomyosin can form a contractile actin purse-string , a rope-like structure of bundled F-actin s...	[ "Filamentous actin ( F-actin ) and non-muscle myosin II motors drive cell motility and cell shape changes that guide large scale tissue movements during embryonic morphogenesis .", "To gain a better understanding of the role of actomyosin in vivo , we have developed a two-dimensional ( 2D ) computational model to...	[ "Recent genetic and mechanical studies of embryonic development reveal a critical role for intracellular scaffolds in generating the shape of the embryo and constructing internal organs .", "In this paper we developed computer simulations of these scaffolds , composed of filamentous actin ( F-actin ) , a rod-like...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genetics and genomics/genetics of disease", "genetics and genomics/complex traits", "genetics and genomics/population genetics" ]	Genome-Wide Association Studies in an Isolated Founder Population from the Pacific Island of Kosrae	journal.pgen.1000365	null	[ [ "The use of isolated populations has a long history in genetic mapping , with benefits including founder effects , reduced genetic diversity , reduced genetic and environmental heterogeneity , and large , multi-generational pedigrees [1]–[3] .", "The resulting reduction in allelic heterogeneity has contri...	[ "It has been argued that the limited genetic diversity and reduced allelic heterogeneity observed in isolated founder populations facilitates discovery of loci contributing to both Mendelian and complex disease .", "A strong founder effect , severe isolation , and substantial inbreeding have dramatically reduced ...	[ "Isolated populations have contributed to the discovery of loci with simple Mendelian segregation and large effects on disease risk or trait variation .", "We hypothesized that the use of isolated populations might also facilitate the discovery of common alleles contributing to complex traits with relatively larg...	2009
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Genetic and Functional Studies Implicate Synaptic Overgrowth and Ring Gland cAMP/PKA Signaling Defects in the Drosophila melanogaster Neurofibromatosis-1 Growth Deficiency	journal.pgen.1003958	null	[ [ "RASopathies , caused by mutations that activate Ras/ERK signaling , are a group of related disorders with features that include facial dysmorphism , skeletal , skin and cardiac defects , cognitive deficits , reduced growth and an increased cancer risk [1] .", "Neurofibromatosis type 1 ( NF1; OMIM 162200 ...	[ "Neurofibromatosis type 1 ( NF1 ) , a genetic disease that affects 1 in 3 , 000 , is caused by loss of a large evolutionary conserved protein that serves as a GTPase Activating Protein ( GAP ) for Ras .", "Among Drosophila melanogaster Nf1 ( dNf1 ) null mutant phenotypes , learning/memory deficits and reduced ove...	[ "Neurofibromatosis type 1 ( NF1 ) is a genetic disease that affects 1 in 3 , 000 and that is caused by loss of a protein that inactivates Ras oncoproteins .", "NF1 is a characteristically variable disease that predisposes patients to several symptoms , the most common of which include benign and malignant tumors ...	2013
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "dengue virus", "medicine and health sciences", "pathology and laboratory medicine", "cost-effectiveness analysis", "economic analysis", "pathogens", "immunology", "geographical locations", "microbiology", "social sciences", "vaccines", "preventive medicine", "viruses", "rna viruses", "i...	Model-based assessment of public health impact and cost-effectiveness of dengue vaccination following screening for prior exposure	journal.pntd.0007482	null	[ [ "A safe and effective dengue vaccine could have a major public health impact , as dengue causes approximately 9 , 000 deaths and between 50–100 million clinically apparent cases worldwide every year [1 , 2] and has a growing geographic distribution [3] .", "The first licensed dengue vaccine , CYD-TDV ( De...	[ "The tetravalent dengue vaccine CYD-TDV ( Dengvaxia ) is the first licensed vaccine against dengue , but recent findings indicate an elevated risk of severe disease among vaccinees without prior dengue virus ( DENV ) exposure .", "The World Health Organization currently recommends CYD-TDV only for individuals wit...	[ "Among several viral diseases transmitted by Aedes aegypti mosquitoes , dengue imposes the greatest and most persistent burden on global health .", "Efforts to curb its spread would benefit greatly from the availability of an effective vaccine .", "Currently , the only licensed dengue vaccine , known as CYD-TDV...	2019
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "virology/persistence and latency", "genetics and genomics/gene expression", "virology/animal models of infection", "virology/emerging viral diseases", "infectious diseases/viral infections", "genetics and genomics/gene function", "infectious diseases/tropical and travel-associated diseases", "virolog...	Comparison of Dengue Virus Type 2-Specific Small RNAs from RNA Interference-Competent and –Incompetent Mosquito Cells	journal.pntd.0000848	null	[ [ "Mosquito cell cultures are used routinely in arbovirology studies to grow viruses and to elucidate aspects of viral infection and replication in mosquitoes .", "Many of these cell lines were established by Peleg and Singh in the 1960's [1] , [2] .", "A mosquito cell line designated C6/36 resulted fro...	[ "The exogenous RNA interference ( RNAi ) pathway is an important antiviral defense against arboviruses in mosquitoes , and virus-specific small interfering ( si ) RNAs are key components of this pathway .", "Understanding the biogenesis of siRNAs in mosquitoes could have important ramifications in using RNAi to c...	[ "Understanding how arthropod-borne viruses ( arboviruses ) establish persistent infections in mosquitoes will help us to find ways to prevent viral disease transmission by these insects .", "RNA silencing pathways in mosquitoes and other insects , particularly RNA interference ( RNAi ) , have been shown to be imp...	2010
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "mycobacterium leprae", "medicine and health sciences", "disabilities", "pathology and laboratory medicine", "tropical diseases", "geographical locations", "india", "randomized controlled trials", "bacterial diseases", "clinical medicine", "signs and symptoms", "pharmaceutics", "neglected tr...	Uniform multidrug therapy for leprosy patients in Brazil (U-MDT/CT-BR): Results of an open label, randomized and controlled clinical trial, among multibacillary patients	journal.pntd.0005725	null	[ [ "In 1981 , the World Health Organization ( WHO ) recommended the use of multidrug therapy ( MDT ) for leprosy .", "Since then , the disease prevalence dropped , but the case detection rate did not decrease and currently many countries still present high detection rates [1] .", "According to the WHO , ...	[ "Leprosy control is based on early diagnosis and multidrug therapy .", "For treatment purposes , leprosy patients can be classified as paucibacillary ( PB ) or multibacillary ( MB ) , according to the number of skin lesions .", "Studies regarding a uniform treatment regimen ( U-MDT ) for all leprosy patients ha...	[ "Since the introduction of multidrug therapy for leprosy in the 80’s , different classification criteria for leprosy patients have been proposed and treatment has been progressively shortened .", "Currently , leprosy patients are classified into paucibacillary/PB and multibacillary/MB based on the number of skins...	2017
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "veterinary diseases", "genetics", "biology", "genetics and genomics", "veterinary science" ]	Introgression of Ivermectin Resistance Genes into a Susceptible Haemonchus contortus Strain by Multiple Backcrossing	journal.ppat.1002534	null	[ [ "Parasitic nematode worms are important human and animal pathogens .", "Human parasites infect well over 1 billion people worldwide and livestock parasites cause major economic production loss to grazing ruminants .", "Control is dependent on the use of a limited number of anthelmintic drugs and inten...	[ "Anthelmintic drug resistance in livestock parasites is already widespread and in recent years there has been an increasing level of anthelmintic drug selection pressure applied to parasitic nematode populations in humans leading to concerns regarding the emergence of resistance .", "However , most parasitic nema...	[ "The use of drugs ( anthelmintics ) to control nematode parasites ( roundworms ) is common in both humans and animals .", "This has led to the widespread development of drug resistance in livestock parasites and serious concerns regarding its emergence in human parasites .", "Haemonchus contortus is a parasitic...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "transfection", "cell motility", "medicine and health sciences", "nuclear staining", "respiratory infections", "gene regulation", "microbiology", "viral structure", "pulmonology", "molecular biology techniques", "research and analysis methods", "contractile proteins", "specimen preparation a...	Actin-Related Protein 2 (ARP2) and Virus-Induced Filopodia Facilitate Human Respiratory Syncytial Virus Spread	journal.ppat.1006062	null	[ [ "RSV is the most important viral cause of severe acute pediatric lower respiratory tract illness worldwide , and also causes substantial morbidity and mortality in the elderly as well as in individuals with severe immunosuppression or cardiopulmonary disease .", "Despite its recognized importance , and de...	[ "Human respiratory syncytial virus ( RSV ) is an enveloped RNA virus that is the most important viral cause of acute pediatric lower respiratory tract illness worldwide , and lacks a vaccine or effective antiviral drug .", "The involvement of host factors in the RSV replicative cycle remains poorly characterized ...	[ "RSV is the most common viral cause of severe acute pediatric lower respiratory tract illness , including pneumonia and bronchiolitis , in young children worldwide .", "In a genome-wide siRNA screen in human lung epithelial A549 cells infected with RSV expressing green fluorescent protein ( RSV-GFP ) , we identif...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biochemistry", "genome complexity", "transposons", "genetic mutation", "retrotransposons", "nucleic acids", "genetics", "biology", "genomics", "molecular cell biology" ]	The Specificity and Flexibility of L1 Reverse Transcription Priming at Imperfect T-Tracts	journal.pgen.1003499	null	[ [ "Retrotransposons are highly repetitive and dispersed sequences , accounting for almost half of our DNA [1] .", "These elements have the ability to proliferate in genomes through an RNA-mediated copy-and-paste mechanism , called retrotransposition .", "LINE-1 ( L1 ) elements are the only autonomously ...	[ "L1 retrotransposons have a prominent role in reshaping mammalian genomes .", "To replicate , the L1 ribonucleoprotein particle ( RNP ) first uses its endonuclease ( EN ) to nick the genomic DNA .", "The newly generated DNA end is subsequently used as a primer to initiate reverse transcription within the L1 RNA...	[ "Jumping genes are DNA sequences present in the genome of most living organisms .", "They contribute to genome dynamics and occasionally result in hereditary genetic diseases or cancer .", "L1 elements are the only autonomously active jumping genes in the human genome .", "They replicate through an RNA–mediat...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "chemical compounds", "gene regulation", "vertebrates", "animals", "organic compounds", "circadian oscillators", "animal models", "osteichthyes", "developmental biology", "model organisms", "experimental organism systems", "acidic amino acids", "amino acids", "chronobiology", "research a...	Extensive Regulation of Diurnal Transcription and Metabolism by Glucocorticoids	journal.pgen.1006512	null	[ [ "The circadian clock is an endogenous oscillator that regulates daily changes of behavior , physiology and metabolism [1] .", "The molecular basis of the circadian clock is a transcriptional-translational feedback loop , a central part of which are E-box enhancer elements [2] .", "To generate physiolo...	[ "Altered daily patterns of hormone action are suspected to contribute to metabolic disease .", "It is poorly understood how the adrenal glucocorticoid hormones contribute to the coordination of daily global patterns of transcription and metabolism .", "Here , we examined diurnal metabolite and transcriptome pat...	[ "Glucocorticoids , steroid hormones of the adrenal gland , are important regulators of metabolism and the stress response .", "They are also widely used as anti-inflammatory drugs .", "Production and release of glucocorticoids show a diurnal pattern regulated by the circadian clock .", "Importantly , altered ...	2016
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "endocrine signaling", "medicine and health sciences", "notch signaling", "pancreas development", "endocrine physiology", "developmental biology", "organism development", "developmental signaling", "endocrine cells", "immunologic techniques", "research and analysis methods", "animal cells", ...	Pancreas lineage allocation and specification are regulated by sphingosine-1-phosphate signalling	journal.pbio.2000949	null	[ [ "The pancreas is the origin of some of the most debilitating and fatal diseases , including pancreatic cancer and diabetes .", "Understanding the signalling pathways and gene regulatory networks underlying pancreas development will shed light in the origins of these diseases and suggest novel therapeutic ...	[ "During development , progenitor expansion , lineage allocation , and implementation of differentiation programs need to be tightly coordinated so that different cell types are generated in the correct numbers for appropriate tissue size and function .", "Pancreatic dysfunction results in some of the most debilit...	[ "The pancreas develops from a field of progenitor cells localised in a restricted region of the embryonic endoderm .", "These progenitor cells proliferate and eventually differentiate to generate the three distinct lineages comprising the endocrine ( which include insulin-producing β cells ) , acinar , and ductal...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Sumoylated NHR-25/NR5A Regulates Cell Fate during C. elegans Vulval Development	journal.pgen.1003992	null	[ [ "Tissue-specific and cell type-specific transcriptional networks underlie virtually every aspect of metazoan development and homeostasis .", "Single TFs , operating within gene-specific regulatory complexes , govern distinct gene regulatory networks in different cells and tissues; thus , combinatorial reg...	[ "Individual metazoan transcription factors ( TFs ) regulate distinct sets of genes depending on cell type and developmental or physiological context .", "The precise mechanisms by which regulatory information from ligands , genomic sequence elements , co-factors , and post-translational modifications are integrat...	[ "Animals precisely control when and where genes are expressed; failure to do so can cause severe developmental defects and pathology .", "Transcription factors must display extraordinary functional flexibility , controlling very different sets of genes in different cell and tissue types .", "To do so , they int...	2013
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "medicine", "infectious diseases", "global health", "neurology", "neurological disorders" ]	Cerebral Toxoplasmosis Mimicking Subacute Meningitis in HIV-Infected Patients; a Cohort Study from Indonesia	journal.pntd.0001994	null	[ [ "In settings of Africa and Asia , the most common cause of subacute meningitis in patients with advanced HIV infection is either tuberculous or cryptococcal infection [1] , [2] .", "However , in many patients , the etiology of subacute meningitis cannot be established [1] , [3] .", "In line with a lar...	[ "HIV-associated subacute meningitis is mostly caused by tuberculosis or cryptococcosis , but often no etiology can be established .", "In the absence of CT or MRI of the brain , toxoplasmosis is generally not considered as part of the differential diagnosis .", "We performed cerebrospinal fluid real time PCR an...	[ "If HIV-infected patients present with seizures , focal neurological symptoms or confusion , a CT-scan or MRI of the brain is normally made .", "If mass lesions are found ( and the CD4 cell count is sufficiently low ) , cerebral toxoplasmosis is suspected , and often treated empirically .", "However , some of t...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "developmental biology", "genetics", "biology", "computational biology", "genetics and genomics" ]	Neurophysiological Defects and Neuronal Gene Deregulation in Drosophila mir-124 Mutants	journal.pgen.1002515	null	[ [ "microRNAs ( miRNAs ) are ∼22 nucleotide ( nt ) regulatory RNAs that function primarily as post-transcriptional repressors .", "In animals , miRNAs have propensity to target mRNAs via 6–7 nt motifs complementary to their 5′ ends , termed “seed” regions [1]–[4] .", "This limited pairing requirement has...	[ "miR-124 is conserved in sequence and neuronal expression across the animal kingdom and is predicted to have hundreds of mRNA targets .", "Diverse defects in neural development and function were reported from miR-124 antisense studies in vertebrates , but a nematode knockout of mir-124 surprisingly lacked detecta...	[ "microRNAs are abundant ∼22 nucleotide RNAs inferred to mediate pervasive post-transcriptional control of most genes .", "Still , relatively little is understood about their endogenous requirements and impact , especially in animal systems .", "We analyzed a knockout of Drosophila mir-124 , which is conserved i...	2012
[ "Introduction", "Results/Discussion", "Methods" ]	[ "fluorescence imaging", "chemical characterization", "medicine and health sciences", "breast tumors", "crystal structure", "condensed matter physics", "cancers and neoplasms", "oncology", "peptide libraries", "molecular biology techniques", "crystallography", "thermodynamics", "research and ...	Peptide probes derived from pertuzumab by molecular dynamics modeling for HER2 positive tumor imaging	journal.pcbi.1005441	null	[ [ "Human epidermal growth factor receptor 2 ( HER2 ) is a prominent target in breast cancer diagnosis and treatment , as approximately 20–30% of patients with breast cancer overexpressing the HER2 receptor [1 , 2] , a 185-kD transmembrane glycoprotein with 1 , 255 amino acids [3] .", "The HER2 gene is a pro...	[ "A high level of HER2 expression in breast cancer correlates with a higher tumor growth rate , high metastatic potential , and a poor long-term patient survival rate .", "Pertuzumab , a human monoclonal antibody , can reduce the effect of HER2 overexpression by preventing HER2 dimerization .", "In this study , ...	[ "Many therapeutic approaches , including the human monoclonal antibodies trastuzumab and pertuzumab , target the human epidermal growth factor receptor 2 ( HER2 ) of any breast cancer that features HER2 overexpression .", "Compared to these antibodies , peptides have many advantages , including lower cost , easie...	2017
[ "Introduction", "Results", "Discussion", "Material and methods" ]	[ "medicine and health sciences", "maternal health", "obstetrics and gynecology", "diabetic endocrinology", "astrocytes", "vertebrates", "mice", "neuroscience", "macroglial cells", "animals", "mammals", "hormones", "endocrine physiology", "fluorescence-activated cell sorting", "organisms",...	Ablating astrocyte insulin receptors leads to delayed puberty and hypogonadism in mice	journal.pbio.3000189	Ablation of insulin receptors in astrocytes reveals that insulin promotes pubertal development and fertility in mice by acting on astrocytes rather than directly affecting neuronal reproductive circuits.	[ [ "Reproduction is essential for species survival .", "Because energy is required to locate a mate , maintain a pregnancy , and rear young , fertility is modulated by the status of energy stores [1–3] .", "Excessive energy expenditure or insufficient caloric intake in humans and rodents delays the puber...	[ "Insulin resistance and obesity are associated with reduced gonadotropin-releasing hormone ( GnRH ) release and infertility .", "Mice that lack insulin receptors ( IRs ) throughout development in both neuronal and non-neuronal brain cells are known to exhibit subfertility due to hypogonadotropic hypogonadism .", ...	[ "Astrocytes are a major cell type in the central nervous system , yet their impact on the neuroendocrine circuits that control fertility is under appreciated .", "Here , we show in mice that ablation of insulin signaling in astrocytes leads to delayed puberty , hypothalamic-pituitary-gonadotropin ( HPG ) axis dys...	2019
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "chemical compounds", "phosphates", "cell cycle and cell division", "cell processes", "g2 phase", "chromatids", "dna damage", "fungi", "model organisms", "dna replication", "experimental organism systems", "dna", "genetic interactions", "schizosaccharomyces", "research and analysis metho...	Lingering single-strand breaks trigger Rad51-independent homology-directed repair of collapsed replication forks in the polynucleotide kinase/phosphatase mutant of fission yeast	journal.pgen.1007013	null	[ [ "Maintenance of genome integrity depends on the accurate repair of DNA lesions that sever one or both strands of the double-helix .", "Single-strand breaks ( SSBs ) are by far the most abundant DNA scission , occurring at frequencies of thousands/cell/day in proliferating human cells [1] .", "SSBs are...	[ "The DNA repair enzyme polynucleotide kinase/phosphatase ( PNKP ) protects genome integrity by restoring ligatable 5’-phosphate and 3’-hydroxyl termini at single-strand breaks ( SSBs ) .", "In humans , PNKP mutations underlie the neurological disease known as MCSZ , but these individuals are not predisposed for c...	[ "DNA is constantly damaged by normal cellular metabolism , for example production of reactive oxygen species , or from exposure to external DNA damaging sources , such as radiation from the sun or chemicals in the environment .", "These genotoxic agents create thousands of single-strand breaks/cell/day in the hum...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine and health sciences", "pathology and laboratory medicine", "host-pathogen interactions", "medical microbiology", "microbial pathogens", "biology and life sciences", "immunology", "microbiology", "pathogenesis", "bacterial pathogens" ]	Role of Calmodulin-Calmodulin Kinase II, cAMP/Protein Kinase A and ERK 1/2 on Aeromonas hydrophila-Induced Apoptosis of Head Kidney Macrophages	journal.ppat.1004018	null	[ [ "Aeromonas hydrophila , a Gram-negative , rod-shaped , facultatively intracellular bacterium is commonly found as part of the normal microbial flora in the aquatic environment [1] .", "The pathogenicity of A . hydrophila is complex and multi-factorial .", "It induces a plethora of symptoms in fish cha...	[ "The role of calcium ( Ca2+ ) and its dependent protease calpain in Aeromonas hydrophila-induced head kidney macrophage ( HKM ) apoptosis has been reported .", "Here , we report the pro-apoptotic involvement of calmodulin ( CaM ) and calmodulin kinase II gamma ( CaMKIIg ) in the process .", "We observed signifi...	[ "Aeromonas hydrophila is a natural fish pathogen and is known to induce apoptosis of HKM .", "Head kidney is an important immune-organ in fish and HKM are critical for immunity against the invading pathogen .", "The mechanisms of cell death induced by A . hydrophila are incompletely characterized .", "We have...	2014
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "molecular neuroscience", "neurobiology of disease and regeneration", "animal genetics", "genetic screens", "genetics", "biology", "genetics of disease", "neuroscience" ]	Aconitase Causes Iron Toxicity in Drosophila pink1 Mutants	journal.pgen.1003478	null	[ [ "Parkinson's disease ( PD ) is the most frequent neurodegenerative movement disorder , but the pathways that explain disease pathology remain poorly understood [1] , [2] .", "While the most recognized pathological feature of PD is the preferential loss of dopaminergic ( DA ) neurons , one of the earliest ...	[ "The PTEN-induced kinase 1 ( PINK1 ) is a mitochondrial kinase , and pink1 mutations cause early onset Parkinson's disease ( PD ) in humans .", "Loss of pink1 in Drosophila leads to defects in mitochondrial function , and genetic data suggest that another PD-related gene product , Parkin , acts with pink1 to regu...	[ "In this work we provide mechanistic insight linking together two of the earliest observations in Parkinson's disease: the excessive build-up of iron in diseased substantia nigra neurons and mitochondrial dysfunction particularly increased reactive oxygen species production at the level of Complex I .", "We ident...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "chemical biology/small molecule chemistry", "microbiology/medical microbiology", "genetics and genomics/chromosome biology", "biochemistry/replication and repair", "public health and epidemiology/infectious diseases", "microbiology/applied microbiology", "microbiology/microbial growth and development",...	Targeting the Replication Initiator of the Second Vibrio Chromosome: Towards Generation of Vibrionaceae-Specific Antimicrobial Agents	journal.ppat.1000663	null	[ [ "The Vibrionaceae are a diverse family of bacteria that includes more than 80 species [1] , [2] .", "Vibrios are gram-negative rods that usually inhabit aquatic habitats , often in association with eukaryotes .", "This large family includes important human pathogens such as V . cholerae , V . parahaem...	[ "The Vibrionaceae is comprised of numerous aquatic species and includes several human pathogens , such as Vibrio cholerae , the cause of cholera .", "All organisms in this family have two chromosomes , and replication of the smaller one depends on rctB , a gene that is restricted to the Vibrionaceae .", "Given ...	[ "Multi-drug resistant bacteria continue to emerge and there is a pressing need for the development of new antibiotics .", "Here , we carried out a cell-based high throughput screen to identify inhibitors of RctB , the initiator of replication of the second chromosome found in all the species of the Vibrionaceae ....	2009
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "immunology/immunity to infections", "microbiology/immunity to infections" ]	Compensatory T Cell Responses in IRG-Deficient Mice Prevent Sustained Chlamydia trachomatis Infections	journal.ppat.1001346	null	[ [ "Chlamydia trachomatis is an obligate intracellular bacterial pathogen that causes frequent infections in humans and significant morbidity throughout the world [1] .", "Ocular infection with C . trachomatis is the leading cause of preventable blindness worldwide and genital infection with C . trachomatis ...	[ "The obligate intracellular pathogen Chlamydia trachomatis is the most common cause of bacterial sexually transmitted diseases in the United States .", "In women C . trachomatis can establish persistent genital infections that lead to pelvic inflammatory disease and sterility .", "In contrast to natural infecti...	[ "Chlamydia trachomatis is the most common cause of bacterial sexually transmitted disease and can lead to pelvic inflammatory disease , ectopic pregnancy , infertility , and other complications in women .", "These serious complications have been difficult to study experimentally in laboratory animals because C . ...	2011
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "developmental biology", "kinetoplastids", "veterinary parasitology", "cell biology", "genome evolution", "evolutionary biology", "molecular biology", "parasite evolution", "life cycles", "biology and life sciences", "molecular evolution", "microbiology", "computational biology", "molecula...	Genome and Phylogenetic Analyses of Trypanosoma evansi Reveal Extensive Similarity to T. brucei and Multiple Independent Origins for Dyskinetoplasty	journal.pntd.0003404	null	[ [ "Trypanosomatid parasites Trypanosoma evansi and T . equiperdum are responsible for animal diseases with extensive pathological and economic impact and closely related to the T . brucei group [1] , [2] .", "The latter includes three subspecies: the human parasite T . b .", "rhodesiense , the zoonotic ...	[ "Two key biological features distinguish Trypanosoma evansi from the T . brucei group: independence from the tsetse fly as obligatory vector , and independence from the need for functional mitochondrial DNA ( kinetoplast or kDNA ) .", "In an effort to better understand the molecular causes and consequences of the...	[ "The single-cell parasite Trypanosoma evansi is the disease-causing trypanosome with the widest geographical distribution .", "The disease , called surra , has significant economic impact primarily due to infections of cattle , horses , and camels .", "Morphologically the parasite is indistinguishable from bloo...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine", "immunity to infections", "immunology", "adaptive immunity", "sexually transmitted diseases", "infectious disease control", "vaccination", "infectious diseases", "aids", "immune response", "antigen processing and recognition", "clinical immunology", "immunity", "vaccine develop...	CTL Escape Mediated by Proteasomal Destruction of an HIV-1 Cryptic Epitope	journal.ppat.1002049	null	[ [ "Multiple lines of evidence suggest that CD8+ cytotoxic T lymphocytes ( CTLs ) play", "a critical role in controlling HIV-1 replication .", "During acute infection , expansion", "of HIV-specific CD8+ T cells ( HS-CTL ) , before appearance of neutralizing", "antibodies , is associated with decr...	[ "Cytotoxic CD8+ T cells ( CTLs ) play a critical role in controlling viral", "infections .", "HIV-infected individuals develop CTL responses against epitopes", "derived from viral proteins , but also against cryptic epitopes encoded by viral", "alternative reading frames ( ARF ) .", "We studied here the m...	[ "In addition to the classical open reading frames encoding for the well", "characterized HIV proteins , HIV exhibits a vast number of alternative reading", "frames that have the potential to encode proteins or polypeptides .", "We have", "previously shown that such reading frames within gag , pol and", "e...	2011
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "medicine and health sciences", "fluorescence", "chemical compounds", "pathology and laboratory medicine", "oxygen", "membrane potential", "salts", "electrophysiology", "fibroblasts", "toxic agents", "toxicology", "electromagnetic radiation", "connective tissue cells", "mitochondria", "b...	Mitochondria are physiologically maintained at close to 50 °C	journal.pbio.2003992	null	[ [ "As the main bioenergetically active organelles of nonphotosynthetic eukaryotes , mitochondria convert part of the free energy released by the oxidation of nutrient molecules into ATP and other useful forms of energy needed by cells .", "However , this energy conversion process is far from being 100% effi...	[ "In endothermic species , heat released as a product of metabolism ensures stable internal temperature throughout the organism , despite varying environmental conditions .", "Mitochondria are major actors in this thermogenic process .", "Part of the energy released by the oxidation of respiratory substrates dri...	[ "To ensure a stable internal temperature , endothermic species make use of the heat released during the final steps of food burning by the mitochondria present in all cells of the organism .", "Indeed , only a fraction of the energy released by the oxidation of respiratory substrates is used to generate ATP , whi...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine", "immune cells", "viruses and cancer", "immunology", "host-pathogen interaction", "microbiology", "cancers and neoplasms", "hematologic cancers and related disorders", "oncology", "bone and soft tissue sarcomas", "gene expression", "biology", "kaposi sarcoma", "viral replication...	Abortive Lytic Reactivation of KSHV in CBF1/CSL Deficient Human B Cell Lines	journal.ppat.1003336	null	[ [ "Kaposi's sarcoma associated herpesvirus ( KSHV ) establishes a persistent infection in the human host .", "Infected human B cells in the circulation of the infected host are likely to constitute a major latent reservoir , from where KSHV can reactivate and spread .", "In addition , the strong associa...	[ "Since Kaposi's sarcoma associated herpesvirus ( KSHV ) establishes a persistent infection in human B cells , B cells are a critical compartment for viral pathogenesis .", "RTA , the replication and transcription activator of KSHV , can either directly bind to DNA or use cellular DNA binding factors including CBF...	[ "Kaposi's sarcoma associated herpesvirus ( KSHV ) establishes a life-long persistent infection in B cells , which constitute the viral reservoir for reactivation and production of progeny virus .", "Viral reactivation is associated with multiple AIDS related malignancies including Kaposi's sarcoma , an endothelia...	2013
[ "Introduction", "Results", "Discussion" ]	[]	Morphological and Stress Vulnerability Indices for Human Coronary Plaques and Their Correlations with Cap Thickness and Lipid Percent: An IVUS-Based Fluid-Structure Interaction Multi-patient Study	journal.pcbi.1004652	null	[ [ "Cardiovascular diseases ( CVD ) , especially acute coronary syndromes , are closely associated with atherosclerotic plaque progression and rupture .", "Accurate assessment of plaque vulnerability is of ultimate importance to CVD research , diagnosis , prevention and proper treatment .", "Plaque vulne...	[ "Plaque vulnerability , defined as the likelihood that a plaque would rupture , is difficult to quantify due to lack of in vivo plaque rupture data .", "Morphological and stress-based plaque vulnerability indices were introduced as alternatives to obtain quantitative vulnerability assessment .", "Correlations b...	[ "Cardiovascular diseases are closely related to atherosclerotic plaque progression and rupture .", "Early detection of vulnerable plaques and prediction of potential plaque rupture and related clinical events are of vital importance .", "Plaque vulnerability , defined as the likelihood that a plaque would ruptu...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine and health sciences", "luciferase", "pathology and laboratory medicine", "chemical compounds", "affinity chromatography", "hela cells", "gene regulation", "pathogens", "enzymes", "biological cultures", "microbiology", "enzymology", "carbohydrates", "organic compounds", "glucose...	Interaction of the Human Papillomavirus E6 Oncoprotein with Sorting Nexin 27 Modulates Endocytic Cargo Transport Pathways	journal.ppat.1005854	null	[ [ "Human Papillomaviruses ( HPVs ) are the causative agents of a large number of human malignancies , chief among which is cervical cancer , with over 500 , 000 reported cases worldwide annually [1 , 2] .", "There are currently more than 150 known types of HPVs , but not all of them are etiological agents o...	[ "A subset of high-risk Human Papillomaviruses ( HPVs ) are the causative agents of a large number of human cancers , of which cervical is the most common .", "Two viral oncoproteins , E6 and E7 , contribute directly towards the development and maintenance of malignancy .", "A characteristic feature of the E6 on...	[ "A unique feature of the high risk Human Papillomavirus ( HPV ) E6 oncoproteins is the presence of a PDZ binding motif ( PBM ) on its extreme C-terminus .", "This motif confers on E6 an ability to interact with a number of cellular proteins which possess PDZ domains , and this activity of E6 is important during t...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "cancer genomics", "medicine and health sciences", "genetic networks", "molecular probe techniques", "basic cancer research", "cloning", "chromatids", "oncology", "network analysis", "genome analysis", "molecular biology techniques", "dna", "gene conversion", "gel electrophoresis", "homo...	Complex Breakpoints and Template Switching Associated with Non-canonical Termination of Homologous Recombination in Mammalian Cells	journal.pgen.1006410	null	[ [ "Double strand breaks ( DSBs ) are dangerous lesions , the misrepair of which can contribute to genomic instability and cancer predisposition , premature aging and immunological deficiency in mammals [1–3] .", "A major trigger to chromosome breakage occurs during attempted replication across a damaged DNA...	[ "A proportion of homologous recombination ( HR ) events in mammalian cells resolve by “long tract” gene conversion , reflecting copying of several kilobases from the donor sister chromatid prior to termination .", "Cells lacking the major hereditary breast/ovarian cancer predisposition genes , BRCA1 or BRCA2 , or...	[ "Complex breakpoints are a recognized feature of cancer genome rearrangements , but the mechanisms that lead to their formation are undefined .", "Although homologous recombination ( HR ) is considered a potentially error-free pathway , cells lacking critical HR genes , such as the major hereditary breast/ovarian...	2016
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "medicine", "infectious diseases", "soil-transmitted helminths", "hookworm infection", "neglected tropical diseases", "immunology", "biology", "hookworm", "ascariasis", "parasitic diseases", "helminth infection" ]	A Cross-Reactive Monoclonal Antibody to Nematode Haemoglobin Enhances Protective Immune Responses to Nippostrongylus brasiliensis	journal.pntd.0002395	null	[ [ "Soil-transmitted intestinal nematodes infect more than 1 billion people worldwide , with detrimental effects ranging from anaemia and impaired mental and physical development to potentially fatal intestinal blockages that can result in anywhere from 12 000–135 000 deaths per year [1] , [2] .", "Worm infe...	[ "Nematode secreted haemoglobins have unusually high affinity for oxygen and possess nitric oxide deoxygenase , and catalase activity thought to be important in protection against host immune responses to infection .", "In this study , we generated a monoclonal antibody ( 48Eg ) against haemoglobin of the nematode...	[ "Nematode haemoglobins are fascinating molecules with unusually high affinity for oxygen .", "This is one example of many unique adaptations that nematodes have acquired to survive in their hosts , as nematode haemoglobin is thought to sequester oxygen to maintain an anaerobic environment , and can break down nit...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "systems biology", "biology", "genomics", "microbiology", "genetics and genomics" ]	Multiple Means to the Same End: The Genetic Basis of Acquired Stress Resistance in Yeast	journal.pgen.1002353	null	[ [ "All organisms must respond to stressful stimuli that result from external environmental changes or internal defects caused by mutation and disease .", "Decades of research have characterized the mechanisms for surviving individual stresses , by mapping downstream protection systems as well as upstream si...	[ "In nature , stressful environments often occur in combination or close succession , and thus the ability to prepare for impending stress likely provides a significant fitness advantage .", "Organisms exposed to a mild dose of stress can become tolerant to what would otherwise be a lethal dose of subsequent stres...	[ "Cells experience stressful conditions in the real world that can threaten physiology .", "Therefore , organisms have evolved intricate defense systems to protect themselves against environmental stress .", "Many organisms can increase their stress tolerance at the first sign of a problem through a phenomenon c...	2011
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "biogeography", "medicine and health sciences", "ecology and environmental sciences", "pathology and laboratory medicine", "influenza", "pathogens", "population genetics", "geographical locations", "microbiology", "australia", "spatial epidemiology", "orthomyxoviruses", "viruses", "seasons...	Continental synchronicity of human influenza virus epidemics despite climactic variation	journal.ppat.1006780	null	[ [ "Seasonal and pandemic influenza remains one of the most important infectious diseases of humans and is associated with high levels of both morbidity and mortality [1] .", "Influenza epidemics occur annually due to the continual accumulation of small changes in surface antigens of influenza virus that esc...	[ "The factors that determine the pattern and rate of spread of influenza virus at a continental-scale are uncertain .", "Although recent work suggests that influenza epidemics in the United States exhibit a strong geographical correlation , the spatiotemporal dynamics of influenza in Australia , a country and cont...	[ "We use a unique combination of large-scale laboratory-confirmed influenza surveillance and genomic sequence data to determine the pattern and determinants of influenza spread through time and space at a continental scale , utilizing 450 , 000 data entries gathered across Australia over a 10-year period ( 2007–2016...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genetics and genomics/microbial evolution and genomics", "evolutionary biology/microbial evolution and genomics", "microbiology/microbial evolution and genomics", "genetics and genomics/population genetics" ]	The Fitness Effects of Random Mutations in Single-Stranded DNA and RNA Bacteriophages	journal.pgen.1000742	null	[ [ "Mutational fitness effects are important for understanding the genetic variability of populations , the relative roles of natural selection and drift , the origin of sex and recombination , or the ability to produce evolutionary innovations , among other processes [1]–[4] .", "Further , they are of pract...	[ "Mutational fitness effects can be measured with relatively high accuracy in viruses due to their small genome size , which facilitates full-length sequencing and genetic manipulation .", "Previous work has shown that animal and plant RNA viruses are very sensitive to mutation .", "Here , we characterize mutati...	[ "The fitness effects of mutations are the raw material for natural selection .", "It has been shown that point mutations typically have strongly deleterious effects in plant and animal RNA viruses , whereas cellular organisms are comparatively more robust .", "Here , we characterize the fitness effects of rando...	2009
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biofilms", "bacteriology", "blood cells", "medicine and health sciences", "immune cells", "immune physiology", "pathology and laboratory medicine", "oxygen", "spleen", "pathogens", "immunology", "microbiology", "organisms", "molecular biology techniques", "mutagenesis and gene deletion ...	An Oxygen-Sensing Two-Component System in the Burkholderia cepacia Complex Regulates Biofilm, Intracellular Invasion, and Pathogenicity	journal.ppat.1006116	null	[ [ "Burkholderia dolosa is a member of the Burkholderia cepacia complex ( BCC ) , which is a group of related Gram-negative bacilli that can be dangerous respiratory pathogens for patients with cystic fibrosis ( CF ) [1 , 2] .", "BCC can also cause outbreaks of bacteremia or respiratory infection in hospital...	[ "Burkholderia dolosa is a member of the Burkholderia cepacia complex ( BCC ) , which is a group of bacteria that cause chronic lung infection in patients with cystic fibrosis ( CF ) and can be associated with outbreaks carrying high morbidity and mortality .", "While investigating the genomic diversity of B . dol...	[ "In people with cystic fibrosis ( CF ) , infection with bacteria in the Burkholderia cepacia complex ( BCC ) is often associated with clinical deterioration .", "In a whole-genome sequencing study of the BCC species B . dolosa , we previously identified the fixL gene of the FixL/FixJ two-component system called F...	2017
[ "Introduction", "Methods", "Results and Discussion" ]	[ "biochemistry", "enzymes", "parasitology", "immunology", "biology", "microbiology", "host-pathogen interaction", "immune response" ]	Ecto-Nucleotidase Activities of Promastigotes from Leishmania (Viannia) braziliensis Relates to Parasite Infectivity and Disease Clinical Outcome	journal.pntd.0001850	null	[ [ "Leishmania is the etiological agent of leishmaniasis , a parasitic disease with diverse clinical manifestations in human beings and other mammals .", "The parasite presents two main stages in their life cycle: the flagellated mobile promastigote , which multiply in the midgut of the sandfly vector and no...	[ "Leishmania ( Viannia ) braziliensis has been associated with a broad range of clinical manifestations ranging from a simple cutaneous ulcer to destructive mucosal lesions .", "Factors leading to this diversity of clinical presentations are not clear , but parasite factors have lately been recognized as important...	[ "Cutaneous leishmaniasis is a widespread tropical disease caused by different species of Leishmania protozoa that are transmitted by infected sandflies .", "Clinical presentations are extremely diverse and dependent on a variety of parasite and host factors that are poorly understood .", "Leishmania ( V . ) bra...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "plant biology/plant-biotic interactions", "cell biology/cell signaling", "immunology/innate immunity", "cell biology/plant cell biology", "cell biology/gene expression" ]	Balanced Nuclear and Cytoplasmic Activities of EDS1 Are Required for a Complete Plant Innate Immune Response	journal.ppat.1000970	null	[ [ "In animals and plants , innate immune responses of individual cells constitute a major barrier to pathogen infection .", "Recognition of microbe- or damage-associated molecules is mediated by germ line encoded receptors whose activation is transduced by intracellular signaling systems to an anti-microbia...	[ "An important layer of plant innate immunity to host-adapted pathogens is conferred by intracellular nucleotide-binding/oligomerization domain-leucine rich repeat ( NB-LRR ) receptors recognizing specific microbial effectors .", "Signaling from activated receptors of the TIR ( Toll/Interleukin-1 Receptor ) -NB-LR...	[ "Plants have evolved a multilayered innate immune system to recognize and respond to potentially destructive microbes in the environment .", "Resistance to invasive biotrophic and hemi-biotrophic pathogens often involves transcriptional mobilization of defenses and programmed death of host cells at infection site...	2010
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "infectious diseases", "medicine and health sciences", "mycetoma", "neglected tropical diseases", "tropical diseases", "fungal diseases" ]	Active Matrix Metalloprotease-9 Is Associated with the Collagen Capsule Surrounding the Madurella mycetomatis Grain in Mycetoma	journal.pntd.0002754	null	[ [ "Madurella mycetomatis is the most prevalent causative organism of eumycetoma , a persistent , progressive granulomatous infection involving subcutaneous tissues and bones [1] .", "Mycetoma lesions are characterized by subcutaneous masses , sinuses and fungal grains , which commonly progress under inappro...	[ "Madurella mycetomatis is the main causative organism of eumycetoma , a persistent , progressive granulomatous infection .", "After subcutaneous inoculation M . mycetomatis organizes itself in grains inside a granuloma with excessive collagen accumulation surrounding it .", "This could be contributing to treatm...	[ "Eumycetoma , mainly caused by the fungus Madurella mycetomatis , is a chronic infection which , without treatment , results in deformation of the infected body part .", "Inside the body , the fungus organises itself in grains which are surrounded by collagen .", "This collagen could act as a natural barrier fo...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "cell death", "biochemistry", "signal transduction", "cellular stress responses", "transcriptional signaling", "stress signaling cascade", "feedback regulation", "medicine and health sciences", "cell biology", "model organisms", "mechanisms of signal transduction", "biology and life sciences",...	Fine Tuning of the UPR by the Ubiquitin Ligases Siah1/2	journal.pgen.1004348	null	[ [ "The endoplasmic reticulum ( ER ) plays a central role in the folding , assembly , and modification of secretory and cell membrane proteins [1] , [2] .", "Deregulated protein folding affects diverse cellular processes , including transcription , translation , cell cycle , and cell death [3] , [4] .", ...	[ "The endoplasmic reticulum ( ER ) responds to changes in intracellular homeostasis through activation of the unfolded protein response ( UPR ) .", "Yet , it is not known how UPR-signaling coordinates adaptation versus cell death .", "Previous studies suggested that signaling through PERK/ATF4 is required for ce...	[ "Maintaining a balanced level of stress ( protein folding , reactive oxygen radicals ) is important for keeping cellular homeostasis ( the ability of a cell to maintain internal equilibrium by adjusting its physiological processes ) .", "The accumulation of stress ( external or internal ) will trigger a well-orch...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "virology/virulence factors and mechanisms", "respiratory medicine/respiratory infections", "immunology/immunomodulation", "immunology/innate immunity", "infectious diseases/viral infections", "biochemistry/cell signaling and trafficking structures", "biochemistry/biomacromolecule-ligand interactions", ...	Differential Regulation of Type I Interferon and Epidermal Growth Factor Pathways by a Human Respirovirus Virulence Factor	journal.ppat.1000587	null	[ [ "Viruses need to interact with host macromolecules to hijack the cellular machinery and replicate .", "These interactions are essential for viruses to target endocytic pathways and penetrate host cells , to recruit cellular transcription and/or translation machinery , and to achieve intracellular migratio...	[ "A number of paramyxoviruses are responsible for acute respiratory infections in children , elderly and immuno-compromised individuals , resulting in airway inflammation and exacerbation of chronic diseases like asthma .", "To understand the molecular pathogenesis of these infections , we searched for cellular ta...	[ "Respiroviruses are important pathogens responsible for acute respiratory tract infections associated with severe airway inflammation in children , elderly and immuno-compromised individuals .", "Their RNA genome encodes for structural proteins that compose viral particles , but also for virulence factors that al...	2009
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "viruses", "virology" ]	Reconstitution of an Infectious Human Endogenous Retrovirus	journal.ppat.0030010	null	[ [ "A characteristic that is unique to retroviruses is their propensity to integrate their genomes into host-cell DNA as an essential part of their replication cycle .", "Thus , if the target cell population of a given retrovirus includes germ cells or their progenitors , retroviral genomes can be inherited ...	[ "The human genome represents a fossil record of ancient retroviruses that once replicated in the ancestors of contemporary humans .", "Indeed , approximately 8% of human DNA is composed of sequences that are recognizably retroviral .", "Despite occasional reports associating human endogenous retrovirus ( HERV )...	[ "Retrovirus genomes integrate into the genomes of host cells .", "If the target cells of a particular retrovirus include germ-line cells , e . g . , sperm or egg cells , then retroviral genomes can be inherited like cellular genes .", "So-called “endogenous” retroviruses have accumulated throughout evolution in...	2007
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "genetics and genomics/disease models", "mathematics/statistics", "genetics and genomics/complex traits", "genetics and genomics/bioinformatics" ]	A Novel Adaptive Method for the Analysis of Next-Generation Sequencing Data to Detect Complex Trait Associations with Rare Variants Due to Gene Main Effects and Interactions	journal.pgen.1001156	null	[ [ "Currently there is great interest in investigating the etiology of complex disease due to rare variants [1]–[6] .", "Until recently , indirect mapping of common variants has been the emphasis of complex trait association studies .", "It has been demonstrated that common variants tend to have modest p...	[ "There is solid evidence that rare variants contribute to complex disease etiology .", "Next-generation sequencing technologies make it possible to uncover rare variants within candidate genes , exomes , and genomes .", "Working in a novel framework , the kernel-based adaptive cluster ( KBAC ) was developed to ...	[ "It has been demonstrated that both rare and common variants are involved in complex disease etiology .", "Until recently it was only possible to perform large scale analysis of common variants .", "With the development of next-generation sequencing technologies , detection and mapping of rare variants have bee...	2010
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "plant anatomy", "enzymes", "gene regulation", "enzymology", "cereal crops", "plant science", "rice", "model organisms", "crops", "mitochondria", "bioenergetics", "inflorescences", "plants", "cellular structures and organelles", "flowering plants", "glumes", "research and analysis me...	A High Temperature-Dependent Mitochondrial Lipase EXTRA GLUME1 Promotes Floral Phenotypic Robustness against Temperature Fluctuation in Rice (Oryza sativa L.)	journal.pgen.1006152	null	[ [ "The sessile plants have evolved various exquisite adaptive strategies to cope with environmental changes [1 , 2] .", "Among them , phenotypic plasticity is the ability of a single genotype capable of producing different phenotypes in response to varying environments [3–6] .", "For an integral high fi...	[ "The sessile plants have evolved diverse intrinsic mechanisms to control their proper development under variable environments .", "In contrast to plastic vegetative development , reproductive traits like floral identity often show phenotypic robustness against environmental variations .", "However , it remains ...	[ "Various mechanisms have evolved to ensure proper organ formation under variable environments in order to complete one organism’s life cycle .", "In angiosperms , vegetative and reproductive organs show a differential plastic development between varied environments , with a low plasticity or high robustness for f...	2016
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "ecology and environmental sciences", "medicine and health sciences", "ecological niches", "physiological processes", "conservation biology", "ecological metrics", "food web structure", "species diversity", "conservation science", "community ecology", "food consumption", "species extinction", ...	Food Web Assembly Rules for Generalized Lotka-Volterra Equations	journal.pcbi.1004727	null	[ [ "Fueled by ongoing rapid decline of biodiversity [1] , ecology is in the midst of a lively debate on the effect of species loss or introduction on food web stability [2 , 3] .", "In food webs , complexity arises from combining a large number of species ( the nodes ) and a large number of relations between...	[ "In food webs , many interacting species coexist despite the restrictions imposed by the competitive exclusion principle and apparent competition .", "For the generalized Lotka-Volterra equations , sustainable coexistence necessitates nonzero determinant of the interaction matrix .", "Here we show that this req...	[ "Human impact currently induces rapid reductions in global biodiversity .", "Assessing the consequences of such modifications requires that ecological science better understand the conditions under which the species in a community can coexist and when not .", "Fundamentally , two species can not coexist indefin...	2016
[ "Introduction", "Materials and methods", "Results", "Discussion" ]	[ "antimicrobials", "cell physiology", "medicine and health sciences", "oxidative stress", "drugs", "microbiology", "antifungals", "cell metabolism", "parasitic protozoans", "metabolomics", "protozoans", "leishmania", "pharmacology", "drug metabolism", "lipids", "antimicrobial resistance...	Sterol 14α-demethylase mutation leads to amphotericin B resistance in Leishmania mexicana	journal.pntd.0005649	null	[ [ "The leishmaniases are a complex of diseases caused by parasitic protozoa of the genus Leishmania which are transmitted between people via the bite of an infected sandfly [1] .", "The specific disease caused by the parasites depends upon which Leishmania species is responsible and ranges from a self-limit...	[ "Amphotericin B has emerged as the therapy of choice for use against the leishmaniases .", "Administration of the drug in its liposomal formulation as a single injection is being promoted in a campaign to bring the leishmaniases under control .", "Understanding the risks and mechanisms of resistance is therefor...	[ "Antimicrobial resistance threatens to reverse many of the great strides made against pathogens responsible for disease .", "Understanding the molecular processes underlying resistance is crucial to quantifying and tackling the problem .", "Here we select resistance in Leishmania parasites to amphotericin B , a...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Infectious Prions Accumulate to High Levels in Non Proliferative C2C12 Myotubes	journal.ppat.1003755	null	[ [ "Prions are the etiological agents responsible for the transmissible spongiform encephalopathies .", "These neurodegenerative diseases affect mammals , are inevitably fatal , and are always associated with the accumulation of a specific post-translationally modified isoform of a normal host glycoprotein ,...	[ "Prion diseases are driven by the strain-specific , template-dependent transconformation of the normal cellular prion protein ( PrPC ) into a disease specific isoform PrPSc .", "Cell culture models of prion infection generally use replicating cells resulting in lower levels of prion accumulation compared to anima...	[ "This manuscript describes the generation of a new cell culture system to study the replication of infectious prions .", "While numerous cell lines exist that can replicate prions , these systems are usually based upon proliferating cells .", "As mammalian cell cultures double approximately every day , prions e...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "molecular biology/dna repair", "cell biology/cell growth and division", "genetics and genomics/chromosome biology" ]	Alternative-NHEJ Is a Mechanistically Distinct Pathway of Mammalian Chromosome Break Repair	journal.pgen.1000110	null	[ [ "Faithful repair of DNA damage is essential to suppress genetic instability and tumorigenesis .", "Conversely , the efficacy of cancer therapies that utilize DNA damaging agents is likely limited by the ability of cancer cells to repair such damage .", "One form of DNA damage that is prone to causing ...	[ "Characterizing the functional overlap and mutagenic potential of different pathways of chromosomal double-strand break ( DSB ) repair is important to understand how mutations arise during cancer development and treatment .", "To this end , we have compared the role of individual factors in three different pathwa...	[ "Changes to the sequence of DNA , or mutations , can disrupt cellular growth control genes , which can lead to cancer development .", "Such mutations likely arise from damage to DNA that is repaired in a way that fails to restore the original sequence .", "One type of DNA damage is a chromosomal double-strand b...	2008
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "immune cells", "immune activation", "immunity to infections", "immunology", "microbiology", "host-pathogen interaction", "carbohydrates", "immunochemistry", "bacterial pathogens", "immune system proteins", "inflammation", "proteins", "medical microbiology", "microbial pathogens", "biolo...	The Lipopolysaccharide from Capnocytophaga canimorsus Reveals an Unexpected Role of the Core-Oligosaccharide in MD-2 Binding	journal.ppat.1002667	null	[ [ "Capnocytophaga canimorsus , a usual member of dog's mouths flora [1] was discovered in 1976 [2] in patients who underwent dramatic infections after having been bitten , scratched or simply licked by a dog .", "The most common syndrome is sepsis , sometimes accompanied by peripheral intravascular coagulat...	[ "Capnocytophaga canimorsus is a usual member of dog's mouths flora that causes rare but dramatic human infections after dog bites .", "We determined the structure of C . canimorsus lipid A . The main features are that it is penta-acylated and composed of a “hybrid backbone” lacking the 4′ phosphate and having a 1...	[ "Capnocytophaga canimorsus , a commensal bacterium in dog's mouths , causes rare but dramatic infections in humans that have been bitten by dogs .", "The disease often begins with mild symptoms but progresses to severe septicemia .", "The lipopolysaccharide ( LPS ) , composed of lipid A , core and O-antigen , i...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "systems biology", "biochemistry", "biochemical simulations", "computer science", "nitrogen metabolism", "computer modeling", "theoretical biology", "metabolic pathways", "biology", "computational biology", "computerized simulations", "metabolism", "genetics and genomics" ]	Functional Modules, Structural Topology, and Optimal Activity in Metabolic Networks	journal.pcbi.1002720	null	[ [ "With the advent of bioinformatics and high-throughput technologies , plentiful sources of information stored in databases are now available to help unveil how a variety of biological entities interact among each other and to elucidate how these interacting networks support phenotypic behaviors in microorgani...	[ "Modular organization in biological networks has been suggested as a natural mechanism by which a cell coordinates its metabolic strategies for evolving and responding to environmental perturbations .", "To understand how this occurs , there is a need for developing computational schemes that contribute to integr...	[ "Biological networks are an inherent concept in systems biology that is useful in elucidating how biological entities—as metabolites or proteins—work together in supporting specific phenotypes in microorganisms .", "Notably , topological analyses carried out over these networks have shown that modular organizatio...	2012
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "biology and life sciences", "veterinary science", "medicine and health sciences" ]	Enhanced Protective Efficacy of Nonpathogenic Recombinant Leishmania tarentolae Expressing Cysteine Proteinases Combined with a Sand Fly Salivary Antigen	journal.pntd.0002751	null	[ [ "Leishmaniasis is one of the greatest health challenges in nearly 98 countries , contributing to 2 million new clinical cases per year in tropical and subtropical regions of the globe [1] .", "The disease is transmitted by sandflies and is manifested in several clinical forms , mainly cutaneous leishmania...	[ "Novel vaccination approaches are needed to prevent leishmaniasis .", "Live attenuated vaccines are the gold standard for protection against intracellular pathogens such as Leishmania and there have been new developments in this field .", "The nonpathogenic to humans lizard protozoan parasite , Leishmania ( L )...	[ "More than 98 countries are reported as endemic for leishmaniasis , a vector-borne disease transmitted by sand flies .", "Drug-resistant forms have emerged and there is an increased need to develop advanced preventive strategies .", "Live attenuated vaccines are the gold standard for protection against intracel...	2014
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine", "drugs and devices", "microbiology", "parasitology", "parasite physiology", "pharmacology", "drug metabolism", "gene expression", "biology", "molecular biology", "pharmacokinetics", "microarrays", "computational biology", "molecular cell biology" ]	Transcriptional Responses of In Vivo Praziquantel Exposure in Schistosomes Identifies a Functional Role for Calcium Signalling Pathway Member CamKII	journal.ppat.1003254	null	[ [ "At least 200 million people are afflicted by schistosomiasis [1] , where clinical symptoms associated with the disease range from fever , headache and lethargy , to severe fibro-obstructive pathological changes , portal hypertension , ascites and hepatosplenomegaly , with complications that are frequently fa...	[ "Treatment for clinical schistosomiasis has relied centrally on the broad spectrum anthelmintic praziquantel; however , there is limited information on its mode of action or the molecular response of the parasite .", "This paper presents a transcriptional and functional approach to defining the molecular response...	[ "Schistosome infected mice were treated orally with a single sub-lethal dose of the anthelmintic praziquantel .", "Parasites were subsequently isolated 0 . 5–24 hours later and analysed by gene expression microarray .", "The transcriptional pattern was influenced by the sex of the parasite .", "Males up-regul...	2013
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "medicine and health sciences", "toxoplasma gondii", "geographical locations", "parasitic diseases", "parasitic protozoans", "ethnicities", "protozoans", "toxoplasma", "molecular biology techniques", "research and analysis methods", "infectious diseases", "artificial gene amplification and ext...	Performance Testing of PCR Assay in Blood Samples for the Diagnosis of Toxoplasmic Encephalitis in AIDS Patients from the French Departments of America and Genetic Diversity of Toxoplasma gondii: A Prospective and Multicentric Study	journal.pntd.0004790	null	[ [ "The protozoan Toxoplasma gondii is a cosmopolitan parasite that virtually infects all warm-blooded animals , including humans who become infected postnatally by ingesting tissue cysts from undercooked meat , consuming food contaminated with oocysts , or by accidentally ingesting oocysts from the environment ...	[ "Toxoplasmic encephalitis in patients with AIDS is a life-threatening disease mostly due to reactivation of Toxoplasma gondii cysts in the brain .", "The main objective of this study was to evaluate the performance of real-time PCR assay in peripheral blood samples for the diagnosis of toxoplasmic encephalitis in...	[ "Diagnosis of toxoplasmic encephalitis ( TE ) in patients with AIDS is not straightforward because clinicians rely initially on an empiric diagnosis based on clinical and radiographic improvement to specific anti-Toxoplasma gondii therapy .", "There is therefore a need for biological tools to improve the diagnosi...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biotechnology", "neuroscience" ]	The foxa2 Gene Controls the Birth and Spontaneous Degeneration of Dopamine Neurons in Old Age	journal.pbio.0050325	The connection between development and neurodegeneration is emphasized via a new mouse knockout of a transcription factor that is critical for dopamine neuron specification, which produces a late-onset, asymmetric degenerative condition in a manner very similar to human Parkinson disease.	[ [ "Midbrain dopamine neurons play important roles in motor control , reward , addiction , attention , and cognition [1 , 2] .", "A progressive loss of dopamine neurons is a defining feature of Parkinson disease .", "This disease will cause increased hardship in many countries , as 30% of the population ...	[ "Parkinson disease affects more than 1% of the population over 60 y old .", "The dominant models for Parkinson disease are based on the use of chemical toxins to kill dopamine neurons , but do not address the risk factors that normally increase with age .", "Forkhead transcription factors are critical regulator...	[ "The restoration of dopamine neurons is a major focus of stem cell biology and regenerative medicine .", "The gradual loss of these neurons is a hallmark of Parkinson disease .", "Dopamine neurons in the midbrain convey important sensory and motor functions to the forebrain .", "We show that the transcription...	2007
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genetics", "biology", "genetics of disease", "genetics and genomics" ]	Trans-Ethnic Fine-Mapping of Lipid Loci Identifies Population-Specific Signals and Allelic Heterogeneity That Increases the Trait Variance Explained	journal.pgen.1003379	null	[ [ "Genome-wide association studies ( GWAS ) have identified many common genetic variants associated with human diseases and complex traits ( www . genome . gov/gwastudies ) , including ∼100 loci associated with triglycerides ( TG ) , high-density lipoprotein cholesterol ( HDL-C ) , low-density lipoprotein chole...	[ "Genome-wide association studies ( GWAS ) have identified ∼100 loci associated with blood lipid levels , but much of the trait heritability remains unexplained , and at most loci the identities of the trait-influencing variants remain unknown .", "We conducted a trans-ethnic fine-mapping study at 18 , 22 , and 18...	[ "Lipid traits are heritable , but many of the DNA variants that influence lipid levels remain unknown .", "In a genomic region , more than one variant may affect gene expression or function , and the frequencies of these variants can differ across populations .", "Genotyping densely spaced variants in individua...	2013
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "medicine and health sciences", "methods and resources", "chemical compounds", "enzymes", "enzymology", "organic compounds", "fungi", "model organisms", "methylation", "nitriles", "experimental organism systems", "amino acids", "epigenetics", "dna", "pharmacology", "chromatin", "dna ...	Coupling S-adenosylmethionine–dependent methylation to growth: Design and uses	journal.pbio.2007050	null	[ [ "Methylation is the transfer of a methyl group from one molecule to another .", "Its importance in gaining bioactivity and acquiring bioavailability of drugs has been recognized by chemists for some time [1] .", "Chemical methylation ordinarily utilizes noxious reagents and generates toxic waste and o...	[ "We present a selection design that couples S-adenosylmethionine–dependent methylation to growth .", "We demonstrate its use in improving the enzyme activities of not only N-type and O-type methyltransferases by 2-fold but also an acetyltransferase of another enzyme category when linked to a methylation pathway i...	[ "Many important biological processes require methylation , e . g . , DNA methylation and synthesis of flavoring compounds , neurotransmitters , and antibiotics .", "Most methylation reactions in cells are catalyzed by S-adenosylmethionine ( SAM ) –dependent methyltransferases ( Mtases ) using SAM as a methyl dono...	2019
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	GSK3β-Dzip1-Rab8 Cascade Regulates Ciliogenesis after Mitosis	journal.pbio.1002129	The asymmetric assembly of a new primary cilium in one of two daughter cells after mitosis is regulated by a cascade involving GSK3β, Dzip1, and Rab8.	[ [ "The primary cilium is an antenna-like organelle projecting from the apical surface of most vertebrate cells and plays pivotal roles in mediating signal transduction for the cell and regulating the balance between cell proliferation and differentiation [1–4] .", "It consists of a basal body , a microtubul...	[ "The primary cilium , which disassembles before mitotic entry and reassembles after mitosis , organizes many signal transduction pathways that are crucial for cell life and individual development .", "However , how ciliogenesis is regulated during the cell cycle remains largely unknown .", "Here we show that GS...	[ "The primary cilium is an antenna-like organelle that projects out from the surface of cells and is present in almost all vertebrate cells , playing crucial roles in many cellular processes , including chemical sensation , signal transduction , and control of cell growth .", "The primary cilium assembles via a dy...	2015
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "cell binding", "cell physiology", "invertebrates", "chemical characterization", "chemical compounds", "cloning", "carbohydrates", "animals", "notch signaling", "organic compounds", "animal models", "xylose", "developmental biology", "drosophila melanogaster", "model organisms", "exper...	Xylosylation of the Notch receptor preserves the balance between its activation by trans-Delta and inhibition by cis-ligands in Drosophila	journal.pgen.1006723	null	[ [ "Notch signaling is a juxtacrine signaling pathway broadly used during animal development and tissue homeostasis [1] .", "Both Notch and its ligands are type I transmembrane proteins containing multiple epidermal growth factor-like ( EGF ) repeats , which are involved in Notch-ligand interactions and are ...	[ "The Drosophila glucoside xylosyltransferase Shams xylosylates Notch and inhibits Notch signaling in specific contexts including wing vein development .", "However , the molecular mechanisms underlying context-specificity of the shams phenotype is not known .", "Considering the role of Delta-Notch signaling in ...	[ "One of the key mechanisms used by neighboring cells to communicate with each other in animals is signaling through an evolutionarily conserved receptor family called Notch .", "Binding of Notch to ligands of the Delta/DLL and Serrate/JAG families from neighboring cells leads to activation of the signaling pathwa...	2017
[ "Introduction", "Results", "Discussion", "Methods" ]	[]	MreB-Dependent Inhibition of Cell Elongation during the Escape from Competence in Bacillus subtilis	journal.pgen.1005299	null	[ [ "In response to nutritional deprivation and high population density , the rod-shaped model Gram-positive bacterium Bacillus subtilis enters stationary phase and develops diverse environmental adaptations , namely competence for genetic transformation , sporulation , cannibalism or biofilm formation [1] .", ...	[ "During bacterial exponential growth , the morphogenetic actin-like MreB proteins form membrane-associated assemblies that move processively following trajectories perpendicular to the long axis of the cell .", "Such MreB structures are thought to scaffold and restrict the movement of peptidoglycan synthesizing m...	[ "In bacterial cells , like in their eukaryotic counterparts , precise spatiotemporal localization of proteins is critical for their cellular function .", "This study shows that the expression and the localization of the bacterial actin-like MreB protein are growth phase-dependent .", "During exponential growth ...	2015
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "medicine and health sciences", "functional genomics", "pathology and laboratory medicine", "gene regulation", "pathogens", "rna extraction", "microbiology", "dna transcription", "viruses", "dna viruses", "extraction techniques", "herpesviruses", "research and analysis methods", "small int...	NLRX1 negatively modulates type I IFN to facilitate KSHV reactivation from latency	journal.ppat.1006350	null	[ [ "Kaposi’s sarcoma-associated herpesvirus ( KSHV ) , also known as human herpesvirus 8 ( HHV-8 ) , is a linear double-stranded DNA virus .", "It is causally linked with Kaposi’s sarcoma ( KS ) , primary effusion lymphoma ( PEL ) and multicentric Castleman’s disease ( MCD ) [1 , 2] .", "In the majority ...	[ "Kaposi’s sarcoma-associated herpesvirus ( KSHV ) is a herpesvirus that is linked to Kaposi’s sarcoma ( KS ) , primary effusion lymphoma ( PEL ) and multicentric Castleman’s disease ( MCD ) .", "KSHV establishes persistent latent infection in the human host .", "KSHV undergoes periods of spontaneous reactivatio...	[ "Kaposi’s sarcoma-associated herpesvirus ( KSHV ) is linked to a number of different human cancers , including Kaposi’s sarcoma ( KS ) , primary effusion lymphoma ( PEL ) and multicentric Castleman’s disease ( MCD ) .", "KSHV predominantly establishes life-long latency in the infected host .", "Lytic reactivati...	2017
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "genome-wide association studies", "medicine and health sciences", "immunology", "tropical diseases", "parasitic diseases", "parasitic protozoans", "anemia", "genetic mapping", "clinical medicine", "protozoans", "genome analysis", "molecular genetics", "major histocompatibility complex", "...	Novel genetic polymorphisms associated with severe malaria and under selective pressure in North-eastern Tanzania	journal.pgen.1007172	null	[ [ "Sub-Saharan Africa bears a disproportionately high share of the global Plasmodium falciparum malaria burden , with 90% of the estimated 212 million annual cases and 92% of 429 , 000 annual deaths , mostly in children under five years of age [1] .", "Whilst the majority of cases of Plasmodium falciparum i...	[ "Significant selection pressure has been exerted on the genomes of human populations exposed to Plasmodium falciparum infection , resulting in the acquisition of mechanisms of resistance against severe malarial disease .", "Many host genetic factors , including sickle cell trait , have been associated with reduce...	[ "Malaria , caused by Plasmodium falciparum parasites , is a major cause of mortality and morbidity in endemic countries of sub-Saharan Africa , including Tanzania .", "Some gene mutations in the human genome , including sickle cell trait , have been associated with reduced risk of developing severe malaria , and ...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "plant anatomy", "stem anatomy", "ecology and environmental sciences", "guard cells", "chemical compounds", "atmospheric science", "plant cell biology", "brassica", "ions", "anions", "computational biology", "stomata", "plant science", "model organisms", "genome analysis", "plants", ...	Natural Variation in Arabidopsis Cvi-0 Accession Reveals an Important Role of MPK12 in Guard Cell CO2 Signaling	journal.pbio.2000322	null	[ [ "Human activities have increased the concentrations of CO2 and harmful air pollutants such as ozone in the troposphere .", "During the last 200 y , the CO2 concentration has increased from 280 to 400 ppm , and it is predicted to double relative to the preindustrial level by 2050 [1] .", "Elevated CO2 ...	[ "Plant gas exchange is regulated by guard cells that form stomatal pores .", "Stomatal adjustments are crucial for plant survival; they regulate uptake of CO2 for photosynthesis , loss of water , and entrance of air pollutants such as ozone .", "We mapped ozone hypersensitivity , more open stomata , and stomata...	[ "Human activities have increased the concentrations of CO2 and harmful air pollutants such as ozone in the troposphere .", "These changes can have detrimental consequences for agricultural productivity .", "Guard cells , which form stomatal pores on leaves , regulate plant gas exchange .", "To maintain photos...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "bacteriology", "medicine and health sciences", "gut bacteria", "pathology and laboratory medicine", "cell cycle and cell division", "pathogens", "cell processes", "bacillus", "microbiology", "bacterial sporulation", "organisms", "prokaryotic models", "model organisms", "molecular biology ...	A Recombination Directionality Factor Controls the Cell Type-Specific Activation of σK and the Fidelity of Spore Development in Clostridium difficile	journal.pgen.1006312	null	[ [ "Endosporulation is an ancient bacterial cell differentiation process allowing the conversion of a vegetative cell into a mature spore through a series of morphological steps [1 , 2] .", "Many bacilli , clostridia and related organisms form bacterial spores .", "The spores have the ability to withstan...	[ "The strict anaerobe Clostridium difficile is the most common cause of nosocomial diarrhea , and the oxygen-resistant spores that it forms have a central role in the infectious cycle .", "The late stages of sporulation require the mother cell regulatory protein σK .", "In Bacillus subtilis , the onset of σK act...	[ "Clostridium difficile , a major cause of antibiotic-associated diarrhea , produces resistant spores that facilitate its persistence in the environment including hospitals .", "C . difficile transmission is mediated by contamination of gut by spores .", "Understanding how this complex developmental process is r...	2016
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "medicine", "public health and epidemiology", "giardiasis", "infectious disease epidemiology", "parasitic diseases", "nutrition", "global health", "neglected tropical diseases", "malnutrition", "infectious diseases", "epidemiology", "gastrointestinal infections", "public health", "socioeco...	High Prevalence of Giardia duodenalis Assemblage B Infection and Association with Underweight in Rwandan Children	journal.pntd.0001677	null	[ [ "Giardia duodenalis ( syn . G . intestinalis , G . lamblia ) is among the most common intestinal protozoa and is the most frequent parasitic agent of gastroenteritis worldwide .", "The regional prevalences of infection differ enormously and may be >30% in children in the African and the Eastern Mediterran...	[ "Giardia duodenalis is highly endemic in East Africa but its effects on child health , particularly of submicroscopic infections , i . e . , those below the threshold of microscopy , and of genetic subgroups ( assemblages ) , are not well understood .", "We aimed at addressing these questions and at examining epi...	[ "Giardia duodenalis is a protozoan parasite causing gastroenteritis .", "Although the parasite occurs worldwide , its regional prevalence varies considerably .", "Using PCR as a highly sensitive molecular diagnostic tool , we detected G . duodenalis in 60% of 583 children younger than five years in southern Rwa...	2012
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "invertebrates", "medicine and health sciences", "reproductive system", "gonads", "chromosome structure and function", "caenorhabditis", "animals", "germ cells", "animal models", "oocytes", "caenorhabditis elegans", "model organisms", "experimental organism systems", "epigenetics", "chro...	C. elegans ZHP-4 is required at multiple distinct steps in the formation of crossovers and their transition to segregation competent chiasmata	journal.pgen.1007776	null	[ [ "During the two specialized divisions of meiosis , a single round of DNA replication is followed by two rounds of segregation that ultimately produce gametes with half the parental number of chromosomes .", "Central to chromosome segregation accuracy is the formation of chiasmata between paired homologous...	[ "Correct segregation of meiotic chromosomes depends on DNA crossovers ( COs ) between homologs that culminate into visible physical linkages called chiasmata .", "COs emerge from a larger population of joint molecules ( JM ) , the remainder of which are repaired as noncrossovers ( NCOs ) to restore genomic integr...	[ "The creation of a viable individual from the fusion of egg and sperm requires that they each contain the correct number of chromosomes .", "This is ensured through the meiotic divisions , which initially fasten identical chromosomes through DNA linkages that hold them together until the cell is ready to separate...	2018
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "chemical neutralization", "cell binding", "cell physiology", "sequencing techniques", "medicine and health sciences", "chemical characterization", "immune physiology", "enzyme-linked immunoassays", "pathology and laboratory medicine", "hepacivirus", "pathogens", "immunology", "biological cu...	Extra-epitopic hepatitis C virus polymorphisms confer resistance to broadly neutralizing antibodies by modulating binding to scavenger receptor B1	journal.ppat.1006235	null	[ [ "Hepatitis C virus ( HCV ) infects over 170 million people worldwide [1] and kills more people in the United States annually than HIV [2] .", "Appalachian regions of the United States saw a >350% increase in the number of new HCV infections from 2009–2012 [3] and recent outbreaks in the United States have...	[ "Broadly-neutralizing monoclonal antibodies ( bNAbs ) may guide vaccine development for highly variable viruses including hepatitis C virus ( HCV ) , since they target conserved viral epitopes that could serve as vaccine antigens .", "However , HCV resistance to bNAbs could reduce the efficacy of a vaccine .", ...	[ "Generation of an immune response that is protective against a wide variety of naturally occurring isolates is necessary for vaccines against highly variable viruses like hepatitis C virus ( HCV ) .", "Two broadly neutralizing human monoclonal antibodies , HC33 . 4 and AR4A , neutralize multiple highly divergent ...	2017
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "death rates", "cell death", "body weight", "medicine and health sciences", "enzyme-linked immunoassays", "immune physiology", "pathology and laboratory medicine", "enzymes", "pathogens", "cell processes", "immunology", "microbiology", "enzymology", "dismutases", "orthomyxoviruses", "e...	Prion protein protects mice from lethal infection with influenza A viruses	journal.ppat.1007049	null	[ [ "The normal cellular prion protein , designated PrPC , is a membrane glycoprotein tethered to the outer cell membrane via a glycosylphosphatidylinositol anchor moiety and expressed most abundantly in brains , particularly by neurons , and to a lesser extent in non-neuronal tissues including hearts , kidneys ,...	[ "The cellular prion protein , designated PrPC , is a membrane glycoprotein expressed abundantly in brains and to a lesser extent in other tissues .", "Conformational conversion of PrPC into the amyloidogenic isoform is a key pathogenic event in prion diseases .", "However , the physiological functions of PrPC r...	[ "Influenza A virus ( IAV ) is an enveloped , negative sense , single-stranded RNA virus , causing seasonal epidemic outbreaks of influenza .", "Anti-influenza agents targeting viral molecules , such as neuraminidase inhibitors , are currently available .", "However , these agents have accelerated emergence of m...	2018
[ "Introduction", "Results", "Discussion", "Conclusion", "Materials and methods" ]	[ "phosphorylation", "nuclear staining", "immunofluorescence staining", "molecular probe techniques", "gene regulation", "immunoblotting", "immunoprecipitation", "molecular biology techniques", "research and analysis methods", "specimen preparation and treatment", "staining", "small interfering ...	Novel function of HATs and HDACs in homologous recombination through acetylation of human RAD52 at double-strand break sites	journal.pgen.1007277	null	[ [ "Ionizing radiation ( IR ) induces deleterious DNA lesions , such as DNA double-strand breaks ( DSB ) .", "In response to DSBs , DNA damage response ( DDR ) signaling is induced .", "Ataxia telangiectasia mutated ( ATM ) protein kinase is one of the central players for phosphorylation-mediated DDR sig...	[ "The p300 and CBP histone acetyltransferases are recruited to DNA double-strand break ( DSB ) sites where they induce histone acetylation , thereby influencing the chromatin structure and DNA repair process .", "Whether p300/CBP at DSB sites also acetylate non-histone proteins , and how their acetylation affects ...	[ "DNA double strand breaks ( DSBs ) are the most dangerous type of DNA damage in cells .", "Homologous recombination ( HR ) is a DSB repair system in which a central player , RAD51 , functions with several proteins , including RAD52 .", "DSBs activate the DNA damage response signaling network , in which the atax...	2018
[ "Introduction", "Methods", "Results", "Discussion" ]	[]	Soil-Transmitted Helminths in Southwestern China: A Cross-Sectional Study of Links to Cognitive Ability, Nutrition, and School Performance among Children	journal.pntd.0003877	null	[ [ "A recent Cochrane Report [1] has raised questions about the nature of the relationship between infection with soil-transmitted helminths ( STHs ) and children’s healthy development .", "In a meta-analysis of 42 papers , the authors of the report found that there was no clear , consistent relationship bet...	[ "Empirical evidence suggests that the prevalence of soil-transmitted helminth ( STH ) infections in remote and poor rural areas is still high among children , the most vulnerable to infection .", "There is concern that STH infections may detrimentally affect children’s healthy development , including their cognit...	[ "Empirical evidence suggests that the prevalence of soil-transmitted helminth ( STH ) infections in remote and poor rural areas is still high among children , the most vulnerable to infection .", "There is concern that STH infections may detrimentally affect children’s healthy development , including their cognit...	2015
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "taxonomy", "biogeography", "organismal evolution", "medicine and health sciences", "ecology and environmental sciences", "pathology and laboratory medicine", "influenza", "pathogens", "population genetics", "microbiology", "orthomyxoviruses", "viruses", "phylogenetics", "data management",...	Genome-wide evolutionary dynamics of influenza B viruses on a global scale	journal.ppat.1006749	null	[ [ "Influenza viruses cause significant morbidity and mortality worldwide and present major challenges for public health .", "Two types of influenza virus circulate widely in human populations: influenza A and influenza B viruses .", "While rates of hospitalization and mortality attributed to influenza B...	[ "The global-scale epidemiology and genome-wide evolutionary dynamics of influenza B remain poorly understood compared with influenza A viruses .", "We compiled a spatio-temporally comprehensive dataset of influenza B viruses , comprising over 2 , 500 genomes sampled worldwide between 1987 and 2015 , including 382...	[ "Influenza B viruses cause roughly one third of the global influenza disease burden .", "However , many important questions regarding the global-scale molecular epidemiology and evolutionary dynamics of influenza B virus have yet to be comprehensively addressed compared to influenza A virus .", "This is in part...	2017
[ "Introduction", "Materials and methods", "Results", "Discussion" ]	[ "biogeography", "taxonomy", "united states", "medicine and health sciences", "ecology and environmental sciences", "pathology and laboratory medicine", "togaviruses", "pathogens", "population genetics", "geographical locations", "microbiology", "alphaviruses", "viruses", "north america", ...	Differing epidemiological dynamics of Chikungunya virus in the Americas during the 2014-2015 epidemic	journal.pntd.0006670	null	[ [ "Chikungunya virus ( CHIKV ) belongs to the Alphavirus genus in the Togaviridae family and is an arthropod-borne virus spread by Aedes mosquitoes .", "CHIKV has a positive-sense single-stranded RNA genome that is 11 . 8 kb in length and encodes both a nonstructural and a structural polyprotein that are se...	[ "Chikungunya virus ( CHIKV ) has been detected sporadically since the 1950s and includes three distinct co-circulating genotypes .", "In late 2013 , the Asian genotype of CHIKV was responsible for the Caribbean outbreak ( CO ) that rapidly became an epidemic throughout the Americas .", "There is a limited under...	[ "Chikungunya is an arboviral disease that causes fever and acute viral febrile illness , which may be followed by months or years of debilitating joint pain in humans .", "There are currently no vaccines or anti-viral drugs to prevent or treat chikungunya virus ( CHIKV ) infection .", "In late 2013 , CHIKV was ...	2018
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "blood cells", "medicine and health sciences", "clinical laboratory sciences", "immune cells", "respiratory infections", "pathology and laboratory medicine", "immunology", "tropical diseases", "geographical locations", "biomarkers", "pulmonology", "bacterial diseases", "signs and symptoms", ...	A Diagnostic Scoring Model for Leptospirosis in Resource Limited Settings	journal.pntd.0004513	null	[ [ "Leptospirosis is a zoonotic infection caused by spirochaetes of the genus Leptospira , with humans being affected as incidental hosts .", "Infection occurs when water or soil contaminated with urine of infected animals ( commonly rodents ) comes into contact with abraded human skin or mucous membrane .",...	[ "Leptospirosis is a zoonotic infection with significant morbidity and mortality .", "The clinical presentation of leptospirosis is known to mimic the clinical profile of other prevalent tropical fevers .", "Laboratory confirmation of leptospirosis is based on the reference standard microscopic agglutination tes...	[ "Leptospirosis is a bacterial disease which is common in tropical countries , and spreads via contaminated rat urine .", "It has a potential for mortality and can cause failure of multiple body systems .", "The features of the disease mimics several other tropical diseases prevalent in the region .", "The mod...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genetics and genomics/gene expression", "microbiology/microbial evolution and genomics", "genetics and genomics/gene function", "microbiology", "molecular biology" ]	The Transcriptional Regulator Rok Binds A+T-Rich DNA and Is Involved in Repression of a Mobile Genetic Element in Bacillus subtilis	journal.pgen.1001207	null	[ [ "In bacteria , horizontal gene transfer typically occurs through natural transformation , conjugation , and transduction and contributes to rapid evolution and the acquisition of new traits [1] , [2] .", "For example , genes needed for pathogenesis , symbiosis , resistance to antibiotics , and metabolism ...	[ "The rok gene of Bacillus subtilis was identified as a negative regulator of competence development .", "It also controls expression of several genes not related to competence .", "We found that Rok binds to extended regions of the B . subtilis genome .", "These regions are characterized by a high A+T content...	[ "There are several mechanisms by which bacteria acquire exogenous DNA .", "Sometimes this genetic material is advantageous for bacterial cells , for example , by making them resistant to antibiotics .", "Other times , foreign DNA has genes that are deleterious to the new host .", "Bacteria have mechanisms for...	2010

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