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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", "Methods", "Results", "Discussion" ]	[ "blood cells", "mycobacterium leprae", "medicine and health sciences", "immune cells", "immunology", "tropical diseases", "geographical locations", "genetic mapping", "bacterial diseases", "neglected tropical diseases", "infectious disease control", "bacteria", "infectious diseases", "whit...	The impact of KIR/HLA genes on the risk of developing multibacillary leprosy	journal.pntd.0007696	null	[ [ "Natural killer ( NK ) cells are crucial components of the innate immune system and provide defence against viral and microbial infections , cancer and other forms of cell stress [1] .", "Until recently , NK cells have been described only as killers because of their cytotoxic function in damaged cells .",...	[ "Killer-cell immunoglobulin-like receptors ( KIRs ) are a group of regulatory molecules able to activate or inhibit natural killer cells upon interaction with human leukocyte antigen ( HLA ) class I molecules .", "Combinations of KIR and HLA may contribute to the occurrence of different immunological and clinical...	[ "Leprosy is a neglected disease with the highest worldwide prevalence , and remains a public health problem in Brazil .", "The innate immune mechanisms are determinants in the management of leprosy and its different clinical manifestations .", "Accordingly , genetic association study provides information about ...	2019
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "virology/mechanisms of resistance and susceptibility, including host genetics", "infectious diseases/hiv infection and aids" ]	Reassessing the Role of APOBEC3G in Human Immunodeficiency Virus Type 1 Infection of Quiescent CD4+ T-Cells	journal.ppat.1000342	null	[ [ "Nonproliferating quiescent CD4+ T-cells are resistant to the infection with human immunodeficiency virus type 1 ( HIV-1 ) unless they are activated by mitogenic stimulation [1]–[5] or by cytokine stimulation [6] .", "Other studies demonstrated that quiescent T-cells at the stage of G0 or G1a of the cell ...	[ "HIV-1 is restricted for infection of primary quiescent T-cells .", "After viral entry , reverse transcription is initiated but is not completed .", "Various hypotheses have been proposed for this cellular restriction including insufficient nucleotide pools and cellular factors , but none have been confirmed as...	[ "In 1990 , we demonstrated that unstimulated quiescent T-lymphocytes are resistant to HIV-1 infection .", "Viruses can get into the cell , and reverse transcription is started , but it is not completed .", "Various hypotheses have been proposed for this blockage including insufficient free nucleotides and inhib...	2009
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genetics", "plant genetics", "epigenetics", "biology", "dna modification", "crop genetics", "genetics and genomics" ]	Heritable Epigenetic Variation among Maize Inbreds	journal.pgen.1002372	null	[ [ "Much of the heritable variation within a species is a consequence of differences in the primary DNA sequence of different individuals .", "However , there is growing evidence for heritable variation in the absence of DNA sequence polymorphisms , termed epigenetic variation [1] .", "Cytosine methylati...	[ "Epigenetic variation describes heritable differences that are not attributable to changes in DNA sequence .", "There is the potential for pure epigenetic variation that occurs in the absence of any genetic change or for more complex situations that involve both genetic and epigenetic differences .", "Methylati...	[ "Heritable variation within a species provides the basis for natural and artificial selection .", "A substantial portion of heritable variation is based on alterations in DNA sequence among individuals and is termed genetic variation .", "There is also evidence for epigenetic variation , which refers to heritab...	2011
[ "Introduction", "Methods", "Results", "Discussion", "Strengths and limitations of the study" ]	[ "children", "medicine and health sciences", "pathology and laboratory medicine", "geographical locations", "tropical diseases", "uganda", "social sciences", "political aspects of health", "parasitic diseases", "political science", "age groups", "neglected tropical diseases", "governments", ...	"Those who died are the ones that are cured". Walking the political tightrope of Nodding Syndrome in northern Uganda: Emerging challenges for research and policy	journal.pntd.0007344	null	[ [ "Nodding Syndrome ( NS ) , a severely debilitating neurological syndrome mainly affecting children , is considered a “political” issue in Uganda , unlike other affected areas such as Tanzania [1] .", "This “politicization” of NS is the result of a long history of ethnic divisions [2] , which are tied up w...	[ "Nodding Syndrome was first reported from Tanzania in the 1960s but appeared as an epidemic in Northern Uganda in the 1990s during the LRA civil war .", "It is characterized by repetitive head nodding , often followed by other types of seizures , developmental retardation and growth faltering with onset occurring...	[ "Nodding Syndrome , a form of epilepsy that occurs in onchocerciasis-endemic areas has affected about 3000 children in Northern Uganda where the epidemic emerged at the time of the civil war .", "Although an association with onchocerciasis has been established , the disease etiology has not yet been identified ."...	2019
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "invertebrates", "medicine and health sciences", "rna interference", "pathology and laboratory medicine", "caenorhabditis", "pathogens", "messenger rna", "endoplasmic reticulum", "microbiology", "cell processes", "animals", "pseudomonas aeruginosa", "animal models", "physiological processe...	Mutations in Nonessential eIF3k and eIF3l Genes Confer Lifespan Extension and Enhanced Resistance to ER Stress in Caenorhabditis elegans	journal.pgen.1006326	null	[ [ "The genetic study of longevity of C . elegans has established how single mutations in conserved signaling pathways may have dramatic effects on animal lifespan [1 , 2] .", "In addition , reduction-of-function mutations or RNAi-mediated knockdown of genes encoding components required for mRNA translation ...	[ "The translation initiation factor eIF3 is a multi-subunit protein complex that coordinates the assembly of the 43S pre-initiation complex in eukaryotes .", "Prior studies have demonstrated that not all subunits of eIF3 are essential for the initiation of translation , suggesting that some subunits may serve regu...	[ "The translation initiation factor eIF3 is the largest and most complex of the eukaryotic initiation factors , comprising 13 subunits in metazoans , and this protein complex plays a critical role in scaffolding key interactions among multiple cofactors required for translation initiation .", "Both evolutionary an...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Dynamics of the Heat Stress Response of Ceramides with Different Fatty-Acyl Chain Lengths in Baker’s Yeast	journal.pcbi.1004373	null	[ [ "Ceramides form a class of sphingolipids with a lipid backbone and a fatty acyl head group .", "Distinct variants of ceramides result from different backbones and fatty acyl CoAs .", "For example , C16-dihydroceramide ( C16-DHC ) is a ceramide with a DHS backbone and a C16 fatty acyl CoA ( palmitoyl C...	[ "The article demonstrates that computational modeling has the capacity to convert metabolic snapshots , taken sequentially over time , into a description of cellular , dynamic strategies .", "The specific application is a detailed analysis of a set of actions with which Saccharomyces cerevisiae responds to heat s...	[ "The heat stress response in yeast is a model system for elucidating how cells organize and execute complex tasks .", "While a genomic response to heat is necessary , it is by itself too slow for immediate means of protecting the cell against damage .", "However , one observes changes in the physiology of the c...	2015
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "medicine and health sciences", "pathology and laboratory medicine", "statistics", "applied mathematics", "spatial epidemiology", "simulation and modeling", "algorithms", "endemic diseases", "mathematics", "research and analysis methods", "public and occupational health", "infectious diseases"...	Sounding the alarm: Defining thresholds to trigger a public health response to monkeypox	journal.pntd.0007034	null	[ [ "Nearly forty years after the successful eradication of smallpox , monkeypox virus continues to lurk in the tropical forests of Central and West Africa .", "Causing a smallpox-like illness , human monkeypox was first described in 1970 in the Democratic Republic of the Congo ( DRC ) , and is widely regarde...	[ "Endemic to the Democratic Republic of the Congo ( DRC ) , monkeypox is a zoonotic disease that causes smallpox-like illness in humans .", "Observed fluctuations in reported cases over time raises questions about when it is appropriate to mount a public health response , and what specific actions should be taken ...	[ "Most of the scientific literature about statistical thresholds for outbreak detection is biased toward large datasets that derive from wealthy countries .", "In the scientific community , it is acknowledged that even objectively determined statistical thresholds can produce varied results when applied to the sam...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biochemistry", "non-clinical medicine", "cell biology", "chemical biology" ]	Partial Restoration of Mutant Enzyme Homeostasis in Three Distinct Lysosomal Storage Disease Cell Lines by Altering Calcium Homeostasis	journal.pbio.0060026	By adapting the protein homeostasis network, altering calcium homeostasis can restore the cell's ability to fold and traffic proteins prone to misfolding, offering a new strategy to ameliorate loss-of-function diseases.	[ [ "Cells usually maintain a balance between protein synthesis , folding , trafficking , aggregation , and degradation—which is referred to as protein homeostasis—by using sensors and networks of pathways [1 , 2] .", "Human loss-of-function diseases are often the result of a disruption of normal protein home...	[ "A lysosomal storage disease ( LSD ) results from deficient lysosomal enzyme activity , thus the substrate of the mutant enzyme accumulates in the lysosome , leading to pathology .", "In many but not all LSDs , the clinically most important mutations compromise the cellular folding of the enzyme , subjecting it t...	[ "Lysosomes are organelles that contain more than 50 hydrolytic enzymes that break down macromolecules in a cell .", "A lysosomal storage disease results from deficient activity of one or more of these enzymes , leading to the accumulation of corresponding substrate ( s ) .", "Currently , lysosomal storage disea...	2008
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biochemistry", "agroecology", "ecology", "biology", "genomics", "evolutionary biology", "microbiology", "genetics and genomics", "agriculture" ]	Plant-Symbiotic Fungi as Chemical Engineers: Multi-Genome Analysis of the Clavicipitaceae Reveals Dynamics of Alkaloid Loci	journal.pgen.1003323	null	[ [ "Alkaloids play key roles in plant ecology by targeting the central and peripheral nervous systems of invertebrate and vertebrate animals , affecting their behavior , eliciting toxicoses , and reducing herbivory [1] .", "Alkaloids are very common in plants as well as certain plant-associated fungi , parti...	[ "The fungal family Clavicipitaceae includes plant symbionts and parasites that produce several psychoactive and bioprotective alkaloids .", "The family includes grass symbionts in the epichloae clade ( Epichloë and Neotyphodium species ) , which are extraordinarily diverse both in their host interactions and in t...	[ "The fungal family , Clavicipitaceae , includes “ergot” fungi that parasitize ears of cereals and have historically caused mass poisonings , as well as “epichloae , ” which are symbionts of grasses .", "Many epichloae are mutualistic symbionts , but some are pathogenic , and others have both mutualistic and patho...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "infectious diseases", "immunology", "plasmodium", "microbiology" ]	The Importance of Human FcγRI in Mediating Protection to Malaria	journal.ppat.0030072	null	[ [ "Malaria continues to kill approximately 2–3 million people each year [1] .", "The success of passive immunization in humans and animals suggests that immunoglobulin ( Ig ) -based therapies could be effective [2 , 3] .", "Manipulating antibody ( Ab ) genes allows the design of Ig with defined class an...	[ "The success of passive immunization suggests that antibody-based therapies will be effective at controlling malaria .", "We describe the development of fully human antibodies specific for Plasmodium falciparum by antibody repertoire cloning from phage display libraries generated from immune Gambian adults .", ...	[ "Malaria rivals HIV and tuberculosis as the world's most deadly infection killing a child every 30 seconds .", "Antibodies and their receptors ( Fc-receptors ) have been shown to be vital for the development of protective immunity , and as such they act as correlates of protection in studies aimed at defining the...	2007
[ "Introduction", "Results / Discussion", "Methods" ]	[ "medicine and health sciences", "neural networks", "brain", "random variables", "neuroscience", "covariance", "systems science", "mathematics", "discrete mathematics", "combinatorics", "neuronal tuning", "computer and information sciences", "musculoskeletal system", "animal cells", "moto...	Neural Population Dynamics during Reaching Are Better Explained by a Dynamical System than Representational Tuning	journal.pcbi.1005175	null	[ [ "Throughout the history of neuroscience research , the question of how motor cortex generates movements has been investigated deeply [1] .", "Yet , substantial and conflicting models have been proposed [2–7] .", "According to the representational view , motor cortex neurons encode abstract or high-lev...	[ "Recent models of movement generation in motor cortex have sought to explain neural activity not as a function of movement parameters , known as representational models , but as a dynamical system acting at the level of the population .", "Despite evidence supporting this framework , the evaluation of representat...	[ "The question of how the brain generates movement has been extensively studied , yet multiple competing models exist .", "Representational approaches relate the activity of single neurons to movement parameters such as velocity and position , approaches useful for the decoding of movement intentions , while the d...	2016
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "organismal evolution", "medicine and health sciences", "cell cycle and cell division", "cell processes", "reproductive physiology", "germ cells", "zygotes", "mutation", "oocytes", "mitochondria", "bioenergetics", "cellular structures and organelles", "gametogenesis", "animal cells", "so...	Selection for Mitochondrial Quality Drives Evolution of the Germline	journal.pbio.2000410	null	[ [ "In distinguishing between the germline and soma , Weismann argued that the division of labour enabled the specialization of cells in somatic tissues , ultimately permitting greater organismal complexity [1] .", "In contrast , germline cells alone retain the capacity to provide genetic information for fut...	[ "The origin of the germline–soma distinction is a fundamental unsolved question .", "Plants and basal metazoans do not have a germline but generate gametes from pluripotent stem cells in somatic tissues ( somatic gametogenesis ) .", "In contrast , most bilaterians sequester a dedicated germline early in develop...	[ "Mammalian germ cells ( eggs and sperm ) are immortal in the sense that they propagate successive generations .", "In contrast , somatic ( body ) cells do not persist to the next generation .", "Yet neither plants nor basal animals such as sponges and corals have a germline; they simply form gametes from stem c...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genetics and genomics/nuclear structure and function" ]	Actin-Related Protein Arp6 Influences H2A.Z-Dependent and -Independent Gene Expression and Links Ribosomal Protein Genes to Nuclear Pores	journal.pgen.1000910	null	[ [ "Genomic DNA is complexed with histones and non-histone proteins to form chromatin , which is organized into active and inactive domains within the interphase nucleus [1]–[3] .", "Histone tail modifications , chromatin compaction , and the subnuclear positioning of chromatin domains contribute epigenetic ...	[ "Actin-related proteins are ubiquitous components of chromatin remodelers and are conserved from yeast to man .", "We have examined the role of the budding yeast actin-related protein Arp6 in gene expression , both as a component of the SWR1 complex ( SWR-C ) and in its absence .", "We mapped Arp6 binding sites...	[ "Actin and the structurally similar actin-related proteins ( ARPs ) are major components of nucleosome remodeling complexes in the nucleus .", "Here we show that budding yeast Arp6 has functions independent of its catalytic chromatin remodeling partner , Swr1 .", "Arp6 binds to multiple promoters and subtelomer...	2010
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "respiratory medicine/respiratory infections", "microbiology/microbial evolution and genomics", "microbiology", "infectious diseases/respiratory infections", "infectious diseases/bacterial infections", "microbiology/microbial physiology and metabolism", "respiratory medicine/respiratory pediatrics", "...	Nutrient Availability as a Mechanism for Selection of Antibiotic Tolerant Pseudomonas aeruginosa within the CF Airway	journal.ppat.1000712	null	[ [ "Microbes are subjected to selection in host environments during the course of chronic infections [1] , [2] , [3] .", "The characteristics selected may have profound impacts on disease outcomes , particularly if they confer increased microbial fitness or resistance to therapy .", "One example of this ...	[ "Microbes are subjected to selective pressures during chronic infections of host tissues .", "Pseudomonas aeruginosa isolates with inactivating mutations in the transcriptional regulator LasR are frequently selected within the airways of people with cystic fibrosis ( CF ) , and infection with these isolates has b...	[ "Chronic infections are distinguished from many other infections in that they are difficult to eradicate with antibiotics .", "Thus , the microbes that cause chronic infections persist within host tissues for long periods despite our best treatment efforts .", "During the course of these chronic infections , th...	2010
[ "Introduction", "Results/Discussion", "Materials and Methods", "Supporting Information" ]	[ "mus (mouse)", "viruses", "in vitro", "virology" ]	Growth of H5N1 Influenza A Viruses in the Upper Respiratory Tracts of Mice	journal.ppat.0030133	null	[ [ "The first outbreak in humans caused by the highly pathogenic H5N1 influenza A virus was reported in Hong Kong in 1997 , and resulted in the deaths of six of 18 infected people [1–3] .", "This event demonstrated for the first time the direct transmission of a highly pathogenic avian influenza virus from b...	[ "Highly pathogenic avian H5N1 influenza A viruses have spread throughout Asia , Europe , and Africa , raising serious worldwide concern about their pandemic potential .", "Although more than 250 people have been infected with these viruses , with a consequent high rate of mortality , the molecular mechanisms resp...	[ "Highly pathogenic avian H5N1 influenza A viruses have spread around the world since 2003 , raising serious worldwide concern about their pandemic potential .", "Although efficient human-to-human transmission of this virus has not yet occurred , the potential of these viruses to acquire the ability is evident .",...	2007
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "blood cells", "innate immune system", "medicine and health sciences", "immune cells", "immune physiology", "cytokines", "pathology and laboratory medicine", "spleen", "immunology", "microbiology", "parasitic diseases", "parasitic protozoans", "protozoan life cycles", "developmental biolog...	Cathepsin B-Deficient Mice Resolve Leishmania major Inflammation Faster in a T Cell-Dependent Manner	journal.pntd.0004716	null	[ [ "A protective immune response against intracellular protozoan parasites of the genus Leishmania is characterized by the development of IFNγ-producing T cells .", "This supports macrophages in the induction of anti-leishmanial effector functions , such as production of nitric oxide [1 , 2] .", "IL-12 ,...	[ "A critical role for intracellular TLR9 has been described in recognition and host resistance to Leishmania parasites .", "As TLR9 requires endolysosomal proteolytic cleavage to achieve signaling functionality , we investigated the contribution of different proteases like asparagine endopeptidase ( AEP ) or cyste...	[ "Cutaneous forms of leishmaniasis are characterized by lesions that progress over months or years and that often leave permanent scars .", "Toll like receptors play an important role in the recognition and initiation of immune responses , and the intracellular TLR9 , a sensor of pathogen double-stranded DNA , pla...	2016
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "infectious diseases/neglected tropical diseases", "immunology/immunity to infections", "respiratory medicine/respiratory infections", "pathology/immunology" ]	Osteopontin Impairs Host Defense during Established Gram-Negative Sepsis Caused by Burkholderia pseudomallei (Melioidosis)	journal.pntd.0000806	null	[ [ "Melioidosis is an important cause of severe sepsis in Southeast Asia and Northern Australia caused by the aerobic gram-negative soil-dwelling bacillus Burkholderia ( B . ) pseudomallei [1] , [2] .", "Infection is thought to occur by cutaneous inoculation or inhalation .", "More than half of patients ...	[ "Melioidosis , caused by infection with Burkholderia ( B . ) pseudomallei , is a severe illness that is endemic in Southeast Asia .", "Osteopontin ( OPN ) is a phosphorylated glycoprotein that is involved in several immune responses including induction of T-helper 1 cytokines and recruitment of inflammatory cells...	[ "Melioidosis is a severe tropical disease caused by infection with the bacterium Burkholderia ( B . ) pseudomallei .", "In northeast Thailand infection with this bacterium is the major cause of community-acquired septicemia with a mortality rate up to 40% .", "Extending the knowledge on the mechanisms of host d...	2010
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "infectious diseases/prion diseases", "neurological disorders/cognitive neurology and dementia", "neurological disorders/prion diseases" ]	Oxidation of Helix-3 Methionines Precedes the Formation of PK Resistant PrPSc	journal.ppat.1000977	null	[ [ "Prions are infectious agents that cause neurodegenerative diseases , such as scrapie , bovine spongiform encephalopathy ( BSE ) and CJD .", "They are believed to be composed mainly of PrPSc , a misfolded form of the GPI-anchored glycoprotein termed PrPC[1] .", "While the function of PrPC has not been...	[ "While elucidating the peculiar epitope of the α-PrP mAb IPC2 , we found that PrPSc exhibits the sulfoxidation of residue M213 as a covalent signature .", "Subsequent computational analysis predicted that the presence of sulfoxide groups at both Met residues 206 and 213 destabilize the α-fold , suggesting oxidati...	[ "The protein only theory , a widely accepted model describing the prion agent , assumes that the mechanism underlying prion disease pathogenesis includes a conformational change of the α-helix rich , soluble and protease sensitive PrPC into an aggregated and protease resistant β-sheet rich PrPSc form .", "Until r...	2010
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "infographics", "action potentials", "medicine and health sciences", "legs", "neural networks", "membrane potential", "limbs (anatomy)", "electrophysiology", "neuroscience", "systems science", "mathematics", "computational neuroscience", "research and analysis methods", "computer and infor...	Linking structure and activity in nonlinear spiking networks	journal.pcbi.1005583	null	[ [ "A fundamental goal in computational neuroscience is to understand how network connectivity and intrinsic neuronal dynamics relate to collective neural activity , and in turn drive neural computation .", "Experimental advances are vastly expanding both the scale and the resolution with which we can measur...	[ "Recent experimental advances are producing an avalanche of data on both neural connectivity and neural activity .", "To take full advantage of these two emerging datasets we need a framework that links them , revealing how collective neural activity arises from the structure of neural connectivity and intrinsic ...	[ "Neuronal networks , like many biological systems , exhibit variable activity .", "This activity is shaped by both the underlying biology of the component neurons and the structure of their interactions .", "How can we combine knowledge of these two things—that is , models of individual neurons and of their int...	2017
[ "Introduction", "Machine learning for species identification", "Challenges in image-based taxa identification", "Status quo", "Open problems and future directions", "A vision of automated identification in the wild" ]	[ "plant anatomy", "flowers", "plant science", "review", "eukaryota", "computer and information sciences", "machine learning", "data acquisition", "artificial intelligence", "computer vision", "flowering plants", "biology and life sciences", "plants", "leaves", "organisms", "fruits" ]	Automated plant species identification—Trends and future directions	journal.pcbi.1005993	null	[ [ "One of the most obvious features of organic life is its remarkable diversity [1] .", "Despite the variation of organisms , a more experienced eye soon discerns that organisms can be grouped into taxa .", "Biology defines taxa as formal classes of living things consisting of the taxon's name and its d...	[ "Current rates of species loss triggered numerous attempts to protect and conserve biodiversity .", "Species conservation , however , requires species identification skills , a competence obtained through intensive training and experience .", "Field researchers , land managers , educators , civil servants , and...	[ "Plant identification is not exclusively the job of botanists and plant ecologists .", "It is required or useful for large parts of society , from professionals ( such as landscape architects , foresters , farmers , conservationists , and biologists ) to the general public ( like ecotourists , hikers , and nature...	2018
[ "Introduction", "Methods", "Results", "Discussion", "Conclusions" ]	[ "health promotion", "medicine and health sciences", "body fluids", "sociology", "tropical diseases", "geographical locations", "social sciences", "ebola hemorrhagic fever", "quarantines", "human families", "neglected tropical diseases", "social communication", "infectious disease control", ...	‘When Ebola enters a home, a family, a community’: A qualitative study of population perspectives on Ebola control measures in rural and urban areas of Sierra Leone	journal.pntd.0006461	null	[ [ "By October 2015 , the failure to control the West Africa Ebola outbreak had resulted in 28 454 cases of Ebola virus disease ( EVD; hereafter referred to as ‘Ebola’ ) , with 11 297 reported deaths in Sierra Leone , Liberia , and Guinea [1] .", "The unprecedented scale of the outbreak has challenged govern...	[ "During the West Africa Ebola outbreak , cultural practices have been described as hindering response efforts .", "The acceptance of control measures improved during the outbreak , but little is known about how and why this occurred .", "We conducted a qualitative study in two administrative districts of Sierra...	[ "The scale of the 2014–15 Ebola epidemic was unprecedented and led to over 11 , 000 deaths in Sierra Leone , Liberia and Guinea .", "What is distinct about the findings of this study is the knowledge gained from experiences and reflections of communities , health workers and Ebola survivors living in the midst of...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Role of the Vibrio cholerae Matrix Protein Bap1 in Cross-Resistance to Antimicrobial Peptides	journal.ppat.1003620	null	[ [ "V . cholerae is the causative agent of the disease cholera , which remains a significant public health problem , causing large numbers of infections and deaths annually in the world [1] .", "During the infection , V . cholerae colonizes the surface of the small intestine where it secretes virulence facto...	[ "Outer membrane vesicles ( OMVs ) that are released from Gram-negative pathogenic bacteria can serve as vehicles for the translocation of effectors involved in infectious processes .", "In this study we have investigated the role of OMVs of the Vibrio cholerae O1 El Tor A1552 strain in resistance to antimicrobial...	[ "Cholera is an epidemic disease that has killed millions of people and continues to be a major health problem worldwide .", "The bacterium V . cholerae , the causative agent of cholera , is highly resistant to antimicrobial peptides , which are important effectors of human innate immunity .", "Moreover , it is ...	2013
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "infectious diseases/protozoal infections", "infectious diseases/neglected tropical diseases" ]	Integrating an NTD with One of “The Big Three”: Combined Malaria and Trachoma Survey in Amhara Region of Ethiopia	journal.pntd.0000197	null	[ [ "Ethiopia is a rapidly developing country that is burdened and held back by a high prevalence of communicable disease .", "Of the so-called ‘big three’ killer diseases , HIV/AIDs , tuberculosis , and malaria , malaria is the most frequent cause of out-patient presentation and in-patient admission nationwi...	[ "Amhara Regional State of Ethiopia has a population of approximately 19 . 6 million , is prone to unstable and epidemic malaria , and is severely affected by trachoma .", "An integrated malaria and trachoma control program is being implemented by the Regional Health Bureau .", "To provide baseline data , a surv...	[ "The “big three” killer diseases are malaria , HIV/AIDS , and tuberculosis; control programs for these diseases are usually well developed and financed .", "The neglected tropical diseases ( NTDs ) are a group of ancient afflictions that are frequently sidelined by planners and are under-resourced .", "Opportun...	2008
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "public and occupational health", "infectious diseases", "socioeconomic aspects of health", "medicine and health sciences", "epidemiology", "dengue fever", "neglected tropical diseases", "tropical diseases", "viral diseases", "health care" ]	Predictive Tools for Severe Dengue Conforming to World Health Organization 2009 Criteria	journal.pntd.0002972	null	[ [ "After successful eradication programs of the dengue vector Aedes mosquitoes in Latin America in the 1940s , both disease and vector have resurged and disseminated globally since the late 1970s [1] , posing substantial disease and economic burdens on tropical and subtropical regions [2] , [3] .", "It is e...	[ "Dengue causes 50 million infections per year , posing a large disease and economic burden in tropical and subtropical regions .", "Only a proportion of dengue cases require hospitalization , and predictive tools to triage dengue patients at greater risk of complications may optimize usage of limited healthcare r...	[ "Dengue is a mosquito-borne tropical disease that poses a large economic and health burden to 40% of the world's population .", "Some dengue patients can evolve into a more severe form of the illness ( severe dengue ) and ideally should be hospitalized when this occurs .", "However , while only a small proporti...	2014
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "antimicrobials", "medicine and health sciences", "body fluids", "pathology and laboratory medicine", "melioidosis", "drugs", "microbiology", "pediatrics", "bacterial diseases", "signs and symptoms", "antibiotics", "pediatric infections", "pharmacology", "infectious diseases", "epidemiol...	Pediatric melioidosis in Sarawak, Malaysia: Epidemiological, clinical and microbiological characteristics	journal.pntd.0005650	null	[ [ "Melioidosis is a serious tropical infectious disease endemic to Southeast Asia and northern Australia , caused by the gram-negative bacillus Burkholderia pseudomallei [1] .", "The bacterium , found in soil and surface water [2] , is acquired through inoculation , inhalation and ingestion [3] .", "In ...	[ "Melioidosis is a serious , and potentially fatal community-acquired infection endemic to northern Australia and Southeast Asia , including Sarawak , Malaysia .", "The disease , caused by the usually intrinsically aminoglycoside-resistant Burkholderia pseudomallei , most commonly affects adults with predisposing ...	[ "Melioidosis is a serious , and often fatal community-acquired infection endemic to Southeast Asia and northern Australia .", "It is caused by the environmental saprophyte Burkholderia pseudomallei , a bacterium that is intrinsically resistant to many commonly used antibiotics .", "Its presence in Sarawak , Mal...	2017
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "serine proteases", "biochemistry", "cell death", "genetics of the immune system", "cell biology", "clinical immunology", "proteins", "immunity", "apoptosis", "enzymes", "biology and life sciences", "proteases", "enzymology", "cell processes", "immunology", "cell-mediated immunity" ]	A Natural Genetic Variant of Granzyme B Confers Lethality to a Common Viral Infection	journal.ppat.1004526	null	[ [ "Cytotoxic lymphocytes , such as natural killer ( NK ) cells and CD8 T cells , are essential for the elimination of tumour cells or cells infected with intracellular pathogens .", "One mechanism cytotoxic lymphocytes utilize to initiate the destruction of target cells is the exocytosis of granules contain...	[ "Many immune response genes are highly polymorphic , consistent with the selective pressure imposed by pathogens over evolutionary time , and the need to balance infection control with the risk of auto-immunity .", "Epidemiological and genomic studies have identified many genetic variants that confer susceptibili...	[ "Granzymes ( Gzm ) are serine proteases expressed by cytotoxic T cells and natural killer cells , and are important for the destruction of virally infected cells .", "To date , the function of these molecules has been assessed exclusively in common laboratory mouse strains that express identical granzyme proteins...	2014
[ "Introduction", "Methods", "Results", "Discussion", "Conclusion" ]	[ "medicine and health sciences", "ecology and environmental sciences", "grasslands", "tropical diseases", "geographical locations", "vertebrates", "plant communities", "animals", "age groups", "plant science", "reptiles", "neglected tropical diseases", "plant ecology", "africa", "snakebit...	Epidemiology, ecology and human perceptions of snakebites in a savanna community of northern Ghana	journal.pntd.0007221	null	[ [ "Snakebite envenomations constitute one of the most important human-wildlife conflicts , causing considerable yet largely insufficiently known magnitudes of socio-economical losses , morbidity and death [1] .", "Globally , out of >3 , 500 snake species , ~600 are venomous , and ~280 are considered medical...	[ "Worldwide , snakebite envenomations total ~2 . 7 million reported cases annually with ~100 , 000 fatalities .", "Since 2009 , snakebite envenomation has intermittently been classified as a very important ‘neglected tropical disease’ by the World Health Organisation .", "Despite this emerging awareness , limite...	[ "Snakebite envenomations cause tens of thousands of deaths and hundred thousands of injuries in many developing tropical countries annually , and sub-Saharan Africa represents an epitome example of this ‘neglected tropical disease’ .", "We here present data collected over a 10-year period applying different metho...	2019
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	QTL Mapping of Sex Determination Loci Supports an Ancient Pathway in Ants and Honey Bees	journal.pgen.1005656	null	[ [ "One of the major developmental events faced by most organisms is whether they become male or female [1 , 2] .", "Mechanisms underlying this choice have major implications for a variety of life history traits , and even the risk of extinction .", "For example , chromosomal sex determination systems , ...	[ "Sex determination mechanisms play a central role in life-history characteristics , affecting mating systems , sex ratios , inbreeding tolerance , etc .", "Downstream components of sex determination pathways are highly conserved , but upstream components evolve rapidly .", "Evolutionary dynamics of sex determin...	[ "Whether a developing embryo becomes male or female has significant downstream consequences .", "Depending on the species , sex can be determined by a wide variety of mechanisms .", "Sex determination systems can evolve rapidly , but how this occurs , and even how widespread the same mechanism is within a given...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "neuroscience/neuronal and glial cell biology", "neurological disorders/epilepsy" ]	An Excitatory Loop with Astrocytes Contributes to Drive Neurons to Seizure Threshold	journal.pbio.1000352	Studies in rodent brain slices suggest that seizures in focal epilepsies are sustained and propagated by the reciprocal interaction between neurons and astroglial cells	[ [ "Focal epilepsies are characterized by a condition of neuronal hyperexcitability that is restricted to the epileptogenic region .", "Focal seizures originate at this region and secondarily spread to distant cortical areas [1]–[5] .", "Several factors , from ion channel mutations to brain injury , may ...	[ "Seizures in focal epilepsies are sustained by a highly synchronous neuronal discharge that arises at restricted brain sites and subsequently spreads to large portions of the brain .", "Despite intense experimental research in this field , the earlier cellular events that initiate and sustain a focal seizure are ...	[ "In focal epilepsy , seizures are generated by a localized , synchronous neuronal electrical discharge that may spread to large portions of the brain .", "Despite intense experimental research in this field , a key question relevant to the human epilepsy condition remains completely unanswered: what are the cellu...	2010
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "infectious diseases", "veterinary diseases", "zoonoses", "medicine and health sciences", "mathematics", "statistics (mathematics)", "population modeling", "epidemiology", "infectious disease epidemiology", "neglected tropical diseases", "biology and life sciences", "tropical diseases", "inf...	Modeling to Predict Cases of Hantavirus Pulmonary Syndrome in Chile	journal.pntd.0002779	null	[ [ "Reports indicate that illness from hantaviruses existed as early as the 1950s [1] , although the virus was only officially recognized in the Americas in 1993 [1]–[3] .", "An outbreak of hantavirus in the Four Corners region of the United States led to investigation and isolation of the Sin Nombre virus (...	[ "Hantavirus pulmonary syndrome ( HPS ) is a life threatening disease transmitted by the rodent Oligoryzomys longicaudatus in Chile .", "Hantavirus outbreaks are typically small and geographically confined .", "Several studies have estimated risk based on spatial and temporal distribution of cases in relation to...	[ "Hantavirus pulmonary syndrome ( HPS ) is a severe disease present in Chile , Argentina and other countries in the Americas .", "Mortality rates for HPS can be as high as 60% for some outbreaks .", "Although hantavirus outbreaks tend to be small , the high death rate , unavailability of a vaccine , and occurren...	2014
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "immunology/immunomodulation", "infectious diseases/neglected tropical diseases", "immunology/immunity to infections" ]	Immunologic Responses to Vibrio cholerae in Patients Co-Infected with Intestinal Parasites in Bangladesh	journal.pntd.0000403	null	[ [ "V . cholerae is a major cause of diarrhea globally and is estimated to cause five million cases of cholera annually , resulting in more than 100 , 000 deaths [1] .", "The vast majority of cases occur in developing countries .", "Cholera is endemic in Bangladesh , with an approximate incidence of 200 ...	[ "Infection with intestinal helminths is common and may contribute to the decreased efficacy of Vibrio cholerae vaccines in endemic compared to non-endemic areas .", "However , the immunomodulatory effects of concomitant intestinal parasitic infection in cholera patients have not been systematically evaluated .", ...	[ "Vibrio cholerae causes cholera , a severe diarrhea that may lead to fatal dehydration if not treated .", "Cholera occurs mostly in impoverished areas where there is poor sanitation and intestinal parasites are also common .", "However , little is known about the relationship between intestinal parasites and ch...	2009
[ "Introduction", "Materials and methods", "Results", "Discussion" ]	[ "invertebrates", "medicine and health sciences", "helminths", "tropical diseases", "parasitic diseases", "parasitic protozoans", "animals", "protozoans", "infectious diseases", "malarial parasites", "cerebral malaria", "helminth infections", "eukaryota", "co-infections", "biology and lif...	Disentangling complex parasite interactions: Protection against cerebral malaria by one helminth species is jeopardized by co-infection with another	journal.pntd.0006483	null	[ [ "Most hosts are co-infected by a range of pathogenic organisms ( e . g . , [1] ) , and interactions between co-infecting parasites can be important determinants of susceptibility to infection ( e . g . , [2] ) as well as the severity of disease symptoms ( e . g . , [3] ) .", "Co-occurring parasites intera...	[ "Multi-species interactions can often have non-intuitive consequences .", "However , the study of parasite interactions has rarely gone beyond the effects of pairwise combinations of species , and the outcomes of multi-parasite interactions are poorly understood .", "We investigated the effects of co-infection ...	[ "Over the last decade , an increasing number of studies have shown that co-infected individuals can show strikingly different disease symptoms than singly infected individuals .", "Among these studies , the potential protective effect of some helminth species on malaria severity has attracted considerable attenti...	2018
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "medicine", "rna interference", "pharmacodynamics", "drugs and devices", "gene expression", "pharmacology", "biology", "molecular cell biology", "drug interactions", "drug metabolism", "molecular biology", "pharmacokinetics", "drug excretion" ]	Regulation of Biotransformation Systems and ABC Transporters by Benznidazole in HepG2 Cells: Involvement of Pregnane X-Receptor	journal.pntd.0001951	null	[ [ "Chagas disease or American trypanosomiasis is an endemic infection caused by the protozoa parasite Trypanosoma cruzi ( T . cruzi ) .", "It is widely extended in Latin America and affects 8 million people , and at least 100 million are at risk of infection [1] .", "Many reports have recognized the occ...	[ "Benznidazole ( BZL ) is the only antichagasic drug available in most endemic countries .", "Its effect on the expression and activity of drug-metabolizing and transporter proteins has not been studied yet .", "Expression and activity of P-glycoprotein ( P-gp ) , Multidrug resistance-associated protein 2 ( MRP2...	[ "Chagas disease is an endemic infection caused by Trypanosoma cruzi .", "Benznidazole ( BZL ) is the only antichagasic drug available in most endemic countries .", "The liver plays a major role in disposition of endogenous and exogenous compounds and their excretion is mainly mediated by transporter proteins ( ...	2012
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "taeniasis", "medicine", "infectious diseases", "test evaluation", "diagnostic medicine", "ectoparasitic infections", "cysticercosis", "trichinellosis", "neglected tropical diseases", "parasitic diseases", "paragonimiasis", "food-borne trematodes", "helminth infection" ]	A Protein Microarray for the Rapid Screening of Patients Suspected of Infection with Various Food-Borne Helminthiases	journal.pntd.0001899	null	[ [ "Food-borne helminthiases ( FBHs ) are considered neglected tropical diseases ( NTDs ) by the World Health Organization ( WHO ) .", "These infections are increasingly found to cause public health problems and pose socio-economic concerns worldwide .", "FBHs are caused by infections by helminths throug...	[ "Food-borne helminthiases ( FBHs ) have become increasingly important due to frequent occurrence and worldwide distribution .", "There is increasing demand for developing more sensitive , high-throughput techniques for the simultaneous detection of multiple parasitic diseases due to limitations in differential cl...	[ "Food-borne helminthiases ( FBHs ) have caused significant problems in public health and also posed socio-economic concerns .", "Common FBHs , such as cysticercosis , trichinellosis , paragonimiasis , sparganosis and angiostrongyliasis , have a worldwide distribution with high morbidity and even death .", "The ...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "transfer rna", "molecular complexes", "nucleases", "enzymes", "synthetic biology", "enzymology", "convergent evolution", "proteins", "ribonucleases", "gene expression", "molecular biology", "biochemistry", "rna", "hydrolases", "rna processing", "ribonucleoproteins", "genetics", "b...	Playing RNase P Evolution: Swapping the RNA Catalyst for a Protein Reveals Functional Uniformity of Highly Divergent Enzyme Forms	journal.pgen.1004506	null	[ [ "RNase P is the endonuclease that generates the 5′ end of tRNAs by removing transcriptional extensions [1]–[3] .", "It is an indispensable enzyme found in essentially all forms of life .", "Despite the apparently simple function and the highly conserved structure of the tRNA substrates , a bewildering...	[ "The RNase P family is a diverse group of endonucleases responsible for the removal of 5′ extensions from tRNA precursors .", "The diversity of enzyme forms finds its extremes in the eukaryal nucleus where RNA-based catalysis by complex ribonucleoproteins in some organisms contrasts with single-polypeptide enzyme...	[ "Many biocatalysts apparently evolved independently more than once , leading to structurally unrelated macromolecules catalyzing the same biochemical reaction .", "The RNase P enzyme family is an exceptional case of this phenomenon called convergent evolution .", "RNase P enzymes use not only unrelated , but ch...	2014
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "schistosoma", "invertebrates", "schistosoma mansoni", "computer-aided drug design", "medicine and health sciences", "drug design", "drug research and development", "helminths", "biology and life sciences", "pharmacology", "animals", "organisms" ]	In Silico Repositioning-Chemogenomics Strategy Identifies New Drugs with Potential Activity against Multiple Life Stages of Schistosoma mansoni	journal.pntd.0003435	null	[ [ "Schistosomiasis is one of the main neglected tropical diseases affecting humans .", "It is caused by flatworms of the genus Schistosoma ( S . mansoni , S . japonicum , S . haematobium , S . intercalatum and S . mekongi ) [1]–[3] .", "This parasitic disease ranks second only after malaria in terms of ...	[ "Morbidity and mortality caused by schistosomiasis are serious public health problems in developing countries .", "Because praziquantel is the only drug in therapeutic use , the risk of drug resistance is a concern .", "In the search for new schistosomicidal drugs , we performed a target-based chemogenomics scr...	[ "Schistosomiasis is a neglected tropical disease caused by schistosome parasites that affects millions of people worldwide .", "The current reliance on a single drug ( Praziquantel ) for treatment and control of the disease calls for the urgent discovery of novel schistosomicidal agents .", "One approach that c...	2015
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "genome-wide association studies", "gene regulation", "animal models", "model organisms", "genome analysis", "experimental organism systems", "molecular genetics", "inbred strains", "research and analysis methods", "small interfering rnas", "animal studies", "gene expression", "mouse models"...	Mouse genome-wide association studies and systems genetics uncover the genetic architecture associated with hepatic pharmacokinetic and pharmacodynamic properties of a constrained ethyl antisense oligonucleotide targeting Malat1	journal.pgen.1007732	null	[ [ "Antisense oligonucleotides ( ASOs ) are highly selective and potent therapeutic agents which has proven effective in treating a variety of disease states including cancer , viral infection and cardio-metabolic , inflammatory and neurological diseases [1–7] .", "Antisense technology uses short synthetic (...	[ "Antisense oligonucleotides ( ASOs ) have demonstrated variation of efficacy in patient populations .", "This has prompted our investigation into the contribution of genetic architecture to ASO pharmacokinetics ( PK ) and pharmacodynamics ( PD ) .", "Genome wide association ( GWA ) and transcriptomic analysis i...	[ "Previous work in the clinic has clearly demonstrated differential patient response to antisense oligonucleotide ( ASO ) drugs .", "However , to date there has been no systematic evaluation of genes associated with this response in vivo .", "In this study , we utilized an advanced genetic methodology in mice to...	2018
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "animal diseases", "rna interference", "gene regulation", "microbiology", "vertebrates", "cloning", "light microscopy", "animals", "mammals", "microscopy", "molecular biology techniques", "epigenetics", "zoology", "research and analysis methods", "small interfering rnas", "swine", "a...	Genetically modified pigs are protected from classical swine fever virus	journal.ppat.1007193	null	[ [ "Classical swine fever virus ( CSFV ) belongs to the genus Pestivirus within the family Flaviviridae [1] .", "CSFV is an enveloped virus that possesses a single-strand positive-sense 12 .", "3kb RNA genome , which contains a long open reading frame that encodes a 3898-amino acid ( aa ) poly-protein [2...	[ "Classical swine fever ( CSF ) caused by classical swine fever virus ( CSFV ) is one of the most detrimental diseases , and leads to significant economic losses in the swine industry .", "Despite efforts by many government authorities to stamp out the disease from national pig populations , the disease remains wi...	[ "Classical swine fever ( CSF ) , caused by classical swine fever virus ( CSFV ) , and is a highly contagious , often fatal porcine disease that causes significant economic losses .", "Due to the economic importance of this virus to the pig industry , the biology and pathogenesis of CSFV have been investigated ext...	2018
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "united states", "medicine and health sciences", "microcephaly", "pathology and laboratory medicine", "nervous system", "pathogens", "immunology", "geographical locations", "microbiology", "social sciences", "health care", "viruses", "north america", "developmental biology", "texas", "...	The potential economic burden of Zika in the continental United States	journal.pntd.0005531	null	[ [ "As the Zika virus epidemic continues to spread internationally , countries such as the United States must determine how much to invest in prevention , control , and response .", "Fundamental to these decisions is an understanding of the potential economic burden of Zika .", "For example , former US P...	[ "As the Zika virus epidemic continues to spread internationally , countries such as the United States must determine how much to invest in prevention , control , and response .", "Fundamental to these decisions is quantifying the potential economic burden of Zika under different scenarios .", "To inform such de...	[ "Our work forecasts the cost and economic burden of the Zika virus across six states in the US which are at the greatest risk of Zika ( Alabama , Florida , Georgia , Louisiana , Mississippi , and Texas ) .", "We evaluated the burden by varying attack rates , scenarios , and circumstances .", "All costs are repo...	2017
[ "Introduction", "Model", "Results", "Discussion" ]	[ "behavioral neuroscience", "animal behavior", "biology", "computational biology", "zoology", "neuroscience" ]	No Need for a Cognitive Map: Decentralized Memory for Insect Navigation	journal.pcbi.1002009	null	[ [ "Desert ants are extremely skillful long-distance navigators , which during their foraging journeys can leave their underground colonies for distances of more than ten thousand times their body length , and then return to their point of departure , an often inconspicuous hole in the desert ground , with amazi...	[ "In many animals the ability to navigate over long distances is an important prerequisite for foraging .", "For example , it is widely accepted that desert ants and honey bees , but also mammals , use path integration for finding the way back to their home site .", "It is however a matter of a long standing deb...	[ "When desert ants search for food , they often have to travel over long distances , more then ten thousand times their body lengths and then turn back to find the nest entrance .", "It is known from many experiments that these animals employ a skylight compass including the sun , a pedometer , and a mechanism cal...	2011
[ "Introduction", "Results", "Discussion", "Methods" ]	[]	Separable Crossover-Promoting and Crossover-Constraining Aspects of Zip1 Activity during Budding Yeast Meiosis	journal.pgen.1005335	null	[ [ "The segregation of homologous chromosomes at meiosis I is essential for the formation of haploid reproductive cells .", "Accurate segregation is dependent on the establishment of one or more associations between homologous chromosomes [1 , 2] .", "For most organisms , crossover recombination events i...	[ "Accurate chromosome segregation during meiosis relies on the presence of crossover events distributed among all chromosomes .", "MutSγ and MutLγ homologs ( Msh4/5 and Mlh1/3 ) facilitate the formation of a prominent group of meiotic crossovers that mature within the context of an elaborate chromosomal structure ...	[ "At the heart of reproductive cell formation is a nuclear division process ( meiosis ) whereby homologous chromosomes segregate from one another .", "Meiotic partner chromosomes establish exclusive associations via a patterned distribution of crossover recombination events .", "During the maturation of recombin...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "cellular stress responses", "functional genomics", "microbiology", "gene function", "model organisms", "cell growth", "microbial physiology", "biology", "cell biology", "genetic screens", "genetics", "yeast and fungal models", "saccharomyces cerevisiae", "genomics", "molecular cell biol...	Genome-Wide Functional Profiling Identifies Genes and Processes Important for Zinc-Limited Growth of Saccharomyces cerevisiae	journal.pgen.1002699	null	[ [ "Zinc is an essential nutrient for all organisms because it is required as a catalytic and/or structural cofactor for hundreds of proteins [1] .", "In addition , recent evidence suggests that zinc may serve as an important secondary messenger in various signal transduction pathways [2] , [3] .", "As a...	[ "Zinc is an essential nutrient because it is a required cofactor for many enzymes and transcription factors .", "To discover genes and processes in yeast that are required for growth when zinc is limiting , we used genome-wide functional profiling .", "Mixed pools of ∼4 , 600 deletion mutants were inoculated in...	[ "Zinc is needed for the growth of all organisms because it acts as a required cofactor for many different proteins .", "Zinc deficiency is a common problem faced by free-living microbes , as well as plants and animals including humans .", "Among bacterial and fungal pathogens , zinc deficiency is also a key pro...	2012
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "bartonella", "medicine and health sciences", "pathology and laboratory medicine", "medical microbiology", "microbial pathogens", "biology and life sciences", "molecular biology techniques", "microbiology", "molecular biology", "bacterial pathogens" ]	Rapid and Sensitive Detection of Bartonella bacilliformis in Experimentally Infected Sand Flies by Loop-Mediated Isothermal Amplification (LAMP) of the Pap31 Gene	journal.pntd.0003342	null	[ [ "Carrion's disease , caused by Bartonella bacilliformis remains truly neglected due to its focal geographical nature , occurring in small rural communities of inter-Andean valleys between altitudes of 500–200 meters above sea level in Peru , Columbia and Ecuador [1] .", "The disease typically presents wit...	[ "Carrion' disease , caused by Bartonella bacilliformis , remains truly neglected due to its focal geographical nature .", "A wide spectrum of clinical manifestations , including asymptomatic bacteremia , and lack of a sensitive diagnostic test can potentially lead to a spread of the disease into non-endemic regio...	[ "Carrion's disease , caused by Bartonella bacilliformis remains truly neglected due to its focal geographical nature .", "A wide spectrum of clinical manifestations , including asymptomatic bacteremia can potentially lead to a spread of the disease into non-endemic regions .", "The PCR-based approach is sensiti...	2014
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "fish", "medicine and health sciences", "vertebrates", "pigments", "animals", "alleles", "epithelial cells", "animal models", "osteichthyes", "developmental biology", "model organisms", "materials science", "experimental organism systems", "chromatophores", "morphogenesis", "pattern fo...	Evolution of Endothelin signaling and diversification of adult pigment pattern in Danio fishes	journal.pgen.1007538	null	[ [ "Mechanisms underlying species differences in adult form remain poorly understood .", "Quantitative genetic analyses and association studies have made progress in identifying loci , and even specific nucleotides , that contribute to morphological differences between closely related species and strains .",...	[ "Fishes of the genus Danio exhibit diverse pigment patterns that serve as useful models for understanding the genes and cell behaviors underlying the evolution of adult form .", "Among these species , zebrafish D . rerio exhibit several dark stripes of melanophores with sparse iridophores that alternate with ligh...	[ "Neural crest derived pigment cells generate the spectacular variation in skin pigment patterns among vertebrates .", "Mammals and birds have just a single skin pigment cell , the melanocyte , whereas ectothermic vertebrates have several pigment cells including melanophores , iridophores and xanthophores , that t...	2018
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "bacteriology", "medicine", "microbiology", "host-pathogen interaction", "animal models", "bacterial diseases", "model organisms", "gastroenterology and hepatology", "microbial growth and development", "bacterial pathogens", "infectious diseases", "bacterial and foodborne illness", "microbia...	ActA Promotes Listeria monocytogenes Aggregation, Intestinal Colonization and Carriage	journal.ppat.1003131	null	[ [ "Listeria monocytogenes ( Lm ) is a facultative intracellular Gram-positive bacterium and the agent of listeriosis , the deadliest foodborne infection in humans , with a mortality rate between 20 to 30% .", "Listeriosis can manifest as gastroenteritis after ingestion of a high inoculum , as septicemia , m...	[ "Listeria monocytogenes ( Lm ) is a ubiquitous bacterium able to survive and thrive within the environment and readily colonizes a wide range of substrates , often as a biofilm .", "It is also a facultative intracellular pathogen , which actively invades diverse hosts and induces listeriosis .", "So far , these...	[ "Listeria monocytogenes ( Lm ) is a ubiquitous bacterium that survives and thrives within the environment , and a facultative intracellular pathogen that induces listeriosis .", "So far , these two complementary facets of Lm biology have been studied independently .", "Here we identify ActA , which is a major L...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "animal models", "drosophila melanogaster", "model organisms", "biology" ]	Drosophila DJ-1 Decreases Neural Sensitivity to Stress by Negatively Regulating Daxx-Like Protein through dFOXO	journal.pgen.1003412	null	[ [ "Oxidative stress , a state of imbalance between the generation and elimination of reactive oxygen and nitrogen species , has been implicated in a variety of neurodegenerative diseases [1]–[3] .", "The central nervous system is presumed to be particularly vulnerable to oxidative stress , as it consumes ab...	[ "DJ-1 , a Parkinson's disease ( PD ) –associated gene , has been shown to protect against oxidative stress in Drosophila .", "However , the molecular mechanism underlying oxidative stress-induced phenotypes , including apoptosis , locomotive defects , and lethality , in DJ-1-deficient flies is not fully understoo...	[ "DJ-1 is an antioxidant protein that has been implicated in autosomal recessive Parkinson's disease ( PD ) , although the mechanism by which DJ-1 deficiency causes PD remains elusive .", "Drosophila DJ-1 mutants are highly sensitive to oxidative stress and UV irradiation , and oxidative stress-induced cell death ...	2013
[ "Introduction", "Study Area and General Methods", "Experiments and Results", "Discussion" ]	[ "medicine", "infectious diseases", "public health and epidemiology", "epidemiology" ]	Towards an Early Warning System for Rhodesian Sleeping Sickness in Savannah Areas: Man-Like Traps for Tsetse Flies	journal.pntd.0001978	null	[ [ "Human African trypanosomiasis ( HAT ) , also known as sleeping sickness , is caused by certain subspecies of Trypanosoma brucei and is transmitted to humans by tsetse flies ( Glossina spp ) [1] .", "Several thousand cases are recorded annually [1] but due to under-diagnosis and poor reporting the true nu...	[ "In the savannahs of East and Southern Africa , tsetse flies ( Glossina spp . ) transmit Trypanosoma brucei rhodesiense which causes Rhodesian sleeping sickness , the zoonotic form of human African trypanosomiasis .", "The flies feed mainly on wild and domestic animals and are usually repelled by humans .", "Ho...	[ "In savannah areas of Africa the incidence of sleeping sickness is commonly low because the species of tsetse fly that spread the disease there feed mainly on wild and domestic animals , and are strongly repelled by humans .", "Environmental stresses can make the flies less responsive to the repellence , so threa...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "germ cells", "meiosis", "genomics", "molecular cell biology", "cell division", "chromosome biology", "speciation", "cellular types", "hybridization", "biology", "evolutionary biology", "evolutionary processes" ]	X Chromosome Control of Meiotic Chromosome Synapsis in Mouse Inter-Subspecific Hybrids	journal.pgen.1004088	null	[ [ "Hybrid sterility ( HS ) is a postzygotic reproductive isolation barrier restricting gene flow between the related taxa during speciation .", "It is defined as a condition where two parental forms fertile inter se produce a hybrid that is sterile [1] .", "One of the most interesting findings coming fr...	[ "Hybrid sterility ( HS ) belongs to reproductive isolation barriers that safeguard the integrity of species in statu nascendi .", "Although hybrid sterility occurs almost universally among animal and plant species , most of our current knowledge comes from the classical genetic studies on Drosophila interspecific...	[ "Genomes of newly emerging species restrict their gene exchange with related taxa in order to secure integrity .", "Hybrid sterility is one of the reproductive isolation mechanisms restricting gene flow between closely related , sexually reproducing organisms .", "We showed that hybrid sterility between two clo...	2014
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "fish", "medicine and health sciences", "in situ hybridization", "molecular probe techniques", "gene regulation", "brain", "vertebrates", "animals", "animal models", "osteichthyes", "developmental biology", "model organisms", "hindbrain", "experimental organism systems", "molecular biolo...	Cooperation, cis-interactions, versatility and evolutionary plasticity of multiple cis-acting elements underlie krox20 hindbrain regulation	journal.pgen.1007581	null	[ [ "Enhancers are short , cis-acting regulatory elements that modulate transcription of target genes , relatively independently of their orientation or distance with respect to the promoter .", "They act as platforms to recruit multiple transcription factors [1] that interact with the transcription machinery...	[ "Cis-regulation plays an essential role in the control of gene expression , and is particularly complex and poorly understood for developmental genes , which are subject to multiple levels of modulation .", "In this study , we performed a global analysis of the cis-acting elements involved in the control of the z...	[ "Animal development relies on the early delimitation of specific embryonic territories that will later participate in the formation of tissues and organs .", "This process is governed by sets of so-called developmental genes .", "The activities of the genes are themselves controlled by associated DNA sequences ...	2018
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "medicine and health sciences", "ontologies", "animal models of disease", "vertebrates", "animals", "mammals", "drug screening", "animal models", "genetics of disease", "data management", "model organisms", "experimental organism systems", "pharmacology", "research and analysis methods", ...	Classification and analysis of a large collection of in vivo bioassay descriptions	journal.pcbi.1005641	null	[ [ "Testing potential therapeutic compounds in animal disease and safety models is a crucial part of preclinical drug discovery [1] .", "Although many in vitro methods have been developed to rapidly screen candidate molecules , no such simple assay system can recapitulate the complexities and dynamics of a l...	[ "Testing potential drug treatments in animal disease models is a decisive step of all preclinical drug discovery programs .", "Yet , despite the importance of such experiments for translational medicine , there have been relatively few efforts to comprehensively and consistently analyze the data produced by in vi...	[ "Before exposing human populations to potential drug treatments , novel compounds are tested in living non-human animals—arguably the most physiologically relevant model system known to drug discovery .", "Yet , high failure rates for new therapies in the clinic demonstrate a growing need for better understanding...	2017
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "molecular biology/bioinformatics", "computer science", "computational biology/systems biology" ]	Network Archaeology: Uncovering Ancient Networks from Present-Day Interactions	journal.pcbi.1001119	null	[ [ "Many biological , social , and technological networks are the product of an evolutionary process that has guided their growth .", "Tracking how networks have changed over time can help us answer questions about why currently observed network structures exist and how they may change in the future [1] .", ...	[ "What proteins interacted in a long-extinct ancestor of yeast ?", "How have different members of a protein complex assembled together over time ?", "Our ability to answer such questions has been limited by the unavailability of ancestral protein-protein interaction ( PPI ) networks .", "To overcome this limit...	[ "Many questions about present-day interaction networks could be answered by tracking how the network changed over time .", "We present a suite of algorithms to uncover an approximate node-by-node and edge-by-edge history of changes of a network when given only a present-day network and a plausible growth model by...	2011
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[]	Dengue Virus Impairs Mitochondrial Fusion by Cleaving Mitofusins	journal.ppat.1005350	null	[ [ "Mitochondria , the powerhouse of cells , participate in various cellular events , such as ATP production , fatty acid synthesis , calcium homeostasis , and apoptosis induction [1 , 2] .", "Their roles in cell signaling are also emerging: mitochondria can sense perturbations of intracellular homeostasis ,...	[ "Mitochondria are highly dynamic subcellular organelles participating in many signaling pathways such as antiviral innate immunity and cell death cascades .", "Here we found that mitochondrial fusion was impaired in dengue virus ( DENV ) infected cells .", "Two mitofusins ( MFN1 and MFN2 ) , which mediate mitoc...	[ "Dengue virus ( DENV ) threatens billions of people worldwide but no licensed vaccine or therapeutics is currently available .", "Knowing more details of DENV pathogenesis , such as antagonism of host immunity and cell death induction , may provide important clues to fight against this thorny disease .", "Incom...	2015
[ "Introduction", "Results and Discussion", "Materials and Methods" ]	[]	Preferred Supramolecular Organization and Dimer Interfaces of Opioid Receptors from Simulated Self-Association	journal.pcbi.1004148	null	[ [ "Experimental evidence accumulated over almost two decades supports the ability of all three major opioid receptor ( OR ) subtypes ( μ-OR , δ-OR , and κ-OR ) to form homomeric and heteromeric complexes , a feature that is common to several other G Protein-Coupled Receptors ( GPCRs ) ( see [1] for a recent rev...	[ "Substantial evidence in support of the formation of opioid receptor ( OR ) di-/oligomers suggests previously unknown mechanisms used by these proteins to exert their biological functions .", "In an attempt to guide experimental assessment of the identity of the minimal signaling unit for ORs , we conducted exten...	[ "Opioid receptors associate with each other in the plasma membrane , following a mechanism that has been implicated in either beneficial or adverse effects , depending on the environment and the interacting partners .", "Whether or not the different opioid receptor subtypes share a similar propensity to form di-/...	2015
[ "Introduction", "Results", "Materials and Methods" ]	[ "biology" ]	Virulence Regulator EspR of Mycobacterium tuberculosis Is a Nucleoid-Associated Protein	journal.ppat.1002621	null	[ [ "Details of the genetic control mechanisms governing the pathogenicity of the etiological agent of human tuberculosis are starting to emerge [1] .", "It has been postulated that the DNA-binding protein EspR [2] controls the virulence of Mycobacterium tuberculosis ( Mtb ) by specifically regulating express...	[ "The principal virulence determinant of Mycobacterium tuberculosis ( Mtb ) , the ESX-1 protein secretion system , is positively controlled at the transcriptional level by EspR .", "Depletion of EspR reportedly affects a small number of genes , both positively or negatively , including a key ESX-1 component , the ...	[ "A major infection mechanism employed by the causative agent of tuberculosis , Mycobacterium tuberculosis ( Mtb ) , is the ESX-1 secretion system .", "It has been postulated that the DNA-binding protein EspR controls the virulence of Mtb by specifically regulating expression of the exported EspA protein , which i...	2012
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "cell death", "organismal evolution", "medicine and health sciences", "pathology and laboratory medicine", "genome evolution", "hepacivirus", "pathogens", "cell processes", "microbiology", "viral structure", "viruses", "rna viruses", "microbial evolution", "pharmacology", "genome complex...	Mutational pathway maps and founder effects define the within-host spectrum of hepatitis C virus mutants resistant to drugs	journal.ppat.1007701	null	[ [ "Direct acting antiviral agents ( DAAs ) have revolutionized the treatment of chronic hepatitis C virus ( HCV ) infection , eliciting nearly 100% cure rates in clinical trials with oral treatments often lasting as short as 8 weeks [1] .", "Efforts are now focused on identifying DAA combinations that preve...	[ "Knowledge of the within-host frequencies of resistance-associated amino acid variants ( RAVs ) is important to the identification of optimal drug combinations for the treatment of hepatitis C virus ( HCV ) infection .", "Multiple RAVs may exist in infected individuals , often below detection limits , at any resi...	[ "The spectrum of viral mutants that exists in infected individuals defines the diversity of drug resistance pathways accessible to any virus .", "Drug combinations that block these pathways the most effectively are likely to elicit the best responses .", "The mutants may lie below detection , rendering treatmen...	2019
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "microarrays", "genome expression analysis", "genomics", "functional genomics", "gene expression", "genetics", "regulatory networks", "biology", "computational biology", "genetics and genomics" ]	Trans-eQTLs Reveal That Independent Genetic Variants Associated with a Complex Phenotype Converge on Intermediate Genes, with a Major Role for the HLA	journal.pgen.1002197	null	[ [ "For many complex traits and diseases , numerous associated single nucleotide polymorphisms ( SNPs ) have been identified through genome-wide association studies ( GWAS ) through genome-wide association studies ( GWAS ) [1] .", "For many of these identified variants it is still unclear through which mecha...	[ "For many complex traits , genetic variants have been found associated .", "However , it is still mostly unclear through which downstream mechanism these variants cause these phenotypes .", "Knowledge of these intermediate steps is crucial to understand pathogenesis , while also providing leads for potential ph...	[ "Many genetic variants have been found associated with diseases .", "However , for many of these genetic variants , it remains unclear how they exert their effect on the eventual phenotype .", "We investigated genetic variants that are known to be associated with diseases and complex phenotypes and assessed whe...	2011
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genetics and genomics/animal genetics", "developmental biology/pattern formation", "genetics and genomics/gene function", "biochemistry/cell signaling and trafficking structures", "developmental biology/molecular development", "developmental biology/developmental molecular mechanisms" ]	Role of the Drosophila Non-Visual ß-Arrestin Kurtz in Hedgehog Signalling	journal.pgen.1001335	null	[ [ "G-protein coupled receptors ( GPCRs ) are seven-transmembrane proteins that play critical roles during development and in the regulation of cellular physiology .", "GPCRs constitute the largest superfamily of cell membrane receptors [1] .", "The major GPCR regulatory pathway involves phosphorylation ...	[ "The non-visual ß-arrestins are cytosolic proteins highly conserved across species that participate in a variety of signalling events , including plasma membrane receptor degradation , recycling , and signalling , and that can also act as scaffolding for kinases such as MAPK and Akt/PI3K .", "In Drosophila melano...	[ "Non-visual β-arrestins are key proteins involved in plasma membrane receptor internalization , recycling , and signalling .", "The activity of β-arrestins is generally linked to seven-transmembrane receptors , but in vertebrates they can also participate in many other signalling pathways .", "Consistently , β-...	2011
[ "Introduction", "Results", "Discussion", "Materials and Methods", "Supporting Information" ]	[ "plant biology", "arabidopsis", "plants", "genetics and genomics" ]	Epigenetic Natural Variation in Arabidopsis thaliana	journal.pbio.0050174	Two ecotypes ofArabidopis show different patterns of DNA methylation, which is heritable. Interestingly, differences in DNA methylation are not reflected in differences in gene expression.	[ [ "In eukaryotic genomes , patterns of cytosine methylation are inherited from cell to cell through the action of maintenance methyltransferase enzymes on symmetrical CG or CNG dinucleotide pairs .", "Maintenance is not perfect , resulting in occasional loss of methylation from one sister chromatid , follow...	[ "Cytosine methylation of repetitive sequences is widespread in plant genomes , occurring in both symmetric ( CpG and CpNpG ) as well as asymmetric sequence contexts .", "We used the methylation-dependent restriction enzyme McrBC to profile methylated DNA using tiling microarrays of Arabidopsis Chromosome 4 in two...	[ "In plants and animals , many DNA sequences are modified by the addition of methyl groups , but the principles governing methylation patterns are not well understood .", "In Arabidopsis , we show that repetitive sequences , derived from mobile ( transposable ) elements , are densely methylated throughout their le...	2007
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "cell biology/cell signaling", "biochemistry/cell signaling and trafficking structures", "infectious diseases/sexually transmitted diseases", "microbiology/cellular microbiology and pathogenesis", "cell biology/cytoskeleton" ]	RNA Interference Screen Identifies Abl Kinase and PDGFR Signaling in Chlamydia trachomatis Entry	journal.ppat.1000021	null	[ [ "Chlamydia species cause a wide range of diseases in humans , including sexually transmitted , ocular , and respiratory tract infections ( reviewed in [1] ) .", "Chronic Chlamydia infections can result in female infertility , blindness , and possibly atherosclerosis [2] .", "Despite the broad spectrum...	[ "To elucidate the mechanisms involved in early events in Chlamydia trachomatis infection , we conducted a large scale unbiased RNA interference screen in Drosophila melanogaster S2 cells .", "This allowed identification of candidate host factors in a simple non-redundant , genetically tractable system .", "From...	[ "Chlamydia trachomatis infections are a worldwide problem; they are the leading cause of preventable blindness in developing nations and the most common cause of sexually transmitted disease in the Western world .", "Binding and entry into host cells are critical steps to the pathogenesis of this obligate intrace...	2008
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "fungal genetics", "fungal structure", "developmental biology", "fungi", "model organisms", "mycelium", "experimental organism systems", "epigenetics", "dna", "morphogenesis", "dna methylation", "chromatin", "research and analysis methods", "mycology", "chromosome biology", "animal stu...	A RID-like putative cytosine methyltransferase homologue controls sexual development in the fungus Podospora anserina	journal.pgen.1008086	null	[ [ "A covalently modified DNA base , the 5-methylcytosine ( 5-meC ) is common in genomes of organisms as diverse as bacteria , fungi , plants and animals .", "In eukaryotes , when present , this epigenetic modification is associated with down-regulation of gene expression and suppression of transposon activi...	[ "DNA methyltransferases are ubiquitous enzymes conserved in bacteria , plants and opisthokonta .", "These enzymes , which methylate cytosines , are involved in numerous biological processes , notably development .", "In mammals and higher plants , methylation patterns established and maintained by the cytosine ...	[ "Sexual reproduction is considered to be essential for long-term persistence of eukaryotic species .", "Sexual reproduction is controlled by strict mechanisms governing which haploids can fuse ( mating ) and which developmental paths the resulting zygote will follow .", "In mammals , differential genomic DNA me...	2019
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "humoral immunity", "animal models", "signal transduction", "drosophila melanogaster", "inflammation", "model organisms", "immunity", "innate immunity", "immune defense", "immunology", "immune suppression", "biology", "molecular cell biology", "immune response" ]	Polydnaviral Ankyrin Proteins Aid Parasitic Wasp Survival by Coordinate and Selective Inhibition of Hematopoietic and Immune NF-kappa B Signaling in Insect Hosts	journal.ppat.1003580	null	[ [ "Parasitic wasps develop within their insect hosts as they devour host bodies .", "Wasp oviposition in Drosophila larvae simultaneously activates humoral and cellular immune reactions .", "In a systemic acute inflammatory reaction , humoral antimicrobial secretions and cytokines from the fat body syne...	[ "Polydnaviruses are mutualists of their parasitoid wasps and express genes in immune cells of their Lepidopteran hosts .", "Polydnaviral genomes carry multiple copies of viral ankyrins or vankyrins .", "Vankyrin proteins are homologous to IκB proteins , but lack sequences for regulated degradation .", "We tes...	[ "Parasitoid wasps are insects whose development takes place within the body of other insects .", "To survive , wasp larvae must overcome the immune defenses of their hosts .", "How parasitic wasps overcome host immunity is not fully understood even though we know that different strategies using venoms , virus-l...	2013
[ "Introduction", "Results/Discussion", "Methods" ]	[ "evolutionary biology/animal genetics", "evolutionary biology/evolutionary and comparative genetics", "genetics and genomics/gene expression", "evolutionary biology/genomics" ]	Widespread Over-Expression of the X Chromosome in Sterile F1 Hybrid Mice	journal.pgen.1001148	null	[ [ "The importance of proper gene regulation to the evolution of reproductive isolation between species is not well understood .", "Several studies have documented abnormal genome-wide patterns of expression in F1 hybrid offspring relative to their parental species [1]–[5] .", "However , two confounding ...	[ "The X chromosome often plays a central role in hybrid male sterility between species , but it is unclear if this reflects underlying regulatory incompatibilities .", "Here we combine phenotypic data with genome-wide expression data to directly associate aberrant expression patterns with hybrid male sterility bet...	[ "The X chromosome plays an important role in the development of reproductive isolation between species , but the basis for this has remained unclear .", "One possible explanation is that sperm development is sensitive to disruption of X-linked gene regulation .", "In mice , evidence linking abnormal gene expres...	2010
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "antimicrobials", "medicine and health sciences", "protein interactions", "pathology and laboratory medicine", "molecular probe techniques", "pathogens", "drugs", "microbiology", "immunoblotting", "plasmid construction", "physiological processes", "cargo proteins", "mutation", "antibacteri...	VgrG and PAAR Proteins Define Distinct Versions of a Functional Type VI Secretion System	journal.ppat.1005735	null	[ [ "Bacteria utilise a variety of mechanisms to deliver specific proteins to the extracellular environment or directly into a target cell , processes collectively termed protein secretion .", "Bacterial protein secretion systems play a critical role in pathogenicity and can also be instrumental for interacti...	[ "The Type VI secretion system ( T6SS ) is widespread among bacterial pathogens and acts as an effective weapon against competitor bacteria and eukaryotic hosts by delivering toxic effector proteins directly into target cells .", "The T6SS utilises a bacteriophage-like contractile machinery to expel a puncturing d...	[ "Pathogenic bacteria use a biological nanomachine called the ‘Type VI secretion system’ ( T6SS ) to fire toxic proteins into other cells .", "These target cells can be rival bacterial cells , allowing the T6SS-wielding bacteria to outcompete other pathogens or harmless bacteria , or cells of a human , animal or p...	2016
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "mycology", "plant science", "plant microbiology", "plant biology", "plant pathogens", "microbial control", "plant pathology", "biology", "microbiology", "pathogenesis" ]	Cell Death Control: The Interplay of Apoptosis and Autophagy in the Pathogenicity of Sclerotinia sclerotiorum	journal.ppat.1003287	null	[ [ "All higher organisms have developed an intrinsic program for cell suicide .", "These programs sense and monitor multiple internal and external cues and when deemed appropriate , instructs the cell to eliminate itself from the organism for the overall survival of the animal , plant or microbe [1] .", ...	[ "Programmed cell death is characterized by a cascade of tightly controlled events that culminate in the orchestrated death of the cell .", "In multicellular organisms autophagy and apoptosis are recognized as two principal means by which these genetically determined cell deaths occur .", "During plant-microbe i...	[ "During plant-microbe interactions , regulated cell death known as programmed cell death ( PCD ) can mediate both resistant and susceptible interactions .", "Sclerotinia sclerotiorum induces an apoptotic spreading cell death during infection , via the secreted virulence determinant oxalic acid .", "Oxalic acid ...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine", "cellular stress responses", "immune cells", "viruses and cancer", "immunology", "microbiology", "host-pathogen interaction", "cancer risk factors", "hematologic cancers and related disorders", "oncology", "cell division", "epigenetics", "viral and bacterial causes of cancer", ...	Induction of p16INK4a Is the Major Barrier to Proliferation when Epstein-Barr Virus (EBV) Transforms Primary B Cells into Lymphoblastoid Cell Lines	journal.ppat.1003187	null	[ [ "The CDKN2A locus at human chromosome 9p21 encodes two important tumour suppressors , p16INK4a and p14ARF ( equivalent to p19ARF in mice ) ; these proteins are both critical regulators of cell proliferation .", "The cyclin-dependent kinase ( CDK ) inhibitor p16INK4a acts upstream of the cyclin D-dependent...	[ "To explore the role of p16INK4a as an intrinsic barrier to B cell transformation by EBV , we transformed primary B cells from an individual homozygous for a deletion in the CDKN2A locus encoding p16INK4a and p14ARF .", "Using recombinant EBV-BAC viruses expressing conditional EBNA3C ( 3CHT ) , we developed a sys...	[ "Epstein-Barr virus ( EBV ) is a causative agent of several types of B cell lymphoma .", "In human B cells , EBV reduces protein levels of at least two tumour suppressors that would otherwise be activated in response to over-expressed oncogenes .", "These proteins are BIM , which induces cell death and p16INK4a...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "immunology/cellular microbiology and pathogenesis", "immunology/immune response", "infectious diseases/protozoal infections", "immunology/immunity to infections", "immunology/leukocyte activation" ]	Differential Regulation of Effector- and Central-Memory Responses to Toxoplasma gondii Infection by IL-12 Revealed by Tracking of Tgd057-Specific CD8+ T Cells	journal.ppat.1000815	null	[ [ "Infection by the intracellular protozoan parasite Toxoplasma gondii causes severe disease in immunocompromised individuals including neonates , transplant recipients , and people with AIDS [1] .", "In healthy individuals however , resistance to toxoplasmosis is mediated by the ability of T lymphocytes to...	[ "Production of the pro-inflammatory cytokine IL-12 by innate phagocytes drives the differentiation of IFN-γ-producing effector T cells during Toxoplasma gondii infection .", "However , the role of IL-12 in the regulation of memory CD8+ T cell differentiation and function during murine toxoplasmosis is unclear .",...	[ "Toxoplasma gondii is a ubiquitous protozoan parasite that causes severe disease in people with compromised immune function .", "It is known that CD8+ T cells are essential for the establishment of protective immunity , primarily through the delivery of the effector cytokine interferon-γ ( IFN-γ ) to Toxoplasma-i...	2010
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "genetic networks", "methods and resources", "vertebrates", "wnt signaling cascade", "animals", "xenopus", "multivariate analysis", "animal models", "developmental biology", "model organisms", "amphibians", "mathematics", "statistics (mathematics)", "network analysis", "genome analysis",...	A molecular atlas of the developing ectoderm defines neural, neural crest, placode, and nonneural progenitor identity in vertebrates	journal.pbio.2004045	null	[ [ "Neural induction and neurulation are the critical molecular and morphogenetic processes that initiate spatial regionalization in the outer germ layer of vertebrate embryos , the ectoderm .", "The ectoderm forms the protective epidermis , the central nervous system , including the brain and spinal cord , ...	[ "During vertebrate neurulation , the embryonic ectoderm is patterned into lineage progenitors for neural plate , neural crest , placodes and epidermis .", "Here , we use Xenopus laevis embryos to analyze the spatial and temporal transcriptome of distinct ectodermal domains in the course of neurulation , during th...	[ "Vertebrate embryo germ layers become progressively regionalized by evolutionarily conserved molecular processes .", "Catching the early steps of this dynamic spatial cell diversification at the scale of the transcriptome was challenging , even with the advent of efficient RNA sequencing .", "We have microdisse...	2017
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "infectious diseases/neglected tropical diseases", "biotechnology/bioengineering" ]	piggybac- and PhiC31-Mediated Genetic Transformation of the Asian Tiger Mosquito, Aedes albopictus (Skuse)	journal.pntd.0000788	null	[ [ "Aedes mosquitoes are responsible for an estimated 50 to 100 million dengue cases worldwide every year , with nearly half the world's population at risk of being infected [1] , [2] .", "The two main vector species , Aedes aegypti ( L . ) and Aedes albopictus ( Skuse ) are also the main vectors of the chik...	[ "The Asian tiger mosquito , Aedes albopictus ( Skuse ) , is a vector of several arboviruses including dengue and chikungunya .", "This highly invasive species originating from Southeast Asia has travelled the world in the last 30 years and is now established in Europe , North and South America , Africa , the Midd...	[ "The Asian tiger mosquito , Aedes albopictus , is a highly invasive mosquito and has spread from South East Asia to Europe , the United States and northern areas of Asia in the past 30 years .", "Aedes mosquitoes transmit a range of viral diseases , including dengue and chikungunya .", "Aedes albopictus is gene...	2010
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "ophthalmology/pediatric ophthalmology", "ophthalmology/eye infections", "public health and epidemiology/epidemiology", "infectious diseases/bacterial infections", "infectious diseases/epidemiology and control of infectious diseases" ]	Reduction and Return of Infectious Trachoma in Severely Affected Communities in Ethiopia	journal.pntd.0000376	null	[ [ "Trachoma remains a leading cause of blindness in poor , arid areas such as sub-Saharan Africa[1] .", "The World Health Organization ( WHO ) has targeted the disease in a control program , relying in part on repeated mass distributions of oral azithromycin to reduce the prevalence of the ocular chlamydial...	[ "Antibiotics are a major tool in the WHO's trachoma control program .", "Even a single mass distribution reduces the prevalence of the ocular chlamydia that causes trachoma .", "Unfortunately , infection returns after a single treatment , at least in severely affected areas .", "Here , we test whether additio...	[ "Trachoma is one of the leading causes of blindness in the developing world .", "The World Health Organization has a multi-pronged approach to controlling the ocular chlamydial infection that causes the disease , including distributing antibiotics to entire communities .", "Even a single community treatment dra...	2009
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "genome-wide association studies", "genome expression analysis", "developmental biology", "stem cells", "induced pluripotent stem cells", "epigenetics", "epigenomics", "cell potency", "embryonic stem cells", "comparative genomics", "biology", "dna modification", "microarrays", "genetics", ...	DNA Methylation Dynamics in Human Induced Pluripotent Stem Cells over Time	journal.pgen.1002085	null	[ [ "DNA methylation is an important epigenetic modification and is a key component in normal differentiation , development and disease [1]–[3] .", "Expression of tissue-specific genes , such as Oct-4 [4] , Nanog [5] , Sry ( sex determining region on Y chromosome ) [6] and MyoD [7] , are induced by spatio-tem...	[ "Epigenetic reprogramming is a critical event in the generation of induced pluripotent stem cells ( iPSCs ) .", "Here , we determined the DNA methylation profiles of 22 human iPSC lines derived from five different cell types ( human endometrium , placental artery endothelium , amnion , fetal lung fibroblast , and...	[ "iPSCs change to resemble ESCs via two phases: the transgene-dependent phase , in which the transcription factors act to transform somatic cells into pluripotent stem cells , and the transgene-independent phase , in which the transcription factors are silenced .", "In this study , we established human iPSCs deriv...	2011
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "computer and information sciences", "plant science", "genetic networks", "gene mapping", "quantitative trait loci", "phenotypes", "network analysis", "gene identification and analysis", "gene expression", "genetics", "gene regulation", "biology and life sciences", "molecular biology techniq...	Integrating transcriptomic network reconstruction and eQTL analyses reveals mechanistic connections between genomic architecture and Brassica rapa development	journal.pgen.1008367	null	[ [ "Plant developmental dynamics are correlated with fitness and yield [1 , 2] .", "Therefore , characterizing the mechanistic connections between the genetic architecture governing plant development and the resulting ontogenetic dynamics of plants in field settings is critically important to improving agric...	[ "Plant developmental dynamics can be heritable , genetically correlated with fitness and yield , and undergo selection .", "Therefore , characterizing the mechanistic connections between the genetic architecture governing plant development and the resulting ontogenetic dynamics of plants in field settings is crit...	[ "We estimate the developmental dynamics of plant growth using mathematical functions to fit continuous functions to discrete plant height data collected throughout growth , and we use the parameters defining these mathematical functions as data .", "We identify genomic regions controlling plant growth and filter ...	2019
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "invertebrates", "medicine and health sciences", "body fluids", "vertebrates", "animals", "organisms", "molecular biology techniques", "dna", "insect vectors", "extraction techniques", "research and analysis methods", "sequence analysis", "infectious diseases", "artificial gene amplificati...	Barcoding blood meals: New vertebrate-specific primer sets for assigning taxonomic identities to host DNA from mosquito blood meals	journal.pntd.0006767	null	[ [ "Females of most mosquito species require a blood meal , taken from a host animal , in order to mature their eggs [1] .", "This requirement enables mosquitoes to vector disease-causing parasites and pathogens between their vertebrate host animals .", "Within an ecosystem , the host-use patterns of the...	[ "The transmission dynamics of mosquito-vectored pathogens are , in part , mediated by mosquito host-feeding patterns .", "These patterns are elucidated using blood meal analysis , a collection of serological and molecular techniques that determine the taxonomic identities of the host animals from which blood meal...	[ "Female mosquitoes take blood meals from diverse vertebrate hosts , including amphibians , birds , mammals , reptiles , and fishes .", "Mosquito species vary in their host-use patterns .", "Identifying which mosquitoes feed from which hosts is critical to understanding how mosquitoes transmit disease-causing pa...	2018
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[]	Polymorphisms in the TOLLIP Gene Influence Susceptibility to Cutaneous Leishmaniasis Caused by Leishmania guyanensis in the Amazonas State of Brazil	journal.pntd.0003875	null	[ [ "Leishmaniasis , a vector-borne disease , is caused by the intracellular protozoan parasites of the Leishmania genus , which are transmitted by the phlebotomine sand fly .", "Leishmania-infection , depending on the Leishmania ( L . ) species and on the host specific immune response , presents a broad spec...	[ "The clinical outcome to Leishmania-infection is determined by the individual adaptive immune T helper cell responses and their interactions with parasitized host cells .", "An early development of a proinflammatory immune response ( Th1 response ) is necessary for Leishmania-infection resolution .", "The Toll-...	[ "Leishmaniasis is an infectious disease caused by the protozoan parasite of the Leishmania genus .", "It is transmitted by infected sandfly ( the phlebotomines ) and caused either visceral or tegumentary leishmaniasis depending on the species .", "In areas of endemicity for leishmaniasis , not all individuals e...	2015
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "medicine and health sciences", "pathology and laboratory medicine", "dose prediction methods", "cell processes", "biomarkers", "toxicology", "toxicity", "pharmaceutics", "drug administration", "pharmacology", "drug metabolism", "pharmacokinetics", "biochemistry", "predictive toxicology", ...	A Comparative Analysis of Drug-Induced Hepatotoxicity in Clinically Relevant Situations	journal.pcbi.1005280	null	[ [ "Drug-induced hepatotoxicity poses a significant problem in drug development and public health [1 , 2] .", "Extensive drug exposure due to overdosing or patient idiosyncrasy may lead to hepatotoxic effects such as drug-induced steatosis or cholestasis [3 , 4 , 5] .", "Such adverse events may even be a...	[ "Drug-induced toxicity is a significant problem in clinical care .", "A key problem here is a general understanding of the molecular mechanisms accompanying the transition from desired drug effects to adverse events following administration of either therapeutic or toxic doses , in particular within a patient con...	[ "Liver toxicity may occur at drug levels above the therapeutic range and is thus a crucial problem in clinical care .", "However , the cellular changes induced by drug administration of therapeutic and toxic doses in humans are still not well understood .", "We here coupled patient-specific drug concentration-t...	2017
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "kala-azar", "medicine and health sciences", "tropical diseases", "geographical locations", "india", "sand flies", "parasitic diseases", "parasitic protozoans", "research design", "protozoans", "leishmania", "neglected tropical diseases", "infectious disease control", "insect vectors", "...	Longitudinal Study of Transmission in Households with Visceral Leishmaniasis, Asymptomatic Infections and PKDL in Highly Endemic Villages in Bihar, India	journal.pntd.0005196	null	[ [ "Visceral leishmaniasis ( VL ) , also known as kala-azar , is a neglected vector-borne disease caused by a protozoan parasite , Leishmania donovani and is transmitted by the bite of infected Phlebotomus argentipes sandflies .", "The estimated number of annual VL cases worldwide is 0 . 2–0 . 4 million per ...	[ "Visceral Leishmaniasis ( VL ) is a neglected tropical disease that afflicts some of the poorest populations in the world including people living in the Bihar state of India .", "Due to efforts from local governments , NGOs and international organizations , the number of VL cases has declined in recent years .", ...	[ "Visceral leishmaniasis ( also known as kala-azar ) caused by infection with L . donovani is a deadly parasitic disease that afflicts some of world’s poorest populations , including the people of the northern Bihar State of India .", "Once transmitted to a human by an infected sandfly , the L . donovani parasite ...	2016
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "medicine and health sciences", "nose", "face", "atmospheric science", "population genetics", "pigments", "respiratory system", "materials science", "population biology", "humidity", "genetic polymorphism", "materials by attribute", "head", "organic pigments", "genetic drift", "nasal c...	Investigating the case of human nose shape and climate adaptation	journal.pgen.1006616	null	[ [ "The shape of the nose , like many other parts of the face , varies both within as well as across human populations .", "For example , the distance between the nasal alare ( wings of the nose ) are significantly larger in individuals of West African , South Asian , and East Asian ancestry as compared to p...	[ "The evolutionary reasons for variation in nose shape across human populations have been subject to continuing debate .", "An import function of the nose and nasal cavity is to condition inspired air before it reaches the lower respiratory tract .", "For this reason , it is thought the observed differences in n...	[ "The study of human adaptation is essential to our understanding of disease etiology .", "Evolutionary investigations into why certain disease phenotypes such as sickle-cell anemia and lactose intolerance occur at different rates in different populations have led to a better understanding of the genetic and envir...	2017
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "infectious diseases/tropical and travel-associated diseases", "biochemistry/drug discovery" ]	A Target-Based High Throughput Screen Yields Trypanosoma brucei Hexokinase Small Molecule Inhibitors with Antiparasitic Activity	journal.pntd.0000659	null	[ [ "African sleeping sickness conjures historical images of disease-induced fatal slumbering striking down men , women , and children , consequently decimating villages of colonial Africa .", "Unfortunately , people living in many countries of sub-Saharan Africa today know that African sleeping sickness is n...	[ "The parasitic protozoan Trypanosoma brucei utilizes glycolysis exclusively for ATP production during infection of the mammalian host .", "The first step in this metabolic pathway is mediated by hexokinase ( TbHK ) , an enzyme essential to the parasite that transfers the γ-phospho of ATP to a hexose .", "Here w...	[ "African sleeping sickness is a disease found in sub-Saharan Africa that is caused by the single-celled parasite Trypanosoma brucei .", "The drugs used widely now to treat infections are 50 years old and notable for their toxicity , emphasizing the need for development of new therapeutics .", "In the search for...	2010
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "mathematics", "diabetes and endocrinology/obesity", "nutrition/obesity", "physiology/integrative physiology", "biochemistry/theory and simulation" ]	Estimating the Continuous-Time Dynamics of Energy and Fat Metabolism in Mice	journal.pcbi.1000511	null	[ [ "Mouse models of obesity have become critically important research tools for discovering molecular mechanisms of body weight regulation .", "But understanding these mechanisms in the context of whole-body physiology requires knowledge of food intake , energy output , and fuel selection [1] .", "Furthe...	[ "The mouse has become the most popular organism for investigating molecular mechanisms of body weight regulation .", "But understanding the physiological context by which a molecule exerts its effect on body weight requires knowledge of energy intake , energy expenditure , and fuel selection .", "Furthermore , ...	[ "The unrelenting obesity epidemic has resulted in intensive basic scientific investigation into the molecular mechanisms of body weight regulation—with the mouse being the organism of choice for such studies .", "We know that any mechanism of body weight regulation must exert its effect by influencing food intake...	2009
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "molecular biology", "biology and life sciences", "parasitology" ]	RNAi Dynamics in Juvenile Fasciola spp. Liver Flukes Reveals the Persistence of Gene Silencing In Vitro	journal.pntd.0003185	null	[ [ "Fasciola spp .", "liver flukes are the causative agents of fascioliasis , or liver fluke disease .", "Their growing importance as human neglected tropical disease pathogens , alongside their impact on animal health , welfare and global food security , is recognised [1]–[3] .", "This pathology is ...	[ "Fasciola spp .", "liver fluke cause pernicious disease in humans and animals .", "Whilst current control is unsustainable due to anthelmintic resistance , gene silencing ( RNA interference , RNAi ) has the potential to contribute to functional validation of new therapeutic targets .", "The susceptibility of ...	[ "RNA interference ( RNAi ) is a method for selectively silencing ( or reducing expression of ) mRNA transcripts , an approach which can be used to interrogate the function of genes and proteins , and enables the validation of potential targets for anthelmintic drugs or vaccines , by investigating the impact of sile...	2014
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "medicine", "infectious diseases", "test evaluation", "diagnostic medicine", "pathology", "global health", "clinical pathology", "dengue fever", "neglected tropical diseases" ]	Evaluation of the Diagnostic Utility of the Traditional and Revised WHO Dengue Case Definitions	journal.pntd.0002385	null	[ [ "Dengue is caused by the four serotypes of dengue virus ( DENV-1-4 ) , a flavivirus transmitted primarily by Aedes aegypti and Ae .", "albopictus mosquitoes .", "Dengue is recognized as a major health problem globally , causing an estimated 100 million cases in over 100 countries in Asia , Africa and ...	[ "Dengue , a mosquito-borne viral illness , is a major public health problem worldwide , and its incidence continues to increase .", "In 2009 , the World Health Organization published guidelines that included a revision of the dengue case definition .", "Compared to the traditional definition , the revised case ...	[ "Dengue , a mosquito-borne viral infectious disease , is a major health problem worldwide .", "Its incidence has dramatically increased in the last 3 decades , particularly in the Americas .", "The traditional World Health Organization dengue case definition was in use for over 30 years , but in 2009 a revised ...	2013
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "computational chemistry", "chemistry", "biology", "computational biology" ]	Using Multiple Microenvironments to Find Similar Ligand-Binding Sites: Application to Kinase Inhibitor Binding	journal.pcbi.1002326	null	[ [ "Structural biology studies have provided large numbers of high-resolution proteins , often bound to small molecule ligands .", "The ability to predict additional ligands that will bind these proteins is an exciting opportunity for understanding drug action and repurposing .", "In some cases , the bin...	[ "The recognition of cryptic small-molecular binding sites in protein structures is important for understanding off-target side effects and for recognizing potential new indications for existing drugs .", "Current methods focus on the geometry and detailed chemical interactions within putative binding pockets , bu...	[ "Small molecule drugs may interact with many proteins .", "Some of these interactions may cause unexpected effects , including side effects or potentially useful therapeutic effects .", "One way to predict these effects is to analyze the three-dimensional structure of target proteins , and identify new binding ...	2011
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "developmental biology", "genetics", "biology", "neuroscience", "genetics and genomics" ]	Mitosis in Neurons: Roughex and APC/C Maintain Cell Cycle Exit to Prevent Cytokinetic and Axonal Defects in Drosophila Photoreceptor Neurons	journal.pgen.1003049	null	[ [ "The near universality of neuronal cell cycle exit implies robust barriers to division .", "These could include additional neuron-specific and redundant barriers to cell cycle entry and progression , and surveillance mechanisms to eliminate neurons that evade them .", "Even in tumors , to date the onl...	[ "The mechanisms of cell cycle exit by neurons remain poorly understood .", "Through genetic and developmental analysis of Drosophila eye development , we found that the cyclin-dependent kinase-inhibitor Roughex maintains G1 cell cycle exit during differentiation of the R8 class of photoreceptor neurons .", "The...	[ "Neurons generally differentiate and never divide again .", "One barrier to understanding the mechanisms has been the paucity of genetic mutations that result in neuronal cell cycles .", "Here we show that mutation in three genes lead to cell cycle re-entry by a particular class of developing photoreceptor neur...	2012
[ "Introduction", "Methods", "Results", "Discussion" ]	[]	Group 2 Innate Lymphoid Cell Proportions Are Diminished in Young Helminth Infected Children and Restored by Curative Anti-helminthic Treatment	journal.pntd.0003627	null	[ [ "Innate lymphoid cells are a recently described cell type that has transformed our understanding of the role of innate immune responses in the generation of adaptive immune responses .", "Group 2 Innate lymphoid cells ( ILC2s ) produce the classical TH2 cytokines IL-5 and IL-13 [1–3] and have been shown t...	[ "Group 2 Innate lymphoid cells ( ILC2s ) are innate cells that produce the TH2 cytokines IL-5 and IL-13 .", "The importance of these cells has recently been demonstrated in experimental models of parasitic diseases but there is a paucity of data on ILC2s in the context of human parasitic infections and in particu...	[ "Understanding how immune responses are generated is critical for vaccine development .", "There are comparatively few studies on the interface between the innate and adaptive immune system in generating protective immune responses .", "Infections with helminth parasites , a cause of neglected tropical diseases...	2015
[ "Introduction", "Materials and methods", "Results", "Discussion" ]	[ "medicine and health sciences", "immune physiology", "pathology and laboratory medicine", "spleen", "crimean-congo hemorrhagic fever", "pathogens", "immunology", "tropical diseases", "microbiology", "vaccines", "preventive medicine", "animal models", "viruses", "model organisms", "dna vi...	Nucleocapsid protein-based vaccine provides protection in mice against lethal Crimean-Congo hemorrhagic fever virus challenge	journal.pntd.0006628	null	[ [ "Crimean-Congo hemorrhagic fever ( CCHF ) is an acute infectious disease with a wide geographic distribution and an average case fatality rate of approximately 20–30% [1 , 2] .", "The etiological agent , CCHF orthonairovirus ( CCHFV ) , belongs to the Orthonairovirus genus of the Nairoviridae family .", ...	[ "Crimean-Congo hemorrhagic fever ( CCHF ) is an acute , often fatal viral disease characterized by rapid onset of febrile symptoms followed by hemorrhagic manifestations .", "The etiologic agent , CCHF orthonairovirus ( CCHFV ) , can infect several mammals in nature but only seems to cause clinical disease in hum...	[ "Crimean-Congo hemorrhagic fever ( CCHF ) is a tick-borne disease that can manifest as a viral hemorrhagic fever syndrome .", "The CCHF virus is widely spread throughout the African continent , the Balkans , the Middle East , Southern Russia and Western Asia where it remains a serious public health concern .", ...	2018
[ "Introduction", "Results and discussion", "Conclusions", "Methods" ]	[ "rna-binding proteins", "chemical bonding", "rna stem-loop structure", "simulation and modeling", "protein structure", "rna isolation", "molecular biology techniques", "hydrogen bonding", "physical chemistry", "research and analysis methods", "rna structure", "proteins", "chemistry", "mole...	Molecular basis for the increased affinity of an RNA recognition motif with re-engineered specificity: A molecular dynamics and enhanced sampling simulations study	journal.pcbi.1006642	null	[ [ "The RNA recognition motif ( RRM ) is the largest family of eukaryotic RNA-binding proteins [1] , involved in virtually all post-transcriptional regulatory events [2] .", "RRMs bind a wide-range of single-stranded RNAs [3] , stem-loops and other RNA structures [2 , 4–6] .", "Therefore , engineering RR...	[ "The RNA recognition motif ( RRM ) is the most common RNA binding domain across eukaryotic proteins .", "It is therefore of great value to engineer its specificity to target RNAs of arbitrary sequence .", "This was recently achieved for the RRM in Rbfox protein , where four mutations R118D , E147R , N151S , and...	[ "RNA is an outstanding target for oncological intervention .", "Engineering the most common RNA binding motif in human proteins ( called RRM ) so as to bind to a specific RNA has an enormous pharmacological potential .", "Yet , it is highly non trivial to design RRM-bearing protein variants with RNA selectivity...	2018
[ "Introduction", "Models", "Results", "Discussion" ]	[ "evolutionary ecology", "statistical mechanics", "applied mathematics", "population genetics", "mathematics", "population modeling", "theoretical ecology", "biophysics simulations", "evolutionary modeling", "biophysics theory", "biology", "evolutionary theory", "population ecology", "nonli...	The Fate of Cooperation during Range Expansions	journal.pcbi.1002994	null	[ [ "Cooperation between organisms has always interested evolutionary biologists [1]–[3] .", "On the one hand , cooperative interactions are widespread in living systems .", "Microbes cooperate to digest food , scavenge for scarce resources , or build a protective biofilm [4]; animals cooperate to hunt or...	[ "Species expand their geographical ranges following an environmental change , long range dispersal , or a new adaptation .", "Range expansions not only bring an ecological change , but also affect the evolution of the expanding species .", "Although the dynamics of deleterious , neutral , and beneficial mutatio...	[ "Cooperation is beneficial for the species as a whole , but , at the level of an individual , defection pays off .", "Natural selection is then expected to favor defectors and eliminate cooperation .", "This prediction is in stark contrast with the abundance of cooperation at all levels of biological systems: f...	2013
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "biophysics", "biochemistry", "plant biology" ]	Analysis of LhcSR3, a Protein Essential for Feedback De-Excitation in the Green Alga Chlamydomonas reinhardtii	journal.pbio.1000577	To prevent photodamage by excess light, plants use different proteins to sense pH changes and to dissipate excited energy states. In green microalgae, however, the LhcSR3 gene product is able to perform both pH sensing and energy quenching functions.	[ [ "In photosynthetic organisms , feedback dissipation of chlorophyll ( Chl ) singlet excited states balances light harvesting with metabolic energy consumption , in order to prevent photodamage due to reactive oxygen species ( ROS ) formation when excess energy is transferred to O2 .", "Both plants and alga...	[ "In photosynthetic organisms , feedback dissipation of excess absorbed light energy balances harvesting of light with metabolic energy consumption .", "This mechanism prevents photodamage caused by reactive oxygen species produced by the reaction of chlorophyll ( Chl ) triplet states with O2 .", "Plants have be...	[ "Reactive oxygen species are formed during photosynthesis , particularly when electron transport is saturated in high light .", "The process of non-photochemical quenching ( NPQ ) helps protect plants against excess light by dissipating the excited states of chlorophyll into heat .", "By doing so , it prevents ...	2011
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "neuroscience/behavioral neuroscience", "genetics and genomics/animal genetics", "neuroscience/sensory systems", "cell biology/cell signaling", "cell biology/neuronal signaling mechanisms" ]	Regulators of AWC-Mediated Olfactory Plasticity in Caenorhabditis elegans	journal.pgen.1000761	null	[ [ "Olfactory adaptation may subserve a food-seeking strategy in C . elegans .", "Since the sources of many odors that are inherently attractive to C . elegans do not , in fact , provide a source of nutrition , the worm may have to discriminate between rewarding and unrewarding stimuli by adapting to nutriti...	[ "While most sensory neurons will adapt to prolonged stimulation by down-regulating their responsiveness to the signal , it is not clear which events initiate long-lasting sensory adaptation .", "Likewise , we are just beginning to understand how the physiology of the adapted cell is altered .", "Caenorhabditis ...	[ "Caenorhabditis elegans is capable of sensing a variety of attractive volatile compounds .", "These odors are the worm's “best guesses” as to how to track down food .", "Employing calculated approximations underlies a foraging strategy that is open to failure .", "When C . elegans track an odor which proves u...	2009
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "genome analysis tools", "mycology", "fungi", "immunity", "innate immunity", "immunology", "biology", "genomics", "microbiology", "host-pathogen interaction", "genetics and genomics", "transcriptomes" ]	Murine Dendritic Cells Transcriptional Modulation upon Paracoccidioides brasiliensis Infection	journal.pntd.0001459	null	[ [ "The thermodimorphic fungus Paracoccidioides brasiliensis is the causative agent of paracoccidioidomycosis ( PCM ) , a systemic human disease that is geographically confined to Latin America .", "PCM is mainly endemic in Argentina , Colombia , Venezuela and especially in Brazil , where it is the most prev...	[ "Limited information is available regarding the modulation of genes involved in the innate host response to Paracoccidioides brasiliensis , the etiologic agent of paracoccidioidomycosis .", "Therefore , we sought to characterize , for the first time , the transcriptional profile of murine bone marrow-derived dend...	[ "Paracoccidioidomycosis is a systemic disease that has an important mortality and morbidity impact in Latin America , mainly affecting rural workers of Argentina , Colombia , Venezuela and Brazil .", "Upon host infection , one of the most important aspects contributing to disease outcome is the initial encounter ...	2012
[ "Introduction", "Methods", "Results", "Discussion" ]	[ "infectious diseases", "tropical diseases", "medicine and health sciences" ]	Is Plasmodium vivax Malaria a Severe Malaria?: A Systematic Review and Meta-Analysis	journal.pntd.0003071	null	[ [ "Plasmodium falciparum and P . vivax are the two major species of malaria infecting humans .", "Although emphasis on P . falciparum is appropriate , the burden of vivax malaria should be given due attention as almost 40% of the world population are at risk of vivax malaria [1] .", "Historical evidence...	[ "Plasmodium vivax is one of the major species of malaria infecting humans .", "Although emphasis on P . falciparum is appropriate , the burden of vivax malaria should be given due attention .", "This study aimed to synthesize the evidence on severe malaria in P . vivax infection compared with that in P . falcip...	[ "Until recently , vivax malaria has received less attention than falciparum malaria and was deemed neglected .", "There has been a surge in studies that documented the contribution of Plasmodium vivax to severe malaria in some endemic countries such as Thailand , Brazil , Indonesia , Papua New Guinea and India ."...	2014
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "ecology", "virology", "infectious diseases/viral infections", "molecular biology", "genetics and genomics" ]	Evidence of Infection by H5N2 Highly Pathogenic Avian Influenza Viruses in Healthy Wild Waterfowl	journal.ppat.1000127	null	[ [ "Wild waterbirds are considered the natural reservoirs of low pathogenic avian influenza ( LPAI ) viruses [1] , [2] , but highly pathogenic avian influenza ( HPAI ) viruses responsible for high mortality in domestic birds do not have recognised wild bird reservoirs [3] .", "Among the 16 hemagglutinin ( HA...	[ "The potential existence of a wild bird reservoir for highly pathogenic avian influenza ( HPAI ) has been recently questioned by the spread and the persisting circulation of H5N1 HPAI viruses , responsible for concurrent outbreaks in migratory and domestic birds over Asia , Europe , and Africa .", "During a large...	[ "Until recently , the highly pathogenic avian influenza ( HPAI ) viruses responsible for high mortality in some domestic poultry were considered not to have a wild bird reservoir , but to emerge in domestic poultry populations from low pathogenic viruses perpetuated in wild waterbirds .", "The rapid spread of H5N...	2008
[ "Introduction", "Results", "Discussion" ]	[ "neuroscience/neurodevelopment", "computational biology/systems biology", "computational biology/computational neuroscience" ]	Burst-Time-Dependent Plasticity Robustly Guides ON/OFF Segregation in the Lateral Geniculate Nucleus	journal.pcbi.1000618	null	[ [ "During the development of the visual system , connections between neurons form and refine in a self-organized manner governed by various mechanisms .", "Initially , target neurons are contacted by multiple RGCs following gradients of molecular cues [1]–[3] .", "As circuits mature , visually-evoked ac...	[ "Spontaneous retinal activity ( known as “waves” ) remodels synaptic connectivity to the lateral geniculate nucleus ( LGN ) during development .", "Analysis of retinal waves recorded with multielectrode arrays in mouse suggested that a cue for the segregation of functionally distinct ( ON and OFF ) retinal gangli...	[ "Many central targets in the brain are involved in the processing of information from the outside world .", "Before information about the visual scene reaches the visual cortex , it is preprocessed in the retina and the lateral geniculate nucleus .", "Connections which relay this information between the differe...	2009
[ "Introduction", "Materials and Methods", "Results", "Discussion" ]	[ "medicine", "infectious diseases", "medicinal chemistry", "chemistry", "biology" ]	In Vitro and In Vivo Efficacy of Ether Lipid Edelfosine against Leishmania spp. and SbV-Resistant Parasites	journal.pntd.0001612	null	[ [ "The impact of the leishmaniases on human health has been grossly underestimated for many years , and this complex of diseases has been classified by the World Health Organization ( WHO ) as one of the most neglected tropical diseases [1] .", "During the last decade , endemic areas have been spreading and...	[ "The leishmaniases are a complex of neglected tropical diseases caused by more than 20 Leishmania parasite species , for which available therapeutic arsenal is scarce and unsatisfactory .", "Pentavalent antimonials ( SbV ) are currently the first-line pharmacologic therapy for leishmaniasis worldwide , but resist...	[ "Leishmaniasis represents a major international health problem , has a high morbidity and mortality rate , and is classified as an emerging and uncontrolled disease by the World Health Organization .", "The migration of population from endemic to nonendemic areas , and tourist activities in endemic regions are sp...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "oncology", "genetics and genomics/gene discovery", "oncology/breast cancer", "genetics and genomics/gene expression", "genetics and genomics/genetics of disease", "molecular biology", "genetics and genomics", "cell biology/gene expression", "genetics and genomics/cancer genetics" ]	Use of DNA–Damaging Agents and RNA Pooling to Assess Expression Profiles Associated with BRCA1 and BRCA2 Mutation Status in Familial Breast Cancer Patients	journal.pgen.1000850	null	[ [ "Rare sequence variants in BRCA1 and BRCA2 that are not predicted to lead to obvious or easily detectable molecular aberrations , such as protein truncation or RNA splicing defects , are currently difficult to classify clinically as pathogenic or neutral .", "These variants attribute to approximately 10% ...	[ "A large number of rare sequence variants of unknown clinical significance have been identified in the breast cancer susceptibility genes , BRCA1 and BRCA2 .", "Laboratory-based methods that can distinguish between carriers of pathogenic mutations and non-carriers are likely to have utility for the classification...	[ "A large number of rare sequence variants of unknown clinical significance have been identified in the breast cancer susceptibility genes , BRCA1 and BRCA2 .", "Laboratory methods to identify which of these variants are mutations would have utility for counseling and clinical decision making when identified in pa...	2010
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "immunology/cellular microbiology and pathogenesis", "microbiology/innate immunity", "immunology/innate immunity", "cell biology/membranes and sorting", "biochemistry/cell signaling and trafficking structures", "microbiology/cellular microbiology and pathogenesis" ]	Atg5-Independent Sequestration of Ubiquitinated Mycobacteria	journal.ppat.1000430	null	[ [ "Mycobacterium marinum ( Mm ) is a close genetic relative of the important human pathogen M . tuberculosis , and shares with M . tuberculosis the ability to infect host macrophages , as well as to induce a similar pathologic response [1] , [2] .", "As in mammalian models of infection with M . tuberculosis...	[ "Like several other intracellular pathogens , Mycobacterium marinum ( Mm ) escapes from phagosomes into the host cytosol where it can polymerize actin , leading to motility that promotes spread to neighboring cells .", "However , only ∼25% of internalized Mm form actin tails , and the fate of the remaining bacter...	[ "M . tuberculosis is one of the world's most prevalent pathogens , infecting one third of humans and contributing to 2 million deaths each year .", "M . marinum ( Mm ) has been increasingly studied as a model of M . tuberculosis due to its relative safety and its shared mechanisms of pathogenesis; for example , p...	2009
[ "Introduction", "Materials and methods", "Results", "Homology model of SmSP2 reveals the trypsin-like active site pocket shielded by additional loops", "Substrate and inhibitor specificity classifies SmSP2 as a trypsin-like enzyme", "SmSP2 releases bradykinin from kininogen and activates plasmin", "Disc...	[ "schistosoma", "invertebrates", "schistosoma mansoni", "medicine and health sciences", "body fluids", "helminths", "enzymes", "enzymology", "parasitic diseases", "animals", "serine proteases", "plasmins", "research and analysis methods", "sequence analysis", "bioinformatics", "proteins...	SmSP2: A serine protease secreted by the blood fluke pathogen Schistosoma mansoni with anti-hemostatic properties	journal.pntd.0006446	null	[ [ "Schistosomiasis ( bilharziasis ) is a chronic infectious disease caused by a trematode blood flukes of the genus Schistosoma .", "A public health problem in 74 developing countries , the parasite infects over 240 million people with up to 700 million people at risk [1 , 2] .", "Adult schistosomes can...	[ "Serine proteases are important virulence factors for many pathogens .", "Recently , we discovered a group of trypsin-like serine proteases with domain organization unique to flatworm parasites and containing a thrombospondin type 1 repeat ( TSR-1 ) .", "These proteases are recognized as antigens during host in...	[ "Schistosomiasis ( bilharziasis ) is a global parasitic infection with more than 240 million people infected .", "It is caused by Schistosoma flatworms that live in the bloodstream .", "Current treatment relies on one drug , and no effective vaccine has yet been developed .", "Proteolytic enzymes ( proteases ...	2018
[ "Introduction", "Results", "Discussion", "Methods" ]	[ "evolutionary biology", "protein folding", "biology", "evolutionary theory", "biophysics" ]	Mutation Induced Extinction in Finite Populations: Lethal Mutagenesis and Lethal Isolation	journal.pcbi.1002609	null	[ [ "On average , mutations hurt organismal fitness , e . g . by destabilizing proteins .", "Thus , left unchecked , new mutations tend to erode fitness and endanger the long-term survival of any species .", "Fortunately , natural selection usually balances against mutational genetic decay by rewarding th...	[ "Reproduction is inherently risky , in part because genomic replication can introduce new mutations that are usually deleterious toward fitness .", "This risk is especially severe for organisms whose genomes replicate “semi-conservatively , ” e . g . viruses and bacteria , where no master copy of the genome is pr...	[ "Most spontaneous mutations hurt organismal fitness , e . g . by destabilizing proteins .", "In many species , the normal mutation rate is strikingly high: on the order of one per genome per replication .", "In the face of these mutations , how can proteins maintain their native structure , and how can populati...	2012
[ "Introduction", "Results", "Discussion", "Materials and Methods" ]	[ "algorithms", "medicine", "oncology", "computer science", "software engineering", "software tools" ]	Integrative Analysis of Deep Sequencing Data Identifies Estrogen Receptor Early Response Genes and Links ATAD3B to Poor Survival in Breast Cancer	journal.pcbi.1003100	null	[ [ "The identification of genes whose expression patterns are altered due to a stimulus is essential as it provides a basis to understand which signaling and metabolic pathways are influenced as a consequence of a stimulus .", "The majority of approaches to identify stimulus-regulated changes in gene express...	[ "Identification of responsive genes to an extra-cellular cue enables characterization of pathophysiologically crucial biological processes .", "Deep sequencing technologies provide a powerful means to identify responsive genes , which creates a need for computational methods able to analyze dynamic and multi-leve...	[ "Cellular processes in mammalian cells are tightly regulated to ensure that the cells function properly as a part of an organism .", "Dysregulation of some of these processes , such as apoptosis , cell proliferation and growth , can lead to cancer .", "One of the most important regulation mechanisms for cellula...	2013
[ "Introduction", "Results", "Discussion", "Materials and methods" ]	[ "invertebrates", "medicine and health sciences", "body fluids", "pathology and laboratory medicine", "pathogens", "microbiology", "animals", "toxicology", "drug screening", "viruses", "toxicity", "rna viruses", "pharmacology", "insect vectors", "infectious diseases", "aedes aegypti", ...	Identification of anti-flaviviral drugs with mosquitocidal and anti-Zika virus activity in Aedes aegypti	journal.pntd.0007681	null	[ [ "Zika virus ( ZIKV ) belongs to the Flavivirus genus , which also includes dengue virus ( DENV ) , West Nile ( WNV ) , yellow fever virus ( YFV ) and Japanese encephalitis viruses ( JEV ) and is mainly transmitted by Aedes mosquitoes , including Ae .", "aegypti and Ae .", "albopictus , in an urban cyc...	[ "Zika virus ( ZIKV ) , an emerging arbovirus belonging to the genus Flavivirus , is transmitted by Aedes mosquitoes .", "ZIKV infection can cause microcephaly of newborn babies and Guillain–Barré syndrome in adults .", "Because no licensed vaccine or specific antiviral treatment is available for ZIKV infection ...	[ "Zika virus ( ZIKV ) is a human threat with a global health burden .", "As many as 86 countries and territories have reported evidence of mosquito-transmitted Zika infection , and there is no effective means of control .", "Recently , several studies have identified FDA-approved drugs exerting anti-ZIKV activit...	2019
[ "Introduction", "Results", "Discussion", "Methods" ]	[]	Rescue of a Plant Negative-Strand RNA Virus from Cloned cDNA: Insights into Enveloped Plant Virus Movement and Morphogenesis	journal.ppat.1005223	null	[ [ "Negative-strand RNA ( NSR ) viruses have major impacts on public health , agriculture and ecology , and they collectively are responsible for some of our most serious human , veterinary , wildlife and plant diseases [1] .", "Plant NSR viruses comprise members of the Rhabdoviridae , Bunyaviridae , Ophiovi...	[ "Reverse genetics systems have been established for all major groups of plant DNA and positive-strand RNA viruses , and our understanding of their infection cycles and pathogenesis has benefitted enormously from use of these approaches .", "However , technical difficulties have heretofore hampered applications of...	[ "Reverse genetics is a powerful tool for fundamental studies of virus biology , pathology and biotechnology applications .", "Although plant negative-strand RNA ( NSR ) viruses consist of members in the Rhabdoviridae , Bunyaviridae , Ophioviridae families and several unassigned genera that collectively account fo...	2015

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