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doi stringlengths 28 28	title stringlengths 19 311	abstract stringlengths 217 5.08k	plain language summary stringlengths 115 4.83k	article stringlengths 3.87k 161k
10.1371/journal.pgen.1002599	Widespread Site-Dependent Buffering of Human Regulatory Polymorphism	The average individual is expected to harbor thousands of variants within non-coding genomic regions involved in gene regulation. However, it is currently not possible to interpret reliably the functional consequences of genetic variation within any given transcription factor recognition sequence. To address this, we c...	A comprehensive understanding of the contribution of individual genome sequences to disease and quantitative traits will require the general ability to predict consequences of genetic variation in non-protein-coding regions, particularly those involved in gene regulation. Here we tested the power to predict such conseq...	A growing number of studies associate variation within regulatory DNA and risk of human disease [1]–[3]. Variation in regulatory DNA may result in modulation of recognition by sequence-specific transcription factors (TFs), resulting in altered gene expression [4]–[6]. That the vast majority of variants emerging from hu...
10.1371/journal.pntd.0007345	A highly expressed intestinal cysteine protease of Ancylostoma ceylanicum protects vaccinated hamsters from hookworm infection	Human hookworms (Necator americanus, Ancylostoma duodenale, and Ancylostoma ceylanicum) are intestinal blood-feeding parasites that infect ~500 million people worldwide and are among the leading causes of iron-deficiency anemia in the developing world. Drugs are useful against hookworm infections, but hookworms rapidly...	Hookworms are voracious, blood-feeding, soil-transmitted nematode parasites. Adult hookworms infect the small intestine, causing iron-deficiency anemia and other complications. Hookworms are among the most disabling parasites of the developing world. Drugs are useful for controlling hookworm disease. However, because p...	Human hookworms (Necator americanus, Ancylostoma duodenale, and Ancylostoma ceylanicum) are soil-transmitted nematodes (STNs) that infect the small intestine and feed on blood [1]. Human STNs encompass three phylogenetically distant parasites: hookworms, large roundworms (Ascaris lumbricoides), and whipworms (Trichuris...
10.1371/journal.pgen.1006446	Mechanisms for Complex Chromosomal Insertions	Chromosomal insertions are genomic rearrangements with a chromosome segment inserted into a non-homologous chromosome or a non-adjacent locus on the same chromosome or the other homologue, constituting ~2% of nonrecurrent copy-number gains. Little is known about the molecular mechanisms of their formation. We identifie...	By traditional cytogenetic techniques, the incidence of microscopically visible chromosomal insertions was estimated to be 1 in 80,000 live births. More recently, by aCGH in conjunction with FISH confirmation of the aCGH findings, insertion events were demonstrated to occur much more frequently (1 in ~500 individuals t...	Chromosomal insertion occurs when a segment of one chromosome is translocated and inserted into an interstitial region of another non-homologous chromosome (interchromosomal insertion), or into a different region of the same chromosome (intrachromosomal insertion). Insertions are considered as complex chromosomal rearr...
10.1371/journal.pcbi.1000904	Graph-Based Analysis of the Metabolic Exchanges between Two Co-Resident Intracellular Symbionts, Baumannia cicadellinicola and Sulcia muelleri, with Their Insect Host, Homalodisca coagulata	Endosymbiotic bacteria from different species can live inside cells of the same eukaryotic organism. Metabolic exchanges occur between host and bacteria but also between different endocytobionts. Since a complete genome annotation is available for both, we built the metabolic network of two endosymbiotic bacteria, Sulc...	Some bacteria, called endocytobionts, permanently live inside the cells of a pluricellular organism and often bring an adaptative advantage to their host by providing compounds that the latter cannot produce or find in its diet. The association may involve several species of bacteria within the same host. The sap-feedi...	Intracellular symbiosis involves a unicellular organism (the endocytobiont) which durably lives inside the cells of the other partner (the host). In the last century, the crucial role of intracellular symbiosis in the ecology and evolution of many eukaryotes was many times demonstrated [1], [2]. Intracellular mutualis...
10.1371/journal.ppat.1000768	Direct Presentation Is Sufficient for an Efficient Anti-Viral CD8+ T Cell Response	The extent to which direct- and cross-presentation (DP and CP) contribute to the priming of CD8+ T cell (TCD8+) responses to viruses is unclear mainly because of the difficulty in separating the two processes. Hence, while CP in the absence of DP has been clearly demonstrated, induction of an anti-viral TCD8+ response ...	Professional antigen presenting cells fragment viral proteins and display some of the resulting peptides bound to MHC molecules at the cell surface. When virus-specific CD8+ T cells recognize these viral peptides they become activated, proliferate, and kill virus-infected cells to help rid the body of the virus. Two pa...	Activated CD8+ T lymphocytes (TCD8+) kill virus infected cells that display virus-derived peptides presented on cell surface MHC I molecules. Hence, TCD8+ play an essential role in the clearance of many primary viral infections. Moreover, the memory TCD8+ that remain after a primary infection or vaccination can also pa...
10.1371/journal.pntd.0002848	Assessing the Relationship between Vector Indices and Dengue Transmission: A Systematic Review of the Evidence	Despite doubts about methods used and the association between vector density and dengue transmission, routine sampling of mosquito vector populations is common in dengue-endemic countries worldwide. This study examined the evidence from published studies for the existence of any quantitative relationship between vector...	Routine sampling of mosquito vector populations is common in dengue-endemic countries worldwide despite doubts about methods used or the correlation between vector density and dengue transmission. This systematic review examined the published evidence investigating associations between vector indices and dengue cases. ...	Global dengue incidence has increased markedly over the past 50 years to the point where it is now the most widespread mosquito-borne arboviral disease. The World Health Organisation (WHO) has estimated that 50–100 million dengue infections occur annually, while a recent study calculated that the true figure may be clo...
10.1371/journal.pmed.1002373	Malaria, malnutrition, and birthweight: A meta-analysis using individual participant data	Four studies previously indicated that the effect of malaria infection during pregnancy on the risk of low birthweight (LBW; <2,500 g) may depend upon maternal nutritional status. We investigated this dependence further using a large, diverse study population. We evaluated the interaction between maternal malaria infec...	More than 125 million pregnant women are at risk of malaria in pregnancy annually, producing detrimental effects on maternal, newborn, and infant health. Maternal undernutrition is estimated to be responsible for 800,000 newborn deaths annually. Prior evidence from 4 small studies indicated that the harmful impact of m...	Annually, over 20 million infants are born low birthweight (LBW; <2,500 g), predominantly in low- and middle-income countries (LMICs) [1]. LBW can have negative impacts on neonatal mortality and childhood neurological, metabolic, and physical development [2]. The World Health Organization (WHO) has set a Global Nutriti...
10.1371/journal.pcbi.1000403	Functional States of the Genome-Scale Escherichia Coli Transcriptional Regulatory System	A transcriptional regulatory network (TRN) constitutes the collection of regulatory rules that link environmental cues to the transcription state of a cell's genome. We recently proposed a matrix formalism that quantitatively represents a system of such rules (a transcriptional regulatory system [TRS]) and allows syste...	Cells are comprised of genomic information that encodes for proteins, the basic building blocks underlying all biological processes. A transcriptional regulatory system (TRS) connects a cell's environmental cues to its genome and in turn determines which genes are turned “on” in response to these cues. Consequently, TR...	Complex regulatory networks control the transcription state of a genome and consequently the functional activity of a cell [1]. Even relatively simple unicellular organisms have evolved complicated networks of regulatory interactions, termed transcriptional regulatory networks (TRNs), to respond to environmental stimul...
10.1371/journal.pntd.0003923	Bacterial Infection and Immune Responses in Lutzomyia longipalpis Sand Fly Larvae Midgut	The midgut microbial community in insect vectors of disease is crucial for an effective immune response against infection with various human and animal pathogens. Depending on the aspects of their development, insects can acquire microbes present in soil, water, and plants. Sand flies are major vectors of leishmaniasis...	Symbiotic microorganisms influence many aspects of the physiology of their hosts. In insects, symbiotic bacteria are able among other things to modulate the immune response and the development of the insect from larval stages to adult. Many bacteria first gain access to insect tissues, such as the gut, during larval de...	Bacterial symbionts significantly influence many aspects of the physiology of their host. In insects, both pathogenic and non-pathogenic bacteria have been shown to modulate immune response, homeostasis, development, and overall health of midgut physiology for both larval and adult stages. Both Gram-positive (G+) and G...
10.1371/journal.pntd.0001383	Induction of CD4+CD25+FOXP3+ Regulatory T Cells during Human Hookworm Infection Modulates Antigen-Mediated Lymphocyte Proliferation	Hookworm infection is considered one of the most important poverty-promoting neglected tropical diseases, infecting 576 to 740 million people worldwide, especially in the tropics and subtropics. These blood-feeding nematodes have a remarkable ability to downmodulate the host immune response, protecting themselves from ...	The hookworm infection is characterized by the long-term survival of the parasite and the concomitant modulation of the host immunity. Among several mechanisms that may account for the suppression of T cell response, we here described the presence and role of T regulatory cells (also known as Tregs) in the human hookwo...	Human hookworm infection is mainly caused by the blood-feeding nematodes Ancylostoma duodenale and Necator americanus, which infects 576 to 740 million people worldwide, especially in the tropics and subtropics [1], [2], [3]. Hookworm is considered one of the thirteen poverty-promoting neglected tropical diseases, and ...
10.1371/journal.pntd.0002275	A Hamster-Derived West Nile Virus Isolate Induces Persistent Renal Infection in Mice	West Nile virus (WNV) can persist long term in the brain and kidney tissues of humans, non-human primates, and hamsters. In this study, mice were infected with WNV strain H8912, previously cultured from the urine of a persistently infected hamster, to determine its pathogenesis in a murine host. We found that WNV H8912...	West Nile virus (WNV) has been reported to persist long term in the brain and kidney tissues of humans, non-human primates, and hamsters. To define a murine model of persistent WNV renal infection, we characterized infection by WNV H8912, an isolate cultured previously from the urine of a persistently infected hamster....	West Nile virus (WNV) is a mosquito-borne flavivirus with a positive-sense, single-stranded RNA genome that encodes three structural proteins: the nucleocapsid protein (C), membrane and envelope (E), and seven nonstructural (NS) proteins [1]–[2]. Human infection results from mosquito bites, blood transfusion, organ tra...
10.1371/journal.ppat.1000996	Viral Protein Inhibits RISC Activity by Argonaute Binding through Conserved WG/GW Motifs	RNA silencing is an evolutionarily conserved sequence-specific gene-inactivation system that also functions as an antiviral mechanism in higher plants and insects. To overcome antiviral RNA silencing, viruses express silencing-suppressor proteins. These viral proteins can target one or more key points in the silencing ...	RNA silencing is an evolutionarily conserved sequence-specific gene-inactivation system that also functions as a major antiviral mechanism in higher plants and insects. Viral RNAs are processed by Dicer-like proteins into small interfering (si) RNAs, which trigger the RNA-induced silencing complex (RISC) assembly. Then...	Most eukaryotes, including plants, make use of a well-conserved RNA silencing mechanism to regulate many essential biological processes, ranging from development and control of physiological activities, to responses to abiotic and biotic stress, in particular antiviral defense [1], [2]. Antiviral defense in plants beg...
10.1371/journal.pntd.0004858	Leptospira Seroprevalence and Risk Factors in Health Centre Patients in Hoima District, Western Uganda	The burden of human leptospirosis in Uganda is unknown. We estimated the seroprevalence of Leptospira antibodies, probable acute/recent leptospirosis, and risk factors for seropositivity in humans in rural Western Uganda. 359 non-pregnant adults visiting the Kikuube and Kigorobya Health Centers were sequentially recrui...	Leptospirosis is an emerging zoonotic disease caused by bacteria of the genus Leptospira. Despite its relatively common frequency, mild/moderate leptospirosis often goes unrecognized, due to its usually non-specific symptoms of fever, vomiting, and malaise. Knowledge of leptospirosis in Uganda is limited, and the disea...	Leptospirosis is a zoonotic bacterial disease with a worldwide distribution that is endemic in subtropical and tropical countries. Transmission occurs through exposure to urine or aborted tissues of infected animals, either through direct contact with carrier animals or contact with contaminated water or soil [1]. Lept...
10.1371/journal.pcbi.1007023	Energetic costs of cellular and therapeutic control of stochastic mitochondrial DNA populations	The dynamics of the cellular proportion of mutant mtDNA molecules is crucial for mitochondrial diseases. Cellular populations of mitochondria are under homeostatic control, but the details of the control mechanisms involved remain elusive. Here, we use stochastic modelling to derive general results for the impact of ce...	Mitochondria, best known for their role in energy production, are crucial to the survival of most of our cells. To respond to energetic demands and mitigate against mutational damage, cells control the mitochondrial populations within them. However, the character of these control mechanisms remains open. As experimenta...	Most human cells contain 100-10,000 copies of mitochondrial DNA (mtDNA) which are situated inside the mitochondria. The proteins encoded by mtDNA are crucial for mitochondrial functionality, and mutations in mtDNA can cause devastating diseases [1–6]. Heteroplasmy, the proportion of mutant mtDNA molecules in a cell, ty...
10.1371/journal.pbio.1000597	EphrinB/EphB Signaling Controls Embryonic Germ Layer Separation by Contact-Induced Cell Detachment	The primordial organization of the metazoan body is achieved during gastrulation by the establishment of the germ layers. Adhesion differences between ectoderm, mesoderm, and endoderm cells could in principle be sufficient to maintain germ layer integrity and prevent intermixing. However, in organisms as diverse as fly...	The formation and maintenance of tissue boundaries is an essential feature of multicellular animals, including humans. Using the frog embryo as a model system, we describe a mechanism of tissue separation that involves repeated cycles of cell attachment and detachment at the boundary between two adjacent tissues. Molec...	When Townes and Holtfreter [1] observed the sorting of mixed embryonic ectoderm, mesoderm, and endoderm cells, they proposed that this segregation of germ layers and the consequent self-assembly of the basic body structure was based on mutual “tissue affinities.” This concept was later refined into Steinberg's [2] Diff...
10.1371/journal.pntd.0003493	Automated High-Content Assay for Compounds Selectively Toxic to Trypanosoma cruzi in a Myoblastic Cell Line	Chagas disease, caused by the protozoan parasite Trypanosoma cruzi, represents a very important public health problem in Latin America where it is endemic. Although mostly asymptomatic at its initial stage, after the disease becomes chronic, about a third of the infected patients progress to a potentially fatal outcome...	Chagas disease is a zoonosis caused by the protozoan parasite Trypanosoma cruzi. Endemic to Central and South America, it affects over 10 million people and many more live in risk transmission areas. Although mostly asymptomatic at its initial acute stage in humans, damages can occur over the years in many tissues such...	Chagas disease, classified by the WHO as a neglected tropical disease, is a zoonosis caused by the Kineoplastid protozoan parasite Trypanosoma cruzi. It is endemic to Central and South America where it stands as a major public health problem [1]. Migratory population movements between endemic and non-endemic regions du...
10.1371/journal.pgen.1004703	The DAF-16 FOXO Transcription Factor Regulates natc-1 to Modulate Stress Resistance in Caenorhabditis elegans, Linking Insulin/IGF-1 Signaling to Protein N-Terminal Acetylation	The insulin/IGF-1 signaling pathway plays a critical role in stress resistance and longevity, but the mechanisms are not fully characterized. To identify genes that mediate stress resistance, we screened for C. elegans mutants that can tolerate high levels of dietary zinc. We identified natc-1, which encodes an evoluti...	What are the mechanisms used by animals to cope with stressful environments that inflict damage or restrict essential processes such as growth, development, and reproduction? One strategy is changes in physiology that increase stress resistance, and an extreme version of this strategy is diapause, an alternative develo...	The ability to cope with fluctuating environmental stresses is critical for animal survival. Environmental stresses include a wide range of factors such as extremes in temperature, oxidation, and metal availability. A stress response might promote tolerance against a specific challenge or provide broad-spectrum resista...
10.1371/journal.pntd.0001453	The Genetic and Molecular Basis of O-Antigenic Diversity in Burkholderia pseudomallei Lipopolysaccharide	Lipopolysaccharide (LPS) is one of the most important virulence and antigenic components of Burkholderia pseudomallei, the causative agent of melioidosis. LPS diversity in B. pseudomallei has been described as typical, atypical or rough, based upon banding patterns on SDS-PAGE. Here, we studied the genetic and molecula...	Burkholderia pseudomallei is an environmental Gram-negative bacterium and the cause of melioidosis, an often life-threatening disease affecting people in Southeast Asia and northern Australia. Melioidosis is usually contracted by bacterial inoculation, ingestion or inhalation. Effective vaccines for melioidosis are cur...	Lipopolysaccharide (LPS) is a major component of the outer membrane of Gram-negative bacteria, playing an important role in cell integrity and in signaling host innate immune response [1]. Structurally, LPS is composed of three major components: lipid A, the bacterial endotoxin that is embedded in the phospholipid bila...
10.1371/journal.pcbi.1005779	Correlated receptor transport processes buffer single-cell heterogeneity	Cells typically vary in their response to extracellular ligands. Receptor transport processes modulate ligand-receptor induced signal transduction and impact the variability in cellular responses. Here, we quantitatively characterized cellular variability in erythropoietin receptor (EpoR) trafficking at the single-cell...	Cell surface receptors translate extracellular ligand concentrations to intracellular responses. Receptor transport between the plasma membrane and other cellular compartments regulates the number of accessible receptors at the plasma membrane that determines the strength of downstream pathway activation at a given lig...	In cells external signals from ligands are transmitted by receptors to intracellular signaling cascades. Receptor signaling is regulated by receptor transport processes between the plasma membrane and other cellular compartments that are subsumed under the term receptor trafficking [1]. In absence of ligand, receptors ...
10.1371/journal.pbio.2004037	The neural system of metacognition accompanying decision-making in the prefrontal cortex	Decision-making is usually accompanied by metacognition, through which a decision maker monitors uncertainty regarding a decision and may then consequently revise the decision. These metacognitive processes can occur prior to or in the absence of feedback. However, the neural mechanisms of metacognition remain controve...	Decision-making is often accompanied by a sense of uncertainty regarding the outcome. In many situations, there is no explicit feedback or cue to indicate whether the decision is correct or not. Fortunately, our brain can evaluate decision uncertainty using the internal signals and subsequently make appropriate adjustm...	Decision-making is a process of evidence accumulation. That evidence may come from sensory signals of external stimuli or from mental representations of internal cognitive operations. Variations in evidence can create uncertainty in the person rendering a decision. The decision maker is normally explicitly or implicitl...
10.1371/journal.pgen.1007353	Patterning mechanisms diversify neuroepithelial domains in the Drosophila optic placode	The central nervous system develops from monolayered neuroepithelial sheets. In a first step patterning mechanisms subdivide the seemingly uniform epithelia into domains allowing an increase of neuronal diversity in a tightly controlled spatial and temporal manner. In Drosophila, neuroepithelial patterning of the embry...	Genetic mechanisms patterning neuroepithelial domains are a critical first step to diversify cellular identity of the developing nervous system. How many cells develop from distinct neuroepithelial domains depends on overall size and growth but also on positioning of boundaries. Using the embryonic optic placode of the...	In the fruit fly Drosophila melanogaster, all parts of the visual system develop from an optic placode, which forms in the dorsolateral region of the embryonic head ectoderm [1–3]. During embryogenesis, neuroepithelial cells of the optic placode are patterned to form two subdomains. The ventroposterior domain gives ris...
10.1371/journal.pntd.0006815	Intrinsic activation of the vitamin D antimicrobial pathway by M. leprae infection is inhibited by type I IFN	Following infection, virulent mycobacteria persist and grow within the macrophage, suggesting that the intrinsic activation of an innate antimicrobial response is subverted by the intracellular pathogen. For Mycobacterium leprae, the intracellular bacterium that causes leprosy, the addition of exogenous innate or adapt...	Our macrophages are equipped with the ability to detect and kill invading pathogens, and yet, these cells of the innate immune system are still subject to infection by intracellular bacterium. In particular, mycobacterium, the type of intracellular bacteria responsible for diseases such as tuberculosis and leprosy, are...	The ability of macrophages (MΦ) to kill intracellular pathogens is critical to the outcome of infection. Addition of exogenous ligands derived from the pathogen such as a Toll-like receptor 2 ligand (TLR2L) or from human immune cells, such as IFN-γ, provides an extrinsic signal to activate a vitamin D-dependent antimic...
10.1371/journal.pntd.0000324	Controlling Tungiasis in an Impoverished Community: An Intervention Study	In Brazil, tungiasis is endemic in some resource-poor communities where various domestic and sylvatic animals act as reservoirs for this zoonosis. To determine the effect of control measures on the prevalence and intensity of infestation of human and animal tungiasis, a repeated cross-sectional survey with intervention...	Tungiasis is a disease caused by the sand flea Tunga penetrans, a parasite prevalent in many impoverished communities in developing countries. The female sand flea penetrates into the skin of animals and humans where it grows rapidly in size, feeds on the host's blood, produces eggs which are expelled into the environm...	Tungiasis is a parasitic disease caused by the sand flea Tunga penetrans. Female fleas penetrate into the epidermis where they undergo a process of so-called neosomy and expel several hundred eggs into the environment. After a period of six weeks, the parasite dies in situ and is sloughed off the epidermis by tissue re...
10.1371/journal.ppat.1007681	The requirement for co-germinants during Clostridium difficile spore germination is influenced by mutations in yabG and cspA	Clostridium difficile spore germination is critical for the transmission of disease. C. difficile spores germinate in response to cholic acid derivatives, such as taurocholate (TA), and amino acids, such as glycine or alanine. Although the receptor with which bile acids are recognized (germinant receptor) is known, the...	Germination by C. difficile spores is one of the very first steps in the pathogenesis of this organism. The transition from the metabolically dormant spore form to the actively-growing, toxin-producing vegetative form is initiated by certain host-derived bile acids and amino acid signals. Despite near universal conserv...	Clostridioides difficile (formerly Clostridium difficile) [1–3] is a Gram-positive, spore-forming pathogenic bacterium, and has become a leading cause of nosocomial diarrhea in the United States [4, 5]. C. difficile infection (CDI) is commonly the result of disruption to the gut microflora caused by antibiotic use [5–7...

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