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10.1371/journal.pntd.0003061 | Transcriptional Correlates of Disease Outcome in Anticoagulant-Treated Non-Human Primates Infected with Ebolavirus | Ebola virus (EBOV) infection in humans and non-human primates (NHPs) is highly lethal, and there is limited understanding of the mechanisms associated with pathogenesis and survival. Here, we describe a transcriptomic analysis of NHPs that survived lethal EBOV infection, compared to NHPs that did not survive. It has be... | Infection of humans and non-human primates (NHPs) with Ebola virus (EBOV) can cause viral hemorrhagic fever, an acute systemic illness which can lead to death. The high case fatality rates (25%–90%) make EBOV a virus of significant concern from a biodefense perspective. To date, there are no FDA-approved post-exposure ... | Ebola virus (EBOV; Filoviridae [1]) infection of humans and non-human primates (NHPs) can cause viral hemorrhagic fever, an acute systemic illness characterized by fever, bleeding diathesis, fulminant shock, and death [2]. Although several studies have identified candidate therapeutics that may mitigate the effects of ... |
10.1371/journal.pntd.0002329 | The Malnutrition-Related Increase in Early Visceralization of Leishmania donovani Is Associated with a Reduced Number of Lymph Node Phagocytes and Altered Conduit System Flow | In a murine model of moderate childhood malnutrition we found that polynutrient deficiency led to a 4–5-fold increase in early visceralization of L. donovani (3 days post-infection) following cutaneous infection and a 16-fold decrease in lymph node barrier function (p<0.04 for all). To begin to understand the mechanist... | The impact of malnutrition in the world is staggering. Malnutrition is thought to directly or indirectly contribute to more than half of all childhood deaths, most of them related to heightened susceptibility to infection. Visceral leishmaniasis (VL), caused by the intracellular protozoan Leishmania donovani, is a prog... | Protein-energy malnutrition (PEM) is thought to be the most frequent cause of human immunodeficiency [1], and greatly predisposes individuals to infectious diseases in resource-poor regions of the world [2]. In its synergy with infection, under-nutrition contributes to approximately 50% of childhood deaths worldwide [3... |
10.1371/journal.pbio.2003619 | Receptors of intermediates of carbohydrate metabolism, GPR91 and GPR99, mediate axon growth | During the development of the visual system, high levels of energy are expended propelling axons from the retina to the brain. However, the role of intermediates of carbohydrate metabolism in the development of the visual system has been overlooked. Here, we report that the carbohydrate metabolites succinate and α-keto... | Development of the visual system requires high levels of energy and tight regulation of multiple factors integrated by axon projections during navigation to their appropriate targets. While intermediates of carbohydrate metabolism have key roles in many biological processes, much less is known about their effects on re... | GPR91 and GPR99 are G-protein-coupled receptors (GPCRs) activated by Krebs cycle intermediates, part of the larger class of carbohydrate metabolites—an observation that renewed interest in a biochemical pathway discovered decades ago [1,2]. GPR91, through its activation by succinate outside the tricarboxylic acid (TCA)... |
10.1371/journal.ppat.1002076 | A Role for TLR4 in Clostridium difficile Infection and the Recognition of Surface Layer Proteins | Clostridium difficile is the etiological agent of antibiotic-associated diarrhoea (AAD) and pseudomembranous colitis in humans. The role of the surface layer proteins (SLPs) in this disease has not yet been fully explored. The aim of this study was to investigate a role for SLPs in the recognition of C. difficile and t... | Clostridium difficile is the leading cause of antibiotic-associated diarrhoea among hospital patients and in severe cases can cause pseudomembranous colitis and even death. There is currently limited information regarding how this pathogen is recognised by the immune system and the key mechanisms necessary for clearanc... | Clostridium difficile is a Gram-positive spore-forming intestinal pathogen. It is the leading cause of nosocomial antibiotic-associated diarrhoea among hospital patients and in severe cases can cause pseudomembranous colitis and even death [1], [2]. The pathogenesis of C. difficile has been attributed to the two major ... |
10.1371/journal.ppat.1000724 | B Cell Activation by Outer Membrane Vesicles—A Novel Virulence Mechanism | Secretion of outer membrane vesicles (OMV) is an intriguing phenomenon of Gram-negative bacteria and has been suggested to play a role as virulence factors. The respiratory pathogens Moraxella catarrhalis reside in tonsils adjacent to B cells, and we have previously shown that M. catarrhalis induce a T cell independent... | Outer membrane vesicles secreted by pathogenic bacteria are recognized as a long-distance delivery system which transports diverse virulence factors, and allows pathogens to interact with the host, and hence the possibility to modify the immune response without close contact. Our study shows that Moraxella catarrhalis ... | Moraxella catarrhalis is one of the major respiratory pathogens in humans causing acute otitis media in children, sinusitis and laryngitis in adults as well as exacerbations in patients diagnosed with chronic obstructive pulmonary disease (COPD) [1],[2]. The M. catarrhalis carriage varies during life from very high in ... |
10.1371/journal.pbio.1001998 | Modulation of the Maladaptive Stress Response to Manage Diseases of Protein Folding | Diseases of protein folding arise because of the inability of an altered peptide sequence to properly engage protein homeostasis components that direct protein folding and function. To identify global principles of misfolding disease pathology we examined the impact of the local folding environment in alpha-1-antitryps... | The function of all proteins is dependent on achieving the correct folded state, a process referred to as protein homeostasis or proteostasis. Cellular proteostasis is maintained by diverse signaling pathways, including the heat shock response (HSR), which protects proteins in the face of acute stress. However, genetic... | The transition from protein folding to misfolding, in both normal physiology and disease, is dynamically managed by multiple proteostatic pathways [1],[2]. The heat shock response (HSR) is a central signaling pathway managing the malleable composition of the proteostasis network (PN) of folding and degradation machiner... |
10.1371/journal.pcbi.1003659 | Protein Conservation and Variation Suggest Mechanisms of Cell Type-Specific Modulation of Signaling Pathways | Many proteins and signaling pathways are present in most cell types and tissues and yet perform specialized functions. To elucidate mechanisms by which these ubiquitous pathways are modulated, we overlaid information about cross-cell line protein abundance and variability, and evolutionary conservation onto functional ... | Cell function is determined by highly organized networks of biological molecules. An important class of protein pathways maintains the transmission of signals from the cell membrane to the nucleus. These signaling pathways are reused for different purposes at an evolutionary scale and in different cell types of the sam... | Proteins do not act in isolation but interact with other proteins to fulfill important cellular functions. Often proteins are organized into pathways, which are tightly controlled cascades of protein binding events (and those of other biomolecules). One important cellular function controlled by pathways is the transmis... |
10.1371/journal.pgen.1000147 | Linkage Disequilibrium-Based Quality Control for Large-Scale Genetic Studies | Quality control (QC) is a critical step in large-scale studies of genetic variation. While, on average, high-throughput single nucleotide polymorphism (SNP) genotyping assays are now very accurate, the errors that remain tend to cluster into a small percentage of “problem” SNPs, which exhibit unusually high error rates... | In large-scale studies of population genetic data, particularly genome-wide association studies, considerable effort may be spent on quality control (QC) to ensure genotype data are accurate. Typically, QC steps are applied independently to individual marker loci, with data from suspicious loci being excluded from subs... | Data quality has been implicated as a source of bias and loss of power in both linkage analyses and population-based association studies [1],[2],[3],[4]. Quality control (QC) is thus a critical step in large-scale studies of genetic variation. While, on average, high-throughput single nucleotide polymorphism (SNP) geno... |
10.1371/journal.pcbi.1001008 | Deciphering the Code for Retroviral Integration Target Site Selection | Upon cell invasion, retroviruses generate a DNA copy of their RNA genome and integrate retroviral cDNA within host chromosomal DNA. Integration occurs throughout the host cell genome, but target site selection is not random. Each subgroup of retrovirus is distinguished from the others by attraction to particular featur... | When HIV-1, murine leukemia virus (MLV), or other retroviruses infect a cell, the virus generates a DNA copy of the viral RNA genome and ligates the cDNA within host chromosomal DNA. This integration reaction occurs at sites throughout the host cell genome, but little is known about how integration sites are selected. ... | Retroviruses and retrotransposons are of profound importance to eukaryotic biology, evolution, and medicine. These retroelements constitute at least 40% of the mass of mammalian genomes [1] and 75% of the maize genome [2]. When retroelements are transcribed they remodel eukaryotic genomes by generating a cDNA and integ... |
10.1371/journal.pntd.0003163 | Predicting the Mosquito Species and Vertebrate Species Involved in the Theoretical Transmission of Rift Valley Fever Virus in the United States | Rift Valley fever virus (RVFV) is a mosquito-borne virus in the family Bunyaviridiae that has spread throughout continental Africa to Madagascar and the Arabian Peninsula. The establishment of RVFV in North America would have serious consequences for human and animal health in addition to a significant economic impact ... | In anticipation of continued pathogen emergence in the U.S. due to globalization climate change, and other factors, the development of proactive management plans and interventions to predict and then intervene is going to be more efficient and effective than retrospective plans developed after pathogen emergence. Effec... | Rift Valley fever virus (RVFV) is an emerging infectious disease in Africa and the Middle East. If introduced to North America, RVFV is capable of serious health and socioeconomic consequences potentially incapacitating large numbers of humans, decimating susceptible farm animals, and instigating heavy restrictions on ... |
10.1371/journal.ppat.1002856 | Surface Proteome Analysis and Characterization of Surface Cell Antigen (Sca) or Autotransporter Family of Rickettsia typhi | Surface proteins of the obligate intracellular bacterium Rickettsia typhi, the agent of murine or endemic typhus fever, comprise an important interface for host-pathogen interactions including adherence, invasion and survival in the host cytoplasm. In this report, we present analyses of the surface exposed proteins of ... | Rickettsia typhi, a member of the typhus group (TG) rickettsia, is the agent of murine or endemic typhus fever – a disease exhibiting mild to severe flu-like symptoms resulting in significant morbidity. It is maintained in a flearodent transmission cycle in urban and suburban environments. The obligate intracellular li... | Rickettsia (Rickettsiales: Rickettsiaceae) are Gram-negative, obligate intracellular bacteria that are maintained in enzootic cycles involving both hematophagous arthropod vectors and vertebrate hosts [1]. Rickettsiae are the causative agents of significant human diseases such as Rocky Mountain spotted fever (R. ricket... |
10.1371/journal.pgen.0030046 | Incorporating Single-Locus Tests into Haplotype Cladistic Analysis in Case-Control Studies | In case-control studies, genetic associations for complex diseases may be probed either with single-locus tests or with haplotype-based tests. Although there are different views on the relative merits and preferences of the two test strategies, haplotype-based analyses are generally believed to be more powerful to dete... | Methods of haplotype-based analysis and single-locus analysis are widely used in genetic association studies. There is no consensus as to the best strategy for the performance of the two methods. Although haplotype-based analysis is a powerful tool, the large number of distinct haplotypes may reduce its efficiency. Hap... | Recent advances in biotechnology such as high-throughput single nucleotide polymorphism (SNP) genotyping have provided useful tools to improve our understanding of the genetic basis of human complex diseases. With these advances, an intense and comprehensive evaluation of candidate genes, linkage regions, and the whole... |
10.1371/journal.pntd.0000384 | Identification of Three Classes of Heteroaromatic Compounds with Activity against Intracellular Trypanosoma cruzi by Chemical Library Screening | The development of new drugs against Chagas disease is a priority since the currently available medicines have toxic effects, partial efficacy and are targeted against the acute phase of disease. At present, there is no drug to treat the chronic stage. In this study, we have optimized a whole cell-based assay for high ... | Chagas disease is caused by infection with the protozoan parasite Trypanosoma cruzi and affects 16 million people in South and Central America. The disease starts with an acute phase where the parasite replicates rapidly and, if it remains untreated, is followed by a chronic phase, which can induce severe pathologies i... | Chagas disease or American trypanosomiasis is a devastating disease caused by the trypanosomatid protozoan Trypanosoma cruzi. It is endemic in 18 countries of Central and South America, putting 120 million of people at risk, with an estimated 16–18 million people currently infected [1]. The disease first manifests itse... |
10.1371/journal.pntd.0002308 | Population Genetics of the Filarial Worm Wuchereria bancrofti in a Post-treatment Region of Papua New Guinea: Insights into Diversity and Life History | Wuchereria bancrofti (Wb) is the primary causative agent of lymphatic filariasis (LF). Our studies of LF in Papua New Guinea (PNG) have shown that it is possible to reduce the prevalence of Wb in humans and mosquitoes through mass drug administration (MDA; diethylcarbamazine with/without ivermectin). While MDAs in the ... | The Global Program to Eliminate Lymphatic Filariasis (LF), initiated by the World Health Organization (WHO), aims to eliminate LF from endemic regions, where 1.34 billion people live at risk of this disease. The causative agent responsible for 90% of LF is the nematode parasite species Wuchereria bancrofti (Wb). The pr... | Lymphatic-dwelling nematodes that cause damage to the lymphatic system (lymphatic filariasis—LF) contribute to significant permanent and long-term disability in the world, second only to mental illness [1]. Acute and chronic morbidity resulting from LF has affected 120 million people living in 81 countries with 1.34 bi... |
10.1371/journal.pgen.1002967 | Inference of Population Splits and Mixtures from Genome-Wide Allele Frequency Data | Many aspects of the historical relationships between populations in a species are reflected in genetic data. Inferring these relationships from genetic data, however, remains a challenging task. In this paper, we present a statistical model for inferring the patterns of population splits and mixtures in multiple popula... | With modern genotyping technology, it is now possible to obtain large amounts of genetic data from many populations in a species. An important question that can be addressed with these data is: what is the history of these populations? There is a long history in population genetics of inferring the relationships among ... | The extant populations in a species result from an often-complex demographic history, involving population splits, gene flow, and changes in population size. It has long been recognized that genetic data can be used to learn about this history [1]–[3]. In humans, early approaches to inferring history from genetics were... |
10.1371/journal.pbio.1002345 | Nociceptive Local Field Potentials Recorded from the Human Insula Are Not Specific for Nociception | The insula, particularly its posterior portion, is often regarded as a primary cortex for pain. However, this interpretation is largely based on reverse inference, and a specific involvement of the insula in pain has never been demonstrated. Taking advantage of the high spatiotemporal resolution of direct intracerebral... | A widely accepted notion is that the insula, especially its posterior portion, plays a specific role in the perception of pain. This has led a number of researchers to consider activity recorded from this so-called “ouch zone” as an objective correlate of pain perception. We provide compelling evidence to the contrary.... | The human insula, in particular the region encompassing the dorsal posterior insula and the adjacent parietal operculum, is generally believed to play a specific role in the perception of pain. There are several reasons behind this belief. First, the insula is an important cortical target for nociceptive inputs ascendi... |
10.1371/journal.pntd.0000836 | Chagas Disease Risk in Texas | Chagas disease, caused by Trypanosoma cruzi, remains a serious public health concern in many areas of Latin America, including México. It is also endemic in Texas with an autochthonous canine cycle, abundant vectors (Triatoma species) in many counties, and established domestic and peridomestic cycles which make compete... | Chagas disease is endemic in Texas and spread through triatomine insect vectors known as kissing bugs, assassin bugs, or cone–nosed bugs, which transmit the protozoan parasite, Trypanosoma cruzi. We examined the threat of Chagas disease due to the three most prevalent vector species and from human case occurrences and ... | Chagas disease, a result of infection by the hemoflagellate kinetoplastid protozoan, Trypanosoma cruzi, remains an important public health threat in Latin America [1] with an estimated 16–18 million human incidences and deaths annually [2]. While the Southern Cone Initiative [3]–[6] has interrupted the transmission of... |
10.1371/journal.pcbi.1000718 | Using Pre-existing Microarray Datasets to Increase Experimental Power: Application to Insulin Resistance | Although they have become a widely used experimental technique for identifying differentially expressed (DE) genes, DNA microarrays are notorious for generating noisy data. A common strategy for mitigating the effects of noise is to perform many experimental replicates. This approach is often costly and sometimes impos... | Though the use of microarrays to identify differentially expressed (DE) genes has become commonplace, it is still not a trivial task. Microarray data are notorious for being noisy, and current DE gene methods do not fully utilize pre-existing biological knowledge to help control this noise. One such source of knowledge... | Since their inception over 13 years ago [1], DNA microarrays have become a staple experimental tool used primarily for exploring the effects of biological interventions on gene expression. Microarrays have enabled a range of experimental queries, including a survey of gene expression across dozens of mammalian tissues ... |
10.1371/journal.pgen.1005215 | Biological Significance of Photoreceptor Photocycle Length: VIVID Photocycle Governs the Dynamic VIVID-White Collar Complex Pool Mediating Photo-adaptation and Response to Changes in Light Intensity | Most organisms on earth sense light through the use of chromophore-bearing photoreceptive proteins with distinct and characteristic photocycle lengths, yet the biological significance of this adduct decay length is neither understood nor has been tested. In the filamentous fungus Neurospora crassa VIVID (VVD) is a crit... | Sensing light from the environment using a variety of photoreceptors is of great adaptive significance for most eukaryotes. A key feature of photoreceptors is the photocycle length, the time taken to decay from the initial signaling light state back to the receptive dark state; however, the significance of photocycle l... | Most organisms and nearly all eukaryotes respond to light in their environment, and do so through the use of proteins specially adapted to respond to light. Such photoreceptor proteins most often sense light through the use of prosthetic groups, chromophores, chosen by evolution for their ability to absorb light of par... |
10.1371/journal.ppat.1000197 | Broadening of Neutralization Activity to Directly Block a Dominant Antibody-Driven SARS-Coronavirus Evolution Pathway | Phylogenetic analyses have provided strong evidence that amino acid changes in spike (S) protein of animal and human SARS coronaviruses (SARS-CoVs) during and between two zoonotic transfers (2002/03 and 2003/04) are the result of positive selection. While several studies support that some amino acid changes between ani... | The SARS-CoV caused a worldwide epidemic of SARS in 2002/03 and was responsible for this zoonotic infectious disease. The role of neutralizing antibody (nAb) mediated immune pressure in the evolution of SARS-CoV during the 2002/03 outbreak and a second 2003/04 zoonotic transmission is unknown. Here we demonstrate nAb r... | A novel coronavirus (CoV), severe acute respiratory syndrome coronavirus (SARS-CoV), caused a worldwide epidemic of SARS with a fatality rate of 9.6% in 2002/03 and later reemerged and resulted in infection of four individuals with full recovery in the winter of 2003/04 [1]–[5]. SARS-CoV has been demonstrated to be a z... |
10.1371/journal.pntd.0002288 | Strongyloides stercoralis: Global Distribution and Risk Factors | The soil-transmitted threadworm, Strongyloides stercoralis, is one of the most neglected among the so-called neglected tropical diseases (NTDs). We reviewed studies of the last 20 years on S. stercoralis's global prevalence in general populations and risk groups.
A literature search was performed in PubMed for articles... | The soil-transmitted threadworm Strongyloides stercoralis is one of the most neglected helminth infections. It is endemic world-wide, yet more prevalent in hot and humid climates as well as resource poor countries with inadequate sanitary conditions. The difficult diagnosis and irregular excretion of larvae lead to an ... | The threadworm Strongyloides stercoralis is a soil-transmitted nematode and one of the most overlooked helminth among the neglected tropical diseases (NTDs) [1]. It occurs almost world-wide, excluding only the far north and south, yet estimates about its prevalence are often little more than educated guesses [2], [3]. ... |
10.1371/journal.ppat.1003628 | Epstein Barr Virus-Induced 3 (EBI3) Together with IL-12 Negatively Regulates T Helper 17-Mediated Immunity to Listeria monocytogenes Infection | Although the protective functions by T helper 17 (Th17) cytokines against extracellular bacterial and fungal infection have been well documented, their importance against intracellular bacterial infection remains unclear. Here, we investigated the contribution of Th17 responses to host defense against intracellular bac... | There is a considerable gap in our understanding of how pathogenic intracellular bacteria escape innate and adaptive host immunity. Production of IL-12, and subsequently IFNγ, upon infection triggers host immunity that prevents early dissemination of pathogenic intracellular pathogens. This is evident in observing the ... | The generation of pathogen-specific T cell responses is essential for the clearance of infectious agents. This involves the differentiation of naïve T cells into distinct pathogen-specific helper T cell lineages in a process that largely depends on the cytokine milieu created by innate immune cells upon their activatio... |
10.1371/journal.pntd.0001451 | Metabolic Variation during Development in Culture of Leishmania donovani Promastigotes | The genome sequencing of several Leishmania species has provided immense amounts of data and allowed the prediction of the metabolic pathways potentially operating. Subsequent genetic and proteomic studies have identified stage-specific proteins and putative virulence factors but many aspects of the metabolic adaptatio... | Leishmania infections are considered neglected tropical diseases as the parasites affect millions of people worldwide but there are limited research efforts aimed at obtaining vaccines and new drugs. Leishmania has a digenetic life cycle alternating between promastigote forms, which develop in the sand-fly, the vector ... | Leishmaniasis remains one of the major infectious diseases with 350 million people at risk in 88 countries worldwide and 2 million estimated new cases every year [1]. The lack of effective chemotherapy and emergence of drug resistance (reviewed in [2]) highlights the need for an improved knowledge of the parasite's cel... |
10.1371/journal.pgen.1007365 | WUSCHEL-RELATED HOMEOBOX4 acts as a key regulator in early leaf development in rice | Rice (Oryza sativa) has long and narrow leaves with parallel veins, similar to other grasses. Relative to Arabidopsis thaliana which has oval-shaped leaves, our understanding of the mechanism of leaf development is insufficient in grasses. In this study, we show that OsWOX4, a member of the WUSCHEL-RELATED HOMEOBOX gen... | Leaves are major photosynthetic organs in plants, and their sizes and shapes are diverse in angiosperms. Proper leaf development is crucial not only for plant body plan but also for efficient photosynthesis. Similar to other grasses, rice has long and narrow leaves with parallel veins, which are distinct from Arabidops... | Proper leaf development in plants is crucial not only for their body plan but also for efficient photosynthesis. Plants are sessile organisms that evolve morphological leaf traits by optimization to their respective natural habitats. Leaves are initiated at the flank of the shoot apical meristem (SAM), which harbors a ... |
10.1371/journal.pgen.1004026 | Translation Enhancing ACA Motifs and Their Silencing by a Bacterial Small Regulatory RNA | GcvB is an archetypal multi-target small RNA regulator of genes involved in amino acid uptake or metabolism in enteric bacteria. Included in the GcvB regulon is the yifK locus, encoding a conserved putative amino acid transporter. GcvB inhibits yifK mRNA translation by pairing with a sequence immediately upstream from ... | The majority of small RNA (sRNA) regulators in bacteria act by inhibiting translation initiation in target messenger RNAs. The study of this regulatory mechanism not only allows a better understanding of sRNA function but it can also provide new insight into aspects of the translation initiation process that remain inc... | A relevant chapter in the expanding field of RNA-mediated gene regulation is devoted to the activities of multi-target trans-encoded small RNAs in bacteria. Acting in concert with chaperon protein Hfq, these RNA regulators function by base-pairing with short, often imperfectly complementary sequences in the 5′ untransl... |
10.1371/journal.pgen.1005231 | Myopathic Lamin Mutations Cause Reductive Stress and Activate the Nrf2/Keap-1 Pathway | Mutations in the human LMNA gene cause muscular dystrophy by mechanisms that are incompletely understood. The LMNA gene encodes A-type lamins, intermediate filaments that form a network underlying the inner nuclear membrane, providing structural support for the nucleus and organizing the genome. To better understand th... | Mutations in the human LMNA gene cause muscular dystrophy that is often accompanied by heart disease. The LMNA gene makes proteins that form a network on the inner side of the nuclear envelope, a structure that reinforces the cell nucleus. How mutations in the LMNA gene cause muscle disease is not well understood. Our ... | The human LMNA gene exemplifies the rich source of genetic variation that exists in the human genome. Over 283 sequence variants and 460 disease-causing mutations have been identified to date. These mutations cause at least 13 distinct clinical diseases, called laminopathies, which have mainly tissue-restricted phenoty... |
10.1371/journal.ppat.1002106 | Detection of Inferred CCR5- and CXCR4-Using HIV-1 Variants and Evolutionary Intermediates Using Ultra-Deep Pyrosequencing | The emergence of CXCR4-using human immunodeficiency virus type 1 (HIV-1) variants is associated with accelerated disease progression. CXCR4-using variants are believed to evolve from CCR5-using variants, but due to the extremely low frequency at which transitional intermediate variants are often present, the kinetics a... | The first step in the infection of a target cell by human immunodeficiency virus type 1 (HIV-1) is binding of the envelope spike to its receptor CD4 and a coreceptor on the cellular surface. HIV-1 variants present early in the course of infection mainly use the coreceptor CCR5, while virus variants that use CXCR4 can a... | The entry of human immunodeficiency virus type 1 (HIV-1) into a target cell is dependent on the binding of the envelope glycoprotein to its receptor CD4 and a coreceptor, either CCR5 or CXCR4. Although the reasons are incompletely understood, primary HIV-1 infection is predominantly established by CCR5-using (R5) HIV-1... |
10.1371/journal.pcbi.1000356 | Estimating the Location and Spatial Extent of a Covert Anthrax Release | Rapidly identifying the features of a covert release of an agent such as anthrax could help to inform the planning of public health mitigation strategies. Previous studies have sought to estimate the time and size of a bioterror attack based on the symptomatic onset dates of early cases. We extend the scope of these me... | Releasing highly pathogenic organisms into an urban population is a form of bioterrorism that could result in a large number of casualties. The first indication that a covert open-air release has occurred is quite likely to be individuals reporting for medical attention. If such an attack is suspected, then public heal... | If clinical cases of anthrax were detected, public health decision makers would want to estimate as soon as possible the features of the exposure event leading to the outbreak in order to determine who has potentially been exposed and should receive prophylaxis [1]. Relevant variables include the date of exposure and t... |
10.1371/journal.pntd.0007559 | Ocular immune responses, Chlamydia trachomatis infection and clinical signs of trachoma before and after azithromycin mass drug administration in a treatment naïve trachoma-endemic Tanzanian community | Trachoma, caused by Chlamydia trachomatis, remains the leading infectious cause of blindness worldwide. Persistence and progression of the resulting clinical disease appears to be an immunologically mediated process. Azithromycin, which is distributed at the community level for trachoma control, has immunomodulatory pr... | Trachoma, caused by conjunctival infection with Chlamydia trachomatis, remains the leading infectious cause of blindness. Repeated infection during childhood can trigger prolonged inflammation, which is the main risk factor for conjunctival scarring. Azithromycin is distributed globally for trachoma control, however it... | Trachoma remains the leading infectious cause of blindness worldwide, with the greatest burden in sub-Saharan Africa [1]. Trachomatous disease is initiated by repeated conjunctival infection with Chlamydia trachomatis, which triggers prolonged inflammatory episodes that contribute to the development of conjunctival sca... |
10.1371/journal.ppat.1004675 | Enhanced CD8 T Cell Responses through GITR-Mediated Costimulation Resolve Chronic Viral Infection | Chronic infections are characterized by the inability to eliminate the persisting pathogen and often associated with functional impairment of virus-specific T-cell responses. Costimulation through Glucocorticoid-induced TNFR-related protein (GITR) can increase survival and function of effector T cells. Here, we report ... | The ability of the immune system to rapidly respond to a viral infection is a prerequisite for the survival of an individual. The immediate reaction of innate immune cells and the subsequent response of antigen-specific lymphocytes is usually effective for rapid neutralization and removal of the invading virus. Yet, su... | The adaptive immune system has evolved to detect and remove virally infected cells. However, multiple viruses, such as human immunodeficiency virus (HIV), hepatitis C virus (HCV) or hepatitis B virus (HBV) have acquired successful counter-measures to escape from anti-viral immunity, thereby preventing complete clearanc... |
10.1371/journal.pgen.1003604 | From Many, One: Genetic Control of Prolificacy during Maize Domestication | A reduction in number and an increase in size of inflorescences is a common aspect of plant domestication. When maize was domesticated from teosinte, the number and arrangement of ears changed dramatically. Teosinte has long lateral branches that bear multiple small ears at their nodes and tassels at their tips. Maize ... | Crop species underwent profound transformations in morphology during domestication. Among crops, maize experienced a more striking change in morphology than other crops. Among the changes in maize from its ancestor, teosinte, was a switch from 100 or more small ears per plant in teosinte to just one or two large ears i... | The “domestication syndrome” of crop plants is a suite of adaptive traits that arose in response to direct and indirect selection pressures during the domestication process [1]–[3]. This suite of traits includes an increase seed or fruit size, larger inflorescences, an increase in apical dominance, more determinate gro... |
10.1371/journal.pntd.0000773 | Screening Mosquito House Entry Points as a Potential Method for Integrated Control of Endophagic Filariasis, Arbovirus and Malaria Vectors | Partial mosquito-proofing of houses with screens and ceilings has the potential to reduce indoor densities of malaria mosquitoes. We wish to measure whether it will also reduce indoor densities of vectors of neglected tropical diseases.
The main house entry points preferred by anopheline and culicine vectors were deter... | Mosquito vectors that transmit filariasis and several arboviruses such as Rift Valley Fever, Chikungunya and O'Nyong nyong as well as malaria co-occur across tropical Africa. These diseases are co-endemic in most rural African countries where they are transmitted by the same mosquito vectors. The only control measure c... | Houses are the main site for contact between humans and night biting mosquito vectors [1], [2]. The impact of improved housing on indoor malaria vector densities [3]–[6] and transmission [7] is well established. In Africa, the primary malaria vectors are nocturnal, endophilic and endophagic mosquitoes of the Anopheles ... |
10.1371/journal.pgen.1001274 | Transcription Initiation Patterns Indicate Divergent Strategies for Gene Regulation at the Chromatin Level | The application of deep sequencing to map 5′ capped transcripts has confirmed the existence of at least two distinct promoter classes in metazoans: “focused” promoters with transcription start sites (TSSs) that occur in a narrowly defined genomic span and “dispersed” promoters with TSSs that are spread over a larger wi... | How are genes transcribed at the right levels and under the right conditions? Transcription regulation in eukaryotes has long been proposed to work by a division of labor: ubiquitous DNA sequence features in the core promoter region, close to the transcription start site (TSS) of genes, were thought to generically enco... | The development of high-throughput sequencing strategies, which generate millions of 5′ sequence tags from capped RNAs transcribed by RNA polymerase II (pol II), has enabled obtaining fine-grained pictures of transcription initiation. Each of the tags originates from a transcription start site (TSSs), and mapping the t... |
10.1371/journal.pntd.0001790 | Quinolone Resistance in Absence of Selective Pressure: The Experience of a Very Remote Community in the Amazon Forest | Quinolones are potent broad-spectrum bactericidal agents increasingly employed also in resource-limited countries. Resistance to quinolones is an increasing problem, known to be strongly associated with quinolone exposure. We report on the emergence of quinolone resistance in a very remote community in the Amazon fores... | Quinolones are broad-spectrum antibiotics which bind to type II topoisomerases (DNA gyrase and topoisomerase IV) and inhibit DNA re-ligation after enzyme cut, exerting a rapid bactericidal activity. They are widely used for the treatment of several community- and hospital-acquired infections and have become in... | Quinolones are broad-spectrum antimicrobial agents with rapid bactericidal activity, overall low toxicity, and the possibility of being administered either orally or parenterally. Thanks to these features, quinolones are drugs of choice for the treatment of several community- and hospital-acquired infections (such as r... |
10.1371/journal.pmed.1002235 | Dementia incidence trend over 1992-2014 in the Netherlands: Analysis of primary care data | Recent reports have suggested declining age-specific incidence rates of dementia in high-income countries over time. Improved education and cardiovascular health in early age have been suggested to be bringing about this effect. The aim of this study was to estimate the age-specific dementia incidence trend in primary ... | The absolute number of persons with dementia is rising due to a growing and ageing population.
Recent studies showed a decline in dementia incidence rates that might be attributed to improved vascular care and better education in more recent years.
Available studies were based on relatively small samples collected in s... | Since dementia care places a heavy social and economic burden on society, future projections of dementia prevalence rates are important for health care planning. In view of a growing and ageing population, an increasing number of older people are at risk for dementia [1]. It is estimated that the prevalence of dementia... |
10.1371/journal.pgen.1004228 | Genome-Wide Diet-Gene Interaction Analyses for Risk of Colorectal Cancer | Dietary factors, including meat, fruits, vegetables and fiber, are associated with colorectal cancer; however, there is limited information as to whether these dietary factors interact with genetic variants to modify risk of colorectal cancer. We tested interactions between these dietary factors and approximately 2.7 m... | High intake of red and processed meat and low intake of fruits, vegetables and fiber are associated with a higher risk of colorectal cancer. We investigate if the effect of these dietary factors on colorectal cancer risk is modified by common genetic variants across the genome (total of about 2.7 million genetic varian... | Colorectal cancer is the third most common neoplasm and the third leading cause of cancer death in both men and women across most ethnic-racial groups [1]. Intake of various dietary factors, most notably, meat, fruits/vegetables, and fiber, have been extensively investigated in relation to colorectal cancer risk. Overa... |
10.1371/journal.pcbi.1000181 | Protein Meta-Functional Signatures from Combining Sequence, Structure, Evolution, and Amino Acid Property Information | Protein function is mediated by different amino acid residues, both their positions and types, in a protein sequence. Some amino acids are responsible for the stability or overall shape of the protein, playing an indirect role in protein function. Others play a functionally important role as part of active or binding s... | Proteins are the main building blocks and functional molecules of the cell. Function is mediated by specific amino acid residues in a protein sequence, in a manner dependent on both their positions and types. Proteins are traditionally described as a sequence of amino acids and, when known, the experimentally determine... | Vast amounts of sequence and structural data are being generated by high-throughput technologies. Functional annotations of the uncharacterized sequences and structures are significantly lagging. The time and cost of experimental techniques required to probe the function of all uncharacterized proteins are prohibitive.... |
10.1371/journal.pcbi.1005621 | Vicus: Exploiting local structures to improve network-based analysis of biological data | Biological networks entail important topological features and patterns critical to understanding interactions within complicated biological systems. Despite a great progress in understanding their structure, much more can be done to improve our inference and network analysis. Spectral methods play a key role in many ne... | Networks are a representation of choice for many problems in biology and medicine including protein interactions, metabolic pathways, evolutionary biology, cancer subtyping and disease modeling to name a few. The key to much of network analysis lies in the spectrum decomposition represented by eigenvectors of the netwo... | Networks are a powerful paradigm for representing relations among objects from micro to macro level. It is no surprise that networks became a representation of choice for many problems in biology and medicine including gene-gene and protein-protein interaction networks [1], diseases [2] and their interrelations [3], ca... |
10.1371/journal.pbio.1000270 | Poised Transcription Factories Prime Silent uPA Gene Prior to Activation | The position of genes in the interphase nucleus and their association with functional landmarks correlate with active and/or silent states of expression. Gene activation can induce chromatin looping from chromosome territories (CTs) and is thought to require de novo association with transcription factories. We identify... | The spatial organization of the genome inside the cell nucleus is important in regulating gene expression and in the response to external stimuli. Examples of changing spatial organization are the repositioning of genes outside chromosome territories during the induction of gene expression, and the gathering of active ... | The spatial folding of chromatin within the mammalian cell nucleus, from the level of whole chromosomes down to single genomic regions, is thought to contribute to the expression status of genes [1]–[3]. Mammalian chromosomes occupy discrete domains called chromosome territories (CTs) and have preferred spatial arrange... |
10.1371/journal.pcbi.1002275 | Gene Expression Divergence is Coupled to Evolution of DNA Structure in Coding Regions | Sequence changes in coding region and regulatory region of the gene itself (cis) determine most of gene expression divergence between closely related species. But gene expression divergence between yeast species is not correlated with evolution of primary nucleotide sequence. This indicates that other factors in cis di... | The unique phenotype of each organism is partly determined by gene expression. Changes in gene expression are an important source of phenotypic variation, and can be caused by changes in regulatory and coding sequences of the gene itself (cis) and changes in regulatory factors (trans). The contribution of cis regulatio... | Proper control of gene expression is central for the unique phenotype of each organism. Phenotypic diversity can be generated through changes in gene expression. Divergence in gene expression of a specific gene between closely related species can result from sequence changes in its coding region and regulatory region (... |
10.1371/journal.pcbi.1006325 | A model for hydrophobic protrusions on peripheral membrane proteins | With remarkable spatial and temporal specificities, peripheral membrane proteins bind to biological membranes. They do this without compromising solubility of the protein, and their binding sites are not easily distinguished. Prototypical peripheral membrane binding sites display a combination of patches of basic and h... | Peripheral membrane proteins bind cellular membranes transiently, and are otherwise soluble proteins. As the interaction between proteins and membranes happens at cellular interfaces they are naturally involved in important interfacial processes such as recognition, signaling and trafficking. Commonly their binding sit... | Biological membranes are ancient and crucial components in the organisation of life. Not only do they define the boundaries of cells and organelles, but they are central to a myriad protein-protein and protein-lipid interactions instrumental in numerous pathways [1–5]. Besides the embedded transmembrane proteins and re... |
10.1371/journal.pntd.0002164 | Combined TLR7/8 and TLR9 Ligands Potentiate the Activity of a Schistosoma japonicum DNA Vaccine | Toll-like receptor (TLR) ligands have been explored as vaccine adjuvants for tumor and virus immunotherapy, but few TLR ligands affecting schistosoma vaccines have been characterized. Previously, we developed a partially protective DNA vaccine encoding the 26-kDa glutathione S-transferase of Schistosoma japonicum (pVAX... | There is evidence that TLR activation can block Treg cell responses and thereby break tolerance to self-antigens. It is expected that the use of TLR ligands as vaccine adjuvants will induce potent anti-pathogen immune responses and simultaneously overcome immune inhibition mediated by Tregs. However, the impact of TLR ... | Schistosomiasis is regarded as one of the most neglected tropical diseases (NTDs) of high importance, and remains a major problem in public health in endemic countries [1], [2]. Although schistosomiasis can be treated with the drug praziquantel [3], high reinfection rates limit its overall success, where repeated admin... |
10.1371/journal.pgen.1000714 | Localized Plasticity in the Streamlined Genomes of Vinyl Chloride Respiring Dehalococcoides | Vinyl chloride (VC) is a human carcinogen and widespread priority pollutant. Here we report the first, to our knowledge, complete genome sequences of microorganisms able to respire VC, Dehalococcoides sp. strains VS and BAV1. Notably, the respective VC reductase encoding genes, vcrAB and bvcAB, were found embedded in d... | Dehalococcoides are free-living sediment and subsurface bacteria with remarkably small, streamlined genomes and an unusual degree of niche specialization. These strictly anaerobic bacteria gain metabolic energy exclusively through a novel type of respiration that results in reductive elimination of chlorides from organ... | Vinyl chloride (VC) – a proven human carcinogen [1] – and other chloroethenes, such as trichloroethene (TCE) and tetrachloroethene (PCE), are among the most frequently detected groundwater contaminants in the United States of America and other industrialized countries [2]. Some members of a deeply branching Chloroflexi... |
10.1371/journal.pcbi.1003771 | Tracing the Evolution of Lineage-Specific Transcription Factor Binding Sites in a Birth-Death Framework | Changes in cis-regulatory element composition that result in novel patterns of gene expression are thought to be a major contributor to the evolution of lineage-specific traits. Although transcription factor binding events show substantial variation across species, most computational approaches to study regulatory elem... | Recent experimental studies showed that the evolution of transcription factor binding sites (TFBS) is highly dynamic, with sites differing a great deal even between closely related mammalian species. Despite the substantial experimental evidence for rapid divergence of regulatory protein-binding events across species, ... | Changes in gene regulation play a key role in the evolution of morphological traits [1]–[3]. At the level of transcription, gene expression is controlled via transcription factor (TF) proteins that selectively bind to cis-regulatory elements in a sequence-specific manner [2], [4]. Utilizing chromatin immunoprecipitatio... |
10.1371/journal.ppat.1000845 | A Genomic Survey of Positive Selection in Burkholderia pseudomallei Provides Insights into the Evolution of Accidental Virulence | Certain environmental microorganisms can cause severe human infections, even in the absence of an obvious requirement for transition through an animal host for replication (“accidental virulence”). To understand this process, we compared eleven isolate genomes of Burkholderia pseudomallei (Bp), a tropical soil microbe ... | With recent advances in genomics now permitting the systematic comparison of dozens, if not hundreds, of closely related bacterial strains, the opportunity arises for developing novel approaches to identify the complete repertoire of molecular factors governing interactions between hosts and pathogens. We explored thes... | Burkholderia pseudomallei (Bp), the causative agent of the often-fatal disease melioidosis, represents one of the most complex bacterial genomes sequenced to date [1]. Comprising two circular chromosomes with a combined length of 7.2 Mb, the Bp genome contains an estimated ∼5800 genes involved in a myriad of functions,... |
10.1371/journal.pcbi.1002648 | How Entorhinal Grid Cells May Learn Multiple Spatial Scales from a Dorsoventral Gradient of Cell Response Rates in a Self-organizing Map | Place cells in the hippocampus of higher mammals are critical for spatial navigation. Recent modeling clarifies how this may be achieved by how grid cells in the medial entorhinal cortex (MEC) input to place cells. Grid cells exhibit hexagonal grid firing patterns across space in multiple spatial scales along the MEC d... | Spatial navigation is a critical competence of all higher mammals, and place cells in the hippocampus represent the large spaces in which they navigate. Recent modeling clarifies how this may occur via interactions between grid cells in the medial entorhinal cortex (MEC) and place cells. Grid cells exhibit hexagonal gr... | Navigating the world requires the brain to learn and maintain memory of spatial positions within various environments. Place cells in the hippocampal areas CA1 and CA3 demonstrate a neural code for position in large spaces that higher mammals inhabit [1] and thereby play a critical role in spatial navigation. CA3 recei... |
10.1371/journal.pcbi.1000055 | The Role of Elastic Stresses on Leaf Venation Morphogenesis | We explore the possible role of elastic mismatch between epidermis and mesophyll as a driving force for the development of leaf venation. The current prevalent ‘canalization’ hypothesis for the formation of veins claims that the transport of the hormone auxin out of the leaves triggers cell differentiation to form vein... | Leaf venation patterns of most angiosperm plants are hierarchical structures that develop during leaf growth. A remarkable characteristic of these structures is the abundance of closed loops: the venation array divides the leaf surface into disconnected polygonal sectors. The initial vein generations are repetitive wit... | For many years leaf venation motifs have marveled people, whether scientists or not. Venation patterns are different from one leaf to another, even in the same plant, but share some common features that are preserved throughout all angiosperm leaves [1]. A remarkable characteristic of these patterns is the vein hierarc... |
10.1371/journal.ppat.1003360 | Rhesus Monkey Rhadinovirus Uses Eph Family Receptors for Entry into B Cells and Endothelial Cells but Not Fibroblasts | Cellular Ephrin receptor tyrosine kinases (Ephrin receptors, Ephs) were found to interact efficiently with the gH/gL glycoprotein complex of the rhesus monkey rhadinovirus (RRV). Since EphA2 was recently identified as a receptor for the Kaposi's sarcoma-associated herpesvirus (KSHV) (Hahn et al., Nature Medicine 2012),... | Here we show that the gH/gL glycoprotein complex of rhesus monkey rhadinovirus binds to and mediates entry of virus into target cells via cellular Ephrin receptor tyrosine kinase proteins. Rhesus monkey rhadinovirus is a gamma-2 herpesvirus that is a close homolog of the human Kaposi's sarcoma-associated herpesvirus (K... | The gamma-2 herpesviruses, also called rhadinoviruses, are a distinct subfamily of the lymphotropic herpesviruses. The rhesus monkey rhadinovirus (RRV) is a natural infectious agent found at high frequency in both captive and feral populations of rhesus monkeys (Macaca mulatta) [1]. RRV is a rhesus monkey homolog of th... |
10.1371/journal.pgen.1004279 | PINK1-Parkin Pathway Activity Is Regulated by Degradation of PINK1 in the Mitochondrial Matrix | Loss-of-function mutations in PINK1, which encodes a mitochondrially targeted serine/threonine kinase, result in an early-onset heritable form of Parkinson's disease. Previous work has shown that PINK1 is constitutively degraded in healthy cells, but selectively accumulates on the surface of depolarized mitochondria, t... | Mitochondria are essential organelles that provide most of the cell's energy and perform many other critical functions. The gradual accumulation of defective mitochondria is thought to play a role in aging and in diseases of the nervous system, including Parkinson's disease. The selective elimination of defective mitoc... | The accumulation of defective mitochondria is strongly implicated in aging, as well as a variety of common age-related diseases [1], [2], [3]. To counteract this accumulation, cells have evolved a number of mitochondrial quality control pathways. While previous work has revealed molecular mechanisms involved in the pre... |
10.1371/journal.pntd.0005874 | Neurogenic mediators contribute to local edema induced by Micrurus lemniscatus venom | Micrurus is one of the four snake genera of medical importance in Brazil. Coral snakes have a broad geographic distribution from the southern United States to Argentina. Micrurine envenomation is characterized by neurotoxic symptoms leading to dyspnea and death. Moreover, various local manifestations, including edema f... | Micrurus venoms have neurotoxic activity that is responsible for the serious sequelae in human envenomation. However, various local manifestations of envenoming have been described in patients bitten by different Micrurus species and edematogenic activity has been experimentally demonstrated. Despite the low frequency ... | Micrurus is one of the four snake genera of medical importance in Brazil. Coral snakes can be found from the southern United States to Argentina [1, 2]. There are at least thirty species in Brazil, and these have a broad geographic distribution and inhabit a variety of habitats [3]. In the state of Bahia, Brazil, M. le... |
10.1371/journal.pcbi.1004153 | Large-Scale Chemical Similarity Networks for Target Profiling of Compounds Identified in Cell-Based Chemical Screens | Target identification is one of the most critical steps following cell-based phenotypic chemical screens aimed at identifying compounds with potential uses in cell biology and for developing novel disease therapies. Current in silico target identification methods, including chemical similarity database searches, are li... | Determining the targets of compounds identified in cell-based high-throughput chemical screens is a critical step for downstream drug development and understanding of compound mechanism of action. However, current computational target prediction approaches like chemical similarity database searches are limited to singl... | The use of chemical screens to identify molecules for the treatment of proliferative diseases like cancer has relied on two major strategies, target-based screening and phenotypic screening [1,2]. Unbiased cell-based screens, including phenotypic screens, have successfully discovered numerous cytotoxic agents that inhi... |
10.1371/journal.pntd.0002843 | Diagnostic Accuracy and Cost-Effectiveness of Alternative Methods for Detection of Soil-Transmitted Helminths in a Post-Treatment Setting in Western Kenya | This study evaluates the diagnostic accuracy and cost-effectiveness of the Kato-Katz and Mini-FLOTAC methods for detection of soil-transmitted helminths (STH) in a post-treatment setting in western Kenya. A cost analysis also explores the cost implications of collecting samples during school surveys when compared to ho... | Accurate methods of diagnosis and optimal strategies to sample the population are essential for the reliable mapping and surveillance of infectious diseases. The current standard for detection of soil-transmitted helminths (STH) entails use of the Kato-Katz diagnostic method. Alternative diagnostic methods, such as flo... | The reliable mapping, surveillance and evaluation of infectious diseases relies upon two key factors: (i) accurate methods of diagnosis and (ii) optimal strategies to sample the population. For the soil-transmitted helminths (STH: Ascaris lumbricoides,Trichuris trichiura and hookworm), the commonly used diagnostic tech... |
10.1371/journal.pntd.0006880 | Growth and adaptation of Zika virus in mammalian and mosquito cells | The recent emergence of Zika virus (ZIKV) in the Americas coincident with increased caseloads of microcephalic infants and Guillain-Barre syndrome has prompted a flurry of research on ZIKV. Much of the research is difficult to compare or repeat because individual laboratories use different virus isolates, growth condit... | The ZIKV scientific field has greatly expanded since the emergence of ZIKV in South and Central America, but a comprehensive comparison of the assays used to examine the phenotypic and replicative properties of ZIKV is limited in the literature. The influence of host, whether insect or mammalian, on viral production an... | Zika virus (ZIKV) is a mosquito-borne virus in the genus Flavivirus, which includes many arthropod-borne viruses (arboviruses) such as dengue virus (DENV) and West Nile virus (WNV). It was originally isolated in 1947 from a sentinel macaque in Uganda and was subsequently found throughout Africa and Asia with minimal re... |
10.1371/journal.ppat.1004280 | Peptidoglycan Recognition Proteins Kill Bacteria by Inducing Oxidative, Thiol, and Metal Stress | Mammalian Peptidoglycan Recognition Proteins (PGRPs) are a family of evolutionary conserved bactericidal innate immunity proteins, but the mechanism through which they kill bacteria is unclear. We previously proposed that PGRPs are bactericidal due to induction of reactive oxygen species (ROS), a mechanism of killing t... | Bacterial infections are still a major cause of morbidity and mortality because of increasing antibiotic resistance. New targets for developing new approaches to antibacterial therapy are needed, because discovering new or improving current antibiotics have become increasingly difficult. One such approach is developing... | Mammalian Peptidoglycan Recognition Proteins (PGRPs) are a family of four evolutionary conserved antibacterial innate immunity proteins [1]–[3]. Three PGRPs (PGLYRP1, PGLYRP3, and PGLYRP4) are directly bactericidal [4], [5] and one PGRP (PGLYRP2) is a peptidoglycan-lytic amidase [6]. PGRPs kill both Gram-positive and G... |
10.1371/journal.pntd.0001276 | Restricted Application of Insecticides: A Promising Tsetse Control Technique, but What Do the Farmers Think of It? | Restricted application of insecticides to cattle is a cheap and safe farmer-based method to control tsetse. In Western Africa, it is applied using a footbath, mainly to control nagana and the tick Amblyomma variegatum. In Eastern and Southern Africa, it might help controlling the human disease, i.e., Rhodesian sleeping... | Restricted application of insecticides to cattle is a cheap and safe farmer-based method to control tsetse and the diseases they transmit, i.e. human and animal African trypanosomoses. The efficiency of this new control method has been demonstrated earlier but no data is available on its perception and adoption intensi... | Tsetse flies (Diptera: Glossinidae) are the vectors of human and animal African trypanosomoses, the former a major neglected disease, and the latter considered among the greatest constraints to livestock production in sub-Saharan Africa. The integrated management of these diseases would require the combination of tsets... |
10.1371/journal.pntd.0002287 | Is Zinc Concentration in Toxic Phase Plasma Related to Dengue Severity and Level of Transaminases? | To determine the relationship between plasma zinc values and the severity of dengue viral infection (DVI) and DVI-caused hepatitis.
A prospective cohort study was conducted during 2008–2010 in hospitalized children aged <15 years confirmed with DVI. Complete blood count, aspartate aminotransferase (AST), alanine aminot... | Dengue viral infection (DVI) is endemic in tropical counties and severe DVI is a significant cause of death, especially in children. Increased vascular endothelial permeability during the defervescence stage of DVI leading to plasma leakage plays an important role in dengue disease severity. Zinc is a protective and cr... | The immunopathogenesis of dengue viral infection (DVI) is not well understood, and the level of disease severity is multifactorial, depending on various factors such as viral virulence, secondary DVI, immune response to DVI, and host factors including genetic and nutritional status [1]–[3]. Plasma leakage during the to... |
10.1371/journal.pgen.1000031 | An Abundant Evolutionarily Conserved CSB-PiggyBac Fusion Protein Expressed in Cockayne Syndrome | Cockayne syndrome (CS) is a devastating progeria most often caused by mutations in the CSB gene encoding a SWI/SNF family chromatin remodeling protein. Although all CSB mutations that cause CS are recessive, the complete absence of CSB protein does not cause CS. In addition, most CSB mutations are located beyond exon 5... | For reasons that are still unclear, genetic defects in DNA repair can cause diseases that resemble aspects of premature ageing (“segmental progerias”). Cockayne syndrome (CS) is a particularly devastating progeria most commonly caused by mutations in the CSB chromatin remodeling gene. About 43 million years ago, before... | The human genome is replete with interlopers — transposable DNA elements, retrotransposable RNA elements such as SINEs and LINEs, and a dizzying variety of lesser-known elements — which together account for as much as half of our DNA [1]. Although much of this “junk” DNA is selfish and surprisingly harmless, the consta... |
10.1371/journal.pntd.0000422 | Diagnosing Schistosomiasis by Detection of Cell-Free Parasite DNA in Human Plasma | Schistosomiasis (bilharzia), one of the most relevant parasitoses of humans, is confirmed by microscopic detection of eggs in stool, urine, or organ biopsies. The sensitivity of these procedures is variable due to fluctuation of egg shedding. Serological tests on the other hand do not distinguish between active and pas... | Bilharzia (schistosomiasis) occurs in the tropics and subtropics and is one of the most important parasite diseases of humans. It is caused by flukes residing in the vessels of the gut or bladder, causing fever, pain, and bleeding. Bladder cancer or esophageal varices may follow. Diagnosis is difficult, requiring detec... | Schistosomiasis, also known as bilharzia, is caused by trematodes of the Schistosomatidae family. It is among the most important parasitic diseases worldwide, with a significant socio-economic impact [1]. More than 200 million people are infected, and about 200,000 may die from the disease each year. On a global scale,... |
10.1371/journal.pbio.0050080 | DNA-Dependent Protein Kinase Inhibits AID-Induced Antibody Gene Conversion | Affinity maturation and class switching of antibodies requires activation-induced cytidine deaminase (AID)-dependent hypermutation of Ig V(D)J rearrangements and Ig S regions, respectively, in activated B cells. AID deaminates deoxycytidine bases in Ig genes, converting them into deoxyuridines. In V(D)J regions, subseq... | To generate highly specific antibodies in response to an immune challenge, the antibody genes in activated B cells mutate at a very high rate over a period of several days. The enzyme that initiates antibody gene mutation is activation-induced cytidine deaminase (AID), the first protein recognized to directly edit DNA ... | In humans and mice, primary antibody (Ig) diversity is produced by V(D)J recombination, which is dependent on the RAG-1 and −2 proteins [1]. Over a lifetime, primary repertoires are largely re-shaped by the processes of Ig somatic hypermutation (SHM) and class switching [2], independent processes which occur in B cells... |
10.1371/journal.pbio.0060030 | Increased Transmission of Mutations by Low-Condition Females: Evidence for Condition-Dependent DNA Repair | Evidence is mounting that mutation rates are sufficiently high for deleterious alleles to be a major evolutionary force affecting the evolution of sex, the maintenance of genetic variation, and many other evolutionary phenomena. Though point estimates of mutation rates are improving, we remain largely ignorant of the b... | A variety of evolutionary phenomena are affected by the rate at which mutations enter a population and how those mutations are distributed amongst individuals. Although it is typically assumed that mutations occur randomly among individuals, this may not be the case. Individuals in poor condition may experience elevate... | Germ-line mutation is the ultimate source of heritable variation, but the vast majority of new mutations affecting fitness are deleterious. The unremitting presence of deleterious mutations causes a reduction in mean fitness, a phenomenon known as mutation load. Mutation load can be substantial even if individual mutat... |
10.1371/journal.pcbi.1002904 | Noise Suppression and Surplus Synchrony by Coincidence Detection | The functional significance of correlations between action potentials of neurons is still a matter of vivid debate. In particular, it is presently unclear how much synchrony is caused by afferent synchronized events and how much is intrinsic due to the connectivity structure of cortex. The available analytical approach... | Whether spike timing conveys information in cortical networks or whether the firing rate alone is sufficient is a matter of controversial debate, touching the fundamental question of how the brain processes, stores, and conveys information. If the firing rate alone is the decisive signal used in the brain, correlations... | Simultaneously recording the activity of multiple neurons provides a unique tool to observe the activity in the brain. The immediately arising question of the meaning of the observed correlated activity between different cells [1], [2] is tightly linked to the problem how information is represented and processed by the... |
10.1371/journal.pgen.1006795 | Tandem duplications lead to novel expression patterns through exon shuffling in Drosophila yakuba | One common hypothesis to explain the impacts of tandem duplications is that whole gene duplications commonly produce additive changes in gene expression due to copy number changes. Here, we use genome wide RNA-seq data from a population sample of Drosophila yakuba to test this ‘gene dosage’ hypothesis. We observe littl... | The enclosed work shows that whole gene duplications rarely affect gene expression, in contrast to widely held views that the adaptive value of duplicate genes is related to additive changes in gene expression due to gene copy number. We further explain how tandem duplications that create shuffled gene structures can f... | Tandem duplications are known as a source of genetic novelty that can contribute new genes with novel functions [1, 2]. For example, duplication of homeobox loci has been associated developmental changes across vertebrates [3]. The globin gene families have achieved functional differences via copy number expansion in m... |
10.1371/journal.pgen.1004376 | Mechanisms of CFTR Functional Variants That Impair Regulated Bicarbonate Permeation and Increase Risk for Pancreatitis but Not for Cystic Fibrosis | CFTR is a dynamically regulated anion channel. Intracellular WNK1-SPAK activation causes CFTR to change permeability and conductance characteristics from a chloride-preferring to bicarbonate-preferring channel through unknown mechanisms. Two severe CFTR mutations (CFTRsev) cause complete loss of CFTR function and resul... | Genetic disorders of ion channels can affect the body's ability to function properly in many ways. CFTR, an ion channel regulating movement of chloride and bicarbonate across cell membranes, is important for absorbing and secreting fluids. If the gene responsible for the CFTR channel is mutated severely, the result is ... | The cystic fibrosis transmembrane conductance regulator (CFTR, GenBank Accession: AH006034.1) is an ATP-binding cassette (ABC) transporter-type protein localized to the apical plasma membrane of epithelial cells. It differs from other ABC transporters in that it acts as a regulated anion channel rather than a transport... |
10.1371/journal.pcbi.1003295 | In Silico Analysis of Cell Cycle Synchronisation Effects in Radiotherapy of Tumour Spheroids | Tumour cells show a varying susceptibility to radiation damage as a function of the current cell cycle phase. While this sensitivity is averaged out in an unperturbed tumour due to unsynchronised cell cycle progression, external stimuli such as radiation or drug doses can induce a resynchronisation of the cell cycle an... | The sensitivity of a cell to a dose of radiation is largely affected by its current position within the cell cycle. While under normal circumstances progression through the cell cycle will be asynchronous in a tumour mass, external influences such as chemo- or radiotherapy can induce a synchronisation. Such a common pr... | Tumours are complex dynamic objects which can adapt to changes in their environmental conditions and accordingly react to treatments such as radiotherapy. Withers was one of the first to note that the now common scheduling of radiotherapy in fractions is efficient, because it exploits these dynamic intra-tumoural effec... |
10.1371/journal.ppat.1007160 | Antibody to Poly-N-acetyl glucosamine provides protection against intracellular pathogens: Mechanism of action and validation in horse foals challenged with Rhodococcus equi | Immune correlates of protection against intracellular bacterial pathogens are largely thought to be cell-mediated, although a reasonable amount of data supports a role for antibody-mediated protection. To define a role for antibody-mediated immunity against an intracellular pathogen, Rhodococcus equi, that causes granu... | Development of effective vaccines for diseases such as tuberculosis, brucellosis and others caused by intracellular pathogens has proved challenging, as data exist supporting both antibody and cellular immune effectors as mediators of protection. To address this problem against an important, and representative, equine ... | Correlates of cellular and humoral immunity to major intracellular, non-viral pathogens capable of informing vaccine development are incompletely understood. It is unknown which ones can form the basis of a highly effective vaccine to prevent diseases such as tuberculosis (TB). Protection studies conducted to date, pri... |
10.1371/journal.pbio.1000483 | Complete Structural Model of Escherichia coli RNA Polymerase from a Hybrid Approach | The Escherichia coli transcription system is the best characterized from a biochemical and genetic point of view and has served as a model system. Nevertheless, a molecular understanding of the details of E. coli transcription and its regulation, and therefore its full exploitation as a model system, has been hampered ... | Transcription, or the synthesis of RNA from DNA, is one of the most important processes in the cell. The central enzyme of transcription is the DNA-dependent RNA polymerase (RNAP), a large, macromolecular assembly consisting of at least five subunits. Historically, much of our fundamental information on the process of ... | RNA in all cellular organisms is synthesized by a complex molecular machine, the DNA-dependent RNA polymerase (RNAP). In bacteria, the catalytically competent core RNAP (subunit composition α2ββ'ω) has a molecular mass of ∼400 kDa. Evolutionary relationships for each of the bacterial core subunits have been identified ... |
10.1371/journal.ppat.1003117 | Assembly of the Type II Secretion System such as Found in Vibrio cholerae Depends on the Novel Pilotin AspS | The Type II Secretion System (T2SS) is a molecular machine that drives the secretion of fully-folded protein substrates across the bacterial outer membrane. A key element in the machinery is the secretin: an integral, multimeric outer membrane protein that forms the secretion pore. We show that three distinct forms of ... | The type 2 secretion system (T2SS) is a sophisticated, multi-component molecular machine that drives the secretion of fully-folded protein substrates across the bacterial outer membrane. In Vibrio cholerae, for example, the T2SS mediates the secretion of cholera toxin. We find that there are three distinct forms of T2S... | Bacterial outer membranes incorporate proteins of at least three well-characterized architectures: β-barrel proteins, lipoproteins and secretins. The integral membrane proteins having a β-barrel architecture are targeted to the outer membrane and assembled by the β-barrel assembly machinery, the BAM complex [1]–[3]. Li... |
10.1371/journal.ppat.1006561 | A parapoxviral virion protein inhibits NF-κB signaling early in infection | Poxviruses have evolved unique proteins and mechanisms to counteract the nuclear factor κB (NF-κB) signaling pathway, which is an essential regulatory pathway of host innate immune responses. Here, we describe a NF-κB inhibitory virion protein of orf virus (ORFV), ORFV073, which functions very early in infected cells. ... | Successful infection of the host by poxviruses relies on control of innate immune responses by virus-encoded immunomodulators. In particular, poxviruses evolved to counteract the NF-κB pathway by encoding multiple inhibitors targeting various levels of NF-κB signaling. We identified a NF-κB inhibitor encoded by ORFV, O... | Orf virus (ORFV), the prototype member of the genus Parapoxvirus (PPV) of the Poxviridae, is the etiologic agent of contagious pustular dermatitis or orf, a ubiquitous disease of sheep and goats [1]. Orf is characterized by inflammatory, often proliferative lesions affecting the skin and the oral mucosa [2]. Lesions ev... |
10.1371/journal.pcbi.1005539 | SteadyCom: Predicting microbial abundances while ensuring community stability | Genome-scale metabolic modeling has become widespread for analyzing microbial metabolism. Extending this established paradigm to more complex microbial communities is emerging as a promising way to unravel the interactions and biochemical repertoire of these omnipresent systems. While several modeling techniques have b... | The microbes residing in the human gut, collectively known as the gut microbiota, have an intimate and complicated relationship with human health. In this study, we aim to enhance the understanding of the relationship between the gut microbiota composition, the metabolite production, the diet, and the metabolic reperto... | Metagenomics has brought forth the opportunity for non-culture-based sampling of microorganisms in various environments. It has revolutionized our understanding of microbial communities and their impact on diverse ecosystems and human health. For example, marine microbes have been estimated to contribute half of the fl... |
10.1371/journal.pntd.0006746 | Vector competence of Aedes bromeliae and Aedes vitattus mosquito populations from Kenya for chikungunya virus | Kenya has experienced outbreaks of chikungunya in the past years with the most recent outbreak occurring in Mandera in the northern region in May 2016 and in Mombasa in the coastal region from November 2017 to February 2018. Despite the outbreaks in Kenya, studies on vector competence have only been conducted on Aedes ... | Kenya experienced its first chikungunya outbreak in 2004/2005 along the coastal area, followed by sporadic outbreaks in Mandera in 2016, and subsequently in Mombasa city in late 2017 and early 2018. Despite the rising risk of transmission of the virus in the country based on evidence of outbreaks in Kenya, vector compe... | Chikungunya virus (CHIKV) is vector-borne virus of genus Alphavirus and family Togaviridae that is principally transmitted from human to humans by Ae. aegypti and Ae. albopictus. The first CHIKV outbreak was documented in Makonde village in Tanzania in 1956 [1, 2] and since then, various outbreaks have been experienced... |
10.1371/journal.pntd.0003913 | Endemicity of Zoonotic Diseases in Pigs and Humans in Lowland and Upland Lao PDR: Identification of Socio-cultural Risk Factors | In Lao People’s Democratic Republic pigs are kept in close contact with families. Human risk of infection with pig zoonoses arises from direct contact and consumption of unsafe pig products. This cross-sectional study was conducted in Luang Prabang (north) and Savannakhet (central-south) Provinces. A total of 59 villag... | In Lao PDR, pigs are an important source of food and income and are kept by many rural residents. This study investigated five diseases that are transmitted between pigs and humans (zoonoses), namely hepatitis E, Japanese encephalitis, trichinellosis, cysticercosis and taeniasis. Humans and pigs in Lao PDR were tested ... | Approximately two thirds (66.9%) of the 6.4 million residents of Lao PDR reside in rural areas and most (83%) of the 0.8 million households are considered agricultural holdings [1]. The majority of these employ mixed farming systems (i.e. keeping both livestock and crops). In recent years, intensification of crop produ... |
10.1371/journal.pntd.0001854 | RNAseq Analysis of the Parasitic Nematode Strongyloides stercoralis Reveals Divergent Regulation of Canonical Dauer Pathways | The infectious form of many parasitic nematodes, which afflict over one billion people globally, is a developmentally arrested third-stage larva (L3i). The parasitic nematode Strongyloides stercoralis differs from other nematode species that infect humans, in that its life cycle includes both parasitic and free-living ... | Parasitic nematodes infect over one billion people worldwide and cause many diseases, including strongyloidiasis, filariasis, and hookworm disease. For many of these parasites, including Strongyloides stercoralis, the infectious form is a developmentally arrested and long-lived thirdstage larva (L3i). Upon enco... | Parasitic nematodes infect over one billion people worldwide, resulting in vast morbidity [1], as well as causing significant agricultural losses from infections of both animals and plants [2]. The infectious form of many parasitic nematodes, including those causing hookworm disease, filariasis, and strongyloidiasis, i... |
10.1371/journal.pntd.0007436 | Wuchereria bancrofti-infected individuals harbor distinct IL-10-producing regulatory B and T cell subsets which are affected by anti-filarial treatment | Despite worldwide mass drug administration, it is estimated that 68 million individuals are still infected with lymphatic filariasis with 19 million hydrocele and 17 million lymphedema reported cases. Despite the staggering number of pathology cases, the majority of LF-infected individuals do not develop clinical sympt... | Regulation of the host`s immune system by filarial nematodes is crucial for the fertility and survival of the nematode. Indeed, the majority of W. bancrofti-infected individuals are characterized by a regulated state including increased regulatory T cells (Treg), IL-10, TGF-β and filarial-specific IgG4 and suppressed T... | Helminths like filarial nematodes are tropical parasitic worms and the infections that they induce are classified as neglected tropical diseases (NTDs). Filarial infections are vector-borne diseases which are transmitted by blood-feeding insects that are common in tropical and subtropical countries. Although the majori... |
10.1371/journal.pcbi.1002843 | Refractoriness in Sustained Visuo-Manual Control: Is the Refractory Duration Intrinsic or Does It Depend on External System Properties? | Researchers have previously adopted the double stimulus paradigm to study refractoriness in human neuromotor control. Currently, refractoriness, such as the Psychological Refractory Period (PRP) has only been quantified in discrete movement conditions. Whether refractoriness and the associated serial ballistic hypothes... | In biology, the control of physiological variables such as body position, blood pressure and body temperature is founded on negative feedback mechanisms governing homeostasic input-output relations. The conceptual models capturing the underlying control principles are often drawn from engineering control theory. The vi... | Our interactions with the environment include stimuli and responses. The concatenation of successive stimulus-response operations is an ongoing process of which we are often unaware. For example, when manoeuvring a car through heavy traffic we brake and accelerate in response to the other vehicles actions. Usually, the... |
10.1371/journal.pgen.1004245 | A Combination of Activation and Repression by a Colinear Hox Code Controls Forelimb-Restricted Expression of Tbx5 and Reveals Hox Protein Specificity | Tight control over gene expression is essential for precision in embryonic development and acquisition of the regulatory elements responsible is the predominant driver for evolution of new structures. Tbx5 and Tbx4, two genes expressed in forelimb and hindlimb-forming regions respectively, play crucial roles in the ini... | The acquisition of limbs during vertebrate evolution was a very successful innovation that enabled this group of species to diversify and colonise land. It has become clear recently that the primary driver behind the evolution of new structures, such as limbs, is the acquisition of novel regulatory elements that contro... | Forelimbs and hindlimbs are derivatives of the lateral plate mesoderm (LPM) that arise at fixed positions along the vertebrate body axis. Limb formation is initiated by limb induction signals from axial tissues [1]. The presumptive limb-forming regions initially express two T-box genes prior to overt limb bud formation... |
10.1371/journal.pbio.1002571 | snRNA 3′ End Processing by a CPSF73-Containing Complex Essential for Development in Arabidopsis | Uridine-rich small nuclear RNAs (snRNAs) are the basal components of the spliceosome and play essential roles in splicing. The biogenesis of the majority of snRNAs involves 3′ end endonucleolytic cleavage of the nascent transcript from the elongating DNA-dependent RNA ploymerase II. However, the protein factors respons... | snRNAs form the RNA components of the spliceosome and are required for spliceosome formation and splicing. The generation of snRNAs involves 3′ end endonucleolytic cleavage of primary snRNA transcripts (pre-snRNAs). The factors responsible for pre-snRNA 3′ end cleavage are known in metazoans, but many of these componen... | Uridine-rich small nuclear RNAs (snRNAs), ~60–200 nucleotide (nt) in length, are conserved noncoding RNAs in eukaryotes [1,2]. As the RNA components of the spliceosome, snRNAs (U1, U2, U4, U5, and U6) play essential roles in spliceosome formation and splicing of pre-messenger RNAs (pre-mRNAs) [1–3]. Most snRNAs are der... |
10.1371/journal.pntd.0006974 | Serological proteomic screening and evaluation of a recombinant egg antigen for the diagnosis of low-intensity Schistosoma mansoni infections in endemic area in Brazil | Despite decades of use of control programs, schistosomiasis remains a global public health problem. To further reduce prevalence and intensity of infection, or to achieve the goal of elimination in low-endemic areas, there needs to be better diagnostic tools to detect low-intensity infections in low-endemic areas in Br... | Schistosomiasis remains a serious global public health problem. Detecting parasite eggs in patient stool samples using the KK method is the standard diagnostic recommended by the World Health Organization (WHO) for infection by S. mansoni. As a result of intensive control strategies, many previously high-endemic areas ... | Schistosomiasis remains as a major worldwide public health problem. Since it is a disease of poverty and limited sanitary facilities, the disease has proved difficult to control for centuries [1]. Schistosomiasis afflicts low-income populations in tropical and subtropical regions with varying levels of morbidity and mo... |
10.1371/journal.pgen.1004563 | Canonical Non-Homologous End Joining in Mitosis Induces Genome Instability and Is Suppressed by M-phase-Specific Phosphorylation of XRCC4 | DNA double-strand breaks (DSBs) can be repaired by one of two major pathways—non-homologous end-joining (NHEJ) and homologous recombination (HR)—depending on whether cells are in G1 or S/G2 phase, respectively. However, the mechanisms of DSB repair during M phase remain largely unclear. In this study, we demonstrate th... | DNA double-strand breaks (DSBs) are highly toxic to cells and often lead to genome instability and cell death. Organisms have several DSB repair mechanisms to prevent such instability. Proper choice of DSB repair pathways is highly regulated during the cell cycle. Inappropriate choice of the DSB repair pathway often re... | Double-strand breaks (DSBs) are one of the most consequential types of DNA damage. DSBs are usually repaired by one of two main repair pathways—canonical non-homologous end joining (C-NHEJ) or homologous recombination (HR) [1], [2]. Recently, however, a third less-characterized repair pathway, referred to as alternativ... |
10.1371/journal.ppat.1001254 | Salivary Gland NK Cells Are Phenotypically and Functionally Unique | Natural killer (NK) cells and CD8+ T cells play vital roles in containing and eliminating systemic cytomegalovirus (CMV). However, CMV has a tropism for the salivary gland acinar epithelial cells and persists in this organ for several weeks after primary infection. Here we characterize a distinct NK cell population tha... | Human cytomegalovirus (HCMV) is a herpesvirus that infects 50–95% of human populations. In immunocompetent individuals, a primary infection often goes unnoticed and when resolved by the adaptive immune response, HCMV enters into a latent phase. The natural mouse pathogen murine CMV (MCMV) is a well-characterized animal... | Human herpesvirus 5, also known as human cytomegalovirus (HCMV), is a prototypical β-herpesvirus. HCMV infection is widespread with 50–95% of the adult population being seropositive. CMVs are opportunistic pathogens that promote their survival by exploiting a defective immune response. Primary HCMV infection is usually... |
10.1371/journal.ppat.1007519 | Guanylate-binding protein 5 licenses caspase-11 for Gasdermin-D mediated host resistance to Brucella abortus infection | Innate immune response against Brucella abortus involves activation of Toll-like receptors (TLRs) and NOD-like receptors (NLRs). Among the NLRs involved in the recognition of B. abortus are NLRP3 and AIM2. Here, we demonstrate that B. abortus triggers non-canonical inflammasome activation dependent on caspase-11 and ga... | Brucella abortus is the causative agent of brucellosis, a zoonotic disease that affects both humans and cattle. In humans, it is characterized by undulant fever and chronic symptoms as arthritis, endocarditis, and meningitis, while in cattle it causes abortion and infertility. Due to its difficult diagnosis and treatme... | Inflammasomes are multiprotein complexes that assemble in response to pathogen- and damage-associated molecular patterns (PAMPs and DAMPs). The NLRP3 inflammasome, via the adaptor molecule ASC, leads to caspase-1 activation and release of proinflammatory cytokines such as IL-1β and IL-18 [1, 2]. An extensive range of s... |
10.1371/journal.pgen.0030143 | Assessing the Significance of Conserved Genomic Aberrations Using High Resolution Genomic Microarrays | Genomic aberrations recurrent in a particular cancer type can be important prognostic markers for tumor progression. Typically in early tumorigenesis, cells incur a breakdown of the DNA replication machinery that results in an accumulation of genomic aberrations in the form of duplications, deletions, translocations, a... | Cancer is a genetic disease caused by genomic mutations that confer an increased ability to proliferate and survive in a specific environment. It is now known that many regions of genomic DNA are deleted or amplified in specific cancer types. These aberrations are believed to occur randomly in the genome. If these aber... | In cancer cells, aberrations can turn on or off various pathways necessary for tumor development and survival [1]. Array comparative genomic hybridization (aCGH) is a highly parallel microarray-based method for detecting DNA copy number aberrations. aCGH detects genomic aberrations at a higher resolution than previous ... |
10.1371/journal.pntd.0006818 | Bile acids drive chemotaxis of Clonorchis sinensis juveniles to the bile duct | Clonorchiasis is a neglected tropical disease caused by Chinese liver fluke, Clonorchis sinensis infection. C. sinensis is a biological carcinogen causing cholangiocarcinoma in humans. In the mammalian host, C. sinensis newly excysted juveniles (CsNEJs) migrate from the duodenum into the bile duct. Bile drives the chem... | We previously reported that Clonorchis sinensis newly excysted juveniles (CsNEJs) were chemotactically attracted to bile. However, there is still a paucity of information regarding which components and what concentration of bile induce the chemotactic behavior. Here, we show, among various bile components tested, two h... | Many parasites seek out and invade hosts using host-emitted chemical cues, exhibiting a trait known as chemotaxis. Recent studies have encompassed a range of examples, including the miracidia of Schistosoma species swim along a chemical gradient toward the snail host [1, 2]. The larvae of Echinostoma species, both mira... |
10.1371/journal.pcbi.1003811 | Communication through Resonance in Spiking Neuronal Networks | The cortex processes stimuli through a distributed network of specialized brain areas. This processing requires mechanisms that can route neuronal activity across weakly connected cortical regions. Routing models proposed thus far are either limited to propagation of spiking activity across strongly connected networks ... | The cortex is a highly modular structure with a large number of functionally specialized areas that communicate with each other through long-range cortical connections. It is has been suggested that communication between spiking neuronal networks (SNNs) requires synchronization of spiking activity which is either provi... | The brain processes sensory stimuli by an organized flow of neuronal activity across a distributed network of specialized cortical areas. This flow requires mechanisms that route neuronal signals from one cortical area to another. However, the exact nature of this routing process remains poorly understood.
Experimenta... |
10.1371/journal.ppat.1004744 | Elucidation of Sigma Factor-Associated Networks in Pseudomonas aeruginosa Reveals a Modular Architecture with Limited and Function-Specific Crosstalk | Sigma factors are essential global regulators of transcription initiation in bacteria which confer promoter recognition specificity to the RNA polymerase core enzyme. They provide effective mechanisms for simultaneously regulating expression of large numbers of genes in response to challenging conditions, and their pre... | Pseudomonas aeruginosa is well known for its high adaptability to a large range of environmental conditions, including those encountered within the human host. Transcription initiation represents a major regulatory target which drives versatility, and enables bacterial adaptation to challenging conditions and expressio... | The ability to maintain homeostasis even in changing environments and under extreme conditions is one of the key traits of living organisms. Pseudomonas aeruginosa is a ubiquitous gram-negative bacterium that can be distinguished by its exceptional high capability to adapt and survive in various and challenging habitat... |
10.1371/journal.pntd.0005672 | LAMPhimerus: A novel LAMP assay for detecting Amphimerus sp. DNA in human stool samples | Amphimeriasis is a fish-borne disease caused by the liver fluke Amphimerus spp. that has recently been reported as endemic in the tropical Pacific side of Ecuador with a high prevalence in humans and domestic animals. The diagnosis is based on the stool examination to identify parasite eggs, but it lacks sensitivity. A... | Amphimeriasis, a fish-borne zoonotic disease caused by the liver fluke Amphimerus spp., is a highly prevalent parasitic infection affecting an indigenous Amerindian group, the Chachi, living in rural and remote tropical areas along the Río Cayapas and its tributaries in the north-western coastal rainforest of Ecuador. ... | Amphimerus spp. are digenean parasitic flatworms in the bile ducts of birds, reptiles and mammals, and they are closely related to the genera Clonorchis and Opisthorchis within the Opisthorchiidae family [1, 2]. As for other members of the Opisthorchiidae family, the life cycle of Amphimerus spp. is highly complex, inv... |
10.1371/journal.pgen.1002520 | Three Essential Ribonucleases—RNase Y, J1, and III—Control the Abundance of a Majority of Bacillus subtilis mRNAs | Bacillus subtilis possesses three essential enzymes thought to be involved in mRNA decay to varying degrees, namely RNase Y, RNase J1, and RNase III. Using recently developed high-resolution tiling arrays, we examined the effect of depletion of each of these enzymes on RNA abundance over the whole genome. The data are ... | RNA turnover is an important way of controlling gene expression. While the characterization of the pathways and enzymes for RNA degradation are well-advanced in Escherichia coli and yeast, studies in Gram-positive bacteria have lagged behind. This tiling array study shows that two essential enzymes, the single-strand s... | The amount of a particular mRNA in the cell is a function of the equilibrium between its synthesis and degradation. The pathways of RNA degradation are fairly well defined in the Gram-negative model bacterium Escherichia coli and in the eukaryotic paradigm Saccharyomyces cerevisiae. In E. coli, degradation of RNA is pr... |
10.1371/journal.pntd.0002438 | Temephos Resistance in Aedes aegypti in Colombia Compromises Dengue Vector Control | Control and prevention of dengue relies heavily on the application of insecticides to control dengue vector mosquitoes. In Colombia, application of the larvicide temephos to the aquatic breeding sites of Aedes aegypti is a key part of the dengue control strategy. Resistance to temephos was recently detected in the deng... | Dengue fever, caused by viruses transmitted by the Aedes aegypti mosquito, is an important threat to public health in many tropical and subtropical countries. In the absence of a vaccine or specific drug treatment, prevention and control of dengue transmission relies on interventions targeting vector mosquito populatio... | Dengue fever is the most rapidly expanding arboviral disease in the world. Approximately 50 million infections occur in 100 countries annually [1], [2], and 60% of those are estimated to occur in the Americas [3]. In Colombia, dengue is considered a major public health problem, with approximately 25 million people at r... |
10.1371/journal.pgen.1003307 | Distinct Molecular Strategies for Hox-Mediated Limb Suppression in Drosophila: From Cooperativity to Dispensability/Antagonism in TALE Partnership | The emergence following gene duplication of a large repertoire of Hox paralogue proteins underlies the importance taken by Hox proteins in controlling animal body plans in development and evolution. Sequence divergence of paralogous proteins accounts for functional specialization, promoting axial morphological diversif... | Animal body plan diversity is controlled by transcription factors that select within each cell of a multi-cellular organism the set of genes to be expressed, eventually allowing distinct fate to emerge according to spatial coordinates. Transcription factors can be grouped based on their DNA binding domains in a few cla... | Hox genes encode homeodomain (HD) containing transcription factors widely used for diversifying animal body plans in development and evolution [1]–[3]. The Hox gene repertoire most likely arose from tandem duplication events of ancestral genes, followed by sequence divergence that promoted the emergence of up to 14 par... |
10.1371/journal.ppat.1002153 | A Protein Thermometer Controls Temperature-Dependent Transcription of Flagellar Motility Genes in Listeria monocytogenes | Facultative bacterial pathogens must adapt to multiple stimuli to persist in the environment or establish infection within a host. Temperature is often utilized as a signal to control expression of virulence genes necessary for infection or genes required for persistence in the environment. However, very little is know... | The ability to sense and respond to environmental changes is essential for the survival of all living organisms. Thermosensors are cellular components that can transform temperature changes into significant cellular responses necessary for adaptation and survival. In this study, we identify a protein thermosensor, GmaR... | Temperature is an important environmental condition to which organisms must adapt. The most universal and well-studied temperature responsive system is the heat shock response, which protects organisms from sudden stress-inducing increases in environmental temperature (reviewed in [1], [2]). However, even for the heat ... |
10.1371/journal.pmed.1002107 | Uptake of Home-Based HIV Testing, Linkage to Care, and Community Attitudes about ART in Rural KwaZulu-Natal, South Africa: Descriptive Results from the First Phase of the ANRS 12249 TasP Cluster-Randomised Trial | The 2015 WHO recommendation of antiretroviral therapy (ART) for all immediately following HIV diagnosis is partially based on the anticipated impact on HIV incidence in the surrounding population. We investigated this approach in a cluster-randomised trial in a high HIV prevalence setting in rural KwaZulu-Natal. We pre... | A study in stable sexual partners in which one partner was HIV-positive and the other partner was HIV-negative (and both partners had disclosed to each other) showed that if the HIV-positive partner was on antiretroviral therapy, there was a 96% reduction in HIV transmission from the HIV-positive partner to the HIV-neg... | Although significant gains have been made in the control of the HIV epidemic in many sub-Saharan countries, the annual number of new HIV infections remains unacceptably high [1]. Approximately 6.3 million people were estimated to be living with HIV in South Africa alone in 2013, of whom 3.1 million were on antiretrovir... |
10.1371/journal.pntd.0005161 | Contribution of Wastewater Irrigation to Soil Transmitted Helminths Infection among Vegetable Farmers in Kumasi, Ghana | Wastewater irrigation is associated with several benefits but can also lead to significant health risks. The health risk for contracting infections from Soil Transmitted Helminths (STHs) among farmers has mainly been assessed indirectly through measured quantities in the wastewater or on the crops alone and only on a l... | Wastewater irrigation in agriculture is a common reality in many developing cities, linked to rapid urbanization. Approximately 50%-90% of urban dwellers in West Africa consume wastewater/ polluted surface water irrigated-vegetables within cities with 10% of the population involved in the practice. Viral, bacterial and... | Wastewater use in agriculture has been promoted as part of the concept of sustainable development. In many cities in developing countries, wastewater irrigation is a common reality linked to rapid urbanization. The practice improves farmers’ livelihoods, contributes to the urban food basket and slightly improves the ur... |
10.1371/journal.pcbi.1000734 | A Human-Specific De Novo Protein-Coding Gene Associated with Human Brain Functions | To understand whether any human-specific new genes may be associated with human brain functions, we computationally screened the genetic vulnerable factors identified through Genome-Wide Association Studies and linkage analyses of nicotine addiction and found one human-specific de novo protein-coding gene, FLJ33706 (al... | For decades, gene duplication, retrotranspositions and gene fusions were believed to be major ways to increase gene number. All involve “mother” genes as the “building blocks” for new genes. However, several recently identified “motherless” genes challenged the idea in that some proteins might have emerged de novo from... | Many mechanisms for the origination of new genes are known, such as tandem gene duplication, retrotransposition, exon shuffling and gene fusion [1]–[5]. By these mechanisms, the origination of new protein coding genes involved “mother” genes that served as blueprints for the new genes. However, recent comparative genom... |
10.1371/journal.ppat.1005921 | Magnaporthe oryzae Glycine-Rich Secretion Protein, Rbf1 Critically Participates in Pathogenicity through the Focal Formation of the Biotrophic Interfacial Complex | Magnaporthe oryzae, the fungus causing rice blast disease, should contend with host innate immunity to develop invasive hyphae (IH) within living host cells. However, molecular strategies to establish the biotrophic interactions are largely unknown. Here, we report the biological function of a M. oryzae-specific gene, ... | Biotrophic pathogens grow inside living host cells by secreting “effector” proteins that suppress host innate immunity. Magnaporthe oryzae, which causes the most serious damage to rice, and recently also to wheat, is a hemibiotrophic fungus. During the biotrophic invasion, a host membrane-rich structure called the biot... | Biotrophic fungi colonize inside living host tissues. To facilitate the biotrophic invasion, fungal pathogens secrete proteins called effectors and modulate host physiology, including the suppression of immune responses [1–3].
Magnaporthe oryzae (synonym of Pyricularia oryzae [4]) is the fungus causing blast disease i... |
10.1371/journal.pcbi.1003397 | Inferring the Source of Transmission with Phylogenetic Data | Identifying the source of transmission using pathogen genetic data is complicated by numerous biological, immunological, and behavioral factors. A large source of error arises when there is incomplete or sparse sampling of cases. Unsampled cases may act as either a common source of infection or as an intermediary in a ... | Molecular data from pathogens may be useful for identifying the source of infection and identifying pairs of individuals such that one host transmitted to the other. Inference of who acquired infection from whom is confounded by incomplete sampling, and given genetic data only, it is not possible to infer the direction... | Phylogenetic trees reconstructed from sequences of pathogens contain information on the past transmission dynamics that would be difficult, if not impossible, to obtain through other means. Over the past two decades, a number of approaches have been proposed to extract epidemiologically relevant information from viral ... |
10.1371/journal.pcbi.1004554 | Learning to Estimate Dynamical State with Probabilistic Population Codes | Tracking moving objects, including one’s own body, is a fundamental ability of higher organisms, playing a central role in many perceptual and motor tasks. While it is unknown how the brain learns to follow and predict the dynamics of objects, it is known that this process of state estimation can be learned purely from... | A basic task for animals is to track objects—predators, prey, even their own limbs—as they move through the world. Because the position estimates provided by the senses are not error-free, higher levels of performance can be, and are, achieved when the velocity and acceleration, as well as the position, of the object a... | Over the last decade, neuroscience has come increasingly to believe that sensory systems represent not merely stimuli, but probability distributions over them. This conclusion follows from two observations. The first is that the apparent stochasticity of the response, R, of a population of neurons inherently represents... |
10.1371/journal.pgen.1001025 | The Caenorhabditis elegans Homolog of Gen1/Yen1 Resolvases Links DNA Damage Signaling to DNA Double-Strand Break Repair | DNA double-strand breaks (DSBs) can be repaired by homologous recombination (HR), which can involve Holliday junction (HJ) intermediates that are ultimately resolved by nucleolytic enzymes. An N-terminal fragment of human GEN1 has recently been shown to act as a Holliday junction resolvase, but little is known about th... | Coordination of DNA repair with cell cycle progression and apoptosis is a central task of the DNA damage response machinery. A key intermediate of recombinational repair and meiotic recombination, first proposed in 1964, involves four-stranded DNA structures. These intermediates have to be resolved upon completion of D... | The correct maintenance and duplication of genetic information is constantly challenged by genotoxic stress. DNA double-strand breaks (DSBs) are amongst the most deleterious lesions. DSBs can be induced by ionizing irradiation (IR) or caused by the stalling of DNA replication forks. In response to DSBs, cells activate ... |
10.1371/journal.pgen.1007115 | Rv0004 is a new essential member of the mycobacterial DNA replication machinery | DNA replication is fundamental for life, yet a detailed understanding of bacterial DNA replication is limited outside the organisms Escherichia coli and Bacillus subtilis. Many bacteria, including mycobacteria, encode no identified homologs of helicase loaders or regulators of the initiator protein DnaA, despite these ... | DNA is the molecule that encodes all of the genetic information of an organism. In order to pass genes onto the next generation, DNA has to first be copied through a process called DNA replication. Most of the initial studies on bacterial DNA replication were performed in Escherichia coli and Bacillus subtilis. While t... | The ability to maintain, replicate, and express genetic information encoded in DNA is critical to all domains of life. DNA replication studies in Escherichia coli and Bacillus subtilis have elucidated the mechanisms of bacterial DNA replication initiation, elongation, and termination, but the applicability of many of t... |
10.1371/journal.pntd.0006730 | Uncovering vector, parasite, blood meal and microbiome patterns from mixed-DNA specimens of the Chagas disease vector Triatoma dimidiata | Chagas disease, considered a neglected disease by the World Health Organization, is caused by the protozoan parasite Trypanosoma cruzi, and transmitted by >140 triatomine species across the Americas. In Central America, the main vector is Triatoma dimidiata, an opportunistic blood meal feeder inhabiting both domestic a... | Chagas disease is caused by the parasite Trypanosoma cruzi, which is spread by triatomine kissing bugs. There are many biotic factors that influence the risk of disease transmission, including the strain of the parasite, the vector movement patterns, the community of microbes interacting with the parasite inside the ve... | Chagas disease (American trypanosomiasis) is caused by the protozoan parasite Trypanosoma cruzi. Considered a neglected disease by the World Health Organization, it is widespread in the Americas, where an estimated 70 million people are at risk of contracting the infection [1]. The disease is most prominent in poor, ru... |
10.1371/journal.pntd.0007170 | Spatio-temporal characterization of Trypanosoma cruzi infection and discrete typing units infecting hosts and vectors from non-domestic foci of Chile | Trypanosoma cruzi is a protozoan parasite that is transmitted by triatomine vectors to mammals. It is classified in six discrete typing units (DTUs). In Chile, domestic vectorial transmission has been interrupted; however, the parasite is maintained in non-domestic foci. The aim of this study was to describe T. cruzi i... | Trypanosoma cruzi is a parasite that infects mammals, transmitted by triatomine insect vectors in America, causing Chagas disease in humans. There are six T. cruzi discrete typing units (DTUs). Our goal was to estimate T. cruzi infection rates and describe the DTUs present in mammals and triatomines of Chile, evaluatin... | Chagas disease is a zoonotic parasitic disease, endemic in 22 countries of America, caused by the flagellated protozoa Trypanosoma cruzi. This disease affects approximately 7 million people in the world and represents the third parasitic disease of major world impact [1]. The parasite is transmitted through contact of ... |
10.1371/journal.pgen.1005837 | Adaptive Remodeling of the Bacterial Proteome by Specific Ribosomal Modification Regulates Pseudomonas Infection and Niche Colonisation | Post-transcriptional control of protein abundance is a highly important, underexplored regulatory process by which organisms respond to their environments. Here we describe an important and previously unidentified regulatory pathway involving the ribosomal modification protein RimK, its regulator proteins RimA and RimB... | Post-transcriptional control of protein abundance is a significant and underexplored regulatory process by which organisms respond to environmental change. We have discovered an important new mechanism for this control in bacteria, based on the covalent modification of a small ribosomal protein by the widespread enzyme... | Post-transcriptional mechanisms for the regulation of protein abundance are critical for the control of diverse cellular processes including metabolism and nutritional stress responses [1,2], virulence and antibiotic production [3] and quorum sensing [4]. In addition to well-studied pathways for mRNA translational cont... |
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