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10.1371/journal.pmed.1002803 | Women’s and girls’ experiences of menstruation in low- and middle-income countries: A systematic review and qualitative metasynthesis | Attention to women’s and girls’ menstrual needs is critical for global health and gender equality. The importance of this neglected experience has been elucidated by a growing body of qualitative research, which we systematically reviewed and synthesised.
We undertook systematic searching to identify qualitative studie... | A growing body of qualitative research has highlighted the importance of menstrual experiences for the health and well-being of women and girls in low- and middle-income countries (LMICs).
Qualitative research has identified an array of factors contributing to experiences but has not developed clear theory to direct in... | Each day, more than 300 million women are menstruating [1]. There is increasing recognition that this natural process is experienced negatively and presents a barrier to health and gender equality in low- and middle-income contexts [2]. A growing body of qualitative research has been critical to highlighting this issue... |
10.1371/journal.pcbi.1003615 | Axonal Noise as a Source of Synaptic Variability | Post-synaptic potential (PSP) variability is typically attributed to mechanisms inside synapses, yet recent advances in experimental methods and biophysical understanding have led us to reconsider the role of axons as highly reliable transmission channels. We show that in many thin axons of our brain, the action potent... | The fundamental signal of the nervous system is the action potential: an electrical spike propagated along neurons and transmitted between them via synapses. Once triggered, action potentials are generally assumed to be robust to noise, and the variability observed at all levels of the nervous system is primarily attri... | The great majority of axons use action potentials (APs) to transmit information reliably to synapses. Once the AP arrives at the synapse the characteristics of its waveform are fundamental in determining the strength and reliability of information transmission, as was extensively shown in the central and peripheral ner... |
10.1371/journal.pntd.0005029 | Colorimetric Detection of Plasmodium vivax in Urine Using MSP10 Oligonucleotides and Gold Nanoparticles | Plasmodium vivax is the most prevalent cause of human malaria in the world and can lead to severe disease with high potential for relapse. Its genetic and geographic diversities make it challenging to control. P. vivax is understudied and to achieve control of malaria in endemic areas, a rapid, accurate, and simple dia... | To control malaria, there is an urgent need for applying innovative diagnostics and new technologies. Nanoparticles can augment detection of malaria at lower parasite levels while providing fast and simple methodology. Novel use of MSP10 and gold nanoparticles to identify Plasmodium vivax’s DNA in urine can be utilized... | Malaria is the most common infectious disease in the tropics and subtropics [1]. Currently, P. vivax is endemic across Asia, the South Pacific, North Africa, Middle East, and South and Central America [2], and has recently reappeared in regions where it had previously been eradicated, including North America and Europe... |
10.1371/journal.ppat.1007543 | Merkel cell polyomavirus Tumor antigens expressed in Merkel cell carcinoma function independently of the ubiquitin ligases Fbw7 and β-TrCP | Merkel cell polyomavirus (MCPyV) accounts for 80% of all Merkel cell carcinoma (MCC) cases through expression of two viral oncoproteins: the truncated large T antigen (LT-t) and small T antigen (ST). MCPyV ST is thought to be the main driver of cellular transformation and has also been shown to increase LT protein leve... | Merkel cell carcinoma (MCC) is a very aggressive and deadly neuroendocrine skin cancer. Merkel cell polyomavirus (MCPyV) contributes to the development and maintenance of 80% of MCCs through the expression of its truncated large tumor antigen (LT-t) and small tumor antigen (ST). MCPyV ST is thought to be primarily resp... | Merkel cell carcinoma (MCC) is an extremely rare, but aggressive, neuroendocrine skin cancer with an incidence of 0.7 cases/100,000 person-years in the United States, and a less than 45% 5-year survival rate, making MCC almost three times as lethal as melanoma [1, 2]. Although MCC was first described in 1972, it wasn’t... |
10.1371/journal.ppat.1003824 | Identification of the Virulence Landscape Essential for Entamoeba histolytica Invasion of the Human Colon | Entamoeba histolytica is the pathogenic amoeba responsible for amoebiasis, an infectious disease targeting human tissues. Amoebiasis arises when virulent trophozoites start to destroy the muco-epithelial barrier by first crossing the mucus, then killing host cells, triggering inflammation and subsequently causing dysen... | Entamoeba histolytica is an intestinal parasite which displays diverse phenotypes with respect to pathogenesis in the human colon. Trophozoites can remain as commensal, without causing evident intestinal damage, or they can destroy the colonic mucosa leading to amoebiasis. Using human colon explants and transcriptome a... | In the human colon, mucus acts as a lubricant facilitating the passage of digestive content, protects the underlying epithelium from mechanical stress, and provides a protective barrier against pathogens. Mucin 2 (MUC2) is the major component of the mucus layer. MUC2 is a heavily glycosylated protein, containing more t... |
10.1371/journal.pcbi.1001108 | A Compact Statistical Model of the Song Syntax in Bengalese Finch | Songs of many songbird species consist of variable sequences of a finite number of syllables. A common approach for characterizing the syntax of these complex syllable sequences is to use transition probabilities between the syllables. This is equivalent to the Markov model, in which each syllable is associated with on... | Complex action sequences in many animals are organized according to syntactical rules that specify how individual actions are strung together. A critical problem for understanding the neural basis of action sequences is how to derive the syntax that captures the statistics of the sequences. Here we solve this problem f... | Complex action sequences in animals and humans are often organized according to syntactical rules that specify how actions are strung together into sequences [1], [2]. Many examples are found in birdsong. Songs of birdsong species such as Bengalese finch [3]–[5], sedge warbler [6], nightingale [7], and willow warbler [... |
10.1371/journal.pgen.1004141 | Age, Gender, and Cancer but Not Neurodegenerative and Cardiovascular Diseases Strongly Modulate Systemic Effect of the Apolipoprotein E4 Allele on Lifespan | Enduring interest in the Apolipoprotein E (ApoE) polymorphism is ensured by its evolutionary-driven uniqueness in humans and its prominent role in geriatrics and gerontology. We use large samples of longitudinally followed populations from the Framingham Heart Study (FHS) original and offspring cohorts and the Long Lif... | Discovering genetic origins of healthspan and lifespan could lead to breakthroughs in increasing the years of healthy and long life. In this paper we characterize the association of the e4 allele of the well-studied ApoE gene with lifespan in two generations of participants of large longitudinal studies, the Framingham... | The Apolipoprotein E (ApoE) common polymorphism (e2, e3, and e4) is one of the most studied genetic variants in humans. The interest in this polymorphism is two-fold. First, the functional diversity of the ApoE polymorphism appears to be a unique signature of humans with no coding variation in this gene even in human's... |
10.1371/journal.pcbi.1000760 | Robustness under Functional Constraint: The Genetic Network for Temporal Expression in Drosophila Neurogenesis | Precise temporal coordination of gene expression is crucial for many developmental processes. One central question in developmental biology is how such coordinated expression patterns are robustly controlled. During embryonic development of the Drosophila central nervous system, neural stem cells called neuroblasts exp... | Cell fate specification is of key importance in the development of multicellular organisms. To specify various cell fates correctly, genetic networks precisely coordinate spatial and temporal gene expression patterns during various developmental stages. One central question in developmental biology is to elucidate the ... | Precise coordination of cell fate decisions is crucial in the development of multicellular organisms. In the developmental processes, where a series of events occurs at a specific place and time, gene regulatory networks are responsible for implementing reliable biological functions [1], [2]. To obtain system-level und... |
10.1371/journal.pntd.0001591 | A Somatically Diversified Defense Factor, FREP3, Is a Determinant of Snail Resistance to Schistosome Infection | Schistosomiasis, a neglected tropical disease, owes its continued success to freshwater snails that support production of prolific numbers of human-infective cercariae. Encounters between schistosomes and snails do not always result in the snail becoming infected, in part because snails can mount immune responses that ... | Schistosomiasis, a neglected tropical disease, owes its continued success to freshwater snails that support production of prolific numbers of human-infective cercariae. Encounters between schistosomes and snails do not always result in the snail becoming infected, in part because snails can mount immune responses that ... | Schistosomiasis is one of the world's most tenacious neglected tropical diseases, infecting an estimated 207 million people, mostly children [1]. The persistence of schistosome parasites stems in part from their use of freshwater snails for their larval development and transmission. Snails are often abundant and diffic... |
10.1371/journal.pgen.1000485 | Additions, Losses, and Rearrangements on the Evolutionary Route from a Reconstructed Ancestor to the Modern Saccharomyces cerevisiae Genome | Comparative genomics can be used to infer the history of genomic rearrangements that occurred during the evolution of a species. We used the principle of parsimony, applied to aligned synteny blocks from 11 yeast species, to infer the gene content and gene order that existed in the genome of an extinct ancestral yeast ... | Genomes evolve in structure as well as in DNA sequence. We used data from 11 different yeast species to investigate the process of structural evolution of the genome on the evolutionary path leading to the bakers' yeast S. cerevisiae. We focused on an ancestor that existed about 100 million years ago. We were able to d... | Inferring the genome organization and gene content of an extinct species has the potential to provide detailed information about the recent evolution of species descended from it. If we know what was present in the genome of an ancestor, we can deduce how a current-day descendant differs from it. We can then ask questi... |
10.1371/journal.ppat.1005215 | Identification of the Mechanisms Causing Reversion to Virulence in an Attenuated SARS-CoV for the Design of a Genetically Stable Vaccine | A SARS-CoV lacking the full-length E gene (SARS-CoV-∆E) was attenuated and an effective vaccine. Here, we show that this mutant virus regained fitness after serial passages in cell culture or in vivo, resulting in the partial duplication of the membrane gene or in the insertion of a new sequence in gene 8a, respectivel... | Zoonotic coronaviruses, including SARS-CoV, Middle East respiratory syndrome (MERS-CoV), porcine epidemic diarrhea virus (PEDV) and swine delta coronavirus (SDCoV) have recently emerged causing high morbidity and mortality in human or piglets. No fully protective therapy is still available for these CoVs. Therefore, th... | Coronaviruses (CoVs) are pathogens responsible for a wide range of existing and emerging diseases in humans and other animals [1]. A novel coronavirus causing the severe acute respiratory syndrome (SARS-CoV) was identified in Southeast China in 2002. SARS-CoV rapidly spread worldwide to more than 30 countries within si... |
10.1371/journal.pcbi.1000930 | Evolution and Optimality of Similar Neural Mechanisms for Perception and Action during Search | A prevailing theory proposes that the brain's two visual pathways, the ventral and dorsal, lead to differing visual processing and world representations for conscious perception than those for action. Others have claimed that perception and action share much of their visual processing. But which of these two neural arc... | The brain has two processing pathways of visual information, the ventral and dorsal streams. A prevailing theory proposes that this division leads to different world representations for conscious perception than those for actions such as grasping or eye movements. Perceptual tasks such as searching for our car keys in ... | Neurophysiology studies of the macaque monkey [1]–[3] support the existence of two functionally distinct neural pathways in the brain mediating the processing of visual information. The behavior of patients with brain damage has led to the proposal that perception is mediated by the ventral stream projecting from the p... |
10.1371/journal.pcbi.1002860 | Adding Protein Context to the Human Protein-Protein Interaction Network to Reveal Meaningful Interactions | Interactions of proteins regulate signaling, catalysis, gene expression and many other cellular functions. Therefore, characterizing the entire human interactome is a key effort in current proteomics research. This challenge is complicated by the dynamic nature of protein-protein interactions (PPIs), which are conditio... | Protein-protein-interactions (PPIs) participate in virtually all biological processes. However, the PPI map is not static but the pairs of proteins that interact depends on the type of cell, the subcellular localization and modifications of the participating proteins, among many other factors. Therefore, it is importan... | The advent of high-throughput techniques to measure and perturb molecular species in a systematic way has enabled researchers to assess the different layers of cellular metabolism under different experimental conditions. Protein-protein interaction (PPI) networks created by a variety of methods including yeast-two-hybr... |
10.1371/journal.pntd.0007092 | Cutaneous leishmaniasis and co-morbid major depressive disorder: A systematic review with burden estimates | Major depressive disorder (MDD) associated with chronic neglected tropical diseases (NTDs) has been identified as a significant and overlooked contributor to overall disease burden. Cutaneous leishmaniasis (CL) is one of the most prevalent and stigmatising NTDs, with an incidence of around 1 million new cases of active... | Cutaneous leishmaniasis is a highly prevalent vector-borne disease affecting large parts of Latin America and the Middle East, as well as parts of Northern Africa. There are several types of Cutaneous leishmaniasis, almost all of which have an active phase characterized by a disfiguring lesion (typically on exposed par... | Cutaneous leishmaniasis (CL) is the most prevalent form of leishmaniasis and 1 of 22 highly prevalent neglected tropical diseases (NTD) [1]. Current disease classifications differentiate aspects of the active (nodular, ulcerative or plaque) CL lesion in terms of its transmission route (“zoonotic” vs “anthroponotic”), g... |
10.1371/journal.pcbi.1004892 | Single-Cell Co-expression Analysis Reveals Distinct Functional Modules, Co-regulation Mechanisms and Clinical Outcomes | Co-expression analysis has been employed to predict gene function, identify functional modules, and determine tumor subtypes. Previous co-expression analysis was mainly conducted at bulk tissue level. It is unclear whether co-expression analysis at the single-cell level will provide novel insights into transcriptional ... | With the development of single-cell sequencing, an increasing number of biological insights were revealed at the single-cell resolution. Here we integrated the expression profiles from single cells and bulk tissues to discover that a majority of gene pairs were specifically co-expressed at single-cell and bulk levels. ... | Gene expression is often coordinated to carry out cellular activities and biological functions [1]. If the expression levels of two genes rise and fall together across different conditions, they are likely to be members of the same protein complex or participate in the same biological pathways. Therefore, co-expression... |
10.1371/journal.pntd.0001181 | Experimental Transmission of Leishmania infantum by Two Major Vectors: A Comparison between a Viscerotropic and a Dermotropic Strain | We quantified Leishmania infantum parasites transmitted by natural vectors for the first time. Both L. infantum strains studied, dermotropic CUK3 and viscerotropic IMT373, developed well in Phlebotomus perniciosus and Lutzomyia longipalpis. They produced heavy late-stage infection and colonized the stomodeal valve, whi... | Leishmaniasis is a disease caused by protozoan parasites which are transmitted through the bites of infected insects called sand flies. The World Health Organization has estimated that leishmaniases cause 1.6 million new cases annually, of which an estimated 1.1 million are cutaneous or mucocutaneous, and 500,000 are v... | Leishmania are intracellular protozoan parasites that establish infection in mammalian hosts following transmission through the bite of an infected phlebotomine sand fly. Visceral leishmaniasis, caused by Leishmania donovani in the Old World and L. infantum in both the Old and New World, invariably leads to death if le... |
10.1371/journal.pmed.1002417 | HIV-1 persistence following extremely early initiation of antiretroviral therapy (ART) during acute HIV-1 infection: An observational study | It is unknown if extremely early initiation of antiretroviral therapy (ART) may lead to long-term ART-free HIV remission or cure. As a result, we studied 2 individuals recruited from a pre-exposure prophylaxis (PrEP) program who started prophylactic ART an estimated 10 days (Participant A; 54-year-old male) and 12 days... | Early initiation of ART following infection may limit the total body burden of HIV.
It is not known if starting ART extremely early after HIV infection will lead to ART-free remission or cure.
We studied 2 individuals who started ART an estimated 10 and 12 days after HIV infection with very low peak viral load measurem... | The development of a cure for HIV infection is a major public health objective [1]. Despite the ability of antiretroviral therapy (ART) to significantly reduce disease-related morbidity and mortality in HIV-1 infection, viral reservoirs persist indefinitely in latently infected cells [2]. HIV persists during ART primar... |
10.1371/journal.pcbi.1006800 | Changes in morphogen kinetics and pollen grain size are potential mechanisms of aberrant pollen aperture patterning in previously observed and novel mutants of Arabidopsis thaliana | Pollen provides an excellent system to study pattern formation at the single-cell level. Pollen surface is covered by the pollen wall exine, whose deposition is excluded from certain surface areas, the apertures, which vary between the species in their numbers, positions, and morphology. What determines aperture patter... | Pollen is renowned for its ability to form beautiful and complex patterns on its surface. One of the most prominent patterns on the pollen surface is formed by apertures, the regions that lack deposition of the pollen wall exine and develop at precise locations which often vary between the species. How aperture pattern... | The process of cell morphogenesis often depends on the ability of cells to form distinct domains of plasma membrane and precisely target deposition of extracellular materials. Pollen presents a powerful model to study the mechanisms that control formation of membrane domains and localization of extracellular structures... |
10.1371/journal.pcbi.1006217 | Quantitative theory of deep brain stimulation of the subthalamic nucleus for the suppression of pathological rhythms in Parkinson’s disease | Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is modeled to explore the mechanisms of this effective, but poorly understood, treatment for motor symptoms of drug-refractory Parkinson’s disease and dystonia. First, a neural field model of the corticothalamic-basal ganglia (CTBG) system is developed that ... | Pathological 13-30 Hz (beta) oscillations within the basal ganglia are a characteristic feature of human Parkinson’s disease which seem to correlate with symptom severity. The origin of these oscillations and the suppressive mechanism of effective deep brain stimulation treatments remains to be shown. We formulate a ph... | Deep brain stimulation (DBS) has become an effective treatment for a number of neurological disorders such as Parkinson’s disease (PD) and essential tremor [1, 2]. In Parkinson’s disease DBS treatments, a macroelectrode is chronically implanted in a target nucleus, typically either the globus pallidus internus (GPi), s... |
10.1371/journal.pcbi.1004920 | Learning from Heterogeneous Data Sources: An Application in Spatial Proteomics | Sub-cellular localisation of proteins is an essential post-translational regulatory mechanism that can be assayed using high-throughput mass spectrometry (MS). These MS-based spatial proteomics experiments enable us to pinpoint the sub-cellular distribution of thousands of proteins in a specific system under controlled... | Sub-cellular localisation of proteins is critical to their function in all cellular processes; proteins localising to their intended micro-environment, e.g organelles, vesicles or macro-molecular complexes, will meet the interaction partners and biochemical conditions suitable to pursue their molecular function. Theref... | Cell biology is currently undergoing a data-driven paradigm shift [1]. Molecular biology tools, imaging, biochemical analyses and omics technologies, enable cell biologists to track the complexity of many fundamental processes such as signal transduction, gene regulation, protein interactions and sub-cellular localisat... |
10.1371/journal.ppat.1001225 | Dimeric 2G12 as a Potent Protection against HIV-1 | We previously showed that broadly neutralizing anti-HIV-1 antibody 2G12 (human IgG1) naturally forms dimers that are more potent than monomeric 2G12 in in vitro neutralization of various strains of HIV-1. In this study, we have investigated the protective effects of monomeric versus dimeric 2G12 against HIV-1 infection... | Most successful vaccines function by eliciting antibodies that bind to the surface of pathogens of interest from the host immunologic repertoire. This should also be the case for an HIV-1 vaccine, but broadly neutralizing anti-HIV-1 antibodies have proven hard to elicit with any reagent. Thus, methods to directly admin... | Human efficacy trials of vaccine candidates designed to elicit antibody-based immunity against HIV-1 have mostly failed [1], [2], raising questions as to whether such an approach to HIV-1 vaccination is at all feasible. A recent human vaccine trial in Thailand [3], however, provided a promising signal of efficacy. Whil... |
10.1371/journal.pgen.1002555 | Interpreting Meta-Analyses of Genome-Wide Association Studies | Meta-analysis is an increasingly popular tool for combining multiple genome-wide association studies in a single analysis to identify associations with small effect sizes. The effect sizes between studies in a meta-analysis may differ and these differences, or heterogeneity, can be caused by many factors. If heterogene... | Genome-wide association studies are an effective means of identifying genetic variants that are associated with diseases. Although many associated loci have been identified, those loci account for only a small fraction of the genetic contribution to the disease. The remaining contribution may be accounted by loci with ... | Meta-analysis is a tool for aggregating information from multiple independent studies [1]–[3]. In genome-wide association studies (GWASs) [4], the use of meta-analysis is becoming more and more popular because one can virtually collect tens of thousands of individuals that will provide power to identify associated vari... |
10.1371/journal.pbio.0050261 | MSN2 and MSN4 Link Calorie Restriction and TOR to Sirtuin-Mediated Lifespan Extension in Saccharomyces cerevisiae | Calorie restriction (CR) robustly extends the lifespan of numerous species. In the yeast Saccharomyces cerevisiae, CR has been proposed to extend lifespan by boosting the activity of sirtuin deacetylases, thereby suppressing the formation of toxic repetitive ribosomal DNA (rDNA) circles. An alternative theory is that C... | There are only a few techniques that reliably promote longevity in multiple, distantly related species. Perhaps the best known, caloric restriction (CR), was first shown to promote lifespan in rodents in the 1930s and has since been shown to work in most species it has been tested on. We and others have previously prop... | In the budding yeast Saccharomyces cerevisiae, replicative lifespan is measured by the number of divisions that a mother cell undergoes before senescing [1–3]. A primary cause of aging in this organism is homologous recombination between ribosomal DNA (rDNA) repeats, resulting in the formation of extrachromosomal rDNA ... |
10.1371/journal.ppat.1002659 | Proteolytic Processing of Nlrp1b Is Required for Inflammasome Activity | Nlrp1b is a NOD-like receptor that detects the catalytic activity of anthrax lethal toxin and subsequently co-oligomerizes into a pro-caspase-1 activation platform known as an inflammasome. Nlrp1b has two domains that promote oligomerization: a NACHT domain, which is a member of the AAA+ ATPase family, and a poorly cha... | Inflammasomes are multi-protein complexes that respond to signals derived from microbial pathogens or damaged tissue. The function of an inflammasome is to activate pro-caspase-1, a protease that contributes to the inflammatory response by generating the cytokines IL-1β and IL-18. A common feature of inflammasomes is t... | Inflammasomes are multi-protein complexes that facilitate the activation of pro-caspase-1 in response to pathogen associated molecular patterns (PAMPS) or endogenous danger associated molecular patterns (DAMPS). A common feature of inflammasomes is that they recruit multiple copies of pro-caspase-1, which allows auto-p... |
10.1371/journal.pmed.1002710 | Metabolic syndrome in pregnancy and risk for adverse pregnancy outcomes: A prospective cohort of nulliparous women | Obesity increases the risk for developing gestational diabetes mellitus (GDM) and preeclampsia (PE), which both associate with increased risk for type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD) in women in later life. In the general population, metabolic syndrome (MetS) associates with T2DM and CVD. Th... | Obesity increases the risk for developing gestational diabetes mellitus (GDM) and preeclampsia (PE), which both associate with increased risk for type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD) in women in later life.
In the general population, metabolic syndrome (MetS) associates with T2DM and CVD.
Th... | Obesity is an established risk factor for pregnancy complications, increasing risk for gestational diabetes mellitus (GDM), preeclampsia (PE), and delivering large for gestational age (LGA) infants, by 2- to 3-fold [1–4], and small for gestational age (SGA) infants, by 24% [5]. Such adverse outcomes place women and the... |
10.1371/journal.pcbi.1004004 | Vesicular Stomatitis Virus Polymerase's Strong Affinity to Its Template Suggests Exotic Transcription Models | Vesicular stomatitis virus (VSV) is the prototype for negative sense non segmented (NNS) RNA viruses which include potent human and animal pathogens such as Rabies, Ebola and measles. The polymerases of NNS RNA viruses only initiate transcription at or near the 3′ end of their genome template. We measured the dissociat... | RNA dependent RNA Polymerases tight association with their template creates an almost infinite dilution transcription machinery. Polymerases are delivered to the host cytoplasm associated with the genome template, however, they initiate transcription only at or near the 3′ end of the genome template. How these polymera... | Transcription is the process of polymerase driven synthesis of mRNA from the genome template. In eukaryotic cells, polymerases engage their promoters through 3D diffusion [1], [2] and have a dissociation constant from their promoters in the range of 40–60 nM [3], [4], [5]. In many viral infections, transcription is the... |
10.1371/journal.pcbi.1003115 | Understanding the Molecular Determinants Driving the Immunological Specificity of the Protective Pilus 2a Backbone Protein of Group B Streptococcus | The pilus 2a backbone protein (BP-2a) is one of the most structurally and functionally characterized components of a potential vaccine formulation against Group B Streptococcus. It is characterized by six main immunologically distinct allelic variants, each inducing variant-specific protection. To investigate the molec... | Group B Streptococcus (GBS) is the leading cause of neonatal invasive diseases and pili, as long filamentous fibers protruding from the bacterial surface, have been discovered as important virulence factors and potential vaccine candidates. The bacterial surface is the main interface between host and pathogen, and the ... | The bacterial surface is the foremost interface between host and pathogen, and recognition of the specific epitopes by the immune system provides the host a key signature to initiate microbial clearance. Identification and characterization of antigenic epitopes is a rapidly expanding field of research with potential co... |
10.1371/journal.pbio.2006409 | A single pair of leucokinin neurons are modulated by feeding state and regulate sleep–metabolism interactions | Dysregulation of sleep and feeding has widespread health consequences. Despite extensive epidemiological evidence for interactions between sleep and metabolic function, little is known about the neural or molecular basis underlying the integration of these processes. D. melanogaster potently suppress sleep in response ... | Neural regulation of sleep and feeding are interconnected and are critical for survival. Many animals reduce their sleep in response to starvation, presumably to forage for food. Here, we find that in the fruit fly Drosophila melanogaster, the neuropeptide leucokinin is required for the modulation of starvation-depende... | Dysregulation of sleep and feeding has widespread health consequences, and reciprocal interactions between these processes underlie a number of pathologies [1–4]. Sleep loss correlates with increased appetite and insulin insensitivity, while short-sleeping individuals are more likely to develop obesity, metabolic syndr... |
10.1371/journal.pcbi.1005129 | Optimized Treatment Schedules for Chronic Myeloid Leukemia | Over the past decade, several targeted therapies (e.g. imatinib, dasatinib, nilotinib) have been developed to treat Chronic Myeloid Leukemia (CML). Despite an initial response to therapy, drug resistance remains a problem for some CML patients. Recent studies have shown that resistance mutations that preexist treatment... | Targeted therapy using imatinib, nilotinib or dasatinib has become standard treatment for chronicle myeloid leukemia. A minority of patients, however, fail to respond to treatment or relapse due to drug resistance. One primary driving factor of drug resistance are point mutations within the driving oncogene. Laboratory... | Chronic Myeloid Leukemia (CML) is an acquired hematopoietic stem cell disorder leading to the over-proliferation of myeloid cells and an increase in cellular output from the bone marrow that is often associated with splenomegaly. The most common driving mutation in CML is a translocation between chromosomes 9 and 22 th... |
10.1371/journal.pntd.0002244 | International External Quality Assessment of Molecular Detection of Rift Valley Fever Virus | Rift Valley fever (RVF) is a viral zoonosis that primarily affects animals resulting in considerable economic losses due to death and abortions among infected livestock. RVF also affects humans with clinical symptoms ranging from an influenza-like illness to a hemorrhagic fever. Over the past years, RVF virus (RVFV) ha... | Rift Valley fever (RVF) is a zoonotic viral disease posing an increasing threat to animals and humans worldwide. Recent severe outbreaks of the disease in animal and human populations in endemic regions and outside the disease's traditional geographic boundaries necessitate the need for evaluating the diagnostic perfor... | Rift Valley fever (RVF) is a mosquito-borne viral zoonosis that primarily affects animals but also has the capacity to infect humans. An epizootic of RVF is usually first indicated by a wave of unexplained abortions as infected pregnant livestock abort virtually 100% of fetuses. The disease is less fatal to humans as m... |
10.1371/journal.pgen.1004096 | New MicroRNAs in Drosophila—Birth, Death and Cycles of Adaptive Evolution | The origin and evolution of new microRNAs (miRNAs) is important because they can impact the transcriptome broadly. As miRNAs can potentially emerge constantly and rapidly, their rates of birth and evolution have been extensively debated. However, most new miRNAs identified appear not to be biologically significant. Aft... | During Metazoan evolution, the architecture of the genome changed dramatically in size, gene number and regulatory elements. Genomic architecture is often assumed to be correlated with morphological complexity. However, it is still not known whether the gene repertoire, both for protein coding and non-coding genes, is ... | MicroRNAs (miRNAs) are a class of small, endogenous RNAs that regulate gene expression post-transcriptionally [1], [2]. Each miRNA gene is first transcribed as a stem-loop (hairpin) RNA structure, 70–90 nt in length in animals, and then processed in several steps into the ∼22-nt mature product, referred to as miR [3]. ... |
10.1371/journal.pbio.1001064 | Cracking the Code of Oscillatory Activity | Neural oscillations are ubiquitous measurements of cognitive processes and
dynamic routing and gating of information. The fundamental and so far unresolved
problem for neuroscience remains to understand how oscillatory activity in the
brain codes information f... | To recognize visual information rapidly, the brain must continuously code
complex, high-dimensional information impinging on the retina, not all of which
is relevant, because a low-dimensional code can be sufficient for both
recognition and behavior (e.g. a fe... | Invasive and noninvasive studies in humans under physiological and pathological
conditions converged on the suggestion that the amplitude and phase of neural
oscillations implement cognitive processes such as sensory representations,
attentional selection, and dynamical r... |
10.1371/journal.pbio.1002115 | Ih Channels Control Feedback Regulation from Amacrine Cells to Photoreceptors | In both vertebrates and invertebrates, photoreceptors’ output is regulated by feedback signals from interneurons that contribute to several important visual functions. Although synaptic feedback regulation of photoreceptors is known to occur in Drosophila, many questions about the underlying molecular mechanisms and ph... | Feedback regulation is a common feature of neural circuits during the process of acquiring information. Therefore, it is important to understand how this phenomenon occurs. Using the primary visual system of the fruit fly Drosophila melanogaster as a model, we systematically investigated the molecular mechanisms and th... | Feedback regulation is common in neural circuit information processing. In both vertebrate and invertebrate visual systems, photoreceptor output is feedback-regulated by interneurons, which is an important mechanism for shaping the transmission of light information [1,2]. In the vertebrate retina, bipolar cells receive... |
10.1371/journal.pgen.1006961 | Positional cloning of quantitative trait nucleotides for blood pressure and cardiac QT-interval by targeted CRISPR/Cas9 editing of a novel long non-coding RNA | Multiple GWAS studies have reported strong association of cardiac QT-interval to a region on HSA17. Interestingly, a rat locus homologous to this region is also linked to QT-intervals. The high resolution positional mapping study located the rat QT-interval locus to a <42.5kb region on RNO10. This region contained no v... | Diseases of the cardiovascular system such as essential hypertension do not have a clear cause, but are known to run in families. The inheritance patterns of essential hypertension and other cardiac diseases suggest that they are not due to a single defective gene but instead are caused by multiple genetic defects that... | It is estimated that hypertension affects nearly 75 million Americans (about 1 in every 3 U.S. adults) [1]. Essential hypertension is the most common type of hypertension and remains a major risk factor for cardiovascular diseases, such as cardiomyopathy [2], coronary artery diseases [3] and peripheral vascular disease... |
10.1371/journal.pcbi.1003052 | Long-range Order in Canary Song | Bird songs range in form from the simple notes of a Chipping Sparrow to the rich performance of the nightingale. Non-adjacent correlations can be found in the syntax of some birdsongs, indicating that the choice of what to sing next is determined not only by the current syllable, but also by previous syllables sung. He... | Bird songs range in form from the simple notes of a Chipping Sparrow to the complex repertoire of the nightingale. Recent studies suggest that bird songs may contain non-adjacent dependencies where the choice of what to sing next depends on the history of what has already been produced. However, the complexity of these... | Brains build complex behaviors from simple modules [1], [2].The ultimate example is speech where sequences of phonemes form words that in turn are rearranged to form sentences. So too, the complex performances of a musician or swordfighter are composed of discrete motor gestures that may be composed of more elementary ... |
10.1371/journal.ppat.1003058 | Infection-Induced Interaction between the Mosquito Circulatory and Immune Systems | Insects counter infection with innate immune responses that rely on cells called hemocytes. Hemocytes exist in association with the insect's open circulatory system and this mode of existence has likely influenced the organization and control of anti-pathogen immune responses. Previous studies reported that pathogens i... | Mosquitoes transmit diseases such as malaria, dengue fever, West Nile virus and lymphatic filariasis. A mosquito initially acquires a pathogen when she ingests a blood meal from an infected person or animal. Then, after a period of development and/or replication in the mosquito gut, the pathogen enters the hemocoel (bo... | Pathogens transmitted by mosquitoes must traverse the insect's open body cavity (hemocoel) during their journey from the midgut to the salivary glands, and this obligate migration places them in direct contact with the insect's circulatory and immune systems. The insect circulatory system consists of hemolymph (blood),... |
10.1371/journal.pcbi.1000270 | Coordinated Concentration Changes of Transcripts and Metabolites in Saccharomyces cerevisiae | Metabolite concentrations can regulate gene expression, which can in turn regulate metabolic activity. The extent to which functionally related transcripts and metabolites show similar patterns of concentration changes, however, remains unestablished. We measure and analyze the metabolomic and transcriptional responses... | Metabolism is the process of converting nutrients into usable energy and the building blocks of cellular structures. Although the biochemical reactions of metabolism are well characterized, the ways in which metabolism is regulated and regulates other biological processes remain incompletely understood. In particular, ... | Cellular metabolism—the process by which nutrients are converted into energy, macromolecular building blocks, and other small organic compounds—depends upon the expression of genes encoding enzymes and their regulators. Well-characterized transcriptional regulatory circuits such as the lac and trp operons in E. coli an... |
10.1371/journal.pcbi.1003707 | Signaling Domain of Sonic Hedgehog as Cannibalistic Calcium-Regulated Zinc-Peptidase | Sonic Hedgehog (Shh) is a representative of the evolutionary closely related class of Hedgehog proteins that have essential signaling functions in animal development. The N-terminal domain (ShhN) is also assigned to the group of LAS proteins (LAS = Lysostaphin type enzymes, D-Ala-D-Ala metalloproteases, Sonic Hedgehog)... | Hedgehog proteins are important “morphogens” that steer embryonic development in concentration-dependent ways. Despite many years of intensive research, the mechanism of morphogen action is still under debate. We have studied properties of ShhN, the actual signaling part of Sonic Hedgehog, by a comprehensive set of com... | Hedgehogs (Hhs) are a conserved family of secreted growth factors essential for development in bilateral animals [1]. Hh proteins realize the so-called morphogen principle [2]: they are secreted by specific cells and form extracellular concentration gradients. These are sensed by receiving cells and translated into spe... |
10.1371/journal.ppat.1000408 | The Defective Prophage Pool of Escherichia coli O157: Prophage–Prophage Interactions Potentiate Horizontal Transfer of Virulence Determinants | Bacteriophages are major genetic factors promoting horizontal gene transfer (HGT) between bacteria. Their roles in dynamic bacterial genome evolution have been increasingly highlighted by the fact that many sequenced bacterial genomes contain multiple prophages carrying a wide range of genes. Enterohemorrhagic Escheric... | Bacterial viruses, known as bacteriophages or phages, are major factors promoting horizontal gene transfer (HGT) between bacteria, and this activity has sparked new interest in light of the discovery that many sequenced bacterial genomes harbor multiple prophages carrying a wide range of genes, including those related ... | Horizontal gene transfer (HGT) is a major mechanism involved in bacterial evolution. In HGT between bacteria, viruses known as bacteriophages (or phages) play particularly important roles as gene transfer vehicles [1],[2]. Incoming temperate bacteriophages parasitize their hosts by integrating their genomes into the ho... |
10.1371/journal.pcbi.1002457 | Automatic Filtering and Substantiation of Drug Safety Signals | Drug safety issues pose serious health threats to the population and constitute a major cause of mortality worldwide. Due to the prominent implications to both public health and the pharmaceutical industry, it is of great importance to unravel the molecular mechanisms by which an adverse drug reaction can be potentiall... | Adverse drug reactions (ADRs) constitute a major cause of morbidity and mortality worldwide. Due to the relevance of ADRs for both public health and pharmaceutical industry, it is important to develop efficient ways to monitor ADRs in the population. In addition, it is also essential to comprehend why a drug produces a... | Drug safety issues can arise during pre-clinical screening, clinical trials and, more importantly, after the drug is marketed and tested for the first time on the population [1]. Although relatively rare once a drug is marketed, drug safety issues constitute a major cause of morbidity and mortality worldwide.
In... |
10.1371/journal.pgen.1007129 | Acute Smc5/6 depletion reveals its primary role in rDNA replication by restraining recombination at fork pausing sites | Smc5/6, a member of the conserved SMC family of complexes, is essential for growth in most organisms. Its exact functions in a mitotic cell cycle are controversial, as chronic Smc5/6 loss-of-function alleles produce varying phenotypes. To circumvent this issue, we acutely depleted Smc5/6 in budding yeast and determined... | Smc5/6 belongs to the SMC (Structural Maintenance of Chromosomes) family of protein complexes, all of which are highly conserved and critical for genome maintenance. To address the roles of Smc5/6 during growth, we rapidly depleted its subunits in yeast and found the main acute effect to be defective ribosomal DNA (rDN... | The conserved Smc5/6 complex (or Smc5/6) is required during normal growth and for coping with genotoxins [1–4]. Due to the essential nature of the complex, studies thus far have examined partial loss of function mutants of the complex in various organisms. As its chronically sick alleles give varied phenotypes, a coher... |
10.1371/journal.pntd.0002821 | Interruption of Infection Transmission in the Onchocerciasis Focus of Ecuador Leading to the Cessation of Ivermectin Distribution | Introduction: A clinically significant endemic focus of onchocerciasis existing in Esmeraldas Province, coastal Ecuador has been under an ivermectin mass drug administration program since 1991. The main transmitting vector in this area is the voracious blackfly, Simulium exiguum. This paper describes the assessments ma... | Onchocerciasis has been known to be endemic in the northwestern coastal riverine jungle areas of the country since the early 1980's. A mass drug administration program with ivermectin was implemented in 1991, and in recent years has included consistent twice a year treatment. The impact of this program, and progress to... | Onchocerciasis was recognized in Ecuador some 30 years ago and extensive work during the 1980s identified the limits of the endemic focus in Esmeraldas Province in north west of coastal jungle area of the country [1], [2]. This was area of increasing population where residents were spreading along the various river sys... |
10.1371/journal.pntd.0000940 | Ecological Modeling of Aedes aegypti (L.) Pupal Production in Rural Kamphaeng Phet, Thailand | Aedes aegypti (L.) is the primary vector of dengue, the most important arboviral infection globally. Until an effective vaccine is licensed and rigorously administered, Ae. aegypti control remains the principal tool in preventing and curtailing dengue transmission. Accurate predictions of vector populations are require... | Dengue infection is the leading cause of arbovirus illness worldwide with an estimated 2.5 billion people at risk. The primary dengue vector, Ae. aegypti, develops mainly in artificial containers in and around human dwellings. Often a small number of container types are responsible for a large proportion of adult mosqu... | The primary mosquito vector of dengue viruses (DENV), Aedes aegypti (L.), is well adapted to living with people and in much of the world is predominantly found among human settlements.[1], [2] Most dengue illness similarly occurs in urban and peri-urban environments, where humans are the only vertebrate host. Immature ... |
10.1371/journal.pgen.1000021 | The Mediator Subunit MDT-15 Confers Metabolic Adaptation to Ingested Material | In eukaryotes, RNA polymerase II (PolII) dependent gene expression requires accessory factors termed transcriptional coregulators. One coregulator that universally contributes to PolII-dependent transcription is the Mediator, a multisubunit complex that is targeted by many transcriptional regulatory factors. For exampl... | All organisms adapt their physiology to external input, such as altered food availability or toxic challenges. Many of these responses are driven by changes in gene transcription. In general, sequence specific DNA-binding regulatory factors are considered the specificity determinants of the transcriptional output. Here... | Eukaryotic gene transcription requires the concerted interplay of many factors. DNA-binding factors nucleate specific regulatory complexes on individual genes, culminating in assembly of functional RNA polymerase II (PolII). These complexes also contain transcriptional cofactors that serve various functions, such as ch... |
10.1371/journal.pgen.1008189 | Host-dependent nitrogen recycling as a mechanism of symbiont control in Aiptasia | The metabolic symbiosis with photosynthetic algae allows corals to thrive in the oligotrophic environments of tropical seas. Different aspects of this relationship have been investigated using the emerging model organism Aiptasia. However, many fundamental questions, such as the nature of the symbiotic relationship and... | The symbiotic relationship with photosynthetic algae is key to the success of reef building corals in the nutrient poor environment of tropical waters. Extensive insight has been obtained from both physiological and “omics” level studies, yet, there are still gaps in our knowledge with respect to the metabolic interact... | The symbiotic relationship between photosynthetic dinoflagellates in the family Symbiodiniaceae [1] and corals is the foundation of the coral reef ecosystem. This metabolic symbiosis is thought to enable corals to thrive in the oligotrophic environment of tropical oceans by allowing efficient recycling of nitrogenous w... |
10.1371/journal.pbio.2001663 | Late Maastrichtian pterosaurs from North Africa and mass extinction of Pterosauria at the Cretaceous-Paleogene boundary | Pterosaurs were the first vertebrates to evolve powered flight and the largest animals to ever take wing. The pterosaurs persisted for over 150 million years before disappearing at the end of the Cretaceous, but the patterns of and processes driving their extinction remain unclear. Only a single family, Azhdarchidae, i... | Pterosaurs were winged cousins of the dinosaurs and lived from around 200 million years ago to 66 million years ago, when the last pterosaurs disappeared during the Cretaceous-Paleogene extinction that wiped out the dinosaurs. The pterosaurs are thought to have declined in diversity before their final extinction, sugge... | Pterosaurs first appear in the fossil record in the Late Triassic [1–3], tens of millions of years before birds took wing [4]. Like birds, pterosaurs were archosaurs capable of powered flight; unlike birds, they flew on membraneous wings, supported by an elongate fourth digit, and walked or climbed on all fours [2,5,6]... |
10.1371/journal.pntd.0007649 | A high-throughput and multiplex microsphere immunoassay based on non-structural protein 1 can discriminate three flavivirus infections | The explosive spread of Zika virus (ZIKV) and associated complications in flavivirus-endemic regions underscore the need for sensitive and specific serodiagnostic tests to distinguish ZIKV, dengue virus (DENV) and other flavivirus infections. Compared with traditional envelope protein-based assays, several nonstructura... | Although there was a decrease of Zika virus (ZIKV) infection since late 2017, the specter of congenital Zika syndrome and its re-emergence in flavivirus-endemic regions emphasize the need for sensitive and specific serological tests to distinguish ZIKV, dengue virus (DENV) and other flaviviruses. Compared with traditio... | Despite a marked decrease of Zika virus (ZIKV) infection since late 2017, the specter of congenital Zika syndrome (CZS) and its re-emergence in flavivirus-endemic regions highlight the need for sensitive and specific diagnostic tests [1–4]. Similar to the laboratory diagnosis for other flaviviruses, detection of nuclei... |
10.1371/journal.pcbi.1003216 | Characterizing Changes in the Rate of Protein-Protein Dissociation upon Interface Mutation Using Hotspot Energy and Organization | Predicting the effects of mutations on the kinetic rate constants of protein-protein interactions is central to both the modeling of complex diseases and the design of effective peptide drug inhibitors. However, while most studies have concentrated on the determination of association rate constants, dissociation rates ... | Within a cell, protein-protein interactions vary considerably in their degree of stickiness. Mutations at protein interfaces can alter the interaction between protein pairs, causing them to dissociate faster or slower. This may lead to an alteration in the dynamics of the cellular networks in which these proteins are i... | Protein-Protein interactions are at the core of all biological systems and the rates at which biomolecules associate and disassociate are the major driving forces behind the complex time-dependent signaling observed in many biological processes. Ordinary Differential Equations (ODEs) are generally used to model these p... |
10.1371/journal.pcbi.1000993 | Spike-Timing-Based Computation in Sound Localization | Spike timing is precise in the auditory system and it has been argued that it conveys information about auditory stimuli, in particular about the location of a sound source. However, beyond simple time differences, the way in which neurons might extract this information is unclear and the potential computational advant... | There is growing evidence that the temporal coordination of spikes is important for neural computation, especially in auditory perception. Yet it is unclear what computational advantage it might provide, if any. We investigated this issue in the context of a difficult auditory task which must be performed quickly by an... | Animals must be able to rapidly estimate the location of the source of an unexpected sound, for example to escape a predator. This is a challenging task because the acoustic signals at the two ears vary with both the source signal and the acoustic environment, and information about source location must be extracted ind... |
10.1371/journal.pcbi.1004241 | Synaptic Homeostasis and Restructuring across the Sleep-Wake Cycle | Sleep is critical for hippocampus-dependent memory consolidation. However, the underlying mechanisms of synaptic plasticity are poorly understood. The central controversy is on whether long-term potentiation (LTP) takes a role during sleep and which would be its specific effect on memory. To address this question, we u... | Sleep is important for long lasting memories. There exists, however, a controversy regarding the mechanisms by which sleep modifies synapses to consolidate enduring memories. One theory posits that sleep weakens synapses, leading to the forgetting of all but the strongest memories. The alternative theory proposes that ... | In the hippocampus, slow-wave sleep (SWS) is characterized by large amplitude, low-frequency oscillations of the local field potential (LFP), concomitant with a phasic regime of neuronal firing, with relatively low mean firing rates and intermittent synchronization [1–4]. In contrast, rapid-eye-movement sleep (REM) dis... |
10.1371/journal.ppat.1000020 | The Effect of Immune Selection on the Structure of the Meningococcal Opa Protein Repertoire | The opa genes of the Gram negative bacterium Neisseria meningitidis encode Opacity-associated outer membrane proteins whose role is to promote adhesion to the human host tissue during colonisation and invasion. Each meningococcus contains 3–4 opa loci, each of which may be occupied by one of a large number of alleles. ... | Neisseria meningitidis is a globally important pathogen that causes 2,000–3,000 cases of invasive meningococcal disease annually in the United Kingdom. The meningococcal Opa proteins are important in mediating adhesion to and invasion of human tissues, and are important for evasion of the host immune response. They are... | The Opacity (Opa) proteins of the bacterial pathogen Neisseria meningitidis mediate adhesion to and invasion of the human nasopharyngeal epithelium [1] via interaction with cell surface saccharides [2] and members of the carcinoembryonic antigen cell adhesion molecule (CEACAM) family of proteins [3],[4]. The opa gene r... |
10.1371/journal.pntd.0003566 | Comparative Analysis of Field-Isolate and Monkey-Adapted Plasmodium vivax Genomes | Significant insights into the biology of Plasmodium vivax have been gained from the ability to successfully adapt human infections to non-human primates. P. vivax strains grown in monkeys serve as a renewable source of parasites for in vitro and ex vivo experimental studies and functional assays, or for studying in viv... | In this study we compare the genome sequences of Plasmodium vivax collected directly from patients with those of parasites propagated in laboratory monkeys. We show that the adaptation and continuous propagation of Plasmodium vivax in monkeys does not induce systematic changes in the genome and, therefore, that these p... | Today approximately 2.5 billion people are at risk of Plasmodium vivax malaria [1]. While transmission of P. falciparum is slowly decreasing in many countries committed to malaria elimination, vivax malaria displays surprising resilience in a majority of these countries [2]. This difference, likely resulting from the i... |
10.1371/journal.pntd.0001795 | Combining Hydrology and Mosquito Population Models to Identify the Drivers of Rift Valley Fever Emergence in Semi-Arid Regions of West Africa | Rift Valley fever (RVF) is a vector-borne viral zoonosis of increasing global importance. RVF virus (RVFV) is transmitted either through exposure to infected animals or through bites from different species of infected mosquitoes, mainly of Aedes and Culex genera. These mosquitoes are very sensitive to environmental con... | Rift Valley fever (RVF) is a zoonotic disease that affects domestic livestock and humans. During inter-epizootic periods, the main infection mechanism is suspected to be through bites by infected mosquitoes, mainly of Aedes and Culex genera. In East Africa, RVF outbreaks are known to be closely associated with heavy ra... | Rift Valley fever (RVF) is a vector-borne disease caused by a virus (RVFV) belonging to the Bunyaviridae family, genus Phlebovirus, that affects domestic livestock (e.g., sheep, cattle, camels, and goats) and humans. In humans, RVF can take different forms [1]. Most human cases are characterized by a ‘dengue-like’ illn... |
10.1371/journal.pbio.1001735 | Heat Shock Transcription Factor σ32 Co-opts the Signal Recognition Particle to Regulate Protein Homeostasis in E. coli | All cells must adapt to rapidly changing conditions. The heat shock response (HSR) is an intracellular signaling pathway that maintains proteostasis (protein folding homeostasis), a process critical for survival in all organisms exposed to heat stress or other conditions that alter the folding of the proteome. Yet desp... | All cells have to adjust to frequent changes in their environmental conditions. The heat shock response is a signaling pathway critical for survival of all organisms exposed to elevated temperatures. Under such conditions, the heat shock response maintains enzymes and other proteins in a properly folded state. The mech... | The heat shock response (HSR) maintains protein homeostasis (proteostasis) in all organisms. The HSR responds to protein unfolding, aggregation, and damage by the rapid and transient production of heat shock proteins (HSPs) and by triggering other cellular protective pathways that help mitigate the stress. Although the... |
10.1371/journal.pgen.1007602 | Homozygous loss-of-function mutations in MNS1 cause laterality defects and likely male infertility | The clinical spectrum of ciliopathies affecting motile cilia spans impaired mucociliary clearance in the respiratory system, laterality defects including heart malformations, infertility and hydrocephalus. Using linkage analysis and whole exome sequencing, we identified two recessive loss-of-function MNS1 mutations in ... | Although no clear explanation is yet provided for the correct establishment of the left-right body asymmetry in human, animal studies have clearly shown that tiny-hair-like organelles in the ventral node of the embryo—called motile nodal monocilia—beat regularly and play an important role in this process. To date, diff... | Cilia assemble on most cell types of the human body to perform diverse biological roles [1]. Non-motile primary cilia function in mechano- and chemosensation as well as in photoreception and olfaction, in addition to an essential role in several signal transduction pathways (noncanonical Wnt and Hedgehog pathways) [2].... |
10.1371/journal.pgen.1001166 | Evidence for a Xer/dif System for Chromosome Resolution in Archaea | Homologous recombination events between circular chromosomes, occurring during or after replication, can generate dimers that need to be converted to monomers prior to their segregation at cell division. In Escherichia coli, chromosome dimers are converted to monomers by two paralogous site-specific tyrosine recombinas... | Bacteria with circular chromosome and active homologous recombination systems have to resolve chromosomal dimers before segregation at cell division. In Escherichia coli, the Xer site-specific recombination system, composed of two recombinases and a specific chromosomal site (dif), is involved in the correct inheritanc... | In Bacteria, homologous recombination is essential during DNA replication to resume stalled replication forks and to repair DNA double and single strand breaks. Odd numbers of homologous recombination events between circular chromosomes generate dimers, which need to be resolved to ensure proper segregation in daughter... |
10.1371/journal.pcbi.0030147 | Distributed Representations Accelerate Evolution of Adaptive Behaviours | Animals with rudimentary innate abilities require substantial learning to transform those abilities into useful skills, where a skill can be considered as a set of sensory–motor associations. Using linear neural network models, it is proved that if skills are stored as distributed representations, then within-lifetime ... | Some behaviours are purely innate (e.g., blinking), whereas other, “apparently innate,” behaviours require a degree of learning to refine them into a useful skill (e.g., nest building). In terms of biological fitness, it matters how quickly such learning occurs, because time spent learning is time spent not eating, or ... | Both evolution and learning may be considered as different types of adaptation. Learning occurs within a lifetime, whereas genetic change occurs across lifetimes [1]. Whereas genetic change ensures that a task can be executed innately, learning permits even the most rudimentary innate ability to be honed into a useful ... |
10.1371/journal.pgen.1003707 | Hard Selective Sweep and Ectopic Gene Conversion in a Gene Cluster Affording Environmental Adaptation | Among the rare colonizers of heavy-metal rich toxic soils, Arabidopsis halleri is a compelling model extremophile, physiologically distinct from its sister species A. lyrata, and A. thaliana. Naturally selected metal hypertolerance and extraordinarily high leaf metal accumulation in A. halleri both require Heavy Metal ... | Existing genetic diversity reflects evolutionary history, but it has rarely been possible to probe for footprints of selection at loci known to functionally govern adaptive traits. Both naturally selected metal hypertolerance and extraordinary leaf metal accumulation of the extremophile Arabidopsis halleri require stro... | Analyses of nucleotide sequence variation bear great promise for advancing our understanding of evolutionary processes. However, such analyses have so far rarely targeted loci of experimentally established roles in naturally selected adaptive traits, and, instead, have mostly been conducted on candidate loci or even an... |
10.1371/journal.pcbi.1003228 | Sensitive Detection of Viral Transcripts in Human Tumor Transcriptomes | In excess of % of human cancer incidents have a viral cofactor. Epidemiological studies of idiopathic human cancers indicate that additional tumor viruses remain to be discovered. Recent advances in sequencing technology have enabled systematic screenings of human tumor transcriptomes for viral transcripts. However, te... | Many human cancers are caused by infections with tumor viruses and identification of these pathogens is considered a critical contribution to cancer prevention. Deep sequencing enables us to systematically investigate viral nucleotide signatures in order to either verify or exclude the existence of viruses in idiopathi... | To date, pathogenic agents are known to be causally related to 20% of human cancer cases [1] and significantly affect the global health burden of this disease [2]. The majority of these agents comprise oncogenic viruses such as human papilloma virus (HPV), Epstein-Barr virus (EBV), hepatitis B virus (HBV), and hepatiti... |
10.1371/journal.pgen.0040002 | Dissecting the Genetic Components of Adaptation of Escherichia coli to the Mouse Gut | While pleiotropic adaptive mutations are thought to be central for evolution, little is known on the downstream molecular effects allowing adaptation to complex ecologically relevant environments. Here we show that Escherichia coli MG1655 adapts rapidly to the intestine of germ-free mice by single point mutations in En... | The mammalian intestine is a privileged physiological site to study how coevolution between hosts and the trillions of bacteria present in the microbiota has shaped the genome of each partner and promoted the development of mutualistic interactions. Herein we have used germ-free mice, a simplified albeit ecologically r... | Bacterial populations are powerful model to explore the mechanisms of evolution. Several in vivo experiments have pointed to the possible important role of pleiotropic adaptive mutations, but their molecular basis remain in most of cases largely elusive [1–3]. Here we have used gnotobiotic mice that offer a simplified ... |
10.1371/journal.pbio.2004986 | Canonical PRC2 function is essential for mammary gland development and affects chromatin compaction in mammary organoids | Distinct transcriptional states are maintained through organization of chromatin, resulting from the sum of numerous repressive and active histone modifications, into tightly packaged heterochromatin versus more accessible euchromatin. Polycomb repressive complex 2 (PRC2) is the main mammalian complex responsible for h... | The formation of mammary glands requires the tight regulation of many genes that govern cell fate decisions in the cells that form them. However, most of these genes remain undefined. The Polycomb repressive complex 2 (PRC2) has a role in gene silencing, and it is comprised of several subunits, which include either Enh... | A central question in biology is how different cell types maintain distinct cell fates despite containing the same genetic material. Organization of DNA into open or closed chromatin states by posttranslational modifications (PTMs) of histones has emerged as a critical mechanism underpinning cell diversity and reflecti... |
10.1371/journal.pgen.1006027 | Chloroplast RNA-Binding Protein RBD1 Promotes Chilling Tolerance through 23S rRNA Processing in Arabidopsis | Plants have varying abilities to tolerate chilling (low but not freezing temperatures), and it is largely unknown how plants such as Arabidopsis thaliana achieve chilling tolerance. Here, we describe a genome-wide screen for genes important for chilling tolerance by their putative knockout mutants in Arabidopsis thalia... | Compared to cold acclimation (enhancement of freezing tolerance by a prior exposure to low non-freezing temperature), the tolerance mechanism to non-freezing chilling temperatures is not well understood. Here, we performed a genome-wide mutant screen for chilling sensitive phenotype and identified 49 candidate genes im... | Low temperature inhibits plant growth in general and limits the geographical distribution of plants. Earlier studies have identified numerous physiological and cellular changes associated with chilling (more than 0°C) or freezing (less than 0°C) conditions, such as alterations in membrane composition, calcium signals, ... |
10.1371/journal.pgen.1003701 | Integration of the Unfolded Protein and Oxidative Stress Responses through SKN-1/Nrf | The Unfolded Protein Response (UPR) maintains homeostasis in the endoplasmic reticulum (ER) and defends against ER stress, an underlying factor in various human diseases. During the UPR, numerous genes are activated that sustain and protect the ER. These responses are known to involve the canonical UPR transcription fa... | Proteins that are placed in membranes or secreted are produced in a cellular structure called the endoplasmic reticulum (ER). An accumulation of misfolded proteins in the ER contributes to many disease states, including diabetes and neurodegeneration. The ER protects against a toxic buildup of misfolded proteins by act... | The endoplasmic reticulum (ER) is responsible for multiple functions in protein synthesis and processing, lipid metabolism, xeno/endobiotic detoxification, and Ca2+ storage (reviewed in [1], [2]). The ER forms a continuous structure with the nuclear envelope and maintains extensive contact with mitochondria [3], [4]. C... |
10.1371/journal.pntd.0006037 | A multi-country study of the economic burden of dengue fever: Vietnam, Thailand, and Colombia | Dengue fever is a major public health concern in many parts of the tropics and subtropics. The first dengue vaccine has already been licensed in six countries. Given the growing interests in the effective use of the vaccine, it is critical to understand the economic burden of dengue fever to guide decision-makers in se... | Dengue fever has been prevalent in South-East Asia and South America. Despite the increase of dengue fever cases, there continues to be a lack of economic assessment partly due to the absence of vaccines until recent times. Many of the previous economic burden studies for dengue fever were not standardized, making them... | Dengue fever is a major public health concern in many parts of the tropics and subtropics. Dengue is a vector-borne viral illness and transmitted to humans by two mosquito vectors: Aedes aegypti and Aedes albopictus. There are four serotypes that cause dengue, with a wide clinical spectrum of symptoms. A previous study... |
10.1371/journal.pntd.0006763 | Rural youths' understanding of gene x environmental contributors to heritable health conditions: The case of podoconiosis in Ethiopia | Assess the feasibility of engaging youth to disseminate accurate information about gene by environmental (GxE) influences on podoconiosis, a neglected tropical lymphedema endemic in southern Ethiopia.
A cross sectional survey was conducted with 377 youth randomly selected from 2 districts of Southern Ethiopia. Measures... | This study considers the feasibility of engaging rural Ethiopian youth as lay health workers (LHWs) with the objective to improve community understanding of the joint influences of genetics and environment on health. Identifying LHWs to accurately convey contributors to the heritable but preventable neglected tropical ... | Advances in genomics are increasing scientific understanding that most health conditions worldwide are caused by the joint influence of genetic and environmental (GxE) factors [1]. However, the mechanisms underlying GxE interactions are complex and not well understood by the public [2]. Accordingly, misunderstandings t... |
10.1371/journal.ppat.1007249 | A seven-helix protein constitutes stress granules crucial for regulating translation during human-to-mosquito transmission of Plasmodium falciparum | The complex life-cycle of the human malaria parasite Plasmodium falciparum requires a high degree of tight coordination allowing the parasite to adapt to changing environments. One of the major challenges for the parasite is the human-to-mosquito transmission, which starts with the differentiation of blood stage parasi... | Plasmodium falciparum is a unicellular parasite responsible for the majority of 440,000 deaths due to malaria every year. Malaria is a vector-borne disease, transmitted by blood-feeding Anopheles mosquitoes. While the high-replicating red blood cell stages are responsible for the symptoms of malaria, the gametocytes, s... | In eukaryotes, proteins comprising seven helix domains are classified as receptors capable of binding a high variety of ligands. Because many of these receptors transduce signals to heterotrimeric G proteins, they are commonly referred to as G protein-coupled receptors (GPCR) (reviewed in [1]). Alternative names includ... |
10.1371/journal.pgen.1002326 | Natural Selection Affects Multiple Aspects of Genetic Variation at Putatively Neutral Sites across the Human Genome | A major question in evolutionary biology is how natural selection has shaped patterns of genetic variation across the human genome. Previous work has documented a reduction in genetic diversity in regions of the genome with low recombination rates. However, it is unclear whether other summaries of genetic variation, li... | While researchers have identified candidate genes that have evolved under positive Darwinian natural selection, less is known about how much of the human genome has been affected by natural selection or whether positive selection has had a greater role at shaping patterns of variation across the human genome than negat... | A substantial amount of effort in human population genetics has been aimed at understanding how natural selection operates in the human genome. However, we lack a basic understanding of the importance of positive natural selection versus negative selection at shaping overall patterns of genome variation. Thus far, most... |
10.1371/journal.pgen.1000458 | The RNA Polymerase Dictates ORF1 Requirement and Timing of LINE and SINE Retrotransposition | Mobile elements comprise close to one half of the mass of the human genome. Only LINE-1 (L1), an autonomous non-Long Terminal Repeat (LTR) retrotransposon, and its non-autonomous partners—such as the retropseudogenes, SVA, and the SINE, Alu—are currently active human retroelements. Experimental evidence shows that Alu ... | SINE retroelement amplification has been extremely successful in the human genome. Although these non-autonomous elements parasitize factors from LINEs, both the human Alu and the cumulative rodent SINEs have generated over one million copies in their respective hosts. Alu-induced mutagenesis is responsible for the maj... | Mobile elements have constantly assaulted genomes, shaping and molding their structure and organization. In particular, mobile elements have flourished in mammals generating between 40–50% of their genomic sequence [1]–[3]. About one third of the human genome can be attributed directly or indirectly to the activity of ... |
10.1371/journal.pcbi.1005566 | Chemomechanical regulation of myosin Ic cross-bridges: Deducing the elastic properties of an ensemble from single-molecule mechanisms | Myosin Ic is thought to be the principal constituent of the motor that adjusts mechanical responsiveness during adaptation to prolonged stimuli by hair cells, the sensory receptors of the inner ear. In this context myosin molecules operate neither as filaments, as occurs in muscles, nor as single or few molecules, as c... | Myosin molecules are biological nanomachines that transduce chemical energy into mechanical work and thus produce directed motion in living cells. These molecules proceed through cyclic reactions in which they change their conformational states upon the binding and release of nucleotides while attaching to and detachin... | The myosin family includes at least 20 structurally and functionally distinct classes [1, 2]. Although they all exhibit a common chemomechanical cycle, myosin molecules have remarkably diverse functions-including intracellular transport, force production in muscles, and cellular migration-as well as important roles in ... |
10.1371/journal.pcbi.1000104 | Circadian Phase Resetting via Single and Multiple Control Targets | Circadian entrainment is necessary for rhythmic physiological functions to be appropriately timed over the 24-hour day. Disruption of circadian rhythms has been associated with sleep and neuro-behavioral impairments as well as cancer. To date, light is widely accepted to be the most powerful circadian synchronizer, mot... | The robust timing, or phase, of the circadian clock is critical in directing and synchronizing molecular, cellular, and organismal behaviors. The clock's failure to maintain precision and adaption is associated with sleeping disorders, depression, and cancer. To better study and control the timing of circadian rhythms,... | Control theoretic tools have been used to model mRNA transcriptional/translational regulatory feedback mechanisms [1], to analyze nonlinear phenomena [2],[3], and to control complex biological behavior [4],[5]. In our research, we couple systems theoretic tools (such as sensitivity analysis) with model predictive contr... |
10.1371/journal.pntd.0006281 | Human T-Lymphotropic Virus type 1c subtype proviral loads, chronic lung disease and survival in a prospective cohort of Indigenous Australians | The Human T-Lymphotropic Virus type 1c subtype (HTLV-1c) is highly endemic to central Australia where the most frequent complication of HTLV-1 infection in Indigenous Australians is bronchiectasis. We carried out a prospective study to quantify the prognosis of HTLV-1c infection and chronic lung disease and the risk of... | The Human T-Lymphotropic Virus type 1 (HTLV-1) infects up to 20 million people worldwide who predominantly reside in resource-limited areas. The virus is associated with a haematological malignancy (adult T-cell leukaemia/lymphoma, ATL), and inflammatory diseases involving organ systems including the spinal cord, eyes ... | The Human T-Lymphotropic Virus type 1 (HTLV-1) is an oncogenic retrovirus that preferentially infects CD4+ T cells[1]. Worldwide, HTLV-1 infects as many as 20 million people who predominantly dwell in areas of high endemicity in south-western Japan and developing countries of the Caribbean basin, South America and sub-... |
10.1371/journal.pcbi.1004901 | Using Combined Diagnostic Test Results to Hindcast Trends of Infection from Cross-Sectional Data | Infectious disease surveillance is key to limiting the consequences from infectious pathogens and maintaining animal and public health. Following the detection of a disease outbreak, a response in proportion to the severity of the outbreak is required. It is thus critical to obtain accurate information concerning the o... | We have developed a Bayesian approach that can estimate the historic trend of incidence from cross-sectional samples, without relying on ongoing surveillance. This could be used to evaluate changing disease trends, or to inform outbreak responses. We combine two or more diagnostic tests to estimate the time since infec... | Infectious disease surveillance is the first line of detection and defence against infectious pathogens and therefore crucial to maintaining animal and public health. However, the current state of disease surveillance has been characterised as deficient in terms of both coverage and reporting speed for both humans [1] ... |
10.1371/journal.ppat.1000338 | The Tetraspanin Protein CD37 Regulates IgA Responses and Anti-Fungal Immunity | Immunoglobulin A (IgA) secretion by plasma cells in the immune system is critical for protecting the host from environmental and microbial infections. However, the molecular mechanisms underlying the generation of IgA+ plasma cells remain poorly understood. Here, we report that the B cell–expressed tetraspanin CD37 inh... | Antibody, or immunoglobulin (Ig), production by plasma cells in the immune system is important for protecting the host from microbial infections. IgA is the most abundant antibody isotype produced in the body. However, the molecular mechanisms underlying the generation of IgA–producing plasma cells remain poorly unders... | Plasma cells (non-dividing antibody-secreting cells, ASC) are terminally differentiated B cells that are central to humoral immunity. Both mucosal and systemic immune responses to infection can induce IgA+ plasma cell formation, resulting in production of secretory and serum IgA respectively. In both pathways, isotype ... |
10.1371/journal.pgen.1006830 | Cleavage of the SUN-domain protein Mps3 at its N-terminus regulates centrosome disjunction in budding yeast meiosis | Centrosomes organize microtubules and are essential for spindle formation and chromosome segregation during cell division. Duplicated centrosomes are physically linked, but how this linkage is dissolved remains unclear. Yeast centrosomes are tethered by a nuclear-envelope-attached structure called the half-bridge, whos... | The nucleus, where the eukaryotic chromosomes are stored, is enclosed by a double-membrane structure called the nuclear envelope. Located at the inner nuclear membrane, a class of highly conserved proteins called SUN-domain proteins regulates a range of nuclear activities at the nuclear periphery, including tethering t... | Centrosomes nucleate microtubules and form a bipolar spindle that separates chromosomes during cell division. Like DNA replication, centrosome duplication occurs only once per cell cycle. Duplicated centrosomes are tethered, and their timely separation ensures accurate chromosome segregation. Supernumerary centrosomes ... |
10.1371/journal.pgen.1003007 | Regulation of ATG4B Stability by RNF5 Limits Basal Levels of Autophagy and Influences Susceptibility to Bacterial Infection | Autophagy is the mechanism by which cytoplasmic components and organelles are degraded by the lysosomal machinery in response to diverse stimuli including nutrient deprivation, intracellular pathogens, and multiple forms of cellular stress. Here, we show that the membrane-associated E3 ligase RNF5 regulates basal level... | Autophagy is an intracellular catabolic process by which a cell's own components are degraded through the lysosomal machinery. Autophagy is implicated in various cellular processes such as growth and development, cancer, and inflammation. Using biochemistry, cell biology, and genetic models, we identify a ubiquitin lig... | Autophagy is an intracellular catabolic process by which cellular components are degraded through the lysosomal machinery. Conserved from yeast to humans, autophagy is fundamental to eukaryotic cell homeostasis [1], [2]. Autophagy functions in diverse cellular processes such as growth and development, cancer, and infla... |
10.1371/journal.pcbi.1005957 | Modeling the interactions of sense and antisense Period transcripts in the mammalian circadian clock network | In recent years, it has become increasingly apparent that antisense transcription plays an important role in the regulation of gene expression. The circadian clock is no exception: an antisense transcript of the mammalian core-clock gene PERIOD2 (PER2), which we shall refer to as Per2AS RNA, oscillates with a circadian... | A better understanding of the molecular mechanisms underlying circadian rhythms will undoubtedly improve the treatment of human health problems related to circadian dysrhythmias. However, the inventory of genes and genetic interactions in the circadian clock is still incomplete. Important players may yet be unknown or ... | Messenger RNAs, which encode proteins, are transcribed in the 5'-to-3' direction from one strand (the sense strand) of a structural gene, under the control of an upstream promoter region. For some genes, an ‘antisense’ RNA molecule is transcribed from the opposite strand, driven by an alternative promoter which often l... |
10.1371/journal.pgen.1003609 | Re-Ranking Sequencing Variants in the Post-GWAS Era for Accurate Causal Variant Identification | Next generation sequencing has dramatically increased our ability to localize disease-causing variants by providing base-pair level information at costs increasingly feasible for the large sample sizes required to detect complex-trait associations. Yet, identification of causal variants within an established region of ... | As next-generation sequencing (NGS) costs continue to fall and genome-wide association study (GWAS) platform coverage improves, the human genetics community is positioned to identify potentially causal variants. However, current NGS or imputation-based studies of either the whole genome or regions previously identified... | The challenges of precise identification of disease-causing variants underlying GWAS signals have recently received much attention [1]–[3]. For post-GWAS statistical analysis that aims to accurately identify potentially causal variants, a major hurdle is the development of methods to distinguish disease-causing variant... |
10.1371/journal.pntd.0003995 | CD4+CD25hiFOXP3+ Regulatory T Cells and Cytokine Responses in Human Schistosomiasis before and after Treatment with Praziquantel | Chronic schistosomiasis is associated with T cell hypo-responsiveness and immunoregulatory mechanisms, including induction of regulatory T cells (Tregs). However, little is known about Treg functional capacity during human Schistosoma haematobium infection.
CD4+CD25hiFOXP3+ cells were characterized by flow cytometry an... | Schistosomiasis, a parasitic worm infection, affects over 240 million people worldwide, especially children in sub-Saharan Africa. It is associated with immune hypo-responsiveness which results in an inability of the immune system to eliminate parasites. Animal models suggest that helminths induce regulatory T cells (T... | The immune system has evolved several regulatory mechanisms to maintain immune homeostasis, prevent autoimmunity and restrain inflammation [1–3]. Many pathogens have developed mechanisms to manipulate the regulatory network of the host to their advantage, thereby generating conditions that ensure their survival for a p... |
10.1371/journal.pgen.1006835 | The yeast protein kinase Sch9 adjusts V-ATPase assembly/disassembly to control pH homeostasis and longevity in response to glucose availability | The conserved protein kinase Sch9 is a central player in the nutrient-induced signaling network in yeast, although only few of its direct substrates are known. We now provide evidence that Sch9 controls the vacuolar proton pump (V-ATPase) to maintain cellular pH homeostasis and ageing. A synthetic sick phenotype arises... | The evolutionary conserved TOR complex 1 controls growth in response to the quality and quantity of nutrients such as carbon and amino acids. The protein kinase Sch9 is the main TORC1 effector in yeast. However, only few of its direct targets are known. In this study, we performed a genome-wide screening looking for mu... | In Saccharomyces cerevisiae, Sch9 is part of the highly conserved TORC1 pathway which plays a central role in the nutrient-induced signaling network, thereby affecting many aspects of yeast physiology such as stress resistance, longevity and cell growth [1–3]. The rapamycin-sensitive TORC1 mediates these effects mainly... |
10.1371/journal.pcbi.1003931 | Pattern of Tick Aggregation on Mice: Larger Than Expected Distribution Tail Enhances the Spread of Tick-Borne Pathogens | The spread of tick-borne pathogens represents an important threat to human and animal health in many parts of Eurasia. Here, we analysed a 9-year time series of Ixodes ricinus ticks feeding on Apodemus flavicollis mice (main reservoir-competent host for tick-borne encephalitis, TBE) sampled in Trentino (Northern Italy)... | Our work analyses a 9-year time series of tick co-feeding patterns on Yellow-necked mice. Our data shows a strong heterogeneity, where most mice are parasitised by a small number of ticks while few host a much larger number. We describe the number of ticks per host by the commonly used Negative Binomial model, by the P... | Several ecological studies have shown that the distribution of ticks on their hosts is often highly aggregated, with a large number of hosts harbouring few parasites and a small number harbouring a large number of them ([1]–[5]; other interesting references could be found in [6]). In addition, the distribution of tick ... |
10.1371/journal.pgen.1005461 | Silencing of X-Linked MicroRNAs by Meiotic Sex Chromosome Inactivation | During the pachytene stage of meiosis in male mammals, the X and Y chromosomes are transcriptionally silenced by Meiotic Sex Chromosome Inactivation (MSCI). MSCI is conserved in therian mammals and is essential for normal male fertility. Transcriptomics approaches have demonstrated that in mice, most or all protein-cod... | During male germ cell formation, the X and the Y chromosomes are inactivated. This process is conserved and it is essential for germ cell generation. It is believed that X/Y silencing affects all protein-coding genes, but the status of miRNAs and other non-coding genes needs further investigation. MicroRNAs from the X-... | Meiotic sex chromosome inactivation (MSCI) describes the transcriptional silencing of the unsynapsed X and Y chromosomes at the onset of pachynema in mammalian male germ cells [1–5]. Inactivation of the sex chromosome results in the formation of a heterochromatic domain called the sex body [6]. MSCI is one example of a... |
10.1371/journal.ppat.1002360 | Sap Transporter Mediated Import and Subsequent Degradation of Antimicrobial Peptides in Haemophilus | Antimicrobial peptides (AMPs) contribute to host innate immune defense and are a critical component to control bacterial infection. Nontypeable Haemophilus influenzae (NTHI) is a commensal inhabitant of the human nasopharyngeal mucosa, yet is commonly associated with opportunistic infections of the upper and lower resp... | The opportunistic pathogen Haemophilus influenzae is a normal inhabitant of the human nasopharynx, and is commonly implicated in respiratory tract infections, particularly of the middle ear (otitis media), sinuses, and lung (pneumonia, chronic obstructive pulmonary disease and cystic fibrosis). We have identified a mul... | Host-derived antimicrobial peptides (AMPs) are typically amphipathic, cationic innate immune defense molecules that target bacterial membranes, disrupt transmembrane potential and trigger cytoplasmic leakage resulting in bacterial cell death [1], [2]. Defensins (α- and β-) and cathelicidin (hCAP-18/LL37) molecules are ... |
10.1371/journal.ppat.1000999 | A Metazoan/Plant-like Capping Enzyme and Cap Modified Nucleotides in the Unicellular Eukaryote Trichomonas vaginalis | The cap structure of eukaryotic messenger RNAs is initially elaborated through three enzymatic reactions: hydrolysis of the 5′-triphosphate, transfer of guanosine through a 5′-5′ triphosphate linkage and N7-methylation of the guanine cap. Three distinctive enzymes catalyze each reaction in various microbial eukaryotes,... | The protozoan parasite Trichomonas vaginalis is the cause of the most common non-viral sexually transmitted disease worldwide. Evolutionary analyses place Trichomonas in a super group called the Excavata, which includes the kinetoplastids and is highly divergent from fungi, metazoa and plants. Despite the vast evolutio... | The 5′ cap is a unique feature of eukaryotic messenger RNAs (mRNA) and eukaryotic viruses not found on eubacterial and archaeal RNAs [1]. The addition of a m7G cap structure, or the cap 0 nucleotide, occurs co-transcriptionally via three consecutive reactions executed by the capping enzymatic apparatus: (i) hydrolysis ... |
10.1371/journal.pcbi.1000716 | Emergence of Spatial Structure in Cell Groups and the Evolution of Cooperation | On its own, a single cell cannot exert more than a microscopic influence on its immediate surroundings. However, via strength in numbers and the expression of cooperative phenotypes, such cells can enormously impact their environments. Simple cooperative phenotypes appear to abound in the microbial world, but explainin... | Cooperation is a fundamental and widespread phenomenon in nature, yet explaining the evolution of cooperation is difficult. Natural selection typically favors individuals that maximize their own reproduction, so how is it that many diverse organisms, from bacteria to humans, have evolved to help others at a cost to the... | Many cell phenotypes alter the growth and division of nearby cells by changing local resource availability [1]–[4]. Some of these phenotypes promote the survival and reproduction of others, and thus qualify as a simple form of cooperation. A cell may be considered cooperative, for example, if it secretes enzymes that f... |
10.1371/journal.pbio.1002180 | A Sensitive and Specific Neural Signature for Picture-Induced Negative Affect | Neuroimaging has identified many correlates of emotion but has not yet yielded brain representations predictive of the intensity of emotional experiences in individuals. We used machine learning to identify a sensitive and specific signature of emotional responses to aversive images. This signature predicted the intens... | Emotions are an important aspect of human experience and behavior; yet, we do not have a clear understanding of how they are processed in the brain. We have identified a neural signature of negative emotion—a neural activation pattern distributed across the brain that accurately predicts how negative a person will feel... | Emotions are a class of psychological states comprised of physiological responses, expressive behavior, and subjective experiences that are central to our daily lives and to multiple forms of psychopathology [1] and chronic medical diseases [2]. Emotional information organizes physiological, cognitive, and motor system... |
10.1371/journal.pntd.0001212 | Polyethyleneimine (PEI) Mediated siRNA Gene Silencing in the Schistosoma mansoni Snail Host, Biomphalaria glabrata | An in vivo, non-invasive technique for gene silencing by RNA interference (RNAi) in the snail, Biomphalaria glabrata, has been developed using cationic polymer polyethyleneimine (PEI) mediated delivery of long double-stranded (ds) and small interfering (si) RNA. Cellular delivery was evaluated and optimized by using a ... | Freshwater snails are important in the transmission of schistosomiasis. As part of an integral control effort to combat the spread of schistosomiasis new intervention tools are being sought. One method is to interrupt the transmission of the causative schistosome parasite during the intra-molluscan phase of its develop... | Biomphalaria glabrata is an intermediate snail host that transmits the digenean platyhelminth parasite, Schistosoma mansoni, in the Western Hemisphere. This snail host is easily maintained in the laboratory outside of its natural environment and, therefore, serves as a useful model organism for conducting studies aimed... |
10.1371/journal.pgen.1003694 | A Flexible Approach for the Analysis of Rare Variants Allowing for a Mixture of Effects on Binary or Quantitative Traits | Multiple rare variants either within or across genes have been hypothesised to collectively influence complex human traits. The increasing availability of high throughput sequencing technologies offers the opportunity to study the effect of rare variants on these traits. However, appropriate and computationally efficie... | Rapid advances in sequencing technology mean that it is now possible to directly assay rare genetic variation. In addition, the availability of almost fully sequenced human genomes by the 1000 Genomes Project allows genotyping at rare variants that are not present on arrays commonly used in genome-wide association stud... | Despite the recent successes of genome-wide association studies (GWAS), which can be well powered under the common disease, common variant hypothesis, the majority of the genetic component of many complex traits remains unexplained. For example, hundreds of common genetic variants, in at least 180 loci, have been assoc... |
10.1371/journal.pntd.0003687 | Phlebotomus sergenti in a Cutaneous Leishmaniasis Focus in Azilal Province (High Atlas, Morocco): Molecular Detection and Genotyping of Leishmania tropica, and Feeding Behavior | Phlebotomus (Paraphlebotomus) sergenti is at least one of the confirmed vectors for the transmission of cutaneous leishmaniasis caused by Leishmania tropica and distributed widely in Morocco. This form of leishmaniasis is considered largely as anthroponotic, although dogs were found infected with Leishmania tropica, su... | In Morocco three Leishmania species have been reported to cause cutaneous leishmaniasis: Leishmania major, Leishmania tropica and less frequently Leishmania infantum. Amongst these clinically important Leishmania species, Leishmania tropica is considered as a public health problem by the Ministry of Health in Morocco a... | Leishmaniases are complex diseases of worldwide distribution caused by >20 Leishmania species, which are parasitic protozoa transmitted by the bite of infected female sand flies. The disease affects 98 Mediterranean and other endemic countries putting a population of 350 million people at risk of infection and causing ... |
10.1371/journal.pntd.0003710 | Using Hospital Discharge Database to Characterize Chagas Disease Evolution in Spain: There Is a Need for a Systematic Approach towards Disease Detection and Control | After the United States, Spain comes second in the list of countries receiving migrants from Latin America, and, therefore, it is the European country with the highest expected number of infected patients of Chagas disease. We have studied the National Health System’s Hospital Discharge Records Database (CMBD) in order... | Chagas disease, caused by the protozoa Trypanosoma cruzi, is endemic in most Latin American countries and it is considered a neglected tropical disease (NTD). T. cruzi transmission is feasible in vector-free world regions. The main non-vectorial routes are congenital transmission, blood transfusion, and solid organ tra... | Chagas disease, also known as American trypanosomiasis, is a potentially life-threatening illness caused by the protozoan parasite, Trypanosoma cruzi (T. cruzi). This disease presents itself in two phases. The initial, acute phase lasts for about two months after infection. In most cases, symptoms are absent or mild, b... |
10.1371/journal.ppat.1000487 | The Glyceraldehyde-3-Phosphate Dehydrogenase and the Small GTPase Rab 2 Are Crucial for Brucella Replication | The intracellular pathogen Brucella abortus survives and replicates inside host cells within an endoplasmic reticulum (ER)-derived replicative organelle named the “Brucella-containing vacuole” (BCV). Here, we developed a subcellular fractionation method to isolate BCVs and characterize for the first time the protein co... | A key determinant for intracellular pathogenic bacteria to ensure their virulence within host cells is their ability to bypass the endocytic pathway and to reach a safe replication niche. Brucella bacteria reach the endoplasmic reticulum (ER) to create their replicating niche called the Brucella-containing vacuole (BCV... | Brucella abortus invades both phagocytic and non-phagocytic cells [1]–[6] residing inside a membrane-bound compartment called the Brucella-containing vacuole (BCV). Bacteria ensure their survival and replication within host cells by avoiding fusion with lysosomes and by controlling interactions with the endoplasmic ret... |
10.1371/journal.ppat.1002765 | The Link between Morphotype Transition and Virulence in Cryptococcus neoformans | Cryptococcus neoformans is a ubiquitous human fungal pathogen. This pathogen can undergo morphotype transition between the yeast and the filamentous form and such morphological transition has been implicated in virulence for decades. Morphotype transition is typically observed during mating, which is governed by pherom... | Although morphogenesis and virulence are commonly associated in many eukaryotic pathogens, the nature of such association is often unknown. For example, Cryptococcus neoformans, a fungal pathogen that causes cryptococcal meningitis, typically undergoes morphological transition between the yeast and the filamentous form... | Adaptation to the host environment by many eukaryotic pathogens is often companied by transition in cellular morphology [1], [2], [3], [4], [5], [6], [7], [8], [9]. The ubiquitous fungal pathogen Cryptococcus neoformans causes more than half a million deaths each year [10]. It can grow in the yeast form as well as the ... |
10.1371/journal.pbio.0060081 | Electrical Neuroimaging Reveals Timing of Attentional Control Activity in Human Brain | Voluntarily shifting attention to a location of the visual field improves the perception of events that occur there. Regions of frontal cortex are thought to provide the top-down control signal that initiates a shift of attention, but because of the temporal limitations of functional brain imaging, the timing and seque... | To extract important details about objects in the environment, people must focus their attention on a specific location in space at any given moment. Research using functional magnetic resonance imaging (fMRI) has suggested that regions of the frontal and parietal lobes work together to control our ability to direct at... | Shifting attention to the expected location of an impending visual stimulus will improve the perception of that stimulus once it occurs there [1]. This perceptual improvement is considered to be a consequence of attentional-control operations that are performed by frontal and parietal regions of the human brain [2,3]. ... |
10.1371/journal.pntd.0003366 | Quantitative PCR in Epidemiology for Early Detection of Visceral Leishmaniasis Cases in India | Studies employing serological, DTH or conventional PCR techniques suggest a vast proportion of Leishmania infected individuals living in regions endemic for Visceral Leishmaniasis (VL) remain asymptomatic. This study was designed to assess whether quantitative PCR (qPCR) can be used for detection of asymptomatic or ear... | Anthroponotic VL caused by Leishmania donovani in the Indian subcontinent accounts for 70% of the world burden of VL. Among the estimated 100,000 cases of VL acquired annually in India, 90% occur in the state of Bihar. Leishmania infection can result in either symptomatic or asymptomatic infection. L. donovani infectio... | The Leishmania spp. parasites of humans are endemic in 98 countries, and more than 350 million people are at risk of infection [1]. Leishmaniasis is a neglected tropical disease, and the most severe form visceral leishmaniasis (VL, also known as kala-azar) is fatal if untreated. VL is primarily an anthroponotic infecti... |
10.1371/journal.ppat.1000865 | Novel Riboswitch Ligand Analogs as Selective Inhibitors of Guanine-Related Metabolic Pathways | Riboswitches are regulatory elements modulating gene expression in response to specific metabolite binding. It has been recently reported that riboswitch agonists may exhibit antimicrobial properties by binding to the riboswitch domain. Guanine riboswitches are involved in the regulation of transport and biosynthesis o... | During the last 30 years, bacterial resistance to antibiotics has become a major problem. This situation is partly because today's antibiotics are mainly based on a limited selection of chemical scaffolds, which makes it easier for bacterial pathogens to quickly develop resistance against new drug derivatives. This rec... | Multiple drug resistance (MDR) has been a growing problem during the last decade, partly due to excessive use of antibiotics in human medicine and food animal production. MDR also stems from the fact that drug design has been largely based on limited chemical scaffolds leaving an opportunity for pathogens to circumvent... |
10.1371/journal.pntd.0002750 | Sm10.3, a Member of the Micro-Exon Gene 4 (MEG-4) Family, Induces Erythrocyte Agglutination In Vitro and Partially Protects Vaccinated Mice against Schistosoma mansoni Infection | The parasitic flatworm Schistosoma mansoni is a blood fluke that causes schistosomiasis. Current schistosomiasis control strategies are mainly based on chemotherapy, but many researchers believe that the best long-term strategy to control disease is a combination of drug treatment and immunization with an anti-schistos... | Schistosomiasis mainly occurs in developing countries and is the most important human helminth infection in terms of global mortality. This parasitic disease affects more than 200 million people worldwide and causes more than 250,000 deaths per year. Current schistosomiasis control strategies are mainly based on chemot... | Schistosomiasis occurs primarily in developing countries and is the most important human helminth infection in terms of global mortality. This parasitic disease affects more than 200 million people worldwide, causing more than 250,000 deaths per year [1]. Furthermore, schistosomiasis is responsible for the loss of up t... |
10.1371/journal.pntd.0004565 | A Simple and Novel Strategy for the Production of a Pan-specific Antiserum against Elapid Snakes of Asia | Snakebite envenomation is a serious medical problem in many tropical developing countries and was considered by WHO as a neglected tropical disease. Antivenom (AV), the rational and most effective treatment modality, is either unaffordable and/or unavailable in many affected countries. Moreover, each AV is specific to ... | Antivenom is the most effective treatment modality for snake envenoming. However, they are specific and effective against only one or a few snake venoms. Production of antivenom against many snake species covering a wide geographic area of some countries or regions e.g., Asia and Africa, is not yet possible. This study... | Snake envenoming is an important medical problem in various developing countries of Asia and Africa [1, 2]. It has been estimated that at least 1.2 million people are affected annually with about 20,000 deaths [3]; however these figures likely represent merely the tip of the iceberg as a result of poor epidemiological ... |
10.1371/journal.pgen.1006495 | Meta-GWAS Accuracy and Power (MetaGAP) Calculator Shows that Hiding Heritability Is Partially Due to Imperfect Genetic Correlations across Studies | Large-scale genome-wide association results are typically obtained from a fixed-effects meta-analysis of GWAS summary statistics from multiple studies spanning different regions and/or time periods. This approach averages the estimated effects of genetic variants across studies. In case genetic effects are heterogeneou... | Large-scale genome-wide association studies are uncovering the genetic architecture of traits which are affected by many genetic variants. In such efforts, one typically meta-analyzes association results from multiple studies spanning different regions and/or time periods. Results from such efforts do not yet capture a... | Large-scale GWAS efforts are rapidly elucidating the genetic architecture of polygenic traits, including anthropometrics [1, 2] and diseases [3–5], as well as behavioral and psychological outcomes [6–8]. These efforts have led to new biological insights, therapeutic targets, and polygenic scores (PGS), and help to unde... |
10.1371/journal.ppat.1004893 | Circumventing Y. pestis Virulence by Early Recruitment of Neutrophils to the Lungs during Pneumonic Plague | Pneumonic plague is a fatal disease caused by Yersinia pestis that is associated with a delayed immune response in the lungs. Because neutrophils are the first immune cells recruited to sites of infection, we investigated the mechanisms responsible for their delayed homing to the lung. During the first 24 hr after pulm... | The pathogen Yersinia pestis is the causative agent of pneumonic plague, as well as a potential bioweapon. The nature of this disease involves an initial non-inflammatory phase where the influx of neutrophils to the lungs is suppressed, allowing bacterial propagation in this organ. Using the mouse model of pneumonic pl... | The recruitment of neutrophils is a fundamental component of the initial phase of the innate immune response to bacterial lung infections, as demonstrated by the selective depletion of neutrophils and the consequences on pathogen clearance from the lungs [1]. In response to infection, neutrophils are mobilized from the... |
10.1371/journal.pcbi.1006793 | Available energy fluxes drive a transition in the diversity, stability, and functional structure of microbial communities | A fundamental goal of microbial ecology is to understand what determines the diversity, stability, and structure of microbial ecosystems. The microbial context poses special conceptual challenges because of the strong mutual influences between the microbes and their chemical environment through the consumption and prod... | The diversity, stability and functional structure of microbial communities have dramatic effects on the health of humans and of ecosystems. The complexity of these communities has so far precluded the development of a general predictive model that would capture the dependence of these features on environmental conditio... | Microbial communities inhabit every corner of our planet, from our own nutrient-rich guts to the remote depths of the ocean floor. Different environments harbor very different levels of microbial diversity: in some samples of non-saline water at mild temperature and pH, nearly 3,000 coexisting types of bacteria can be ... |
10.1371/journal.pbio.1001497 | Indirect Evolution of Hybrid Lethality Due to Linkage with Selected Locus in Mimulus guttatus | Most species are superbly and intricately adapted to the environments in which they live. Adaptive evolution by natural selection is the primary force shaping biological diversity. Differences between closely related species in ecologically selected characters such as habitat preference, reproductive timing, courtship ... | Adaptive evolution by natural selection is the primary force generating biological diversity. A critical question is whether the evolution of hybrid incompatibility, which is essential for the maintenance of species diversity, is caused by adaptive evolution. In this article, we investigate one of the most widely cited... | Adaptation to local environmental conditions by natural selection is the primary cause of evolutionary change in natural populations. Ecological adaptation can cause reproductive isolation when selection acts on traits that influence the likelihood of intermating in nature, such as habitat preference, reproductive timi... |
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