doi stringlengths 28 28 | title stringlengths 19 311 | abstract stringlengths 217 5.08k | plain language summary stringlengths 115 4.83k | article stringlengths 3.87k 161k |
|---|---|---|---|---|
10.1371/journal.pntd.0001336 | Vegetation and the Importance of Insecticide-Treated Target Siting for Control of Glossina fuscipes fuscipes | Control of tsetse flies using insecticide-treated targets is often hampered by vegetation re-growth and encroachment which obscures a target and renders it less effective. Potentially this is of particular concern for the newly developed small targets (0.25 high × 0.5 m wide) which show promise for cost-efficient contr... | Sleeping Sickness (Human African Trypanosomiasis) is a serious threat to health and development in sub-Saharan Africa. Due to lack of vaccines and prophylactic drugs, vector control is the only method of disease prevention. Small (0.25×0.5 m) insecticide-treated targets have been shown to be cost-efficient for several ... | The major vectors of Human African Trypanosomiasis (HAT) are in the Palpalis group tsetse flies, especially the G. fuscipes subspecies, which are responsible for transmission of >90% of reported HAT cases [1], [2]. In the present situation with limited drug and no vaccine availability, vector control remains an importa... |
10.1371/journal.pbio.0060068 | Functional Adaptation of a Plant Receptor- Kinase Paved the Way for the Evolution of Intracellular Root Symbioses with Bacteria | Nitrogen-fixing root nodule symbioses (RNS) occur in two major forms—Actinorhiza and legume-rhizobium symbiosis—which differ in bacterial partner, intracellular infection pattern, and morphogenesis. The phylogenetic restriction of nodulation to eurosid angiosperms indicates a common and recent evolutionary invention, b... | As an adaptation to nutrient limitations in terrestrial ecosystems, most plants form Arbuscular Mycorrhiza (AM), which is a symbiotic relationship between phosphate-delivering fungi and plant roots that dates back to the earliest land plants. More recently, a small group including the legumes and close relatives has ev... | Nitrogen limits plant growth in many terrestrial ecosystems. Evolutionary adaptations to this constraint include symbiotic associations with bacteria that are capable of converting atmospheric nitrogen into ammonium. Extracellular associations of plants with diverse groups of nitrogen-fixing bacteria are phylogenetical... |
10.1371/journal.pgen.1006072 | Keap1-Independent Regulation of Nrf2 Activity by Protein Acetylation and a BET Bromodomain Protein | Mammalian BET proteins comprise a family of bromodomain-containing epigenetic regulators with complex functions in chromatin organization and gene regulation. We identified the sole member of the BET protein family in Drosophila, Fs(1)h, as an inhibitor of the stress responsive transcription factor CncC, the fly orthol... | Nrf2-related transcription factors regulate gene expression programs that protect organisms against chemical or oxidative stress. Nrf2-activating drugs hold promise for the treatment of diseases that are connected to oxidative stress or inflammation. We identified Fs(1)h, a bromodomain-containing BET protein, as a nega... | Nrf2 transcription factors are critically important for the health, homeostasis and longevity of multicellular organisms [1–3]. When cells are confronted with oxidative or chemical stress, Nrf2 stimulates the expression of gene products that protect cell integrity including antioxidants, redox regulators, phase II deto... |
10.1371/journal.pntd.0000618 | Complete In Vitro Life Cycle of Trypanosoma congolense: Development of Genetic Tools | Animal African trypanosomosis, a disease mainly caused by the protozoan parasite Trypanosoma congolense, is a major constraint to livestock productivity and has a significant impact in the developing countries of Africa. RNA interference (RNAi) has been used to study gene function and identify drug and vaccine targets ... | Trypanosoma congolense is a parasite responsible for severe disease of African livestock. Its life cycle is complex and divided into two phases, one in the tsetse fly vector and one in the bloodstream of the mammalian host. Molecular tools for gene function analyses in parasitic organisms are essential. Previous studie... | Animal African Trypanosomosis (AAT) is a severe disease caused by several species of African trypanosomes, flagellate protozoan parasites transmitted by an insect fly vector. It affects domestic livestock in sub-Saharan Africa and consequently has a severe economic impact [1]–[3]. AAT is widely spread affecting 40 coun... |
10.1371/journal.ppat.1001047 | Bacteriophage Lysin Mediates the Binding of Streptococcus mitis to Human Platelets through Interaction with Fibrinogen | The binding of bacteria to human platelets is a likely central mechanism in the pathogenesis of infective endocarditis. We have previously found that platelet binding by Streptococcus mitis SF100 is mediated by surface components encoded by a lysogenic bacteriophage, SM1. We now demonstrate that SM1-encoded lysin contr... | The binding of bacteria to human platelets is thought to be a central event in the development of endocarditis (a life-threatening cardiovascular infection). We have previously found that platelet binding by Streptococcus mitis is mediated by surface components encoded by a bacteriophage contained within the host bacte... | The pathogenesis of infective endocarditis is a complex process, involving numerous host-pathogen interactions [1], [2]. A key interaction for disease establishment and progression is the binding of microbes to human components, including platelets, fibrinogen, fibrin, and fibronectin [3], [4], [5], [6], [7], [8]. Alth... |
10.1371/journal.pgen.1002604 | Gene Reactivation by 5-Aza-2′-Deoxycytidine–Induced Demethylation Requires SRCAP–Mediated H2A.Z Insertion to Establish Nucleosome Depleted Regions | 5-Aza-2′-deoxycytidine, approved by the FDA for the treatment of myelodysplastic syndrome (MDS), is incorporated into the DNA of dividing cells where it specifically inhibits DNA methylation by forming covalent complexes with the DNA methyltransferases (DNMTs). In an effort to study the correlations between DNA methyla... | Epigenetic changes, which include chemical modifications to the DNA and changes in the proteins that package DNA to fit into a cell, play an important role in gene expression regulation. The fact that a number of abnormal epigenetic changes that lead to the silencing of genes occur during tumorigenesis has prompted the... | The eukaryotic genome is compacted into chromatin and associated proteins. The fundamental repeating unit of chromatin is the nucleosome, which contains ∼147 bp of DNA wrapped around a histone protein octamer [1]. However, chromatin conformations change during various cellular processes, such as the cell cycle, transcr... |
10.1371/journal.pntd.0006248 | Host preferences support the prominent role of Hyalomma ticks in the ecology of Crimean-Congo hemorrhagic fever | Crimean-Congo hemorrhagic fever virus (CCHFV) is a tick-borne zoonotic agent that is maintained in nature in an enzootic vertebrate-tick-vertebrate cycle. Hyalomma genus ticks have been implicated as the main CCHFV vector and are key in maintaining silent endemic foci. However, what contributes to their central role in... | Crimean-Congo hemorrhagic fever virus (CCHFV), a cause of severe hemorragic disease in humans, is maintained in nature in a tick-vertebrate-tick enzootic cycle characterized by silent persistence of endemic foci with intermittent epidemics. Most studies support ticks of the genus Hyalomma as the main CCHFV vectors, but... | Crimean-Congo hemorrhagic fever (CCHF) is a tick-borne zoonotic disease seen exclusively in humans that can progress from mild, non-specific signs to a severe and fatal hemorrhagic disease. The etiologic agent, Crimean-Congo hemorrhagic fever virus (CCHFV; family Nairoviridae, genus Orthonairovirus), is transmitted to ... |
10.1371/journal.pcbi.1003408 | Searching for Collective Behavior in a Large Network of Sensory Neurons | Maximum entropy models are the least structured probability distributions that exactly reproduce a chosen set of statistics measured in an interacting network. Here we use this principle to construct probabilistic models which describe the correlated spiking activity of populations of up to 120 neurons in the salamande... | Sensory neurons encode information about the world into sequences of spiking and silence. Multi-electrode array recordings have enabled us to move from single units to measuring the responses of many neurons simultaneously, and thus to ask questions about how populations of neurons as a whole represent their input sign... | Physicists have long hoped that the functional behavior of large, highly interconnected neural networks could be described by statistical mechanics [1]–[3]. The goal of this effort has been not to simulate the details of particular networks, but to understand how interesting functions can emerge, collectively, from lar... |
10.1371/journal.ppat.1000062 | A Cysteine Protease Is Critical for Babesia spp. Transmission in Haemaphysalis Ticks | Vector ticks possess a unique system that enables them to digest large amounts of host blood and to transmit various animal and human pathogens, suggesting the existence of evolutionally acquired proteolytic mechanisms. We report here the molecular and reverse genetic characterization of a multifunctional cysteine prot... | Ticks are important ectoparasites among the blood-feeding arthropods and serve as vectors of many deadly diseases of humans and animals. Of tick-transmitted pathogens, Babesia, an intracellular haemoprotozoan parasite causing a malaria-like disease, called babesiosis, gain increasing interest due to its zoonotic signif... | The ixodid ticks are obligate hematophagous organisms that belong to the phylum Arthropda, and are classified with spiders and scorpions in the class Arachnida [1]. Ticks are long-term blood-pool feeders, while mosquitoes are short-term vessel-feeders, and the process of blood digestion in ticks differs mechanistically... |
10.1371/journal.pcbi.1004010 | Exploring O2 Diffusion in A-Type Cytochrome c Oxidases: Molecular Dynamics Simulations Uncover Two Alternative Channels towards the Binuclear Site | Cytochrome c oxidases (Ccoxs) are the terminal enzymes of the respiratory chain in mitochondria and most bacteria. These enzymes couple dioxygen (O2) reduction to the generation of a transmembrane electrochemical proton gradient. Despite decades of research and the availability of a large amount of structural and bioch... | Cytochrome c oxidases (Ccoxs), the terminal enzymes of the respiratory electron transport chain in eukaryotes and many prokaryotes, are key enzymes in aerobic respiration. These proteins couple the reduction of molecular dioxygen to water with the creation of a transmembrane electrochemical proton gradient. Over the la... | Cytochrome c oxidases (Ccoxs) are the terminal enzymes of the respiratory chain in eukaryotes and in aerobic prokaryotes (reviewed in [1]). These integral membrane proteins belong to the heme-copper oxidases superfamily and couple dioxygen (O2) reduction to the translocation of protons across the membrane. Ccox takes u... |
10.1371/journal.ppat.1001220 | HIV Capsid is a Tractable Target for Small Molecule Therapeutic Intervention | Despite a high current standard of care in antiretroviral therapy for HIV, multidrug-resistant strains continue to emerge, underscoring the need for additional novel mechanism inhibitors that will offer expanded therapeutic options in the clinic. We report a new class of small molecule antiretroviral compounds that dir... | Although the current standard of care for Human Immunodeficiency Virus (HIV) is high, viral resistance has emerged to every drug currently in the clinic, in some cases rendering the entire class ineffective for patients. A new class of antiretroviral drugs would be effective against strains of HIV-1 that are resistant ... | Highly active antiretroviral therapies (HAART) against human immunodeficiency virus type 1 (HIV-1) have proven in recent years to be extremely effective at reducing viral load and significantly delaying disease progression [1]. However, there remains a pressing need to discover and develop new classes of HIV inhibitors... |
10.1371/journal.ppat.0030077 | Epigenomic Modifications Predict Active Promoters and Gene Structure in Toxoplasma gondii | Mechanisms of gene regulation are poorly understood in Apicomplexa, a phylum that encompasses deadly human pathogens like Plasmodium and Toxoplasma. Initial studies suggest that epigenetic phenomena, including histone modifications and chromatin remodeling, have a profound effect upon gene expression and expression of ... | Apicomplexan parasites, including Toxoplasma gondii, are responsible for a variety of deadly infections, but little is understood about how these important pathogens regulate gene expression. Initial studies suggest that alterations in chromatin structure regulate expression of virulence traits. To understand the relat... | Toxoplasma gondii is an obligate intracellular apicomplexan parasite responsible for encephalitis in immunocompromised individuals and birth defects when a fetus is exposed in utero [1,2]. The life cycle of T. gondii is complex, with multiple differentiation steps that are critical to survival of the parasite in its hu... |
10.1371/journal.pgen.1003962 | Translation Initiation Factors eIF3 and HCR1 Control Translation Termination and Stop Codon Read-Through in Yeast Cells | Translation is divided into initiation, elongation, termination and ribosome recycling. Earlier work implicated several eukaryotic initiation factors (eIFs) in ribosomal recycling in vitro. Here, we uncover roles for HCR1 and eIF3 in translation termination in vivo. A substantial proportion of eIF3, HCR1 and eukaryotic... | Protein synthesis (translation) utilizes genetic information carriers, mRNAs, as templates for the production of proteins of various cellular functions. Typically it is divided into four phases: initiation, elongation, termination and ribosomal recycling. In this article we argue that the strict mechanistic separation ... | Protein synthesis or mRNA translation is a complex and highly conserved process that can be separated into initiation, elongation, termination and ribosome recycling phases. Although these four phases are distinct in time, there is a longstanding notion for some form of communication among them. Notably, several initia... |
10.1371/journal.pgen.1000090 | Combined Analysis of Murine and Human Microarrays and ChIP Analysis Reveals Genes Associated with the Ability of MYC To Maintain Tumorigenesis | The MYC oncogene has been implicated in the regulation of up to thousands of genes involved in many cellular programs including proliferation, growth, differentiation, self-renewal, and apoptosis. MYC is thought to induce cancer through an exaggerated effect on these physiologic programs. Which of these genes are respo... | The targeted inactivation of oncogenes may be a specific and effective treatment of cancer. However, how oncogene inactivation leads to tumor regression is not clear. Previously, we have shown that even the brief inactivation of the MYC oncogene can result in the sustained regression of at least some tumors. To underst... | Overexpression of MYC is one of the most frequent events in human tumorigenesis [1]. MYC overexpression is thought to induce tumorigenesis by causing inappropriate gene expression resulting in autonomous cellular growth, proliferation, and the inhibition of cellular differentiation [2],[3]. Many laboratories have condi... |
10.1371/journal.pntd.0003587 | Head and Neck Mycetoma: The Mycetoma Research Centre Experience | Mycetoma is a unique neglected tropical disease which is endemic in what is known as the “mycetoma belt”. The disease has many devastating impacts on patients and communities in endemic area and is characterised by massive deformity, destruction and disability. Mycetoma is commonly seen in the foot and hand and less fr... | Although head and neck mycetoma is a rare disease entity yet it is a dreadful disease for the patient, the family and the treating physician. It is potentially fatal and the most challenging to treat. The current study highlighted that, most patients were young adult males, from rural areas of the Sudan and of low soci... | Mycetoma is one of the neglected tropical diseases, characterised by massive deformity, disability and can be fatal if not managed properly and timely [1–3]. It is a chronic, specific, granulomatous, progressive subcutaneous inflammatory disease that spreads to involve the skin, deep structures and bones [4,5]. The dis... |
10.1371/journal.pgen.1000328 | Arabidopsis CULLIN3 Genes Regulate Primary Root Growth and Patterning by Ethylene-Dependent and -Independent Mechanisms | CULLIN3 (CUL3) together with BTB-domain proteins form a class of Cullin-RING ubiquitin ligases (called CRL3s) that control the rapid and selective degradation of important regulatory proteins in all eukaryotes. Here, we report that in the model plant Arabidopsis thaliana, CUL3 regulates plant growth and development, no... | Ubiquitin-mediated proteolysis plays a central role in controlling intracellular levels of essential regulatory molecules in all eukaryotic organisms. This protein degradation pathway has a large number of components, including hundreds of ubiquitin protein ligases (E3s) that are predicted to have regulatory roles in c... | Regulation of protein stability through the ubiquitin proteasome system (UPS) is now considered as a major mechanism underlying many cellular and organismal processes, such as cell division, DNA repair, quality control of newly produced proteins, developmental and immune defense pathways, and in plants, light and phyto... |
10.1371/journal.pntd.0005708 | Chronic Trichuris muris infection causes neoplastic change in the intestine and exacerbates tumour formation in APC min/+ mice | Incidences of infection-related cancers are on the rise in developing countries where the prevalence of intestinal nematode worm infections are also high. Trichuris muris (T. muris) is a murine gut-dwelling nematode that is the direct model for human T. trichiura, one of the major soil-transmitted helminth infections o... | It is estimated that now 2 billion people currently live with chronic parasitic worm infections. As the incidences of cancer increase worldwide, the importance of these chronic inflammatory conditions on the development of cancer becomes more important. Several bacterial, viral and parasitic infections are already know... | Colon cancer is one of the leading causes of death within the western world and prevalence in developing countries has increased in the last decade [1]. There exists a strong link between inflammation and cancer [2]. This is emphasized in the colon where individuals with inflammatory bowel disease are predisposed to th... |
10.1371/journal.pgen.1000871 | Mislocalization of XPF-ERCC1 Nuclease Contributes to Reduced DNA Repair in XP-F Patients | Xeroderma pigmentosum (XP) is caused by defects in the nucleotide excision repair (NER) pathway. NER removes helix-distorting DNA lesions, such as UV–induced photodimers, from the genome. Patients suffering from XP exhibit exquisite sun sensitivity, high incidence of skin cancer, and in some cases neurodegeneration. Th... | XPF-ERCC1 is a nuclease that plays a critical role in DNA repair. Mutations in XPF are linked to xeroderma pigmentosum, characterized by sun sensitivity, high incidence of skin cancer, and neurodegeneration, or XFE progeroid syndrome, a disease of accelerated aging. Herein we report the unexpected finding that mutation... | Xeroderma pigmentosum (XP) is a rare autosomal recessive disease characterized by photosensitivity and a greater than a 1000-fold increased risk of skin cancer in sun-exposed areas of the skin [1]. In approximately 20% of patients, there is also progressive neurodegeneration leading to loss of coordinated motion, visio... |
10.1371/journal.pbio.0060060 | Phenotypic Mismatches Reveal Escape from Arms-Race Coevolution | Because coevolution takes place across a broad scale of time and space, it is virtually impossible to understand its dynamics and trajectories by studying a single pair of interacting populations at one time. Comparing populations across a range of an interaction, especially for long-lived species, can provide insight ... | Arms races between natural enemies can lead to the rapid evolution of extreme traits, high degrees of specialization, and the formation of new species. They also serve as the ecological model for the evolution of drug resistance by diseases and for host–pathogen interactions in general. Revealing who wins these arms ra... | The process of coevolution plays out on a wide spatial and temporal stage [1]. At any point in space and time, we might observe a given pair of interacting populations occupying any position within the range of their coevolutionary trajectory: from the early stages of escalation, to equilibrium, to cost-induced descala... |
10.1371/journal.pgen.1002776 | The CCR4-NOT Complex Is Implicated in the Viability of Aneuploid Yeasts | To identify the genes required to sustain aneuploid viability, we screened a deletion library of non-essential genes in the fission yeast Schizosaccharomyces pombe, in which most types of aneuploidy are eventually lethal to the cell. Aneuploids remain viable for a period of time and can form colonies by reducing the ex... | Aneuploidy is a major cause of abortive development and is implicated in tumorigenesis in humans. Recent studies revealed that the increased need for protein degradation might account for the detrimental effects of aneuploidy on a cell. Here, we investigated the genetic systems responsible for aneuploid viability. Usin... | Aneuploidy is defined as a deviation from a multiple of the basic chromosome number and is a major cause of developmental defects in animals and humans [1]. Aneuploidy is implicated in tumorigenesis [2]. Aneuploidy is caused by errors in chromosome transmission and generally occurs at a low rate, but rates increase whe... |
10.1371/journal.pgen.1002408 | Drosophila Ribosomal Protein Mutants Control Tissue Growth Non-Autonomously via Effects on the Prothoracic Gland and Ecdysone | The ribosome is critical for all aspects of cell growth due to its essential role in protein synthesis. Paradoxically, many Ribosomal proteins (Rps) act as tumour suppressors in Drosophila and vertebrates. To examine how reductions in Rps could lead to tissue overgrowth, we took advantage of the observation that an RpS... | Ribosomes are required for protein synthesis, which is essential for cell growth and division, thus mutations that reduce Rp expression would be expected to limit cell growth. Paradoxically, heterozygous deletion or mutation of certain Rps can actually promote growth and proliferation and in some cases bestow predispos... | One of the early phenotypic classes identified in Drosophila was the Minutes, which were classified based on the heterozygous adults having short slender bristles on the body, a generally smaller body size and a delay in the onset of metamorphosis [1]. It has long been considered that understanding the basis for these ... |
10.1371/journal.pntd.0003353 | Genetic Diversity and Population Structure of Trypanosoma brucei in Uganda: Implications for the Epidemiology of Sleeping Sickness and Nagana | While Human African Trypanosomiasis (HAT) is in decline on the continent of Africa, the disease still remains a major health problem in Uganda. There are recurrent sporadic outbreaks in the traditionally endemic areas in south-east Uganda, and continued spread to new unaffected areas in central Uganda. We evaluated the... | Human African Trypanosomiasis (HAT) is a major health problem in Uganda, as there are recurrent sporadic outbreaks of the disease in traditionally endemic areas in south-east Uganda, and continued spread to new unaffected areas in central Uganda. In this study, we evaluate the evolutionary dynamics underpinning the ori... | Trypanosoma brucei is a unicellular protozoan parasite, which causes human and animal trypanosomiasis in tropical Africa, transmitted by tsetse flies (Glossina spp). Trypanosoma brucei consists of three subspecies: T. b. brucei (Tbb), T. b. gambiense (Tbg), and T. b. rhodesiense (Tbr) that are morphologically indisting... |
10.1371/journal.pgen.1007711 | Gata4 regulates hedgehog signaling and Gata6 expression for outflow tract development | Dominant mutations of Gata4, an essential cardiogenic transcription factor (TF), were known to cause outflow tract (OFT) defects in both human and mouse, but the underlying molecular mechanism was not clear. In this study, Gata4 haploinsufficiency in mice was found to result in OFT defects including double outlet right... | Gata4 is an important transcription factor that regulates the development of the heart. Human possessing a single copy of Gata4 mutation display congenital heart defects (CHD), including double outlet right ventricle (DORV). DORV is an alignment problem in which both the Aorta and Pulmonary Artery originate from the ri... | Congenital Heart Defects (CHDs) occur in approximately 1% of live births [1] and are the most common serious birth defects in humans [2, 3]. Approximately one third of the CHDs involve malformations of the outflow tract (OFT), which leads to significant morbidity and mortality of children and adults [4]. Multiple OFT a... |
10.1371/journal.pntd.0004387 | A Sero-epidemiological Approach to Explore Transmission of Mycobacterium ulcerans | The debilitating skin disease Buruli ulcer (BU) is caused by infection with Mycobacterium ulcerans. While various hypotheses on potential reservoirs and vectors of M. ulcerans exist, the mode of transmission has remained unclear. Epidemiological studies have indicated that children below the age of four are less expose... | Buruli ulcer is a debilitating skin disease caused by Mycobacterium ulcerans. Although the understanding of this enigmatic pathogen has improved after decades of research, the mode of transmission is yet to be fully elucidated. Recent epidemiological studies have shown an underrepresentation of Buruli ulcer cases in ch... | Buruli ulcer (BU) is a neglected tropical skin disease presenting with a wide range of cutaneous manifestations, from non-ulcerated nodules, plaques or oedema to characteristic necrotizing ulcers [1]. While BU cases have been reported in more than 30 countries worldwide, most patients are from infection foci located in... |
10.1371/journal.pcbi.1003140 | Distinct Allelic Patterns of Nanog Expression Impart Embryonic Stem Cell Population Heterogeneity | Nanog is a principal pluripotency regulator exhibiting a disperse distribution within stem cell populations in vivo and in vitro. Increasing evidence points to a functional role of Nanog heterogeneity on stem cell fate decisions. Allelic control of Nanog gene expression was reported recently in mouse embryonic stem cel... | Nanog is a key factor influencing the decision of a stem cell to remain pluripotent or differentiate. Each embryonic stem cell (ESC) in a population exhibits fluctuating Nanog levels resulting in heterogeneity which affects cell fate specification. The allelic regulation of Nanog was demonstrated recently but its impli... | Nanog is a principal pluripotency regulator of embryonic stem cells (ESCs) in the early blastocyst. Mouse ESC (mESC) self-renewal is supported by Nanog in the absence of leukemia inhibitory factor (LIF) [1], [2] while Nanog knockdowns experience changes in global gene expression and loss of pluripotency [3]–[5]. In hum... |
10.1371/journal.pcbi.1002432 | Feedforward Inhibition and Synaptic Scaling – Two Sides of the Same Coin? | Feedforward inhibition and synaptic scaling are important adaptive processes that control the total input a neuron can receive from its afferents. While often studied in isolation, the two have been reported to co-occur in various brain regions. The functional implications of their interactions remain unclear, however.... | The inputs a neuron receives from its presynaptic partners strongly fluctuate as a result of either varying sensory information or ongoing intrinsic activity. To represent this wide range of signals effectively, neurons use various mechanisms that regulate the total input they receive. On the one hand, feedforward inhi... | As part of an ever-changing world, brain activity changes continuously. The fraction of neurons active in a region at each given moment fluctuates significantly driven by changes in the environment and intrinsic dynamics. Ideally, regions receiving this activity as input should be able to represent incoming signals rel... |
10.1371/journal.pgen.1006092 | Identification of Multiple Proteins Coupling Transcriptional Gene Silencing to Genome Stability in Arabidopsis thaliana | Eukaryotic genomes are regulated by epigenetic marks that act to modulate transcriptional control as well as to regulate DNA replication and repair. In Arabidopsis thaliana, mutation of the ATXR5 and ATXR6 histone methyltransferases causes reduction in histone H3 lysine 27 monomethylation, transcriptional upregulation ... | In eukaryotic genomes cellular processes such as transcription and replication need to be tightly controlled in order to promote genomic stability and prevent deleterious mutations. In Arabidopsis thaliana, two redundant histone methyltransferases, ATXR5 and ATXR6, are responsible for the deposition of a silencing epig... | The genome represents a biological entity that is necessarily static yet retains a level of plasticity. Cells must faithfully replicate their genomes to avoid deleterious mutations, but also must be responsive to external stimuli. Eukaryotes have evolved multiple layers of epigenetic regulation that allow the genome to... |
10.1371/journal.pcbi.1006227 | General differential Hebbian learning: Capturing temporal relations between events in neural networks and the brain | Learning in biologically relevant neural-network models usually relies on Hebb learning rules. The typical implementations of these rules change the synaptic strength on the basis of the co-occurrence of the neural events taking place at a certain time in the pre- and post-synaptic neurons. Differential Hebbian learnin... | Which learning rules can be used to capture the temporal relations between activation events involving pairs of neurons in artificial neural networks? Previous computational research proposed various differential Hebbian learning (DHL) rules that rely on the activation of neurons and time derivatives of their activatio... | Most learning rules used in bio-inspired or bio-constrained neural-network models of brain derive from Hebb’s idea [1, 2] for which “cells that fire together, wire together” [3]. The core of the mathematical implementations of this idea is multiplication. This captures the correlation between the pre- and post-synaptic... |
10.1371/journal.pgen.1000236 | Two Pathways Recruit Telomerase to Saccharomyces cerevisiae Telomeres | The catalytic subunit of yeast telomerase, Est2p, is a telomere associated throughout most of the cell cycle, while the Est1p subunit binds only in late S/G2 phase, the time of telomerase action. Est2p binding in G1/early S phase requires a specific interaction between telomerase RNA (TLC1) and Ku80p. Here, we show tha... | Duplication of linear DNA is complicated by the fact that conventional DNA polymerases cannot copy their ends. From yeasts to humans, replication of DNA ends, called telomeres, is accomplished by a telomere-dedicated reverse transcriptase called telomerase that uses its RNA subunit as a template. We show that there are... | Telomerase is a specialized reverse transcriptase that lengthens the 3′ end of telomeric DNA. In Saccharomyces cerevisiae, the template for telomere elongation is a short stretch within the 1158 base TLC1 telomerase RNA. Est2p is the S. cerevisiae telomerase catalytic subunit, while Est1p and Est3p are two telomerase s... |
10.1371/journal.pgen.1008057 | Cellular response to small molecules that selectively stall protein synthesis by the ribosome | Identifying small molecules that inhibit protein synthesis by selectively stalling the ribosome constitutes a new strategy for therapeutic development. Compounds that inhibit the translation of PCSK9, a major regulator of low-density lipoprotein cholesterol, have been identified that reduce LDL cholesterol in preclinic... | A fundamentally new approach to treat human diseases caused by “undruggable” proteins would be to use small molecules to selectively inhibit their synthesis by the ribosome. Here we compare two related compounds (PF846, PF8503) that selectively stall human translation to the effects of a more general translation inhibi... | Proteins are the main druggable therapeutic targets for the treatment of human diseases, ranging from metabolic disease, to cancer and dementia [1]. Most therapeutic strategies consist of inactivating key protein enzymatic or binding activities by using small molecules or antibodies. However, many proteins remain “undr... |
10.1371/journal.pgen.1003941 | Activin Signaling Targeted by Insulin/dFOXO Regulates Aging and Muscle Proteostasis in Drosophila | Reduced insulin/IGF signaling increases lifespan in many animals. To understand how insulin/IGF mediates lifespan in Drosophila, we performed chromatin immunoprecipitation-sequencing analysis with the insulin/IGF regulated transcription factor dFOXO in long-lived insulin/IGF signaling genotypes. Dawdle, an Activin liga... | It is widely known that reduced insulin/IGF signaling slows aging in many contexts. This process requires the forkhead transcription factor (FOXO). FOXO modulates the expression of many genes, and the list of those associated with slow aging is impressive. But there are few data indicating the mechanisms or genes throu... | Reduced insulin/IGF-1 signaling increases the lifespan of nematodes, flies and rodents [1], [2]. In Caenorhabditis elegans, mutants in insulin-like receptor daf-2 live twice as long as wild type [3], [4]. Mutation of insulin receptor InR and insulin receptor substrate (chico) increase adult lifespan in the fruit fly Dr... |
10.1371/journal.pcbi.1005291 | A General Shear-Dependent Model for Thrombus Formation | Modeling the transport, activation, and adhesion of platelets is crucial in predicting thrombus formation and growth following a thrombotic event in normal or pathological conditions. We propose a shear-dependent platelet adhesive model based on the Morse potential that is calibrated by existing in vivo and in vitro ex... | Hemostasis (thrombus formation) is the normal physiological response that prevents significant blood loss after vascular injury. The resulting clots can form under different flow conditions in the veins as well as the arteries. The excessive and undesirable formation of clots (i.e., thrombosis) in our circulatory syste... | Platelets are fundamental to both hemostasis and thrombosis in many vascular diseases, including abdominal aortic aneurysm (AAA), thoracic aortic aneurysm and dissection (TAAD), and carotid atherosclerosis [1–3]. Normal platelets do not interact with the healthy artery wall. In cases of endothelial injury or exposure o... |
10.1371/journal.ppat.1004856 | An Ultrasensitive Mechanism Regulates Influenza Virus-Induced Inflammation | Influenza viruses present major challenges to public health, evident by the 2009 influenza pandemic. Highly pathogenic influenza virus infections generally coincide with early, high levels of inflammatory cytokines that some studies have suggested may be regulated in a strain-dependent manner. However, a comprehensive ... | Vaccines suffice for protecting public health against seasonal influenza viruses, but when unexpected strains appear against which the vaccine does not confer protection, alternative treatments are necessary. In this work, we used gene expression and virus growth data from influenza-infected mice to determine how moder... | Invading pathogens induce acute inflammation when molecular signatures are detected by pattern recognition receptors (PRRs; e.g., RIG-I like receptors [RLRs] and Toll-like receptors [TLRs]) expressed on tissue-resident immune cells and non-immune cell types. PRR ligation triggers innate immune responses and leads to th... |
10.1371/journal.pgen.1004455 | The EJC Binding and Dissociating Activity of PYM Is Regulated in Drosophila | In eukaryotes, RNA processing events in the nucleus influence the fate of transcripts in the cytoplasm. The multi-protein exon junction complex (EJC) associates with mRNAs concomitant with splicing in the nucleus and plays important roles in export, translation, surveillance and localization of mRNAs in the cytoplasm. ... | The multi-protein exon junction complex (EJC) is deposited at exon-exon junctions on mRNAs upon splicing. EJCs, with Y14, Mago, eIF4AIII and Barentsz proteins at their core, are landmarks of the nuclear history of RNAs and play important roles in their post-transcriptional regulation. In mammalian cells, the Y14-Mago i... | In eukaryotes, post-transcriptional regulation of gene expression plays important roles in development and differentiation. These include RNA processing events in the nucleus, such as splicing, which also affects 3′ end processing of the RNA, mRNA export, localization, translational enhancement and decay [1]–[5]. The m... |
10.1371/journal.pntd.0004312 | 3D Architecture of the Trypanosoma brucei Flagella Connector, a Mobile Transmembrane Junction | Cellular junctions are crucial for the formation of multicellular organisms, where they anchor cells to each other and/or supportive tissue and enable cell-to-cell communication. Some unicellular organisms, such as the parasitic protist Trypanosoma brucei, also have complex cellular junctions. The flagella connector (F... | Trypanosoma brucei is an uni-cellular parasite transmitted to humans and cattle by the bloodsucking tsetse fly. Once swimming in the mammalian bloodstream, it causes the devastating African sleeping sickness in humans and nagana in cattle. During its complex life cycle, it undergoes many cell shape changes, which are i... | Cellular junctions are crucial for the formation of tissues, pathogen/host cell interactions and communication between cells, e.g., the plasmodesmata in plants and the gap junctions in animals. However, junctions can also exist within a single cell, such as the top connectors between sterocilia and the kinocilium on ou... |
10.1371/journal.pgen.1005211 | Early Lineage Priming by Trisomy of Erg Leads to Myeloproliferation in a Down Syndrome Model | Down syndrome (DS), with trisomy of chromosome 21 (HSA21), is the commonest human aneuploidy. Pre-leukemic myeloproliferative changes in DS foetal livers precede the acquisition of GATA1 mutations, transient myeloproliferative disorder (DS-TMD) and acute megakaryocytic leukemia (DS-AMKL). Trisomy of the Erg gene is req... | An excess number of genes in trisomy on human chromosome 21 leads to the development of specific diseases in human Down syndrome. An excess copy of the gene, ERG, an ETS family transcription factor, has been implicated in abnormal blood system development in Down syndrome. In this study we show how trisomy of Erg in a ... | Down syndrome (DS) is the commonest human aneuploidy [1]. DS infants with trisomy of human chromosome 21 (HSA21) are uniquely predisposed to a transient myeloproliferative disorder (DS-TMD) and acute megakaryocytic leukemia (DS-AMKL) [2]. DS-TMD, usually characterised by the presence of peripheral immature myeloblasts/... |
10.1371/journal.pbio.1001319 | Competing Sound Sources Reveal Spatial Effects in Cortical Processing | Why is spatial tuning in auditory cortex weak, even though location is important to object recognition in natural settings? This question continues to vex neuroscientists focused on linking physiological results to auditory perception. Here we show that the spatial locations of simultaneous, competing sound sources dra... | When a listener is presented with many sound sources at once, it is easier to understand a particular source when it comes from a different spatial location than the other competing sources. However, past studies of auditory cortex generally find that in response to a single sound source, there is not a precise represe... | Past studies of spatial effects in auditory cortex have focused on how spatial location is encoded. These studies typically find that single-unit spatial tuning in cortex is weak [1]–[4], not topographically organized [5],[6], and not encoded independently of other perceptually important features [7]. There is good evi... |
10.1371/journal.ppat.1004369 | Symbionts Commonly Provide Broad Spectrum Resistance to Viruses in Insects: A Comparative Analysis of Wolbachia Strains | In the last decade, bacterial symbionts have been shown to play an important role in protecting hosts against pathogens. Wolbachia, a widespread symbiont in arthropods, can protect Drosophila and mosquito species against viral infections. We have investigated antiviral protection in 19 Wolbachia strains originating fro... | In recent years it has been discovered that many organisms are infected with bacterial symbionts that protect them against pathogens. Wolbachia is a bacterial symbiont that is found in many species of insects, and several strains are known to protect the insects against viral infection. We took 19 strains of Wolbachia ... | Heritable symbionts are major players in arthropod evolution owing to their high incidence and the diversity of effects they have on their host's phenotype [1]–[3]. Primary (obligate) symbionts are mutualists that play some essential role — typically synthesizing nutrients missing from the insect's diet — and they ofte... |
10.1371/journal.ppat.1007102 | Manganese acquisition is essential for virulence of Enterococcus faecalis | Manganese (Mn) is an essential micronutrient that is not readily available to pathogens during infection due to an active host defense mechanism known as nutritional immunity. To overcome this nutrient restriction, bacteria utilize high-affinity transporters that allow them to compete with host metal-binding proteins. ... | Enterococcus faecalis is a leading cause of hospital-acquired infections that are often difficult to treat due to their exceptional multidrug resistance. Manganese (Mn) is an essential micronutrient for bacterial pathogens during infection. To prevent infection, the host limits Mn bioavailability to invading bacteria i... | While normal residents of the gastrointestinal (GI) tract of animals and humans, enterococci are also the third most frequent cause of hospital-acquired infections and a major threat to public health due to the alarming rise of multidrug-resistant isolates [1]. Enterococcal infections in humans are mainly caused by Ent... |
10.1371/journal.ppat.1002898 | Roles of ATM and ATR-Mediated DNA Damage Responses during Lytic BK Polyomavirus Infection | BK polyomavirus (BKPyV) is an emerging pathogen whose reactivation causes severe disease in transplant patients. Unfortunately, there is no specific anti-BKPyV treatment available, and host cell components that affect the infection outcome are not well characterized. In this report, we examined the relationship between... | BK polyomavirus (BKPyV) is a human pathogen that establishes a persistent sub-clinical infection in healthy humans. When patients are immunosuppressed, particularly in kidney and bone marrow transplantation, the virus can reactivate and result in severe disease. BKPyV-related disease has risen due to the use of newer i... | BK polyomavirus (BKPyV) was first isolated in 1971 from a renal transplant patient [1] and has gained much interest in the past two decades due to its disease prevalence in immunocompromised patients [2]. Infection with BKPyV is ubiquitous in healthy individuals but does not lead to any known clinical disease. Under im... |
10.1371/journal.pbio.2005388 | Centromeric signaling proteins boost G1 cyclin degradation and modulate cell size in budding yeast | Cell size scales with ploidy in a great range of eukaryotes, but the underlying mechanisms remain unknown. Using various orthogonal single-cell approaches, we show that cell size increases linearly with centromere (CEN) copy number in budding yeast. This effect is due to a G1 delay mediated by increased degradation of ... | It has been known for a long time that cells increase their size with the amount of DNA across the whole evolutionary scale. Moreover, within a given species and differentiation status, cells increase their size in an exquisitely proportional manner to the number of chromosomes. This correlation has been observed in fu... | Most cells under unaltered conditions of growth are able to maintain their size within a strict range, and a current view sustains that the cell cycle and cell growth machineries should be interconnected by specific molecular mechanisms ensuring cell size homeostasis [1–5]. Budding yeast cells control their size mainly... |
10.1371/journal.ppat.1005030 | BRCA1 Regulates IFI16 Mediated Nuclear Innate Sensing of Herpes Viral DNA and Subsequent Induction of the Innate Inflammasome and Interferon-β Responses | The innate immune system pattern recognition receptors (PRR) are the first line of host defenses recognizing the various pathogen- or danger-associated molecular patterns and eliciting defenses by regulating the production of pro-inflammatory cytokines such as IL-1β, IL-18 or interferon β (IFN-β). NOD-like receptors (N... | Invasion of a host cell by pathogens, including viruses, is sensed by pattern-recognition receptors resulting in the elicitation of the host innate defenses such as the formation of multi-protein inflammasome complexes, inflammatory IL-1β and IL-18 cytokine production and interferon-β production via the cytoplasmic STI... | Sensing of microbial nucleic acids by pattern-recognition receptors (PRRs) is a crucial step for an effective innate immune response [1]. The best established function of PRRs like NLRPs (NOD-like receptors with PYRIN (PYD) domain) and ALRs (absent in melanoma 2 [AIM2]-like receptors) is their ability to sense pathogen... |
10.1371/journal.pcbi.1003273 | Molecular Mechanical Differences between Isoforms of Contractile Actin in the Presence of Isoforms of Smooth Muscle Tropomyosin | The proteins involved in smooth muscle's molecular contractile mechanism – the anti-parallel motion of actin and myosin filaments driven by myosin heads interacting with actin – are found as different isoforms. While their expression levels are altered in disease states, their relevance to the mechanical interaction of... | Dependent on the required physiological function, smooth muscle executes relatively fast contraction-relaxation cycles or maintains long-term contraction. The proteins driving contraction – amongst them actin, tropomyosin, and the contraction-driving myosin motor – can show small changes in the way they are constructed... | Differential expression of smooth muscle contractile proteins has been associated with organismal development [1], contractile phenotypes [2]–[4], and pathologies, e.g. preterm labour, hypertrophic bladder, or airway hyper-responsiveness [5]–[7]. While the role of the smooth muscle myosin isoforms has been extensively ... |
10.1371/journal.ppat.1003580 | Polydnaviral Ankyrin Proteins Aid Parasitic Wasp Survival by Coordinate and Selective Inhibition of Hematopoietic and Immune NF-kappa B Signaling in Insect Hosts | Polydnaviruses are mutualists of their parasitoid wasps and express genes in immune cells of their Lepidopteran hosts. Polydnaviral genomes carry multiple copies of viral ankyrins or vankyrins. Vankyrin proteins are homologous to IκB proteins, but lack sequences for regulated degradation. We tested if Ichnoviral Vankyr... | Parasitoid wasps are insects whose development takes place within the body of other insects. To survive, wasp larvae must overcome the immune defenses of their hosts. How parasitic wasps overcome host immunity is not fully understood even though we know that different strategies using venoms, virus-like particles, or v... | Parasitic wasps develop within their insect hosts as they devour host bodies. Wasp oviposition in Drosophila larvae simultaneously activates humoral and cellular immune reactions. In a systemic acute inflammatory reaction, humoral antimicrobial secretions and cytokines from the fat body synergize with hematopoietic pro... |
10.1371/journal.pgen.0030077 | Genetic and Physical Mapping of DNA Replication Origins in Haloferax volcanii | The halophilic archaeon Haloferax volcanii has a multireplicon genome, consisting of a main chromosome, three secondary chromosomes, and a plasmid. Genes for the initiator protein Cdc6/Orc1, which are commonly located adjacent to archaeal origins of DNA replication, are found on all replicons except plasmid pHV2. Howev... | Haloferax volcanii is a member of the archaea, which are renowned for thriving in extreme environments. Archaea have circular chromosomes like bacteria but use enzymes similar to those found in eukaryotes to replicate their DNA. Few archaeal species have systems for genetics, and this has limited our understanding of D... | In all prokaryotic organisms, and in certain unicellular eukaryotes, DNA replication is thought to initiate at well-defined chromosomal sites. These origins of replication serve as assembly sites for the protein machinery that unwinds the DNA duplex and initiates bidirectional DNA synthesis [1,2]. Bacterial chromosomes... |
10.1371/journal.pgen.1003473 | Scavenger Receptors Mediate the Role of SUMO and Ftz-f1 in Drosophila Steroidogenesis | SUMOylation participates in ecdysteroid biosynthesis at the onset of metamorphosis in Drosophila melanogaster. Silencing the Drosophila SUMO homologue smt3 in the prothoracic gland leads to reduced lipid content, low ecdysone titers, and a block in the larval–pupal transition. Here we show that the SR-BI family of Scav... | Steroid hormones are cholesterol derivates that control many aspects of animal physiology, including development of the adult organisms, growth, energy storage, and reproduction. In insects, pulses of the steroid hormone ecdysone precede molting and metamorphosis, the regulation of hormonal synthesis being a crucial st... | Larval molting and metamorphosis in Drosophila melanogaster relies on pulses of ecdysteroid hormones. During the larval stages, the prothoracic gland (PG) is the tissue responsible for the synthesis of the steroid hormone ecdysone that is secreted to the hemolymph and converted to 20-hydroxyecdysone (20E) in target tis... |
10.1371/journal.pcbi.1003614 | Reciprocal Regulation as a Source of Ultrasensitivity in Two-Component Systems with a Bifunctional Sensor Kinase | Two-component signal transduction systems, where the phosphorylation state of a regulator protein is modulated by a sensor kinase, are common in bacteria and other microbes. In many of these systems, the sensor kinase is bifunctional catalyzing both, the phosphorylation and the dephosphorylation of the regulator protei... | Bacteria often use two-component systems to sense and respond to environmental changes, which involves autophosphorylation of a sensor kinase and phosphotransfer to a cognate response regulator. However, despite conservation of this ‘classical’ scheme there exist substantial variations in the mechanism of phosphotransf... | Two-component systems (TCSs) are modular signal transduction systems which are utilized by bacteria and other microbes to respond to intracellular or environmental stimuli [1], [2]. ‘Classical’ TCSs consist of a sensor histidine kinase (HK) and a cognate response regulator (RR), which often acts as a transcription fact... |
10.1371/journal.pcbi.1007154 | Resurgent Na+ Current Offers Noise Modulation in Bursting Neurons | Neurons utilize bursts of action potentials as an efficient and reliable way to encode information. It is likely that the intrinsic membrane properties of neurons involved in burst generation may also participate in preserving its temporal features. Here we examined the contribution of the persistent and resurgent comp... | The nervous system extracts meaningful information from natural environments to guide precise behaviors. Sensory neurons encode and relay such complex peripheral information as electrical events, known as action potentials or spikes. The timing intervals between the spikes carry stimulus-relevant information. Therefore... | Real-time signal detection in uncertain settings is a fundamental problem for information and communication systems. Our nervous system performs the daunting task of extracting meaningful information from natural environments and guides precise behaviors. Sensory neurons for instance use efficient coding schemes such a... |
10.1371/journal.ppat.0030110 | Mycobacterium tuberculosis nuoG Is a Virulence Gene That Inhibits Apoptosis of Infected Host Cells | The survival and persistence of Mycobacterium tuberculosis depends on its capacity to manipulate multiple host defense pathways, including the ability to actively inhibit the death by apoptosis of infected host cells. The genetic basis for this anti-apoptotic activity and its implication for mycobacterial virulence hav... | The infection-induced suicide of host cells following invasion by intracellular pathogens is an ancient defense mechanism observed in multicellular organisms of both the animal and plant kingdoms. It is therefore not surprising that persistent pathogens of viral, bacterial, and protozoal origin have evolved to inhibit ... | Tuberculosis is an infectious disease of enormous and increasing global importance. Currently, about one third of all humans are latently infected with its etiologic agent, Mycobacterium tuberculosis (Mtb), and an estimated 2.5 million people die of tuberculosis annually [1]. After infection of a mammalian host, Mtb is... |
10.1371/journal.pcbi.1001046 | Decrypting the Sequence of Structural Events during the Gating Transition of Pentameric Ligand-Gated Ion Channels Based on an Interpolated Elastic Network Model | Despite many experimental and computational studies of the gating transition of pentameric ligand-gated ion channels (pLGICs), the structural basis of how ligand binding couples to channel gating remains unknown. By using a newly developed interpolated elastic network model (iENM), we have attempted to compute a likely... | Pentameric ligand-gated ion channels are a family of membrane proteins that open/close an ion-conducting channel in response to the binding of specific ligands. Some members of the family, including nicotinic acetylcholine receptors, play key physiological roles in signal transduction at synapses. Despite many experime... | Pentameric ligand-gated ion channels (pLGICs) are a family of membrane proteins that open/close an ion-conducting channel in response to an increase/decrease in the binding affinity for specific ligands [1], [2], [3], [4]. Some members of the family, including nicotinic acetylcholine receptors (AChRs, [5]), play key ph... |
10.1371/journal.pntd.0001532 | Fatal Dengue Hemorrhagic Fever in Adults: Emphasizing the Evolutionary Pre-fatal Clinical and Laboratory Manifestations | A better description of the clinical and laboratory manifestations of fatal patients with dengue hemorrhagic fever (DHF) is important in alerting clinicians of severe dengue and improving management.
Of 309 adults with DHF, 10 fatal patients and 299 survivors (controls) were retrospectively analyzed. Regarding causes o... | Fatality rate and causes of fatality in dengue-affected patients greatly varied from one reported series to another. A better understanding of the clinical and laboratory manifestations of fatal patients with dengue hemorrhagic fever (DHF) is important in alerting clinicians of severe dengue and improving management. I... | Dengue is the most prevalent mosquito-borne viral infection in the world [1]. Clinically, dengue ranges from asymptomatic, nonspecific febrile illness, classic dengue, to dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS) [1]. Fatality rate and causes of fatality in dengue-affected patients greatly varied from on... |
10.1371/journal.pgen.1005020 | microRNAs Regulate Cell-to-Cell Variability of Endogenous Target Gene Expression in Developing Mouse Thymocytes | The development and homeostasis of multicellular organisms relies on gene regulation within individual constituent cells. Gene regulatory circuits that increase the robustness of gene expression frequently incorporate microRNAs as post-transcriptional regulators. Computational approaches, synthetic gene circuits and ob... | microRNAs are integral to many developmental processes and may 'canalise' development by reducing cell-to-cell variation in gene expression. This idea is supported by computational studies that have modeled the impact of microRNAs on the expression of their targets and the construction of artificial incoherent feedforw... | The complexity of developmental processes in metazoans relies on mechanisms that confer a degree of robustness against environmental and genetic variation [1]. microRNAs are small non-coding RNAs that negatively regulate gene expression at the post-transcriptional level by reducing mRNA stability and/or translation. Th... |
10.1371/journal.ppat.1003525 | The Smallest Capsid Protein Mediates Binding of the Essential Tegument Protein pp150 to Stabilize DNA-Containing Capsids in Human Cytomegalovirus | Human cytomegalovirus (HCMV) is a ubiquitous herpesvirus that causes birth defects in newborns and life-threatening complications in immunocompromised individuals. Among all human herpesviruses, HCMV contains a much larger dsDNA genome within a similarly-sized capsid compared to the others, and it was proposed to requi... | Human cytomegalovirus (HCMV) causes birth defects in newborns and life-threatening complications in immunocompromised individuals, such as AIDS patients and organ transplant recipients. The smallest capsid protein (SCP) – only 8 kDa molecular mass as compared to the 155 kDa major capsid protein – has been demonstrated ... | Human cytomegalovirus (HCMV), the prototype of betaherpesvirus subfamily of the Herpesviridae, is a leading viral cause of birth abnormalities and a major life-threatening pathogen in AIDS and organ transplant patients [1]. HCMV virion shares a common architecture with other herpesviruses and consists of a polymorphic ... |
10.1371/journal.pntd.0001707 | Geographical Distribution of Trypanosoma cruzi Genotypes in Venezuela | Chagas disease is an endemic zoonosis native to the Americas and is caused by the kinetoplastid protozoan parasite Trypanosoma cruzi. The parasite is also highly genetically diverse, with six discrete typing units (DTUs) reported TcI – TcVI. These DTUs broadly correlate with several epidemiogical, ecological and pathol... | Chagas disease is caused by a protozoan parasite called Trypanosoma cruzi. T. cruzi infects a wide variety of mammal species in Latin America as well as man, and is spread by multiple species of blood sucking triatomine insect vectors. The presence of genetic diversity in T. cruzi in the Americas is well established, w... | Trypanosoma cruzi, the etiological agent of Chagas disease, infects approximately 8 million people in Latin America [1]. A further 20 million people are at risk of infection. Chagas disease is widely dispersed across 21 countries in the Americas, with a natural distribution (in wild transmission cycles) from the Southe... |
10.1371/journal.pcbi.1002689 | Spike-Timing Dependence of Structural Plasticity Explains Cooperative Synapse Formation in the Neocortex | Structural plasticity governs the long-term development of synaptic connections in the neocortex. While the underlying processes at the synapses are not fully understood, there is strong evidence that a process of random, independent formation and pruning of excitatory synapses can be ruled out. Instead, there must be ... | Structural plasticity has been observed even in the adult mammalian neocortex – in seemingly static neuronal circuits structural remodeling is continuously at work. Still, it has been shown that the connection patterns between pairs of neurons are not random. In contrast, there is evidence that the synaptic contacts be... | The structure of neocortical networks of neurons changes in time: new synapses are formed, maturate, and eventually are pruned again, in the adult as well as in the developing animal [1], [2], for recent reviews see [3], [4], [5]. The majority (about ) of excitatory synaptic contacts terminate on dendritic spines [6], ... |
10.1371/journal.pntd.0000433 | Early Exposure of Infants to GI Nematodes Induces Th2 Dominant Immune Responses Which Are Unaffected by Periodic Anthelminthic Treatment | We have previously shown a reduction in anaemia and wasting malnutrition in infants <3 years old in Pemba Island, Zanzibar, following repeated anthelminthic treatment for the endemic gastrointestinal (GI) nematodes Ascaris lumbricoides, hookworm and Trichuris trichiura. In view of the low intensity of worm infections i... | Infants and very young children commonly become infected with intestinal nematode infections. However, the worm burdens are generally very light, so a beneficial effect of deworming on wasting malnutrition and anaemia in this age group which we have demonstrated was unexpected and the mechanism unclear. To investigate ... | In endemic countries infants are exposed to gastrointestinal (GI) nematode infections soon after birth and infection intensity increases during childhood. Helminth infections in children are associated with malnutrition [1],[2], linear growth stunting [3] as well as iron deficiency anaemia [4],[5], effects related to t... |
10.1371/journal.pbio.1001360 | Regulation of DNA Replication within the Immunoglobulin Heavy-Chain Locus During B Cell Commitment | The temporal order of replication of mammalian chromosomes appears to be linked to their functional organization, but the process that establishes and modifies this order during cell differentiation remains largely unknown. Here, we studied how the replication of the Igh locus initiates, progresses, and terminates in b... | Each time a mammalian cell duplicates its genome in preparation for cell division it activates thousands of so called “DNA origins of replication.” The timely and complete duplication of the genome depends on careful orchestration of origin activation, which is modified when cells differentiate to perform a specific fu... | During the S phase, mammalian chromosomes replicate in a precise temporal order, with the timing of replication typically changing gradually across hundreds of kilobases. Cell differentiation induces regional changes in the order of replication which can affect 45%, or more, of the mouse genome [1]. Various studies hav... |
10.1371/journal.pntd.0001673 | Sporotrichosis in Sub-Himalayan India | Sporotrichosis is endemic in the Sub-Himalayan belt, which ranges from the northern to the north-eastern Indian subcontinent. Similar to many parts of the developing world, sporotrichosis is commonly recognized clinically in this region however consolidated epidemiological data is lacking. We report epidemiological, cl... | Sporotrichosis is a sub-acute or chronic granulomatous fungal infection involving mainly the skin and subcutaneous tissue with neighbouring lymphatics. It is caused by thermally dimorphic fungus, Sporothrix schenckii, which is prevalent worldwide. Consequent to trauma, the fungus establishes itself in skin and subcutan... | Sporotrichosis is a sub-acute or chronic granulomatous mycotic infection involving primarily the skin and subcutaneous tissue with neighbouring lymphatics. It is caused by thermo-dimorphic fungus, Sporothrix schenckii which is prevalent worldwide growing on timber, sphagnum moss, plant detritus, soil, etc. Consequent t... |
10.1371/journal.ppat.1000281 | Estimation of Transmission Parameters of H5N1 Avian Influenza Virus in Chickens | Despite considerable research efforts, little is yet known about key epidemiological parameters of H5N1 highly pathogenic influenza viruses in their avian hosts. Here we show how these parameters can be estimated using a limited number of birds in experimental transmission studies. Our quantitative estimates, based on ... | Outbreaks of highly pathogenic H5N1 avian influenza in poultry first occurred in China in 1996. Since that time, the virus has become endemic in Asia, and has been the cause of outbreaks in Africa and Europe. Although many aspects of H5N1 virus biology have been studied in detail, surprisingly little is known about the... | Highly pathogenic avian influenza virus strains of the H5 or H7 subtypes are noted for being highly contagious among various bird species and inducing high mortality rates in poultry. Although outbreaks of highly pathogenic avian influenza have been reported since the 1950s the current focus is on the H5N1 subtype. The... |
10.1371/journal.pntd.0001592 | Population Structure and Transmission Dynamics of Plasmodium vivax in the Republic of Korea Based on Microsatellite DNA Analysis | In order to control malaria, it is important to understand the genetic structure of the parasites in each endemic area. Plasmodium vivax is widely distributed in the tropical to temperate regions of Asia and South America, but effective strategies for its elimination have yet to be designed. In South Korea, for example... | Vivax malaria is widely prevalent, mainly in Asia and South America with 390 million reported cases in 2009. Worldwide, in the same year, 2.85 billion people were at risk. Plasmodium vivax is prevalent not only in tropical and subtropical areas but also in temperate areas where there are no mosquitoes in cold seasons. ... |
Plasmodium vivax, the second most prevalent species of the human malaria parasite, is widely distributed around the world, especially in Asia and South America; it ranges from tropical to temperate areas [1], [2]. In these countries, the proportion of P. falciparum cases is gradually decreasing due to the impa... |
10.1371/journal.pntd.0006590 | A novel cell-free method to culture Schistosoma mansoni from cercariae to juvenile worm stages for in vitro drug testing | The arsenal in anthelminthic treatment against schistosomiasis is limited and relies almost exclusively on a single drug, praziquantel (PZQ). Thus, resistance to PZQ could constitute a major threat. Even though PZQ is potent in killing adult worms, its activity against earlier stages is limited. Current in vitro drug s... | Schistosomiasis remains a major health threat, predominantly in developing countries. Even though there has been some progress in search of new drugs, praziquantel remains the only available drug. Probably the most important advance in the search for new drugs was in vitro transformation of cercariae and their subseque... | Schistosomiasis, a chronic and debilitating helminthic disease, is one of the most important neglected tropical diseases (NTD). The WHO estimates that more than 206 million people are currently infected and in need of chemotherapy world-wide [1]. Moreover, over 200,000 people die each year due to the sequelae of the di... |
10.1371/journal.pgen.1007782 | Telomere length-dependent transcription and epigenetic modifications in promoters remote from telomere ends | Telomere-binding proteins constituting the shelterin complex have been studied primarily for telomeric functions. However, mounting evidence shows non-telomeric binding and gene regulation by shelterin factors. This raises a key question—do telomeres impact binding of shelterin proteins at distal non-telomeric sites? H... | Telomeres (special DNA-protein assemblies that protect chromosome ends) affect ageing and diseases such as cancer. Although this has been recognized for many years, biological processes that connect telomeres to ageing, cancer and other cellular functions remain to be fully understood. Certain proteins, believed to be ... | The shelterin complex comprises a group of proteins that confer stability to telomeres[1–6]. Components of shelterin and other telomeric proteins, for example, RAP1, TRF1 and TRF2, and POT1 have been extensively studied in telomere homeostasis[7–10], DNA replication[11–15], repair and genomic stability[16–21]. Previous... |
10.1371/journal.ppat.1007313 | Promyelocytic leukemia (PML) nuclear bodies (NBs) induce latent/quiescent HSV-1 genomes chromatinization through a PML NB/Histone H3.3/H3.3 Chaperone Axis | Herpes simplex virus 1 (HSV-1) latency establishment is tightly controlled by promyelocytic leukemia (PML) nuclear bodies (NBs) (or ND10), although their exact contribution is still elusive. A hallmark of HSV-1 latency is the interaction between latent viral genomes and PML NBs, leading to the formation of viral DNA-co... | An understanding of the molecular mechanisms contributing to the persistence of a virus in its host is essential to be able to control viral reactivation and its associated diseases. Herpes simplex virus 1 (HSV-1) is a human pathogen that remains latent in the PNS and CNS of the infected host. The latency is unstable, ... | Herpes simplex virus 1 (HSV-1) is a human pathogen with neurotropic tropism and the causal agent of cold sores and more severe CNS pathologies such as encephalitis [1]. After the initial infection, HSV-1 remains latent in neuronal ganglia with the main site of latency being the trigeminal (or Gasserian) ganglion (TG). ... |
10.1371/journal.pcbi.1006976 | Fast and robust deconvolution of tumor infiltrating lymphocyte from expression profiles using least trimmed squares | Gene-expression deconvolution is used to quantify different types of cells in a mixed population. It provides a highly promising solution to rapidly characterize the tumor-infiltrating immune landscape and identify cold cancers. However, a major challenge is that gene-expression data are frequently contaminated by many... | Rapidly emerging evidence suggests that the tumor immune microenvironment not only predisposes cancer patients to diverse treatment outcomes but also represents a promising source of biomarkers for better patient stratification. Different from the immunohistochemistry-based scoring practice, which focuses on a few sele... | Immune checkpoint blockade has revolutionized the rational design of neoadjuvant cancer therapies. Compelling evidence suggests that a favorable tumor immune microenvironment underpins better clinical responses to radiotherapy, chemotherapy, and immunotherapy [1–3]. Immunohistochemistry (IHC)-based immunoscores, which ... |
10.1371/journal.ppat.1005667 | CD4 T Cell-Derived IFN-γ Plays a Minimal Role in Control of Pulmonary Mycobacterium tuberculosis Infection and Must Be Actively Repressed by PD-1 to Prevent Lethal Disease | IFN-γ–producing CD4 T cells are required for protection against Mycobacterium tuberculosis (Mtb) infection, but the extent to which IFN-γ contributes to overall CD4 T cell-mediated protection remains unclear. Furthermore, it is not known if increasing IFN-γ production by CD4 T cells is desirable in Mtb infection. Here ... | The development of novel tuberculosis vaccines has been hindered by the poor understanding of the mechanisms of host-protection. It has been long-held that IFN-γ is the principle effector of CD4 T cell-mediated resistance to Mtb infection, but Mtb-specific CD4 T cells produce low amounts of IFN-γ in vivo, leading to th... | Mycobacterium tuberculosis (Mtb) infection is a leading cause of global morbidity and mortality. In 2014 there were 9.6 million new cases of tuberculosis (TB) and 1.5 million deaths resulting from Mtb infection [1]. The only available vaccine against Mtb infection, Bacillus Calmette-Guérin (BCG), is an attenuated strai... |
10.1371/journal.ppat.1000432 | Genetic Dissection of an Exogenously Induced Biofilm in Laboratory and Clinical Isolates of E. coli | Microbial biofilms are a dominant feature of many human infections. However, developing effective strategies for controlling biofilms requires an understanding of the underlying biology well beyond what currently exists. Using a novel strategy, we have induced formation of a robust biofilm in Escherichia coli by utiliz... | Both in the wild and in the clinical setting many bacterial species live within surface-attached communities called biofilms. It is still unclear the extent to which the biofilm lifestyle and its associated phenotypes, such as hyper-tolerance to antimicrobial agents, can be attributed to structural characteristics of t... | Biofilms are an integral component in the life-cycle of many microorganisms. Compared to their planktonic complement, however, bacterial biofilms have remained poorly understood, mostly due to the inherent complexities associated with biofilm studies, including spatial heterogeneity of the biofilm structure, longer gen... |
10.1371/journal.pgen.1002537 | Parkinson's Disease–Associated Kinase PINK1 Regulates Miro Protein Level and Axonal Transport of Mitochondria | Mutations in Pten-induced kinase 1 (PINK1) are linked to early-onset familial Parkinson's disease (FPD). PINK1 has previously been implicated in mitochondrial fission/fusion dynamics, quality control, and electron transport chain function. However, it is not clear how these processes are interconnected and whether they... | Parkinson's disease (PD) is the second most common neurodegenerative disease. It mainly affects movement in elderly people and was traditionally considered a sporadic disease with no known cause. Discoveries of genes associated with familial PD (FPD) have demonstrated that PD pathogenesis can be significantly influence... | PD is a neurodegenerative disorder characterized by the dysfunction and loss of dopaminergic (DA) neurons in the substantia nigra, although neurons in other brain regions are affected as well. Mutations in PINK1 and Parkin are linked to familial forms of early-onset PD [1], [2]. PINK1 encodes a Ser/Thr kinase with a mi... |
10.1371/journal.pcbi.1003200 | Predicting Disease Risk Using Bootstrap Ranking and Classification Algorithms | Genome-wide association studies (GWAS) are widely used to search for genetic loci that underlie human disease. Another goal is to predict disease risk for different individuals given their genetic sequence. Such predictions could either be used as a “black box” in order to promote changes in life-style and screening fo... | Genome-wide association studies are widely used to search for genetic loci that underlie human disease. Another goal is to predict disease risk for different individuals given their genetic sequence. Such predictions could either be used as a “black box” in order to promote changes in life-style and screening for early... | Genome-wide association studies (GWAS) have recently become the dominant method for searching for the genetic basis that underlies human diseases [1]–[3]. A typical GWAS consists of a collection of genotypes from affected (cases) and healthy (controls) individuals, allowing researches to search for single nucleotide po... |
10.1371/journal.pntd.0000130 | Transcriptional Changes in the Hookworm, Ancylostoma caninum, during the Transition from a Free-Living to a Parasitic Larva | Third-stage larvae (L3) of the canine hookworm, Ancylostoma caninum, undergo arrested development preceding transmission to a host. Many of the mRNAs up-regulated at this stage are likely to encode proteins that facilitate the transition from a free-living to a parasitic larva. The initial phase of mammalian host invas... | Hookworms are soil-transmitted nematodes that parasitize hundreds of millions of people in developing countries. Here we describe the genes expressed when hookworm larvae make the transition from a developmentally arrested free-living form to a tissue-penetrating parasitic stage. Ancylostoma caninum can be “tricked” in... | Parasitic nematodes are of considerable medical, veterinary and agricultural importance. For example, it is estimated that the morbidity attributable to hookworms, Trichuris and Ascaris, the three most prevalent parasitic nematodes in humans globally, could be as high as 39 disability adjusted life years (DALY) [1]. Th... |
10.1371/journal.pmed.1002183 | Patient-Reported Barriers to Adherence to Antiretroviral Therapy: A Systematic Review and Meta-Analysis | Maintaining high levels of adherence to antiretroviral therapy (ART) is a challenge across settings and populations. Understanding the relative importance of different barriers to adherence will help inform the targeting of different interventions and future research priorities.
We searched MEDLINE via PubMed, Embase, ... | Despite more than two decades of research on adherence to antiretroviral therapy (ART) and more than 17 million HIV-positive individuals on treatment, adherence to ART remains a major challenge.
This review aimed to assess the most frequently reported barriers to adherence by patients experiencing adherence challenges.... | Global targets for scaling up antiretroviral therapy (ART) include ensuring that 90% of patients on ART achieve viral suppression. This gives a renewed emphasis to ensuring optimal levels of adherence. Negative outcomes of longer-term suboptimal adherence include increased risk of disease progression [1], drug resistan... |
10.1371/journal.pntd.0006527 | The initial effectiveness of liposomal amphotericin B (AmBisome) and miltefosine combination for treatment of visceral leishmaniasis in HIV co-infected patients in Ethiopia: A retrospective cohort study | North-west Ethiopia faces the highest burden world-wide of visceral leishmaniasis (VL) and HIV co-infection. VL-HIV co-infected patients have higher (initial) parasitological failure and relapse rates than HIV-negative VL patients. Whereas secondary prophylaxis reduces the relapse rate, parasitological failure rates re... | North-west Ethiopia faces the highest burden world-wide of visceral leishmaniasis (VL) and HIV co-infection. VL treatment outcomes in HIV co-infected patients are associated with high initial treatment (parasitological) failure and recurrence rates after cure (relapse). With secondary chemoprophylaxis, the risk of rela... | Visceral leishmaniasis (VL) is a protozoan infection caused by the Leishmania donovani species complex [1]. In East Africa and the Indian subcontinent, it is caused by L. donovani, whereas in the Mediterranean region and South America, by L. infantum [2]. Ethiopia is among the top six high burden countries, with approx... |
10.1371/journal.pntd.0003188 | Aedes hensilli as a Potential Vector of Chikungunya and Zika Viruses | An epidemic of Zika virus (ZIKV) illness that occurred in July 2007 on Yap Island in the Federated States of Micronesia prompted entomological studies to identify both the primary vector(s) involved in transmission and the ecological parameters contributing to the outbreak. Larval and pupal surveys were performed to id... | Arthropod-borne viruses (arboviruses) cause significant human morbidity and mortality throughout the world. Zika virus, which is reported to be transmitted by Aedes (Stegomyia) species mosquitoes, caused an outbreak on the island of Yap, in the Federated States of Micronesia in 2007. This was the first described outbre... | Outbreaks of arboviral disease have been documented in islands of the western Pacific including The Federated States of Micronesia (FSM) and Palau. Multiple dengue outbreaks have been reported in the western pacific [1]–[4] with an outbreak of dengue 4 virus occurring in Palau in 1995 after a 7 year absence of dengue o... |
10.1371/journal.pntd.0004663 | Impact of Helminth Infection on the Clinical and Microbiological Presentation of Chagas Diseases in Chronically Infected Patients | Helminth infections are highly prevalent in tropical and subtropical countries, coexisting in Chagas disease endemic areas. Helminth infections in humans may modulate the host immune system, changing the Th1/Th2 polarization. This immunological disturbance could modify the immune response to other infections. The aim o... | Helminth infections (viz. Strongyloides stercoralis, hookworms, Ascaris lumbricoides, Trichuris trichiura) are highly prevalent in tropical and subtropical areas, and some of these infections may persist in the human host for many years after leaving the endemic area. It is known that helminth infection in humans may m... | Chagas disease is a parasitic infection caused by the hemoflagellated protozoan Trypanosoma cruzi. Chagas disease is an endemic disease of Latin America affecting rural and poor population; nevertheless, progressive urbanization and the increase of population mobility during last decades, have made Chagas disease an ur... |
10.1371/journal.ppat.1003956 | Male-Killing Spiroplasma Induces Sex-Specific Cell Death via Host Apoptotic Pathway | Some symbiotic bacteria cause remarkable reproductive phenotypes like cytoplasmic incompatibility and male-killing in their host insects. Molecular and cellular mechanisms underlying these symbiont-induced reproductive pathologies are of great interest but poorly understood. In this study, Drosophila melanogaster and i... | Symbiotic bacteria are ubiquitously associated with diverse insects, and affect their host biology in a variety of ways. In Drosophila fruit flies, infection with Spiroplasma symbionts often causes male-specific embryonic mortality, resulting in the production of all-female offspring. This striking phenotype is called ... | Symbiotic microorganisms are ubiquitously associated with diverse insects, and affect their host biology in a variety of ways [1], [2]. Some symbionts play important biological roles such as provisioning of essential nutrients to their hosts [3], helping food digestion for their hosts [4], or improving the fitness of t... |
10.1371/journal.pntd.0002658 | Parasite-Antigen Driven Expansion of IL-5− and IL-5+ Th2 Human Subpopulations in Lymphatic Filariasis and Their Differential Dependence on IL-10 and TGFβ | Two different Th2 subsets have been defined recently on the basis of IL-5 expression – an IL-5+Th2 subset and an IL-5−Th2 subset in the setting of allergy. However, the role of these newly described CD4+ T cells subpopulations has not been explored in other contexts.
To study the role of the Th2 subpopulation in a chro... | Th2 cells are CD4+ T cells that produce a unique set of cytokines - IL-4, IL-5 and IL-13. Th2 cells are commonly associated with allergies, asthma and helminth infections. A common helminth infection that infects over 120 million people worldwide is lymphatic filarial infection caused by filarial parasites. We show her... | Th2 cells were initially characterized as expressing the cytokines – IL-4, IL-5 and IL-13 [1]. Although Th2 cells can express a variety of other cytokines, these three cytokines remain the hallmark Th2 cytokines. Each Th2 cytokine has a well-defined and relatively specific function. While IL-4 is the major driving forc... |
10.1371/journal.ppat.1007328 | Function of BriC peptide in the pneumococcal competence and virulence portfolio | Streptococcus pneumoniae (pneumococcus) is an opportunistic pathogen that causes otitis media, sinusitis, pneumonia, meningitis and sepsis. The progression to this pathogenic lifestyle is preceded by asymptomatic colonization of the nasopharynx. This colonization is associated with biofilm formation; the competence pat... | Pneumococcal biofilms occur in chronic otitis media, chronic rhinosinusitis, and nasopharyngeal colonization. These biofilms are an important component of pneumococcal epidemiology, particularly in influencing transmission, maintenance of asymptomatic colonization, and development of disease. The transcriptional progra... | Bacteria form sessile communities termed biofilms, where they interact with each other to engage in collaborative and/or competitive behaviors [1]. In Streptococcus pneumoniae (pneumococcus), these cell-cell interactions are commonly mediated by secreted peptides that interact with both producing and neighboring cells ... |
10.1371/journal.ppat.1006011 | Cytoadhesion to gC1qR through Plasmodium falciparum Erythrocyte Membrane Protein 1 in Severe Malaria | Cytoadhesion of Plasmodium falciparum infected erythrocytes to gC1qR has been associated with severe malaria, but the parasite ligand involved is currently unknown. To assess if binding to gC1qR is mediated through the P. falciparum erythrocyte membrane protein 1 (PfEMP1) family, we analyzed by static binding assays an... | Plasmodium falciparum sequesters in vital organs. This phenomenon mediated by cytoadhesion of infected-erythrocytes to host receptors in the microvasculature, contributes to the development of severe malaria. Although cytoadhesion to Endothelial Protein-C Receptor has a central role in severe malaria, other host recept... | Case fatality rates for severe malaria (SM) remain unacceptably high even after administration of effective anti-malarial drugs [1]. There is an urgent need to develop novel interventions against life-threatening malaria. However, the mechanisms underlying the clinical heterogeneity and spectrum of malaria [2] remain l... |
10.1371/journal.pgen.1003318 | HIV Infection Disrupts the Sympatric Host–Pathogen Relationship in Human Tuberculosis | The phylogeographic population structure of Mycobacterium tuberculosis suggests local adaptation to sympatric human populations. We hypothesized that HIV infection, which induces immunodeficiency, will alter the sympatric relationship between M. tuberculosis and its human host. To test this hypothesis, we performed a n... | Human tuberculosis (TB) caused by Mycobacterium tuberculosis kills 1.5 million people each year. M. tuberculosis has been affecting humans for millennia, suggesting that different strain lineages may be adapted to specific human populations. The combination of a particular strain lineage and its corresponding patient p... | Host–pathogen co-evolution plays an important role in the biology of infectious diseases [1]. Coevolution between interacting host and pathogen species is difficult to demonstrate formally, but indirect evidence can be obtained by studying geographical patterns, which can indicate local adaptation of particular pathoge... |
10.1371/journal.pcbi.1006925 | Colony entropy—Allocation of goods in ant colonies | Allocation of goods is a key feature in defining the connection between the individual and the collective scale in any society. Both the process by which goods are to be distributed, and the resulting allocation to the members of the society may affect the success of the population as a whole. One of the most striking ... | We study how food is distributed in colonies of ants. Food collected by a small fraction of ants is distributed throughout the colony through a series of mouth-to-mouth interactions. An interesting interplay exists between food dissemination and food mixing within the colony. High levels of dissemination are important ... | Food sharing in social insects is a compelling example of cooperation within a population [1–7]. Ants and bees can store a considerable amount of liquids in a pre-digestion storage organ called the ‘crop’ [8–10]. The stored food can later be regurgitated and passed on to others by mouth-to-mouth feeding (oral trophalla... |
10.1371/journal.pcbi.1004886 | To Cooperate or Not to Cooperate: Why Behavioural Mechanisms Matter | Mutualistic cooperation often requires multiple individuals to behave in a coordinated fashion. Hence, while the evolutionary stability of mutualistic cooperation poses no particular theoretical difficulty, its evolutionary emergence faces a chicken and egg problem: an individual cannot benefit from cooperating unless ... | Mutualistic behaviours wherein several individuals act together for a common benefit, such as a collective hunt, are often deemed of minor interest by theoreticians in evolutionary biology. These behaviours benefit all the individuals involved, and therefore, so the argument goes, their evolution is straightforward. Ho... | It is well known that, in the absence of genetic relatedness, altruistic behaviours in which individuals pay a fitness cost for the benefit of others cannot evolve by natural selection [1, 2]. However, it is often assumed that mutualistic behaviours, wherein individuals collectively gain a common benefit [28, 29], do n... |
10.1371/journal.pgen.1007790 | miR-3607-3p suppresses non-small cell lung cancer (NSCLC) by targeting TGFBR1 and CCNE2 | Accumulating evidence indicates that miRNAs can be promising diagnostic and/or prognostic markers for various cancers. In this study, we identified a novel miRNA, miR-3607-3p, and its targets in non-small cell lung cancer (NSCLC). The expression of miR-3607-3p was measured and its correlation with patient prognosis was... | We first showed downregulation of miR-3607-3p in NSCLC tissues and demonstrated that miR-3607-3p may act as an independent predictor of overall survival. Serum miR-3607-3p may be a novel marker of patients with NSCLC. We further found that miR-3607-3p possesses the potency to suppress NSCLC growth and metastasis and in... | Lung cancer is one of the most frequently diagnosed cancers and the leading cause of cancer death in developed and developing countries [1]. It was estimated that there were 1,241,600 new cases of lung cancer in males and 583,100 in females in 2014 [1]. In China, it is estimated that approximately 733,300 new cases wer... |
10.1371/journal.pgen.1008335 | Telomere-binding proteins Taz1 and Rap1 regulate DSB repair and suppress gross chromosomal rearrangements in fission yeast | Genomic rearrangements (gross chromosomal rearrangements, GCRs) threatens genome integrity and cause cell death or tumor formation. At the terminus of linear chromosomes, a telomere-binding protein complex, called shelterin, ensures chromosome stability by preventing chromosome end-to-end fusions and regulating telomer... | Tips of chromosomes, telomeres, are bound and protected by a telomere-binding protein complex called shelterin. Most previous studies focused on shelterin’s telomere-specific role, and its general role in genome maintenance has not been explored extensively. In this study, we first set up an assay measuring the spontan... | The integrity of chromosomal DNA can be compromised by mutations that vary in size, ranging from small perturbations, such as point mutations and short insertions/deletions, to large changes, such as deletions, duplications, inversions, and translocations of long chromosome segments. The latter are collectively called ... |
10.1371/journal.pbio.1002478 | Indirect Fitness Benefits Enable the Spread of Host Genes Promoting Costly Transfer of Beneficial Plasmids | Bacterial genes that confer crucial phenotypes, such as antibiotic resistance, can spread horizontally by residing on mobile genetic elements (MGEs). Although many mobile genes provide strong benefits to their hosts, the fitness consequences of the process of transfer itself are less clear. In previous studies, transfe... | In bacteria, genes can move between cells, sometimes with the donor host cell actively involved in the gene transfer mechanisms. This movement of genes is called horizontal gene transfer, and it increases the prevalence of mobile genes in bacterial populations. However, it is not clear if donor host cells benefit from ... | MGEs such as plasmids or phages are defined by their ability to undergo horizontal gene transfer (HGT) between bacterial hosts [1], and are widespread in nature. Genes present on MGEs often affect their hosts’ fitness in a specific environment [2]. Particularly, many mobile genes increase virulence or antibiotic resist... |
10.1371/journal.ppat.1007405 | Polymicrobial sepsis influences NK-cell-mediated immunity by diminishing NK-cell-intrinsic receptor-mediated effector responses to viral ligands or infections | The sepsis-induced cytokine storm leads to severe lymphopenia and reduced effector capacity of remaining/surviving cells. This results in a prolonged state of immunoparalysis, that contributes to enhanced morbidity/mortality of sepsis survivors upon secondary infection. The impact of sepsis on several lymphoid subsets ... | Sepsis is an exaggerated host response to infection that can initially lead to significant morbidity/mortality and a long-lasting state of immunoparalysis in sepsis survivors. Sepsis-induced immunoparalysis functionally impairs numerous lymphocyte populations, including NK-cells. However, the scope and underlying mecha... | Sepsis is fatal to approximately 250,000 Americans every year and presents a significant economic burden (>$20 billion annually). The cytokine storm, which characterizes a septic event, is the result of a mismanaged infection and is composed of both pro- and anti-inflammatory cytokines [1]. However, the ~75% of patient... |
10.1371/journal.pgen.1006785 | The bantam microRNA acts through Numb to exert cell growth control and feedback regulation of Notch in tumor-forming stem cells in the Drosophila brain | Notch (N) signaling is central to the self-renewal of neural stem cells (NSCs) and other tissue stem cells. Its deregulation compromises tissue homeostasis and contributes to tumorigenesis and other diseases. How N regulates stem cell behavior in health and disease is not well understood. Here we show that N regulates ... | Stem cells are functional units in the development, maintenance, and regeneration of tissues in multicellular organisms. Defects in stem cell regulation can compromise tissue homeostasis and result in proliferative or degenerative diseases. Our understanding of the molecular and cellular mechanisms regulating the in vi... | Balancing self-renewal with differentiation is a key property of all stem cells [1–3]. Tipping such balance can have detrimental consequences, resulting in lineage depletion or tumorigenesis. N signaling is critically required for lineage homeostasis of both Drosophila and mammalian NSCs [3–5]. In the Drosophila larval... |
10.1371/journal.pgen.1003066 | Spastic Paraplegia Mutation N256S in the Neuronal Microtubule Motor KIF5A Disrupts Axonal Transport in a Drosophila HSP Model | Hereditary spastic paraplegias (HSPs) comprise a group of genetically heterogeneous neurodegenerative disorders characterized by spastic weakness of the lower extremities. We have generated a Drosophila model for HSP type 10 (SPG10), caused by mutations in KIF5A. KIF5A encodes the heavy chain of kinesin-1, a neuronal m... | Hereditary spastic paraplegias (HSPs) comprise a group of inherited neurological diseases. The main feature of HSP is progressive stiffness of the lower limbs due to a dysfunction of nerve cells. We study HSP type 10, which is caused by mutations in the neuronal motor protein KIF5A. HSP type 10 is inherited in an autos... | Hereditary spastic paraplegia (HSP) is a group of genetically heterogeneous neurodegenerative disorders characterized by distal axonopathy that affects the longest axons in the corticospinal tract [1], [2]. To date, 48 HSP loci have been described. The three most common causes of HSP - accounting for more than 50% of a... |
10.1371/journal.pntd.0005947 | How does competition among wild type mosquitoes influence the performance of Aedes aegypti and dissemination of Wolbachia pipientis? | Wolbachia has been deployed in several countries to reduce transmission of dengue, Zika and chikungunya viruses. During releases, Wolbachia-infected females are likely to lay their eggs in local available breeding sites, which might already be colonized by local Aedes sp. mosquitoes. Therefore, there is an urgent need ... | Several countries are seeking new vector control tools to reduce the transmission of arboviruses such as dengue, chikungunya and Zika. One of these innovative approaches relies on the release of Aedes aegypti mosquitoes infected with the endosymbiont Wolbachia, since this bacterium can block the aforementioned viruses ... | Infectious diseases caused by arboviruses are a growing global health concern. Among the disease vectors, mosquitoes from the genus Aedes and mostly important Ae. aegypti (Linnaeus, 1762) and Ae. albopictus (Skuse, 1894) have a prominent role in transmitting several arboviruses to humans. In the last 50 years, dengue v... |
10.1371/journal.pgen.1003874 | A Novel Highly Divergent Protein Family Identified from a Viviparous Insect by RNA-seq Analysis: A Potential Target for Tsetse Fly-Specific Abortifacients | In tsetse flies, nutrients for intrauterine larval development are synthesized by the modified accessory gland (milk gland) and provided in mother's milk during lactation. Interference with at least two milk proteins has been shown to extend larval development and reduce fecundity. The goal of this study was to perform... | Tsetse flies are the sole vector for African trypanosomes, causative agents of sleeping sickness in humans and nagana in cattle. Transcriptome and proteome analyses were utilized to examine the underlying mechanisms of tsetse lactation that occur during each reproductive cycle. These analyses revealed a dramatic shift ... | Tsetse reproductive biology is unusual among insects. Female tsetse give birth to a fully mature third instar larva (viviparity) after an extended intrauterine gestation. This reproductive strategy limits the capacity of tsetse mothers to only 8–10 offspring per lifetime [1]. To accommodate intrauterine larval developm... |
10.1371/journal.ppat.1005965 | A Viral Immunity Chromosome in the Marine Picoeukaryote, Ostreococcus tauri | Micro-algae of the genus Ostreococcus and related species of the order Mamiellales are globally distributed in the photic zone of world's oceans where they contribute to fixation of atmospheric carbon and production of oxygen, besides providing a primary source of nutrition in the food web. Their tiny size, simple cell... | We propose that chromosome 19 of O. tauri is specialized in defence against viral attack, a constant threat for all planktonic life, and that the most likely cause of resistance is the over-expression of numerous predicted glycosyltransferase genes. O. tauri thus provides an amenable model for molecular analysis of gen... | Eukaryotic micro-algae of the genus Ostreococcus and related species of the order Mamiellales are globally distributed in the photic zone of the world's oceans where they contribute to fixation of atmospheric carbon and production of oxygen, besides providing a primary source of nutrition in the food web [1–3]. Their t... |
10.1371/journal.pgen.1005824 | Specific Hsp100 Chaperones Determine the Fate of the First Enzyme of the Plastidial Isoprenoid Pathway for Either Refolding or Degradation by the Stromal Clp Protease in Arabidopsis | The lifespan and activity of proteins depend on protein quality control systems formed by chaperones and proteases that ensure correct protein folding and prevent the formation of toxic aggregates. We previously found that the Arabidopsis thaliana J-protein J20 delivers inactive (misfolded) forms of the plastidial enzy... | In this paper we report a relatively simple mechanism by which plant chloroplasts deal with inactive forms of DXS, the main rate-determining enzyme for the production of plastidial isoprenoids relevant for photosynthesis and development. We provide evidence supporting that particular members of the Hsp100 chaperone fam... | Organelles like mitochondria and plastids play fundamental roles in all eukaryotic organisms. In particular, plastids were acquired by a symbiosis between photosynthetic cyanobacteria and eukaryotic cells. Today, plastids (like mitochondria) are intimately integrated into the metabolism of plant cells but they still re... |
10.1371/journal.pgen.1000515 | A Genome-Wide Screen for Regulators of TORC1 in Response to Amino Acid Starvation Reveals a Conserved Npr2/3 Complex | TORC1 is a central regulator of cell growth in response to amino acid availability, yet little is known about how it is regulated. Here, we performed a reverse genetic screen in yeast for genes necessary to inactivate TORC1. The screen consisted of monitoring the expression of a TORC1 sensitive GFP-based transcriptiona... | Before a eukaryotic cell commits to cell division it must be large enough so that both daughter cells would be of viable size. The control of cell size is largely mediated by nutritional input signals via an evolutionarily conserved protein complex termed TORC1. In particular, TORC1 has been shown to sense the level of... | The Target of Rapamycin (TOR) kinase has emerged as a central processing unit that can incorporate signals from diverse pathways regarding the availability of glucose, oxygen and amino acids [1]. The TOR kinase is a large scaffolding protein-kinase that is highly conserved in all eukaryotes. In recent years, TOR has be... |
10.1371/journal.pcbi.1002382 | Paradoxical Evidence Integration in Rapid Decision Processes | Decisions about noisy stimuli require evidence integration over time. Traditionally, evidence integration and decision making are described as a one-stage process: a decision is made when evidence for the presence of a stimulus crosses a threshold. Here, we show that one-stage models cannot explain psychophysical exper... | In models of decision making, evidence is accumulated until it crosses a threshold. The amount of evidence is directly related to the strength of the sensory input for the decision alternatives. Such one-stage models predict that if two stimulus alternatives are presented in succession, the stimulus alternative present... | Decision making is of crucial interest in many disciplines such as psychology [1], [2], neuroscience [3]–[5], economics [6], [7], and machine learning [8]. Binary decision theories relate to situations where an observer (or machine) is confronted with one of two possible noisy stimuli ‘A’ and ‘B’. A decision has to be ... |
10.1371/journal.pcbi.1004104 | A Biologically Plausible Computational Theory for Value Integration and Action Selection in Decisions with Competing Alternatives | Decision making is a vital component of human and animal behavior that involves selecting between alternative options and generating actions to implement the choices. Although decisions can be as simple as choosing a goal and then pursuing it, humans and animals usually have to make decisions in dynamic environments wh... | In high-pressure situations, such as driving on a highway or flying a plane, people have limited time to select between competing options while acting. Each option is usually accompanied with reward benefits (e.g., avoid traffic) and action costs (e.g., fuel consumption) that characterize the value of the option. The v... | From very simple decisions, such as selecting what to wear or choosing a place for dinner, to more complex decisions, such as trading in the stock market, we usually have to select among competing options. Selecting between alternatives requires assigning and integrating values along a multitude of dimensions with diff... |
10.1371/journal.ppat.1003989 | Modified Vaccinia Virus Ankara Triggers Type I IFN Production in Murine Conventional Dendritic Cells via a cGAS/STING-Mediated Cytosolic DNA-Sensing Pathway | Modified vaccinia virus Ankara (MVA) is an attenuated poxvirus that has been engineered as a vaccine against infectious agents and cancers. Our goal is to understand how MVA modulates innate immunity in dendritic cells (DCs), which can provide insights to vaccine design. In this study, using murine bone marrow-derived ... | Modified vaccinia virus Ankara (MVA) is an attenuated vaccinia strain with large deletions of the parental genome that render it non-replicative in mammalian cells. MVA is a safe and effective vaccine against both smallpox and monkeypox. MVA has been investigated as a vaccine vector for infectious diseases and cancers.... | Poxviruses are large cytoplasmic DNA viruses that cause human and veterinary diseases. Variola virus (the causative agent of smallpox) and monkeypox virus are important human pathogens [1]–[3]. Modified vaccinia virus Ankara (MVA) is an attenuated vaccinia virus that was developed through serial passaging in chicken em... |
10.1371/journal.pntd.0007467 | On lifestyle trends, health and mosquitoes: Formulating welfare levels for control of the Asian tiger mosquito in Greece | The expansion of urban ecosystems and climate change, both outcomes of massive lifestyle changes, contribute to a series of side effects such as environmental deterioration, spread of diseases, increased greenhouse gas emissions and introduction of invasive species. In the case of the Athens metropolitan area, an invas... | This paper is based on several years’ collaboration among researchers from various disciplines, key health policy makers and stakeholders in an attempt to evaluate the economic dimensions related to the presence of the Asian Tiger Mosquito (Aedes albopictus) and the challenges of tackling mosquito-borne disease outbrea... | Recent reports highlight the impacts and risks to human and natural systems linked to global warming of 1.5°C compared to temperatures in the pre-industrial period [1]. The implications of rising temperatures for human health around the globe include changes in disease vector survival and pathogen development, and the ... |
10.1371/journal.pcbi.1005895 | Functional interrogation of Plasmodium genus metabolism identifies species- and stage-specific differences in nutrient essentiality and drug targeting | Several antimalarial drugs exist, but differences between life cycle stages among malaria species pose challenges for developing more effective therapies. To understand the diversity among stages and species, we reconstructed genome-scale metabolic models (GeMMs) of metabolism for five life cycle stages and five specie... | Malaria kills nearly one-half million people a year and over 1 billion people are at risk of becoming infected by the parasite. Plasmodial infections are difficult to treat for a myriad of reasons, but the ability of the organism to remain latent in hosts and the complex life cycles greatly contributed to the difficult... | Malaria is a worldwide problem of clinical significance causing an estimated 483,000 deaths, with a disproportionate percentage occurring in children less than 5 years of age, according to the World Health Organization[1]. Additionally, 1.2 billion people are at high risk of contracting the infection[1]. Plasmodium is ... |
10.1371/journal.pcbi.1003570 | Phylodynamic Inference for Structured Epidemiological Models | Coalescent theory is routinely used to estimate past population dynamics and demographic parameters from genealogies. While early work in coalescent theory only considered simple demographic models, advances in theory have allowed for increasingly complex demographic scenarios to be considered. The success of this appr... | Mathematical models play an important role in our understanding of what processes drive the complex population dynamics of infectious pathogens. Yet developing statistical methods for fitting models to epidemiological data is difficult. Epidemiological data is often noisy, incomplete, aggregated across different scales... | Genealogies can provide valuable information about the demographic history of a population because the demography of a population can dramatically shape the structure of a genealogy [1], [2]. For example, fluctuations in population size will shift the distribution of branching events, or coalescent times, over a geneal... |
10.1371/journal.pntd.0002541 | Severe South American Ocular Toxoplasmosis Is Associated with Decreased Ifn-γ/Il-17a and Increased Il-6/Il-13 Intraocular Levels | In a cross sectional study, 19 French and 23 Colombian cases of confirmed active ocular toxoplasmosis (OT) were evaluated. The objective was to compare clinical, parasitological and immunological responses and relate them to the infecting strains. A complete ocular examination was performed in each patient. The infecti... | Ocular toxoplasmosis (OT), due to protozoan parasite Toxoplasma gondii, is a potential complication of both acquired and congenital infection, leading to visual impairment in numerous countries and being responsible for 30 to 50% of uveitis cases in immunocompetent individuals. In this study we confirmed the presence o... | Infection with the protozoan parasite Toxoplasma gondii is a leading cause of visual impairment in numerous countries, being responsible for 30 to 50% of uveitis cases in immunocompetent individuals [1]. Ocular toxoplasmosis (OT) is a potential complication of both acquired and congenital toxoplasmosis [2]. The inciden... |
10.1371/journal.pgen.1000449 | Microarray Profiling of Phage-Display Selections for Rapid Mapping of Transcription Factor–DNA Interactions | Modern computational methods are revealing putative transcription-factor (TF) binding sites at an extraordinary rate. However, the major challenge in studying transcriptional networks is to map these regulatory element predictions to the protein transcription factors that bind them. We have developed a microarray-based... | Specific interactions between protein transcription factors (TFs) and their DNA recognition sites are central to the regulation of gene expression. Inter-species conservation of these TF binding sites (TFBS), and their statistical enrichment in sets of co-expressed genes, facilitates their large-scale prediction throug... | The arrival of complete genomes and microarray technology has fueled a revolution in computational predictions of transcriptional regulatory elements, both through inter-species comparative genomics [1],[2] and mapping sequence to gene expression [3]. Application of these approaches to well-studies systems such as Sacc... |
10.1371/journal.pntd.0006779 | A systematic review of antimicrobial resistance in Salmonella enterica serovar Typhi, the etiological agent of typhoid | The temporal and spatial change in trends of antimicrobial resistance (AMR) in typhoid have not been systematically studied, and such information will be critical for defining intervention, as well as planning sustainable prevention strategies.
To identify the phenotypic trends in AMR, 13,833 individual S. Typhi isolat... | Typhoid is an invasive bacterial disease causing 26 million illness episodes globally, each year particularly in South Asia and sub-Saharan Africa afflicting children and poorer sections of society disproportionally. AMR is increasingly recognized among S. Typhi lineages spreading from South Asia to Africa, with resist... | Enteric fever is a systemic infection, caused by the Gram-negative bacteria Salmonella enterica subspecies enterica serovars Typhi and Paratyphi A, that continues to be a significant cause of morbidity and mortality in endemic regions. Annually, it is estimated that over 26 million people are culture positive for S. Ty... |
Subsets and Splits
No community queries yet
The top public SQL queries from the community will appear here once available.