id stringlengths 20 20 | year int64 2.01k 2.02k | title stringlengths 21 249 | sections stringlengths 4.88k 32.5k | headings stringclasses 217
values | abstract stringlengths 32 4.12k | summary stringlengths 227 2.45k | keywords stringlengths 7 1.31k ⌀ | toc stringclasses 267
values |
|---|---|---|---|---|---|---|---|---|
journal.pntd.0007649 | 2,019 | A high-throughput and multiplex microsphere immunoassay based on non-structural protein 1 can discriminate three flavivirus infections | Despite a marked decrease of Zika virus ( ZIKV ) infection since late 2017 , the specter of congenital Zika syndrome ( CZS ) and its re-emergence in flavivirus-endemic regions highlight the need for sensitive and specific diagnostic tests 1–4 ., Similar to the laboratory diagnosis for other flaviviruses , detection of ... | Introduction, Methods, Results, Discussion | The explosive spread of Zika virus ( ZIKV ) and associated complications in flavivirus-endemic regions underscore the need for sensitive and specific serodiagnostic tests to distinguish ZIKV , dengue virus ( DENV ) and other flavivirus infections ., Compared with traditional envelope protein-based assays , several nons... | Although there was a decrease of Zika virus ( ZIKV ) infection since late 2017 , the specter of congenital Zika syndrome and its re-emergence in flavivirus-endemic regions emphasize the need for sensitive and specific serological tests to distinguish ZIKV , dengue virus ( DENV ) and other flaviviruses ., Compared with ... | dengue virus, medicine and health sciences, enzyme-linked immunoassays, immune physiology, pathology and laboratory medicine, pathogens, immunology, microbiology, viruses, rna viruses, antibodies, immunologic techniques, research and analysis methods, immune system proteins, serology, proteins, medical microbiology, mi... | null |
journal.pntd.0004831 | 2,016 | The Burden of Zoonoses in Kyrgyzstan: A Systematic Review | Zoonoses are diseases in humans , which are naturally transmissible directly or indirectly from vertebrate animals ., Of 1415 species of infectious organisms know to be human pathogens , 61% are zoonotic 1 ., The Food and Agriculture Organization of the United Nations ( FAO ) , the World Health Organization ( WHO ) and... | Introduction, Materials and Methods, Results, Discussion | Zoonotic disease ( ZD ) pose a serious threat to human health in low-income countries ., In these countries the human burden of disease is often underestimated due to insufficient monitoring because of insufficient funding ., Quantification of the impact of zoonoses helps in prioritizing healthcare needs ., Kyrgyzstan ... | Zoonoses are diseases transmitted from vertebrate animals to humans ., They can cause a variety of symptoms ranging from mild gastrointestinal complaints to debilitating illness and even death ., Especially in low-income countries where animals play an important role for many , the burden of these diseases can be subst... | medicine and health sciences, tropical diseases, parasitic diseases, salmonellosis, brucellosis, bacterial diseases, rabies, neglected tropical diseases, veterinary science, campylobacteriosis, echinococcosis, public and occupational health, infectious diseases, veterinary diseases, zoonoses, helminth infections, biolo... | null |
journal.pcbi.1000611 | 2,009 | Distributed Dynamical Computation in Neural Circuits with Propagating Coherent Activity Patterns | To understand brain function , it is essential to study the collective electrical activity of neural circuits 1 ., This activity typically exhibits intriguing spatiotemporally organized patterns: they are commonly observed in multi-unit electrophysiological recording , EEG local field potential recording , MEG , optica... | Introduction, Discussion | Activity in neural circuits is spatiotemporally organized ., Its spatial organization consists of multiple , localized coherent patterns , or patchy clusters ., These patterns propagate across the circuits over time ., This type of collective behavior has ubiquitously been observed , both in spontaneous activity and ev... | The brain processes information with extraordinary efficiency , and can perform feats such as effortlessly recognizing objects from among thousands of possibilities within a fraction of a second ., This is accomplished because the brain represents and processes information in a distributed fashion and in a dynamical wa... | biophysics/theory and simulation, computational biology/computational neuroscience | null |
journal.pgen.0030147 | 2,007 | Adaptive Evolution of Conserved Noncoding Elements in Mammals | Phenotypic evolution proceeds both by changes in protein coding sequences and by changes in gene expression that determine when , where , and how much genes are expressed 1–3 ., Although recent genome-wide studies have begun the process of identifying genes that show signals of adaptive evolution in coding sequences 4 ... | Introduction, Results, Discussion, Methods, Supporting Information | Conserved noncoding elements ( CNCs ) are an abundant feature of vertebrate genomes ., Some CNCs have been shown to act as cis-regulatory modules , but the function of most CNCs remains unclear ., To study the evolution of CNCs , we have developed a statistical method called the “shared rates test” to identify CNCs tha... | Conservation of DNA sequences across evolutionary history is a highly informative signal for identifying regions with important biological functions ., In particular , conserved noncoding regions have been shown to be good candidates for containing regulatory elements that have roles in gene regulation ., Recent studie... | evolutionary biology, genetics and genomics, mammals, computational biology | null |
journal.pgen.1002236 | 2,011 | A Comprehensive Map of Mobile Element Insertion Polymorphisms in Humans | Retrotransposons are endogenous genomic sequences that copy and paste into locations throughout host genomes 1–3 ., Most mobile elements annotated in the human reference genome are remnants of ancient retrotransposition events and are no longer capable of active retrotransposition ., However , a fraction of mobile elem... | Introduction, Results, Discussion, Materials and Methods | As a consequence of the accumulation of insertion events over evolutionary time , mobile elements now comprise nearly half of the human genome ., The Alu , L1 , and SVA mobile element families are still duplicating , generating variation between individual genomes ., Mobile element insertions ( MEI ) have been identifi... | We embarked on this study to explore the 1000 Genomes Project ( 1000GP ) pilot dataset as a substrate for Mobile Element Insertion ( MEI ) discovery and analysis ., MEI is already well known as a significant component of genetic variation in the human population ., However the full extent and effects of MEI can only be... | functional genomics, genetic mutation, genome evolution, genome scans, neutral theory, population genetics, genome sequencing, mutation, genome analysis tools, genome databases, mutation types, mutation databases, genetic polymorphism, biology, genetics, genomics, computational biology, genetics and genomics, human gen... | null |
journal.pcbi.1006142 | 2,018 | Systematic interrogation of diverse Omic data reveals interpretable, robust, and generalizable transcriptomic features of clinically successful therapeutic targets | More than half of drug candidates that advance beyond phase I clinical trials fail due to lack of efficacy 1 , 2 ., One possible explanation for these failures is sub-optimal target selection 3 ., Many factors must be considered when selecting a target for drug discovery 4 , 5 ., Intrinsic factors include the likelihoo... | Introduction, Results, Discussion, Conclusion, Methods | Target selection is the first and pivotal step in drug discovery ., An incorrect choice may not manifest itself for many years after hundreds of millions of research dollars have been spent ., We collected a set of 332 targets that succeeded or failed in phase III clinical trials , and explored whether Omic features de... | Drug discovery often begins with a hypothesis that changing the abundance or activity of a target—a biological molecule , usually a protein—will cure a disease or ameliorate its symptoms ., Whether a target hypothesis translates into a successful therapy depends in part on the characteristics of the target , but it is ... | medicine and health sciences, tissue proteins, phase iii clinical investigation, protein expression, clinical medicine, mathematics, artificial intelligence, pharmacology, molecular biology techniques, discrete mathematics, combinatorics, research and analysis methods, computer and information sciences, proteins, gene ... | null |
journal.pcbi.1005389 | 2,017 | Bayesian phylogeography of influenza A/H3N2 for the 2014-15 season in the United States using three frameworks of ancestral state reconstruction | Bayesian phylogeography has emerged as a powerful approach to analyzing virus spread ., It utilizes sequence data to perform ancestral reconstruction and estimate the most likely lineages of the viruses in rooted , time-measured phylogenies 1 using nucleotide substitution models , molecular clocks , and coalescent prio... | Introduction, Results, Discussion | Ancestral state reconstructions in Bayesian phylogeography of virus pandemics have been improved by utilizing a Bayesian stochastic search variable selection ( BSSVS ) framework ., Recently , this framework has been extended to model the transition rate matrix between discrete states as a generalized linear model ( GLM... | For the better part of the last decade , epidemiological researchers have employed a Bayesian framework to reconstruct phylogenetic trees and determine the spatiotemporal relationships between clades of viruses ., Recently , an extension of this framework has enabled direct assessment of how various demographic , geogr... | biogeography, taxonomy, ecology and environmental sciences, medicine and health sciences, pathology and laboratory medicine, influenza, atmospheric science, pathogens, population genetics, immunology, microbiology, orthomyxoviruses, viruses, preventive medicine, seasons, phylogenetics, data management, rna viruses, pop... | null |
journal.pgen.1004037 | 2,014 | Intrasubtype Reassortments Cause Adaptive Amino Acid Replacements in H3N2 Influenza Genes | The genome of influenza A virus consists of 8 segments , each represented by an RNA molecule ., Coinfection of a cell by viruses of different genotypes occasionally leads to reassortments , i ., e ., formation of genotypes containing molecules from different sources ., Most of the major Influenza A pandemics during the... | Introduction, Results, Discussion, Methods | Reassortments and point mutations are two major contributors to diversity of Influenza A virus; however , the link between these two processes is unclear ., It has been suggested that reassortments provoke a temporary increase in the rate of amino acid changes as the viral proteins adapt to new genetic environment , bu... | Influenza A is a rapidly evolving virus with genome composed of eight distinct RNA molecules called segments ., This genetic structure allows formation of new combinations of segments when a cell is coinfected by multiple viral strains , in a process called reassortment ., While “antigenic drift” – the process of conti... | organismal evolution, genome evolution, population genetics, microbiology, parallel evolution, mutation, microbial evolution, forms of evolution, comparative genomics, biology, evolutionary theory, evolutionary genetics, viral evolution, natural selection, virology, co-infections, genomics, evolutionary biology, genomi... | null |
journal.pcbi.1000927 | 2,010 | Synaptic Plasticity Controls Sensory Responses through Frequency-Dependent Gamma Oscillation Resonance | Synchronous oscillations 1–3 in neural networks are thought to be important to sensory and cognitive functions 4 , 5 ., In particular , gamma band oscillations ( 30∼70Hz ) have been observed in various neural circuits 6 , 7 , and their role has been intensively studied 8–11 ., Gamma oscillations synchronize the respons... | Introduction, Results, Discussion, Methods | Synchronized gamma frequency oscillations in neural networks are thought to be important to sensory information processing , and their effects have been intensively studied ., Here we describe a mechanism by which the nervous system can readily control gamma oscillation effects , depending selectively on visual stimuli... | In the nervous system , a network of neurons shows interesting population activities ., One example is a various frequency of synchronized oscillations which are thought to be important to sensory functions ., In particular , it has been reported that gamma frequency rhythms ( 30∼70Hz ) in the cortex can significantly ... | neuroscience/theoretical neuroscience, biophysics/theory and simulation, computational biology/systems biology, computational biology/computational neuroscience | null |
journal.pcbi.1002879 | 2,013 | An Integrative Model of Ion Regulation in Yeast | A feature of fungal physiology is the ability to adapt successfully to a variety of environmental perturbations , including ionic 1 , osmotic 2 and pH stress 3 ., All of these stresses have a substantial impact on intracellular K+/Na+ concentrations and other important physiological parameters of the cell such as cell ... | Introduction, Results, Discussion, Methods | Yeast cells are able to tolerate and adapt to a variety of environmental stresses ., An essential aspect of stress adaptation is the regulation of monovalent ion concentrations ., Ion regulation determines many fundamental physiological parameters , such as cell volume , membrane potential , and intracellular pH . It i... | Ion regulation is fundamental to cell physiology ., The concentrations of monovalent ions , such as H+ , K+ and Na+ , determine many physiological parameters such as cell volume , plasma membrane potential and intracellular pH . In yeast cells , these parameters are maintained within a narrow range during the adaptatio... | systems biology, biochemical simulations, regulatory networks, biology, computational biology | null |
journal.pbio.0060146 | 2,008 | Dynamics and Design Principles of a Basic Regulatory Architecture Controlling Metabolic Pathways | In the past several years , genomic approaches have dramatically accelerated the discovery of biological regulatory networks ., Combined with detailed biochemical and genetic studies , these approaches have yielded the intricate wiring diagrams for many biological systems ., Although revealing , such wiring diagrams ar... | Introduction, Results, Discussion, Materials and Methods | The dynamic features of a genetic networks response to environmental fluctuations represent essential functional specifications and thus may constrain the possible choices of network architecture and kinetic parameters ., To explore the connection between dynamics and network design , we have analyzed a general regulat... | Single-cell organisms must constantly adjust their gene expression programs to survive in a changing environment ., Interactions between different molecules form a regulatory network to mediate these changes ., While the network connections are often known , figuring out how the network responds dynamically by looking ... | biochemistry, cell biology, computational biology, biophysics, genetics and genomics | A quantitative, high-temporal resolution study of gene induction in a metabolic pathway reveals an intricate connection between the regulatory architecture and the dynamic response of the system, pointing to possible principles underlying the design of these pathways. |
journal.pcbi.1005815 | 2,017 | Automated deconvolution of structured mixtures from heterogeneous tumor genomic data | Tumor heterogeneity is now recognized as a pervasive feature of cancer biology with implications for every step of cancer development , progression , metastasis , and mortality ., Most solid tumors exhibit some form of hypermutability phenotype 1 , leading to extensive genomic variability as tumor cell populations expa... | Introduction, Materials and methods, Results, Discussion | With increasing appreciation for the extent and importance of intratumor heterogeneity , much attention in cancer research has focused on profiling heterogeneity on a single patient level ., Although true single-cell genomic technologies are rapidly improving , they remain too noisy and costly at present for population... | One of the major challenges in making sense of cancer genomics is high heterogeneity cell-to-cell , as a tumor is typically made up of multiple cell populations with distinct genomes and gene expression patterns ., The difficulty of working with such data has led to interest in computationally inferring the components ... | cancer genomics, taxonomy, medicine and health sciences, breast tumors, cancers and neoplasms, basic cancer research, oncology, phylogenetics, data management, materials science, copy number variation, materials by structure, genome complexity, computer and information sciences, breast cancer, comparative genomics, evo... | null |
journal.pntd.0006983 | 2,019 | TIM-1 serves as a receptor for Ebola virus in vivo, enhancing viremia and pathogenesis | Zaire ebolavirus ( EBOV ) is one of five species of ebolaviruses within the Filoviridae family ., EBOV continues to cause significant outbreaks in sub-Saharan Africa with case fatality rates as high as 90% 1 ., All filoviruses have a broad species and cellular tropism ., With the exception of lymphocytes , most cells w... | Introduction, Materials and methods, Results, Discussion | T cell immunoglobulin mucin domain-1 ( TIM-1 ) is a phosphatidylserine ( PS ) receptor , mediating filovirus entry into cells through interactions with PS on virions ., TIM-1 expression has been implicated in Ebola virus ( EBOV ) pathogenesis; however , it remains unclear whether this is due to TIM-1 serving as a filov... | T cell immunoglobulin mucin domain-1 ( TIM-1 ) is one of a number of phosphatidylserine ( PS ) receptors that mediate clearance of apoptotic bodies by binding PS on the surface of dead or dying cells ., Enveloped viruses mimic apoptotic bodies by exposing PS on the outer leaflet of the viral membrane ., While TIM-1 has... | blood cells, cell motility, innate immune system, medicine and health sciences, vesicular stomatitis virus, immune cells, pathology and laboratory medicine, immune physiology, cytokines, spleen, pathogens, immunology, microbiology, viruses, animal models, developmental biology, model organisms, rna viruses, experimenta... | null |
journal.ppat.1002583 | 2,012 | Preferential Entry of Botulinum Neurotoxin A Hc Domain through Intestinal Crypt Cells and Targeting to Cholinergic Neurons of the Mouse Intestine | Botulinum neurotoxins ( BoNTs ) are responsible for a severe nervous disease in man and animals known as botulism , characterized by skeletal muscle flaccid paralysis and respiratory arrest , resulting from inhibition of acetylcholine ( ACh ) release in peripheral cholinergic nerve terminals ., BoNTs are produced by Cl... | Introduction, Results, Discussion, Materials and Methods | Botulism , characterized by flaccid paralysis , commonly results from botulinum neurotoxin ( BoNT ) absorption across the epithelial barrier from the digestive tract and then dissemination through the blood circulation to target autonomic and motor nerve terminals ., The trafficking pathway of BoNT/A passage through th... | Botulism is a severe and often fatal disease in man and animals characterized by flaccid paralysis ., Clostridium botulinum produces a potent neurotoxin ( botulinum neurotoxin ) responsible for all the symptoms of botulism ., Botulism is most often acquired by ingesting preformed botulinum neurotoxin in contaminated fo... | medicine, biology, microbiology, molecular cell biology, toxicology | null |
journal.pgen.1005053 | 2,015 | Phenotype Specific Analyses Reveal Distinct Regulatory Mechanism for Chronically Activated p53 | The TP53 ( p53 ) tumor suppressor , a stress-responsive transcription factor ( TF ) , is somatically mutated in more than 50% of human cancers , with a range between 10% and nearly 100% depending on the tumor type ., Furthermore , germ line mutations of p53 , in both humans and mice , predispose individuals to malignan... | Introduction, Results, Discussion, Materials and Methods | The downstream functions of the DNA binding tumor suppressor p53 vary depending on the cellular context , and persistent p53 activation has recently been implicated in tumor suppression and senescence ., However , genome-wide information about p53-target gene regulation has been derived mostly from acute genotoxic cond... | The p53 transcription factor is a frequently mutated tumour suppressor that contributes to repairing or eliminating damaged cells ., Levels of p53 are typically regulated through its stability; it is constantly produced and degraded , so that upon stress , p53 is up-regulated quickly ., This acutely induced p53 has bee... | null | null |
journal.pbio.1001352 | 2,012 | Reversing the Outcome of Synapse Elimination at Developing Neuromuscular Junctions In Vivo: Evidence for Synaptic Competition and Its Mechanism | Physiological evidence that axons completely lose connections with some postsynaptic cells as part of naturally occurring development was first observed at the neuromuscular junction in mammals more than 40 years ago 1 ., Since then analogous axonal loss has been seen in many parts of the central and peripheral nervous... | Introduction, Results, Discussion, Materials and Methods | During mammalian development , neuromuscular junctions and some other postsynaptic cells transition from multiple- to single-innervation as synaptic sites are exchanged between different axons ., It is unclear whether one axon invades synaptic sites to drive off other inputs or alternatively axons expand their territor... | Early in development , neurons make multiple synaptic connections with their target cells ., Over time , many of these connections disappear , leaving behind a fraction of the original connections ., Because this pruning occurs when mammals first leave the uterus , its thought that this type of remodeling may serve to ... | motor systems, developmental neuroscience, synaptic plasticity, biology, neuroscience | Competition between neurons for the same synaptic sites at the developing neuromuscular junction drives synaptic rearrangements. |
journal.ppat.1006413 | 2,017 | Genomic fossils reveal adaptation of non-autonomous pararetroviruses driven by concerted evolution of noncoding regulatory sequences | Similar to virus–host interactions , virus–virus interactions , especially those occurring during mixed plant virus infections in nature , have complex outcomes ranging from antagonism to synergism 1 , 2 ., Such interactions between different virus species affect their adaptation 1 , 2 ., Numerous virus-derived sequenc... | Introduction, Results, Discussion, Materials and methods | The interplay of different virus species in a host cell after infection can affect the adaptation of each virus ., Endogenous viral elements , such as endogenous pararetroviruses ( PRVs ) , have arisen from vertical inheritance of viral sequences integrated into host germline genomes ., As viral genomic fossils , these... | This paper addresses the adaptive strategies of ancient defective viruses recorded in grass genomes ., We mined numerous virus segments from various grass genomes and assembled several defective pararetrovirus ( non-autonomous PRV ) species ., We attempted to understand how these non-autonomous PRVs can complete parasi... | taxonomy, oryza, computational biology, microbiology, phylogenetics, data management, phylogenetic analysis, genome analysis, paleontology, sequence motif analysis, paleogenetics, plants, microbial genomics, research and analysis methods, sequence analysis, viral genomics, computer and information sciences, grasses, se... | null |
journal.pntd.0001523 | 2,012 | A Novel G Protein-Coupled Receptor of Schistosoma mansoni (SmGPR-3) Is Activated by Dopamine and Is Widely Expressed in the Nervous System | The bloodfluke Schistosoma mansoni is one of three species of schistosomes that cause significant disease in humans ., Approximately 200 million people are infected and another 600 million are at risk of infection ., Over 90% of all human schistosomiasis is due to S . mansoni ., This species exists in Africa , the Midd... | Introduction, Materials and Methods, Results, Discussion | Schistosomes have a well developed nervous system that coordinates virtually every activity of the parasite and therefore is considered to be a promising target for chemotherapeutic intervention ., Neurotransmitter receptors , in particular those involved in neuromuscular control , are proven drug targets in other helm... | Bloodflukes of the genus Schistosoma are the causative agents of human schistosomiasis , a debilitating disease that afflicts over 200 million people worldwide ., There is no vaccine for schistosomiasis and treatment relies heavily on a single drug , praziquantel ., Recent reports of praziquantel resistance raise conce... | biology, molecular cell biology, zoology, neuroscience | null |
journal.pcbi.1005529 | 2,017 | Modelling of the cancer cell cycle as a tool for rational drug development: A systems pharmacology approach to cyclotherapy | Pharmacokinetic and pharmacodynamic ( PK/PD ) models of anticancer drug action have many potential applications 1–3 ., Among the most promising are the ability to match tumours with particular gene expression profiles to selective treatments 4 , the ability to search for potential synthetic lethalities 5 , and the abil... | Introduction, Results, Discussion, Materials and methods | The dynamic of cancer is intimately linked to a dysregulation of the cell cycle and signalling pathways ., It has been argued that selectivity of treatments could exploit loss of checkpoint function in cancer cells , a concept termed “cyclotherapy” ., Quantitative approaches that describe these dysregulations can provi... | Neoplastic transformation results from mutations , chromosomal abnormalities , or expression changes affecting components of the cell cycle , the signalling pathways leading into it , and the apoptosis pathways resulting from cell cycle arrest ., Cytotoxic agents , but also newer drugs that target the cell cycle and it... | cell death, medicine and health sciences, cell cycle and cell division, cancer treatment, cell processes, departures from diploidy, oncology, pharmacodynamics, pharmacology, synthesis phase, aneuploidy, signal transduction, apoptotic signaling cascade, cell biology, apoptosis, genetics, biology and life sciences, cell ... | null |
journal.pcbi.1005347 | 2,017 | Multiscale mutation clustering algorithm identifies pan-cancer mutational clusters associated with pathway-level changes in gene expression | Somatic mutations are amongst the most frequent genomic aberrations associated with cancer ., Moreover , primary human cancer samples usually contain tens to hundreds of somatic mutations , depending on the tissue of origin 1 ., The identification of mutations that alter the function of protein coding genes , and a mol... | Introduction, Results and discussion, Conclusion, Methods | Cancer researchers have long recognized that somatic mutations are not uniformly distributed within genes ., However , most approaches for identifying cancer mutations focus on either the entire-gene or single amino-acid level ., We have bridged these two methodologies with a multiscale mutation clustering algorithm th... | Identifying driver mutations in cancer has been a major challenge in cancer research , with the ultimate goal of understanding the detailed molecular origins of cancer and providing genetically personalized treatments ., For decades , the cancer research community has known that mutations in certain genes—such as tumor... | medicine and health sciences, applied mathematics, carcinomas, endometrial carcinoma, cancers and neoplasms, simulation and modeling, oncology, algorithms, mutation, mathematics, clustering algorithms, nonsense mutation, research and analysis methods, proteins, gene expression, gynecological tumors, somatic mutation, b... | null |
journal.pcbi.1000045 | 2,008 | The Dynamics of Human Body Weight Change | Obesity , anorexia nervosa , cachexia , and starvation are conditions that have a profound medical , social and economic impact on our lives ., For example , the incidence of obesity and its co-morbidities has increased at a rapid rate over the past two decades 1 , 2 ., These conditions are characterized by changes in ... | Introduction, Results, Discussion, Methods | An imbalance between energy intake and energy expenditure will lead to a change in body weight ( mass ) and body composition ( fat and lean masses ) ., A quantitative understanding of the processes involved , which currently remains lacking , will be useful in determining the etiology and treatment of obesity and other... | Understanding the dynamics of human body weight change has important consequences for conditions such as obesity , starvation , and wasting syndromes ., Changes of body weight are known to result from imbalances between the energy derived from food and the energy expended to maintain life and perform physical work ., H... | mathematics, biophysics/theory and simulation, diabetes and endocrinology/obesity, nutrition/obesity, computational biology/metabolic networks, physiology/integrative physiology, diabetes and endocrinology/type 2 diabetes | null |
journal.pntd.0003952 | 2,015 | Role of sph2 Gene Regulation in Hemolytic and Sphingomyelinase Activities Produced by Leptospira interrogans | Leptospirosis is a neglected zoonotic disease that afflicts humans and animals 1–3 ., Although the disease occurs worldwide , it is observed most frequently in tropical countries , where conditions for environmental survival and transmission are most favorable 4 ., The causative organisms are spirochetes belonging to t... | Introduction, Materials and Methods, Results, Discussion | Pathogenic members of the genus Leptospira are the causative agents of leptospirosis , a neglected disease of public and veterinary health concern ., Leptospirosis is a systemic disease that in its severest forms leads to renal insufficiency , hepatic dysfunction , and pulmonary failure ., Many strains of Leptospira pr... | The spirochete Leptospira causes leptospirosis , a potentially deadly disease of humans and animals ., Candidate factors that promote infection include hemolysins encoded by several leptospiral genes ., Hemolysins rupture red blood cells in vitro ., Some hemolysins are sphingomyelinases , which target sphingomyelin in ... | null | null |
journal.pcbi.1003316 | 2,013 | Conformational Changes in Talin on Binding to Anionic Phospholipid Membranes Facilitate Signaling by Integrin Transmembrane Helices | Integrins are cell surface receptors involved in many essential cellular processes , such as cell migration , and in pathological defects , such as thrombosis and cancer 1 ., Integrins are αβ heterodimers ., Each subunit has a large ectodomain , a single transmembrane ( TM ) helix and a short flexible cytoplasmic tail ... | Introduction, Results/Discussion, Methods | Integrins are heterodimeric ( αβ ) cell surface receptors that are activated to a high affinity state by the formation of a complex involving the α/β integrin transmembrane helix dimer , the head domain of talin ( a cytoplasmic protein that links integrins to actin ) , and the membrane ., The talin head domain contains... | Transmission of signals across the cell membrane is an essential process for all living organisms ., Integrins are one example of cell surface receptors ( αβ ) which , uniquely , form a bidirectional signalling pathway across the membrane ., Integrins are crucial for many cellular processes and play key roles in pathol... | null | null |
journal.pgen.1007049 | 2,017 | Long-lasting masculinizing effects of postnatal androgens on myelin governed by the brain androgen receptor | The incidence and clinical course of many neurological disorders differ between sexes , and elucidating the underlying biological basis has become a high priority challenge 1 , 2 ., The potential impact of sex differences in brain structure has long been neglected ., They were indeed believed to be restricted to specif... | Introduction, Results, Discussion, Matherials and methods | The oligodendrocyte density is greater and myelin sheaths are thicker in the adult male mouse brain when compared with females ., Here , we show that these sex differences emerge during the first 10 postnatal days , precisely at a stage when a late wave of oligodendrocyte progenitor cells arises and starts differentiat... | Sex differences in brain structure are of great scientific and medical interest because the incidence and progress of many neurological and psychiatric disorders differ between males and females ., They affect neural networks and also the myelin sheaths that insulate and protect axons and thus allow the rapid conductio... | plant anatomy, stem anatomy, medicine and health sciences, internodes, nervous system, brain, neuroscience, macroglial cells, hormones, plant science, testosterone, nerve fibers, research and analysis methods, androgens, specimen preparation and treatment, staining, animal cells, axons, corpus callosum, glial cells, my... | null |
journal.ppat.1006179 | 2,017 | Co-infecting Reptarenaviruses Can Be Vertically Transmitted in Boa Constrictor | Boid inclusion body disease ( BIBD ) is a transmissible , progressive and generally fatal disease of boid snakes ., First described in the 1970s , BIBD subsequently emerged as a major problem in boid snake collections worldwide 1 , 2 ., Several genera of boid species have been reported as susceptible to the disease , b... | Introduction, Results, Discussion, Materials And Methods | Boid inclusion body disease ( BIBD ) is an often fatal disease affecting mainly constrictor snakes ., BIBD has been associated with infection , and more recently with coinfection , by various reptarenavirus species ( family Arenaviridae ) ., Thus far BIBD has only been reported in captive snakes , and neither the incub... | Members of the genus Reptarenavirus are “newcomers” of the family Arenaviridae and have been associated with boid inclusion body disease ( BIBD ) , an economically important , fatal disease of captive boid snakes ., Recently , we and others observed that snakes with BIBD commonly harbour several S and L segments ( aren... | reverse transcriptase-polymerase chain reaction, sequencing techniques, medicine and health sciences, body fluids, biological cultures, brain, vertebrates, animals, next-generation sequencing, developmental biology, reptiles, genome analysis, cell cultures, molecular biology techniques, embryos, kidneys, research and a... | null |
journal.pcbi.1000699 | 2,010 | Estimating the Stochastic Bifurcation Structure of Cellular Networks | One of the primary goals of systems biology is to uncover the dynamics of cellular networks ., Sometimes , this has meant collecting time-series data and applying tools for time-series analysis such as Fourier methods to identify periodically expressed genes 1–3 or temporal clustering to identify different dynamic “mod... | Introduction, Results, Discussion, Materials and Methods | High throughput measurement of gene expression at single-cell resolution , combined with systematic perturbation of environmental or cellular variables , provides information that can be used to generate novel insight into the properties of gene regulatory networks by linking cellular responses to external parameters .... | Decades ago , Waddington , and later Kauffman , likened the dynamics of a differentiating cell to a marble rolling downhill on bumpy terrain—the epigenetic landscape ., In this metaphor , the valleys of the landscape represent the paths that cells can follow towards a stable cell type , and the fate of the cell is dete... | molecular biology/bioinformatics, computational biology/systems biology | null |
journal.ppat.1006714 | 2,017 | A mobile loop near the active site acts as a switch between the dual activities of a viral protease/deubiquitinase | Ubiquitin ( Ub ) is a 76-residue protein that is highly conserved throughout the eukaryotic kingdom ., Attachment of Ub to cellular proteins ( referred to as ubiquitylation ) is recognized as a key regulatory pathway , critical to a number of major cellular processes , including protein homeostasis , intracellular sign... | Introduction, Results, Discussion, Materials and methods | The positive-strand RNA virus Turnip yellow mosaic virus ( TYMV ) encodes an ovarian tumor ( OTU ) -like protease/deubiquitinase ( PRO/DUB ) protein domain involved both in proteolytic processing of the viral polyprotein through its PRO activity , and in removal of ubiquitin chains from ubiquitylated substrates through... | Viruses have much smaller genomes than their hosts ., Consequently , they often encode proteins which are multifunctional ., For instance , some viral proteases have a dual function , being also deubiquitinases , i . e . enzymes capable of removing ubiquitin tags grafted onto proteins and that often target them for des... | plant anatomy, microbial mutation, crystal structure, molecular dynamics, condensed matter physics, microbiology, brassica, crystals, plant science, model organisms, materials science, experimental organism systems, crystallography, plants, materials by structure, arabidopsis thaliana, research and analysis methods, so... | null |
journal.ppat.1002084 | 2,011 | The Intrinsic Antiviral Defense to Incoming HSV-1 Genomes Includes Specific DNA Repair Proteins and Is Counteracted by the Viral Protein ICP0 | Mammalian cells have evolved complex defenses to protect themselves from viral infections ., Innate and adaptive immune responses are well-characterized , but resistance mediated by pre-existing cellular factors has recently emerged as another important arm of antiviral defense ., In contrast to the canonical immune re... | Introduction, Results, Discussion, Materials and Methods | Cellular restriction factors responding to herpesvirus infection include the ND10 components PML , Sp100 and hDaxx ., During the initial stages of HSV-1 infection , novel sub-nuclear structures containing these ND10 proteins form in association with incoming viral genomes ., We report that several cellular DNA damage r... | The cellular DNA damage response pathway monitors damage to genomic DNA ., We investigated whether cellular DNA damage response proteins can also respond to incoming viral genetic material and how they impact virus growth ., Using Herpes Simplex Virus type 1 ( HSV-1 ) , we present evidence that DNA repair proteins are ... | biology, microbiology, molecular cell biology | null |
journal.pbio.0050077 | 2,007 | The Sorcerer II Global Ocean Sampling Expedition: Northwest
Atlantic through Eastern Tropical Pacific | The concept of microbial diversity is not well defined ., It can either refer to the genetic, ( taxonomic or phylogenetic ) diversity as commonly measured by molecular genetics methods , or, to the biochemical ( physiological ) diversity measured in the laboratory with pure or mixed, cultures ., However , we know surpr... | Introduction, Results, Discussion, Materials and Methods, Supporting Information | The worlds oceans contain a complex mixture of micro-organisms that are for the most, part , uncharacterized both genetically and biochemically ., We report here a metagenomic, study of the marine planktonic microbiota in which surface ( mostly marine ) water samples, were analyzed as part of the Sorcerer II Global Oce... | Marine microbes remain elusive and mysterious , even though they are the most abundant, life form in the ocean , form the base of the marine food web , and drive energy and, nutrient cycling ., We know so little about the vast majority of microbes because only a, small percentage can be cultivated and studied in the la... | viruses, archaea, ecology, virology, microbiology, computational biology, evolutionary biology, genetics and genomics, eubacteria | TheSorcerer II GOS expedition, data sampling, and analysis is described.
The immense diversity in the sequence data required novel comparative genomic assembly
methods, which uncovered genomic differences that marker-based methods could not. |
journal.pntd.0005238 | 2,017 | Molecular Mimicry between Chikungunya Virus and Host Components: A Possible Mechanism for the Arthritic Manifestations | Chikungunya fever is caused by a arbovirus belonging to Family Togaviridae and Genus Alphavirus ., CHIKV is positive sense RNA virus with about 11 . 8 kb long genome ., The prevalence of CHIKV has increased globally ., It caused massive outbreaks when it re- emerged in 2005 in French Reunion islands where it affected a... | Introduction, Methods, Results, Discussion | Chikungunya virus ( CHIKV ) , a reemerging pathogen causes a self limited illness characterized by fever , headache , myalgia and arthralgia ., However , 10–20% affected individuals develop persistent arthralgia which contributes to considerable morbidity ., The exact molecular mechanisms underlying these manifestation... | The outcome of Chikungunya virus infection is usually benign but persistent arthritis has been reported in 10–20% of patients after Chikungunya fever ., However , some reports have suggested that similarity between host proteins and viral proteins ( molecular mimicry ) leads to immune mediated damage ., However , this ... | medicine and health sciences, immune physiology, pathology and laboratory medicine, togaviruses, chikungunya infection, pathogens, immunology, tropical diseases, microbiology, alphaviruses, viruses, muscle regeneration, developmental biology, chikungunya virus, rna viruses, signs and symptoms, organism development, neg... | null |
journal.pbio.2005970 | 2,018 | CellProfiler 3.0: Next-generation image processing for biology | Image analysis software is now used throughout biomedical research in order to reduce subjective bias and quantify subtle phenotypes when working with microscopy images ., Automated microscopes are further transforming modern research ., Experiments testing chemical compounds or genetic perturbations can reach a scale ... | Introduction, Results, Future directions, Materials and methods | CellProfiler has enabled the scientific research community to create flexible , modular image analysis pipelines since its release in 2005 ., Here , we describe CellProfiler 3 . 0 , a new version of the software supporting both whole-volume and plane-wise analysis of three-dimensional ( 3D ) image stacks , increasingly... | The “big-data revolution” has struck biology: it is now common for robots to prepare cell samples and take thousands of microscopy images ., Looking at the resulting images by eye would be extremely tedious , not to mention subjective ., Thus , many biologists find they need software to analyze images easily and accura... | open science, blastocysts, methods and resources, engineering and technology, signal processing, applied mathematics, biologists, simulation and modeling, algorithms, developmental biology, scientists, mathematics, science and technology workforce, research and analysis methods, specimen preparation and treatment, embr... | null |
journal.pcbi.1000635 | 2,010 | Network-Free Inference of Knockout Effects in Yeast | High-throughput technologies are routinely used to map molecular interactions within the cell ., These include chromatin immuno-precipitation experiments for measuring protein-DNA interactions ( PDIs ) 1 , and yeast two-hybrid assays 2 and co-immunoprecipitation screens 3 for measuring protein-protein interactions ( PP... | Introduction, Results/Discussion, Materials and Methods | Perturbation experiments , in which a certain gene is knocked out and the expression levels of other genes are observed , constitute a fundamental step in uncovering the intricate wiring diagrams in the living cell and elucidating the causal roles of genes in signaling and regulation ., Here we present a novel framewor... | Observing a complex biological system in steady state is often insufficient for a thorough understanding of its working ., For such inference , perturbation experiments are necessary and are traditionally employed ., In this work we focus on perturbations in which a gene is knocked out and as a result multiple genes ch... | computational biology/systems biology, computational biology/transcriptional regulation | null |
journal.pntd.0004259 | 2,015 | Assessment of Inhibitors of Pathogenic Crimean-Congo Hemorrhagic Fever Virus Strains Using Virus-Like Particles | Crimean-Congo hemorrhagic fever ( CCHF ) is a rapidly progressing inflammatory illness with high case fatality rates and a vast endemic area 1–6 ., The etiological agent , CCHF virus ( CCHFV ) , is a tri-segmented virus belonging to the Nairovirus genus of the Bunyaviridae family; it is primarily maintained in and tran... | Introduction, Materials and Methods, Results, Discussion | Crimean-Congo hemorrhagic fever ( CCHF ) is an often lethal , acute inflammatory illness that affects a large geographic area ., The disease is caused by infection with CCHF virus ( CCHFV ) , a nairovirus from the Bunyaviridae family ., Basic research on CCHFV has been severely hampered by biosafety requirements and la... | The tick-borne Crimean-Congo hemorrhagic fever virus ( CCHFV ) is the causative agent of a frequently life-threatening disease ., CCHFV is present in a wide geographic area with potential for expansion ., Moreover , CCHFV segmented genome reassortment leads to new strains with potentially different virulence ., Studyin... | null | null |
journal.ppat.1004499 | 2,014 | Restriction of Francisella novicida Genetic Diversity during Infection of the Vector Midgut | Genetic diversity within a single microbial species can lead to infection of hosts with mixtures of pathogen genotypes ., Remarkably , studies across numerous systems have demonstrated that mixed-genotype infections are more common than infections with a single clonal variant 1–5 ., The degree of genotypic diversity , ... | Introduction, Results, Discussion, Materials and Methods | The genetic diversity of pathogens , and interactions between genotypes , can strongly influence pathogen phenotypes such as transmissibility and virulence ., For vector-borne pathogens , both mammalian hosts and arthropod vectors may limit pathogen genotypic diversity ( number of unique genotypes circulating in an are... | Co-infection , the presence of multiple genotypes of the same pathogen species within an infected individual , is common ., Genotype diversity , defined as the number of unique genotypes , and the interaction between genotypes , can strongly influence virulence and pathogen transmission ., Understanding how genotypic d... | medicine and health sciences, vector-borne diseases, microbiology, bacterial diseases, population modeling, bacterial pathogens, veterinary science, animal models of infection, infectious diseases, veterinary diseases, zoonoses, veterinary microbiology, medical microbiology, microbial pathogens, infectious disease mode... | null |
journal.pgen.1000721 | 2,009 | Evolutionary Convergence and Nitrogen Metabolism in Blattabacterium strain Bge, Primary Endosymbiont of the Cockroach Blattella germanica | In 1887 , Blochmann first described symbiotic bacteria in the fatty tissue of blattids 1 ., Later , Buchner 2 suggested that symbionts are involved in the decomposition of metabolic end-products from the insect host ., A classic example is the cockroach ., Several pioneering studies correlated the presence of cockroach... | Introduction, Results/Discussion, Materials and Methods | Bacterial endosymbionts of insects play a central role in upgrading the diet of their hosts ., In certain cases , such as aphids and tsetse flies , endosymbionts complement the metabolic capacity of hosts living on nutrient-deficient diets , while the bacteria harbored by omnivorous carpenter ants are involved in nitro... | Bacterial endosymbionts from insects are subjected to a process of genome reduction from the moment they interact with their host , especially when the symbiosis is strict ( the partners live together permanently ) and the endosymbiont is maternally inherited ., The type of genes that are retained correlates with speci... | genetics and genomics/genome projects, genetics and genomics/microbial evolution and genomics, evolutionary biology/microbial evolution and genomics, evolutionary biology/evolutionary and comparative genetics | null |
journal.ppat.1007445 | 2,018 | Whole genome screen reveals a novel relationship between Wolbachia levels and Drosophila host translation | Insects are common vectors for devastating human viruses such as Zika , Yellow Fever , and Dengue ., A novel preventative strategy has emerged to combat vector-borne diseases that exploits the consequences of vector-insect infection with the bacteria Wolbachia pipientis 1–4 ., Wolbachia is a vertically transmitted , gr... | Introduction, Results, Discussion, Materials and methods | Wolbachia is an intracellular bacterium that infects a remarkable range of insect hosts ., Insects such as mosquitos act as vectors for many devastating human viruses such as Dengue , West Nile , and Zika ., Remarkably , Wolbachia infection provides insect hosts with resistance to many arboviruses thereby rendering the... | Insects such as mosquitos act as vectors to spread devastating human diseases such as Dengue , West Nile , and Zika ., It is critical to develop control strategies to prevent the transmission of these diseases to human populations ., A novel strategy takes advantage of an endosymbiotic bacterium Wolbachia pipientis ., ... | invertebrates, medicine and health sciences, rna interference, pathology and laboratory medicine, cell processes, genomic library screening, animals, wolbachia, invertebrate genomics, animal models, drosophila melanogaster, model organisms, experimental organism systems, epigenetics, molecular biology techniques, bacte... | null |
journal.pcbi.1002582 | 2,012 | Activity Dependent Degeneration Explains Hub Vulnerability in Alzheimers Disease | Like many other complex networks , the human brain contains parts that are better connected to the rest than others: ‘hub’ regions ., Evidence is increasing that a collection of brain hub regions forms a ‘structural core’ or ‘connectivity backbone’ that facilitates cognitive processing 1 , 2 , 3 ., Brain hub regions ar... | Introduction, Results, Discussion, Materials and Methods | Brain connectivity studies have revealed that highly connected ‘hub’ regions are particularly vulnerable to Alzheimer pathology: they show marked amyloid-β deposition at an early stage ., Recently , excessive local neuronal activity has been shown to increase amyloid deposition ., In this study we use a computational m... | An intriguing recent observation is that deposition of the amyloid-β protein , one of the hallmarks of Alzheimers disease , mainly occurs in brain regions that are highly connected to other regions ., To test the hypothesis that these ‘hub’ regions are more vulnerable due to a higher neuronal activity level , we examin... | medicine, neurobiology of disease and regeneration, neural networks, neuroscience, mathematics, computational neuroscience, alzheimer disease, biology, dementia, nonlinear dynamics, central nervous system, neurological disorders, neurology, neurophysiology | null |
journal.pntd.0001650 | 2,012 | Genetic Characterization of Trypanosoma cruzi DTUs in Wild Triatoma infestans from Bolivia: Predominance of TcI | Trypanosoma cruzi , the agent of Chagas disease , is a serious threat to health in the Americas , accounting for the highest disease burden in Latin American , with eight to nine million people infected and 25–90 million at risk 1–3 ., This parasite , which belongs to the order Kinetoplastida , is mainly transmitted by... | Introduction, Materials and Methods, Results, Discussion | The current persistence of Triatoma infestans ( one of the main vectors of Chagas disease ) in some domestic areas could be related to re-colonization by wild populations which are increasingly reported ., However , the infection rate and the genetic characterization of the Trypanosoma cruzi strains infecting these pop... | Chagas disease is a neglected parasitic disease transmitted by bugs ( vectors ) and represents a serious health problem in the Americas ., Although the transmission generally occurs in the houses where the bugs are living , wild populations of vectors are now considered a problem because these populations might enter t... | medicine, infectious diseases, biology, population biology, evolutionary biology | null |
journal.pgen.1007582 | 2,018 | Structure and function of archaeal histones | In eukaryotes , octameric histone cores compact DNA by wrapping an approximately 150-bp unit twice around its surface , forming a nucleosome 12 , 13 ., Nucleosomes interact with each other , yielding an additional level of DNA organization in the form of a fibre ., Besides a role in compaction , histones also play role... | Introduction, Histones are found in some newly discovered Archaea, Conclusion, Methods | The genomes of all organisms throughout the tree of life are compacted and organized in chromatin by association of chromatin proteins ., Eukaryotic genomes encode histones , which are assembled on the genome into octamers , yielding nucleosomes ., Post-translational modifications of the histones , which occur mostly o... | Both Archaea and eukaryotes express histones , but whereas the tertiary structure of histones is conserved , the quaternary structure of histone–DNA complexes is very different ., In a recent study , the crystal structure of the archaeal hypernucleosome was revealed to be an “endless” core of interacting histones that ... | chemical compounds, dna-binding proteins, microbiology, organic compounds, review, archaea, basic amino acids, amino acids, epigenetics, chromatin, chromosome biology, proteins, gene expression, chemistry, histones, nucleosomes, archaean biology, biochemistry, eukaryota, cell biology, organic chemistry, genetics, biolo... | null |
journal.ppat.1003249 | 2,013 | Dimeric RNA Recognition Regulates HIV-1 Genome Packaging | Retroviruses are RNA viruses that replicate through a DNA phase , in which viral DNA is integrated into the host genome to form a provirus 1 ., Retroviral genomes in virions are dimers , consisting of two copies of full-length , unspliced RNA , each of which encodes all of the genetic information needed for virus repli... | Introduction, Results, Discussion, Methods | How retroviruses regulate the amount of RNA genome packaged into each virion has remained a long-standing question ., Our previous study showed that most HIV-1 particles contain two copies of viral RNA , indicating that the number of genomes packaged is tightly regulated ., In this report , we examine the mechanism tha... | Viruses must package their genomes in particles to pass their genetic information to the next generation ., Although many aspects of RNA packaging are well-studied , how retroviruses regulate the number of genomes in the particle is currently unknown ., Based on the dimeric nature of retroviral genomes in particles , i... | medicine, biology | null |
journal.pgen.1006739 | 2,017 | Predicting the impact of Lynch syndrome-causing missense mutations from structural calculations | Due to mutations , stress , or failures during synthesis , cells produce proteins that misfold ., Accumulation of misfolded proteins represents a considerable threat to cells , which have therefore evolved efficient protein quality control ( PQC ) mechanisms 1–3 ., These rely on molecular chaperones that either refold ... | Introduction, Results, Discussion, Materials and methods | Accurate methods to assess the pathogenicity of mutations are needed to fully leverage the possibilities of genome sequencing in diagnosis ., Current data-driven and bioinformatics approaches are , however , limited by the large number of new variations found in each newly sequenced genome , and often do not provide di... | The protein quality control system targets misfolded proteins for degradation ., So far it has not been possible from sequence or structural data to predict the biological stability of a misfolded protein , or the effect of mutations on intracellular protein levels ., Here we demonstrate that in silico saturation mutag... | medicine and health sciences, pathology and laboratory medicine, gene regulation, genetic diseases, mutation, hereditary nonpolyposis colorectal cancer, chaperone proteins, autosomal dominant diseases, thermodynamics, missense mutation, small interfering rnas, proteins, gene expression, pathogenesis, biophysics, clinic... | null |
journal.pcbi.1003913 | 2,014 | Inference of Epidemiological Dynamics Based on Simulated Phylogenies Using Birth-Death and Coalescent Models | In many applications determining the past dynamics of populations is of interest ., In an epidemiological context in particular , the interest lies in knowing two quantities: the basic reproductive ratio and the growth rate of the epidemic ., is a key parameter that determines the probability and the extent of spread o... | Introduction, Results, Discussion, Materials and Methods | Quantifying epidemiological dynamics is crucial for understanding and forecasting the spread of an epidemic ., The coalescent and the birth-death model are used interchangeably to infer epidemiological parameters from the genealogical relationships of the pathogen population under study , which in turn are inferred fro... | The control or prediction of an epidemic outbreak requires the quantification of the parameters of transmission and recovery ., These parameters can be inferred from phylogenetic relationships among the pathogen strains isolated from infected individuals ., The coalescent and the birth-death process are two mathematica... | phylogenetics, plant science, medicine and health sciences, infectious disease epidemiology, epidemiology, plant pathology, biology and life sciences, population biology, evolutionary biology, evolutionary systematics | null |
journal.pntd.0002253 | 2,013 | Schistosoma japonicum Soluble Egg Antigens Attenuate Invasion in a First Trimester Human Placental Trophoblast Model | Schistosomes are parasitic worms endemic to many parts of Africa , South America and Southeast Asia ., They represent a significant disease burden in endemic regions , and have been estimated to be responsible for as many as 13–15 million disability-adjusted life years ( DALYs ) lost per year , with the true number pot... | Introduction, Materials and Methods, Results, Discussion | Schistosomiasis affects nearly 40 million women of reproductive age , and is known to elicit a pro-inflammatory signature in the placenta ., We have previously shown that antigens from schistosome eggs can elicit pro-inflammatory cytokine production from trophoblast cells specifically; however , the influence of these ... | Approximately 40 million women of childbearing age suffer from schistosome infection globally at any given time ., Multiple studies in rodent models , as well as a few reports in humans , suggest that schistosome infection results in poor pregnancy outcomes ., We have previously shown that antigens released from schist... | medicine, infectious diseases, schistosomiasis, obstetrics and gynecology, pregnancy, global health, neglected tropical diseases | null |
journal.pgen.1001374 | 2,011 | Genome-Wide Association Analysis of Soluble ICAM-1 Concentration Reveals Novel Associations at the NFKBIK, PNPLA3, RELA, and SH2B3 Loci | A member of the immunoglobulin superfamily of adhesion receptors , ICAM-1 is expressed on endothelial cells where it serves as a receptor for the leukocyte integrins LFA-1 and Mac-1 1 ., A soluble form of ICAM-1 ( sICAM-1 ) is present in plasma and is thought to arise from proteolytic cleavage of the extra-cellular dom... | Introduction, Results, Discussion, Methods | Soluble ICAM-1 ( sICAM-1 ) is an endothelium-derived inflammatory marker that has been associated with diverse conditions such as myocardial infarction , diabetes , stroke , and malaria ., Despite evidence for a heritable component to sICAM-1 levels , few genetic loci have been identified so far ., To comprehensively a... | Soluble Intercellular Adhesion Molecule 1 ( sICAM-1 ) is an inflammatory marker that has been associated with several common diseases such as diabetes , heart disease , stroke , and malaria ., While it is known that blood concentrations of sICAM-1 are at least partially genetically determined , our current knowledge of... | cardiovascular disorders/coronary artery disease, immunology/genetics of the immune system, genetics and genomics/complex traits | null |
journal.pcbi.1005884 | 2,018 | Cardinal features of involuntary force variability can arise from the closed-loop control of viscoelastic afferented muscles | Involuntary fluctuations in muscle force are inherent to human motor control ., Evidence suggests that this apparent ‘noise’ is functionally significant for movement execution and learning 1–5 ., Furthermore , amplification of force variability or distortion of its frequency content is an almost universal phenomenon wh... | Introduction, Results, Discussion, Materials and methods | Involuntary force variability below 15 Hz arises from , and is influenced by , many factors including descending neural drive , proprioceptive feedback , and mechanical properties of muscles and tendons ., However , their potential interactions that give rise to the well-structured spectrum of involuntary force variabi... | Involuntary fluctuations in muscle force are an unavoidable consequence of human motor control and underlie movement execution errors ., Amplification and distortion of involuntary force variability are common phenomena found in various neurological conditions and in fatigue ., However , the underlying mechanisms for t... | medicine and health sciences, classical mechanics, myoclonus, pathology and laboratory medicine, fatigue, engineering and technology, signal processing, biomechanics, noise reduction, simulation and modeling, signs and symptoms, research and analysis methods, musculoskeletal mechanics, muscle physiology, sensory physio... | null |
journal.pntd.0003878 | 2,015 | Machine Learning Models and Pathway Genome Data Base for Trypanosoma cruzi Drug Discovery | In the 1980’s the pharmaceutical industry took advantage of advances in molecular biology/genetic engineering and began replacing phenotypic , whole-cell HTS with target-based screening assays 1 ., Target-based screens using simple recombinant protein enzymatic assays offer advantages in terms of cost and scalability .... | Introduction, Methods, Results, Discussion | Chagas disease is a neglected tropical disease ( NTD ) caused by the eukaryotic parasite Trypanosoma cruzi ., The current clinical and preclinical pipeline for T . cruzi is extremely sparse and lacks drug target diversity ., In the present study we developed a computational approach that utilized data from several publ... | Chagas disease is a neglected tropical disease ( NTD ) caused by the eukaryotic parasite Trypanosoma cruzi ., The disease is endemic to Latin America but is increasingly found in North America and Europe , primarily through immigration , and the spread of this disease is bringing new attention to the need for novel , s... | null | null |
journal.pntd.0002545 | 2,013 | The Burden of Cholera in Uganda | Cholera was first reported in Uganda in 1971 , when 757 cases were reported to the World Health Organization ( WHO ) ., During the subsequent years up to 1993 , Uganda reported cholera cases every 2–4 years to the WHO ., From 1994 to 1998 , cholera was reported annually in Uganda 1 ., In 1998 , Uganda reported almost 5... | Introduction, Methods, Results, Discussion | In 2010 , the World Health Organization released a new cholera vaccine position paper , which recommended the use of cholera vaccines in high-risk endemic areas ., However , there is a paucity of data on the burden of cholera in endemic countries ., This article reviewed available cholera surveillance data from Uganda ... | Uganda has reported cholera cases to the World Health Organization every year since 1997 ., Thus , the country may consider the introduction of a WHO-prequalified oral cholera vaccine ., This article reviews cholera surveillance data from 1997–2010 with a focus on the 2005–2010 time period to identify high risk populat... | null | null |
journal.pcbi.1000490 | 2,009 | Pushing Structural Information into the Yeast Interactome by High-Throughput Protein Docking Experiments | In the last decade , many genome-sequencing projects started delivering nearly complete lists of the macromolecules present in several model organisms ., However , taken individually , knowing the components reveal relatively little about how complex systems , such as a eukaryotic cell , assemble and coordinate the man... | Introduction, Methods, Results/Discussion | The last several years have seen the consolidation of high-throughput proteomics initiatives to identify and characterize protein interactions and macromolecular complexes in model organisms ., In particular , more that 10 , 000 high-confidence protein-protein interactions have been described between the roughly 6 , 00... | Proteins are the main perpetrators of most biological processes ., However , they seldom act alone , and most cellular functions are , in fact , carried out by large macromolecular complexes and regulated through intricate protein-protein interaction networks ., Consequently , large efforts have been devoted to unveil ... | biochemistry/structural genomics, computational biology/protein structure prediction, computational biology/macromolecular structure analysis | null |
journal.pcbi.1004295 | 2,015 | Inferring Regulatory Networks from Experimental Morphological Phenotypes: A Computational Method Reverse-Engineers Planarian Regeneration | Advances in developmental biology and regenerative medicine require a mechanistic understanding of the generation and repair processes that construct and repair complex anatomical structures 1 ., For example , a salamander can regenerate complete limbs , eyes , tails , and jaws 2; a tail grafted to its flank will , wit... | Introduction, Results, Discussion, Methods | Transformative applications in biomedicine require the discovery of complex regulatory networks that explain the development and regeneration of anatomical structures , and reveal what external signals will trigger desired changes of large-scale pattern ., Despite recent advances in bioinformatics , extracting mechanis... | Developmental and regenerative biology experiments are producing a huge number of morphological phenotypes from functional perturbation experiments ., However , existing pathway models do not generally explain the dynamic regulation of anatomical shape due to the difficulty of inferring and testing non-linear regulator... | null | null |
journal.pcbi.1000301 | 2,009 | Understanding Pitch Perception as a Hierarchical Process with Top-Down Modulation | Modelling the neural processing of pitch is essential for understanding the perceptual phenomenology of music and speech ., Pitch , one of the most important features of auditory perception , is usually associated with periodicities in sounds 1 ., Hence , a number of models of pitch perception are based upon a temporal... | Introduction, Methods, Results, Discussion | Pitch is one of the most important features of natural sounds , underlying the perception of melody in music and prosody in speech ., However , the temporal dynamics of pitch processing are still poorly understood ., Previous studies suggest that the auditory system uses a wide range of time scales to integrate pitch-r... | Pitch is one of the most important features of natural sounds ., The pitch sensation depends strongly on its temporal context , as happens , for example , in the perception of melody in music and prosody in speech ., However , the temporal dynamics of pitch processing are poorly understood ., Perceptual studies have sh... | otolaryngology/audiology, computational biology/computational neuroscience | null |
journal.pntd.0002171 | 2,013 | Transcriptional Profiling of the Circulating Immune Response to Lassa Virus in an Aerosol Model of Exposure | Lassa virus ( LASV ) is a segmented negative-strand RNA virus and a member of the Arenavirus genus ., LASV is a human pathogen that is endemic to several countries in West Africa ., It is estimated to infect more than 300 , 000 people each year , killing over 3 , 000 with fatality rate for Lassa fever ( LF ) being appr... | Introduction, Materials and Methods, Results, Discussion | Lassa virus ( LASV ) is a significant human pathogen that is endemic to several countries in West Africa ., Infection with LASV leads to the development of hemorrhagic fever in a significant number of cases , and it is estimated that thousands die each year from the disease ., Little is known about the complex immune m... | Lassa virus ( LASV ) , a member of the Arenaviridae family , is a viral hemorrhagic fever causing virus endemic to several countries in West Africa with a history of sporadic importation into the United States ., It has been characterized as a Category A agent , and despite the significant public health issues posed by... | immune activation, immunology, host-pathogen interaction, microbiology, animal models, adaptive immunity, model organisms, immune defense, immunoregulation, animal models of infection, biology, immune response, macaque, immunity, virology, innate immunity | null |
journal.pntd.0005822 | 2,017 | Predicting spatial spread of rabies in skunk populations using surveillance data reported by the public | A central focus for disease ecologists and epidemiologists is to quantify processes that determine geographic spread of disease 1 ., Surveillance systems , which rely on reporting by the public 2–5 , provide data that can improve understanding disease dynamics and planning interventions ., However , passive surveillanc... | Introduction, Methods, Results, Discussion | Prevention and control of wildlife disease invasions relies on the ability to predict spatio-temporal dynamics and understand the role of factors driving spread rates , such as seasonality and transmission distance ., Passive disease surveillance ( i . e . , case reports by public ) is a common method of monitoring eme... | Rabies is a deadly zoonotic infection with a global distribution ., In 2012 , an epizootic of skunk rabies established in northern Colorado , USA and spread rapidly through three counties ., The epizootic was documented through reports of dead skunks by the public ., We examined the reports to determine how rapidly rab... | epizootics, biogeography, animal types, medicine and health sciences, ecology and environmental sciences, animal diseases, pathology and laboratory medicine, pathogens, population genetics, tropical diseases, microbiology, spatial epidemiology, animals, viruses, rabies, mathematics, rna viruses, forecasting, statistics... | null |
journal.pgen.1005614 | 2,015 | Genus-Wide Comparative Genomics of Malassezia Delineates Its Phylogeny, Physiology, and Niche Adaptation on Human Skin | Over 100 years ago Malassezia was recognized as an inhabitant of human skin and implicated in a common skin disorder i . e . seborrheic dermatitis 1 ., Since then , Malassezia has been found on the skin of all tested warm blooded animals 2 , 3 , including dogs , horses , pigs , goats , cats and lambs 4–8 , and associat... | Introduction, Results, Discussion, Methods | Malassezia is a unique lipophilic genus in class Malasseziomycetes in Ustilaginomycotina , ( Basidiomycota , fungi ) that otherwise consists almost exclusively of plant pathogens ., Malassezia are typically isolated from warm-blooded animals , are dominant members of the human skin mycobiome and are associated with com... | Malassezia are the dominant eukaryotic residents of human skin and are associated with the most common skin disorders , including dandruff , atopic dermatitis , eczema , and others ., Despite significant effort , the role of Malassezia in skin disease and homeostasis remains unclear ., Malassezia are also unique among ... | null | null |
journal.pgen.1006298 | 2,016 | Nuclear Localised MORE SULPHUR ACCUMULATION1 Epigenetically Regulates Sulphur Homeostasis in Arabidopsis thaliana | Sulphur ( S ) is one of the essential macronutrients required for plant growth and plays a pivotal role in plant development and metabolism ., Plants take up S in the form of inorganic sulphate from the rhizosphere mainly by two high-affinity sulphate transporters , SULTR1;1 and SULTR1;2 1–3 ., Before reduction , sulph... | Introduction, Results, Discussion, Materials and Methods | Sulphur ( S ) is an essential element for all living organisms ., The uptake , assimilation and metabolism of S in plants are well studied ., However , the regulation of S homeostasis remains largely unknown ., Here , we report on the identification and characterisation of the more sulphur accumulation1 ( msa1-1 ) muta... | Sulphur is an essential element for all living organisms including plants ., Plants take up sulphur from the soil mainly in the form of inorganic sulphate ., The uptake of sulphate and assimilation of sulphur have been well studied ., However , the regulation of sulphur accumulation in plants remains largely unknown .,... | biotechnology, plant anatomy, chemical compounds, salts, brassica, sulfur, organisms, plant science, model organisms, genetically modified plants, epigenetics, dna, molecular biology techniques, plants, dna methylation, chromatin, genetic engineering, arabidopsis thaliana, research and analysis methods, genetically mod... | null |
journal.pcbi.1003324 | 2,013 | Quantifying Chaperone-Mediated Transitions in the Proteostasis Network of E. coli | Protein homeostasis ( proteostasis ) is essential for the viability of an organism ., The disruption of protein homeostasis involving the misfolding and subsequent aggregation of proteins is implicated in many diseases , including Downs syndrome , type-II diabetes , Alzheimers , Parkinsons and Huntingtons disease 1–4 .... | Introduction, Results, Discussion, Methods | For cells to function , the concentrations of all proteins in the cell must be maintained at the proper levels ( proteostasis ) ., This task – complicated by cellular stresses , protein misfolding , aggregation , and degradation – is performed by a collection of chaperones that alter the configurational landscape of a ... | To maintain proper amounts of folded , functional proteins , cells use systems of chaperones to correct misfolded proteins , disassemble aggregates , and provide sheltered environments in which proteins fold to their native structure ., Typically , an individual system is studied in isolation , and its effects on a giv... | null | null |
journal.pntd.0001047 | 2,011 | Individual Predisposition, Household Clustering and Risk Factors for Human Infection with Ascaris lumbricoides: New Epidemiological Insights | Much of our understanding of the epidemiology of Ascaris lumbricoides infections of humans has been acquired from the analysis of worm counts collected from infected individuals ., The only practical way of obtaining such data is by chemo-expulsion ., This procedure is best performed using anthelmintic drugs which para... | Introduction, Methods, Results, Discussion | Much of our current understanding of the epidemiology of Ascaris lumbricoides infections in humans has been acquired by analyzing worm count data ., These data are collected by treating infected individuals with anthelmintics so that worms are expelled intact from the gastrointestinal tract ., Analysis of such data est... | Numerous analyses have found that people infected with roundworm ( Ascaris lumbricoides ) are predisposed to harbor either many or few worms ., Members of the same household also tend to harbor similar numbers of worms ., These phenomena are called individual predisposition and household clustering respectively ., In t... | infectious diseases/helminth infections, infectious diseases/epidemiology and control of infectious diseases, mathematics/statistics | null |
journal.pbio.2005317 | 2,018 | Amino acid starvation sensing dampens IL-1β production by activating riboclustering and autophagy | Dietary amino acid restriction , without malnutrition , offers enormous health benefits , including longevity of lifespan 1 , acute stress resistance , increased insulin sensitivity , and modulation of inflammation 2 , 3 ., However , the underlying mechanisms through which amino acid restriction extends its beneficial ... | Introduction, Results, Discussion, Materials and methods | Activation of the amino acid starvation response ( AAR ) increases lifespan and acute stress resistance as well as regulates inflammation ., However , the underlying mechanisms remain unclear ., Here , we show that activation of AAR pharmacologically by Halofuginone ( HF ) significantly inhibits production of the proin... | Reduced intake of food ( also known as dietary restriction ) without malnutrition has been shown to benefit health in humans and animals , including an increase in life expectancy , metabolic fitness , and resistance to acute stress ., Recent studies have attributed the benefits associated with dietary restriction to t... | blood cells, cell death, innate immune system, medicine and health sciences, autophagic cell death, immune cells, immune physiology, cytokines, pathology and laboratory medicine, gene regulation, immunology, cell processes, messenger rna, animal models, developmental biology, model organisms, signs and symptoms, experi... | null |
journal.pcbi.1007090 | 2,019 | Connecting signaling and metabolic pathways in EGF receptor-mediated oncogenesis of glioblastoma | Diseases like cancer involve a large range of components that interact via complex and highly dynamic networks 1–3 , and are interconnected with biochemical pathways 4–7 ., These multipath interconnections may allow cancer and other diseases to take alternate routes and bypass the effects of therapeutic interventions .... | Introduction, Results, Discussion, Materials and methods | As malignant transformation requires synchronization of growth-driving signaling ( S ) and metabolic ( M ) pathways , defining cancer-specific S-M interconnected networks ( SMINs ) could lead to better understanding of oncogenic processes ., In a systems-biology approach , we developed a mathematical model for SMINs in... | Complex and highly dynamic interconnected networks allow cancer to take different routes and circumvent chemotherapy ., Therefore , understanding these context-specific networks and their dynamics of molecular interactions driven by different oncogenic signaling and metabolic pathways is very much needed to predict dru... | protein interaction networks, signaling networks, protein expression, network analysis, molecular biology techniques, research and analysis methods, computer and information sciences, oncogenic signaling, proteins, metabolic pathways, ras signaling, proteomics, metabolism, molecular biology, molecular biology assays an... | null |
journal.pgen.1002914 | 2,012 | A Sexual Ornament in Chickens Is Affected by Pleiotropic Alleles at HAO1 and BMP2, Selected during Domestication | Domestication is the strongest form of short term , highly directional selection known to man ., Darwin himself cited domestication as a model for evolution 1 ., The domestication process itself is associated with a whole raft of changes in phenotype , despite intentional selection on only a few traits ., For example ,... | Introduction, Results, Discussion, Materials and Methods | Domestication is one of the strongest forms of short-term , directional selection ., Although selection is typically only exerted on one or a few target traits , domestication can lead to numerous changes in many seemingly unrelated phenotypes ., It is unknown whether such correlated responses are due to pleiotropy or ... | The genetic analysis of phenotypes and the identification of the causative underlying genes remain central to molecular and evolutionary biology ., By utilizing the domestication process , it is possible to exploit the large differences between domesticated animals and their wild counterparts to study both this and the... | animal genetics, genomics, functional genomics, gene expression, genetics, biology, evolutionary biology, evolutionary genetics, genetics and genomics | null |
journal.pgen.1001064 | 2,010 | Ancient Protostome Origin of Chemosensory Ionotropic Glutamate Receptors and the Evolution of Insect Taste and Olfaction | Ionotropic glutamate receptors ( iGluRs ) are a conserved family of ligand-gated ion channels present in both eukaryotes and prokaryotes ., By regulating cation flow across the plasma membrane in response to binding of extracellular glutamate and related ligands , iGluRs represent an important signalling mechanism by w... | Introduction, Results, Discussion, Materials and Methods | Ionotropic glutamate receptors ( iGluRs ) are a highly conserved family of ligand-gated ion channels present in animals , plants , and bacteria , which are best characterized for their roles in synaptic communication in vertebrate nervous systems ., A variant subfamily of iGluRs , the Ionotropic Receptors ( IRs ) , was... | Ionotropic glutamate receptors ( iGluRs ) are a family of cell surface proteins best known for their role in allowing neurons to communicate with each other in the brain ., We recently discovered a variant class of iGluRs in the fruit fly ( Drosophila melanogaster ) , named Ionotropic Receptors ( IRs ) , which function... | evolutionary biology, genetics and genomics/comparative genomics, neuroscience/sensory systems | null |
journal.pgen.1000080 | 2,008 | BRCA1 and BRCA2 Missense Variants of High and Low Clinical Significance Influence Lymphoblastoid Cell Line Post-Irradiation Gene Expression | Approximately 7% of breast cancer cases occur in women with a strong family history of the disease 1 ., Mutations in BRCA1 and BRCA2 account for a considerable proportion of these familial breast cancer cases , with the average cumulative risk in BRCA1 and BRCA2 mutation carriers by age 70 years estimated at 65% and 45... | Introduction, Results, Discussion, Materials and Methods | The functional consequences of missense variants in disease genes are difficult to predict ., We assessed if gene expression profiles could distinguish between BRCA1 or BRCA2 pathogenic truncating and missense mutation carriers and familial breast cancer cases whose disease was not attributable to BRCA1 or BRCA2 mutati... | Inherited mutations in the genes BRCA1 and BRCA2 increase risk of breast cancer and contribute to a proportion of breast cancer families ., However , more than half of the reported sequence alterations in BRCA1 and BRCA2 are currently of unknown clinical significance ., We analysed gene expression in lymphoblastoid cel... | oncology/breast cancer, genetics and genomics/gene function, genetics and genomics/cancer genetics, genetics and genomics/gene expression | null |
journal.pgen.1005122 | 2,015 | SERPINB11 Frameshift Variant Associated with Novel Hoof Specific Phenotype in Connemara Ponies | Many of the signaling molecules involved in patterning ectodermal derivatives , such as teeth and hair , are also involved in organizing mammalian distal limb appendages , including nails , claws and hooves 1 ., Perissodactyla ( odd-toed ungulates ) are a diverse group of mammals that include the horse , zebra and donk... | Introduction, Results, Discussion, Materials and Methods | Horses belong to the order Perissodactyla and bear the majority of their weight on their third toe; therefore , tremendous force is applied to each hoof ., An inherited disease characterized by a phenotype restricted to the dorsal hoof wall was identified in the Connemara pony ., Hoof wall separation disease ( HWSD ) m... | Inherited diseases affecting only the nails in humans are rare; however , humans do not support themselves entirely on one appendage ., Horses bear their entire weight on their third toe , resulting in a large amount of force on each hoof ., An inherited disease characterized by a phenotype restricted to separation and... | null | null |
journal.pgen.1005137 | 2,015 | HOMER2, a Stereociliary Scaffolding Protein, Is Essential for Normal Hearing in Humans and Mice | Targeted genomic enrichment and massively parallel sequencing ( TGE+MPS ) have revolutionized the field of hereditary hearing loss ( HHL ) by making comprehensive genetic testing for deafness a clinical reality and by accelerating the discovery of novel deafness-causing genes 1 , 2 ., To date over 80 genes have been ca... | Introduction, Results and Discussion, Materials and Methods | Hereditary hearing loss is a clinically and genetically heterogeneous disorder ., More than 80 genes have been implicated to date , and with the advent of targeted genomic enrichment and massively parallel sequencing ( TGE+MPS ) the rate of novel deafness-gene identification has accelerated ., Here we report a family s... | The most frequent sensory disorder worldwide is hearing impairment ., It impacts over 5% of the world population ( 360 million persons ) , and is characterized by extreme genetic heterogeneity ., Over 80 genes have been implicated in isolated ( also referred to as ‘non-syndromic’ ) hearing loss , and abundant evidence ... | null | null |
journal.pcbi.1000818 | 2,010 | Fast- or Slow-inactivated State Preference of Na+ Channel Inhibitors: A Simulation and Experimental Study | Sodium channels are the key proteins in action potential firing for most excitable cells ., They exhibit a complex , membrane potential-dependent gating behavior 1 ., Even minor disturbances in the gating behavior can lead to hyperexcitability , which can be one of the causes of various disorders such as epilepsy , mig... | Introduction, Results, Discussion, Methods | Sodium channels are one of the most intensively studied drug targets ., Sodium channel inhibitors ( e . g . , local anesthetics , anticonvulsants , antiarrhythmics and analgesics ) exert their effect by stabilizing an inactivated conformation of the channels ., Besides the fast-inactivated conformation , sodium channel... | Sodium channels are the key proteins for action potential firing in most excitable cells ., Inhibitor drugs prevent excitation ( local anesthetics ) , regulate excitability ( antiarrhythmics ) , or prevent overexcitation ( antiepileptic , antispastic and neuroprotective drugs ) by binding to the channel and keeping it ... | physiology/neuronal signaling mechanisms, biophysics/biomacromolecule-ligand interactions, neuroscience/neurobiology of disease and regeneration, pharmacology | null |
journal.pcbi.1003224 | 2,013 | Swimming in Light: A Large-Scale Computational Analysis of the Metabolism of Dinoroseobacter shibae | The Roseobacter clade is a versatile group of Gram-negative α-proteobacteria , which can be found in all oceans worldwide ., Especially during phytoplankton blooms they account for a large fraction of the marine bacterial community 1 , 2 ., Here , we focus on the aerobic anoxygenic phototroph Dinoroseobacter shibae DFL... | Introduction, Results, Discussion, Materials and Methods | The Roseobacter clade is a ubiquitous group of marine α-proteobacteria ., To gain insight into the versatile metabolism of this clade , we took a constraint-based approach and created a genome-scale metabolic model ( iDsh827 ) of Dinoroseobacter shibae DFL12T ., Our model is the first accounting for the energy demand o... | The oceans are home to a large variety of microorganisms , which interact in several ways with world-wide metabolic cycles ., A representative of an important group of marine bacteria called the Roseobacter clade is Dinoroseobacter shibae ., This organism is known to use a variant of photosynthesis to obtain energy fro... | null | null |
journal.pntd.0003497 | 2,015 | Ecotype Evolution in Glossina palpalis Subspecies, Major Vectors of Sleeping Sickness | A capital step for species diversification is the initiation of some kind of disruptive selection , driving the newly diverged group of entities to some level of genetic adaptive divergence 1 , 2 ., There has been a continuous debate on the respective role of geography and ecology in speciation , especially the speed a... | Introduction, Material and Methods, Results, Discussion | The role of environmental factors in driving adaptive trajectories of living organisms is still being debated ., This is even more important to understand when dealing with important neglected diseases and their vectors ., In this paper , we analysed genetic divergence , computed from seven microsatellite loci , of 614... | The role of environmental factors in driving adaptive trajectories of living organisms is still being debated ., This is even more important to understand when dealing with important and /or neglected diseases and their vectors ., In this paper , we analysed genetic divergence , computed from several genetic markers , ... | null | null |
journal.pcbi.1004170 | 2,015 | Detailed Contact Data and the Dissemination of Staphylococcus aureus in Hospitals | Chains of transmission in communicable diseases are often identified by ad hoc strategies , combining retrospective information on locations attended and pathogen genetics to identify time-consistent transmission paths . 1, In contrast with such undertakings , “digital epidemiology” propose to use new technologies to p... | Introduction, Materials and Methods, Results, Discussion, Conclusion | Close proximity interactions ( CPIs ) measured by wireless electronic devices are increasingly used in epidemiological models ., However , no evidence supports that electronically collected CPIs inform on the contacts leading to transmission ., Here , we analyzed Staphylococcus aureus carriage and CPIs recorded simulta... | Recent advances in communication technologies allow monitoring high-resolution contact networks ., Close proximity interactions ( CPIs ) measured by wireless sensors are increasingly used to inform contact networks for the dissemination of pathogens in computational models , although empirical justification is lacking ... | null | null |
journal.pcbi.1000072 | 2,008 | Transient Cognitive Dynamics, Metastability, and Decision Making | The dynamical approach for studying brain activity has a long history and is currently one of strong interest 1–7 ., Cognitive functions are manifested through the generation and transformation of cooperative modes of activity ., Different brain regions participate in these processes in distinct ways depending on the s... | Introduction, Results, Discussion, Methods | The idea that cognitive activity can be understood using nonlinear dynamics has been intensively discussed at length for the last 15 years ., One of the popular points of view is that metastable states play a key role in the execution of cognitive functions ., Experimental and modeling studies suggest that most of thes... | The modeling of the temporal structure of cognitive processes is a key step for understanding cognition ., Cognitive functions such as sequential learning , short-term memory , and decision making in a changing environment cannot be understood using only the traditional view based on classical concepts of nonlinear dyn... | mathematics, neuroscience/cognitive neuroscience, computational biology/computational neuroscience, computational biology | null |
journal.pgen.1003676 | 2,013 | The Genome of Spraguea lophii and the Basis of Host-Microsporidian Interactions | Microsporidia are a diverse phylum of obligate intracellular parasites related to fungi ., Over 1300 species have been described in approximately 160 genera and , as is the case for other microbial eukaryotes , a vast undescribed diversity is thought to exist in the environment 1 ., Microsporidia are important pathogen... | Introduction, Results, Discussion, Materials and Methods | Microsporidia are obligate intracellular parasites with the smallest known eukaryotic genomes ., Although they are increasingly recognized as economically and medically important parasites , the molecular basis of microsporidian pathogenicity is almost completely unknown and no genetic manipulation system is currently ... | Microsporidia are unusual intracellular parasites that infect a broad range of animal cells ., In comparison to their fungal relatives , microsporidian genomes have shrunk during evolution , encoding as few as 2000 proteins ., This minimal molecular repertoire makes them a reduced model system for understanding host-pa... | parastic protozoans, mycology, genomics, protozoology, host-pathogen interaction, microbiology, biology, proteomics, parasitology | null |
journal.pntd.0004355 | 2,016 | Multiplicity of Infection and Disease Severity in Plasmodium vivax | A common observation in many malaria endemic areas is that there are patients concurrently infected by more than one distinct parasite genotype ., These infections are usually referred to as multiclonal infections ., In addition to the frequency of multiclonal infections , molecular epidemiologists estimate the average... | Introduction, Materials and Methods, Results, Discussion | Multiplicity of infection ( MOI ) refers to the average number of distinct parasite genotypes concurrently infecting a patient ., Although several studies have reported on MOI and the frequency of multiclonal infections in Plasmodium falciparum , there is limited data on Plasmodium vivax ., Here , MOI and the frequency... | Previous studies on rodent malarias and mathematical models have postulated a link between multiclonal infections and disease severity ., This association has been tested in Plasmodium falciparum mostly in Africa with limited information on P . vivax ., Furthermore , there is a paucity of information from areas with lo... | null | null |
journal.pgen.1004028 | 2,013 | MBD3 Localizes at Promoters, Gene Bodies and Enhancers of Active Genes | Since its discovery in the late 1990s by a number of investigators , the Mi-2/nucleosome remodeling and histone deacetylase ( NuRD ) complex has been proposed to regulate chromatin structure and promote transcriptional repression via its intrinsic nucleosome remodeling and histone deacetylation activities 1 ., Although... | Introduction, Results, Discussion, Methods | The Mi-2/nucleosome remodeling and histone deacetylase ( NuRD ) complex is a multiprotein machine proposed to regulate chromatin structure by nucleosome remodeling and histone deacetylation activities ., Recent reports describing localization of NuRD provide new insights that question previous models on NuRD action , b... | Chromatin structure is tightly regulated by multiple mechanisms; its dysregulation is associated with developmental abnormalities and disease ., The Mi-2/nucleosome remodeling and histone deacetylase ( NuRD ) complex is proposed to regulate chromatin structure by changing the location and/or the chemical properties of ... | null | null |
journal.pgen.1003255 | 2,013 | Transposon Variants and Their Effects on Gene Expression in Arabidopsis | While transposable elements ( TEs ) constitute a large fraction of plant , animal and human genomes 1–3 , their contribution to genome size can change rapidly during evolutionary time ., In some taxa , TEs have been responsible for two-fold differences in genome size that arose over a few million years or less ., These... | Introduction, Results, Discussion, Methods | Transposable elements ( TEs ) make up the majority of many plant genomes ., Their transcription and transposition is controlled through siRNAs and epigenetic marks including DNA methylation ., To dissect the interplay of siRNA–mediated regulation and TE evolution , and to examine how TE differences affect nearby gene e... | Transposable elements ( TEs ) are selfish DNA sequences ., Together with their immobilized derivatives , they account for a large fraction of eukaryotic genomes ., TEs can affect nearby gene activity , either directly by disrupting regulatory sequences or indirectly through the host mechanisms used to prevent TE prolif... | transposons, genomics, molecular cell biology, plant science, genome evolution, plant evolution, plant biology, plant genomics, biology, computational biology, epigenomics, molecular biology, genetics and genomics | null |
journal.pntd.0001577 | 2,012 | Analysing Spatio-Temporal Clustering of Meningococcal Meningitis Outbreaks in Niger Reveals Opportunities for Improved Disease Control | Meningococcal meningitis ( MM ) , caused by the bacterium Neisseria meningitidis ( Nm ) , is a major health problem in sub-Saharan Africa ., The highest incidences of the disease are observed in the so-called “African Meningitis Belt” where annual recurrent epidemics occur during the very hot , dry season 1 ., In Niger... | Introduction, Methods, Results, Discussion | Meningococcal meningitis is a major health problem in the “African Meningitis Belt” where recurrent epidemics occur during the hot , dry season ., In Niger , a central country belonging to the Meningitis Belt , reported meningitis cases varied between 1 , 000 and 13 , 000 from 2003 to 2009 , with a case-fatality rate o... | Meningococcal meningitis ( MM ) is an infection of the meninges caused by a bacterium , Neisseria meningitidis , transmitted through respiratory and throat secretions ., It can cause brain damage and results in death in 5–15% of cases ., Large epidemics of MM occur almost every year in sub-Saharan Africa during the hot... | medicine, bacterial diseases, infectious diseases, geography, public health and epidemiology, computer science, epidemiology, earth sciences, public health, geoinformatics, human geography | null |
journal.pcbi.1004122 | 2,015 | Kinetically-Defined Component Actions in Gene Repression | The initial steps by which steroid receptors induce or repress target gene transcription are the same ., After steroid binding to the intracellular receptor , the resulting complex is activated/transformed to a form with increased affinity for DNA 1 and is concentrated in the nucleus , where it is recruited to DNA sequ... | Introduction, Results, Discussion, Methods | Gene repression by transcription factors , and glucocorticoid receptors ( GR ) in particular , is a critical , but poorly understood , physiological response ., Among the many unresolved questions is the difference between GR regulated induction and repression , and whether transcription cofactor action is the same in ... | While the initial steps in steroid-regulated gene induction and repression are known to be identical , the same cannot be said of cofactors that modulate steroid-regulated gene activity ., We describe the conditions under which a theoretical model for gene repression reveals the kinetically-defined mechanism and relati... | null | null |
journal.pcbi.1005625 | 2,017 | Identifying direct contacts between protein complex subunits from their conditional dependence in proteomics datasets | Many proteins assemble into large macromolecular complexes with essential cellular functions ., The three dimensional arrangement of proteins in a complex is vital to the complex’s function and knowledge of this arrangement would be highly valuable in understanding the mechanism of function ., Conserved protein complex... | Introduction, Methods, Results and discussion, Conclusion | Determining the three dimensional arrangement of proteins in a complex is highly beneficial for uncovering mechanistic function and interpreting genetic variation in coding genes comprising protein complexes ., There are several methods for determining co-complex interactions between proteins , among them co-fractionat... | Proteins physically associate into complexes in order to carry out the essential functions of life ., Knowing how proteins are physically arranged three dimensionally in these complexes provides clues towards how they work ., In principle , the associations between proteins in large-scale proteomics datasets should oft... | chemical bonding, protein interactions, protein structure prediction, protein structure, research and analysis methods, physical chemistry, proteins, biological databases, chemistry, cross-linking, proteomics, molecular biology, proteasomes, protein structure comparison, biochemistry, protein complexes, proteomic datab... | null |
journal.pgen.1003104 | 2,012 | Deciphering the Transcriptional-Regulatory Network of Flocculation in Schizosaccharomyces pombe | Flocculation is an inherent characteristic of yeasts involving asexual aggregation of cells into flocs that separate rapidly from the medium ( reviewed recently in 1 , 2 ) ., Individual yeast cells transition into this morphological state as an adaptation to various environmental stresses by shielding the inner cells o... | Introduction, Results, Discussion, Materials and Methods | In the fission yeast Schizosaccharomyces pombe , the transcriptional-regulatory network that governs flocculation remains poorly understood ., Here , we systematically screened an array of transcription factor deletion and overexpression strains for flocculation and performed microarray expression profiling and ChIP–ch... | Flocculation is a process that involves yeast cells adhering to one another to form clumps called flocs ., This trait is important for industrial yeast applications as it provides a cost-effective and efficient method to remove yeast cells ., The adherence between cells occurs by the binding of glycoproteins known as f... | genomics, functional genomics, model organisms, gene expression, genetics, molecular genetics, biology, computational biology, yeast and fungal models, microbiology, genetics and genomics | null |
journal.pgen.1007285 | 2,018 | Global characterization of copy number variants in epilepsy patients from whole genome sequencing | Structural variants ( SVs ) are defined as genetic mutations affecting more than 50 base pairs and encompass several types of rearrangements: deletion , duplication , novel insertion , inversion and translocation ., Deletions and duplications , which affect DNA copy number , are collectively known as copy number varian... | Introduction, Results, Discussion, Materials and methods | Epilepsy will affect nearly 3% of people at some point during their lifetime ., Previous copy number variants ( CNVs ) studies of epilepsy have used array-based technology and were restricted to the detection of large or exonic events ., In contrast , whole-genome sequencing ( WGS ) has the potential to more comprehens... | Epilepsy is a common neurological disorder affecting around 3% of the population ., In some cases , epilepsy is caused by brain trauma or other brain anomalies but there are often no clear causes ., Genetic factors have been associated with epilepsy in the past such as rare genetic variations found by linkage studies a... | computer applications, medicine and health sciences, population genetics, catalogs, twins, genomic databases, developmental biology, genome analysis, population biology, research and analysis methods, epilepsy, computer and information sciences, monozygotic twins, genetic polymorphism, biological databases, heredity, n... | null |
journal.ppat.1007062 | 2,018 | Metabolic reprogramming of Kaposi’s sarcoma associated herpes virus infected B-cells in hypoxia | Kaposi’s sarcoma associated herpesvirus ( KSHV ) is the etiological agent of Kaposi sarcoma , primary effusion lymphoma and multicentric Castleman disease 1–3 ., By altering the expression of core metabolic enzymes , KSHV infected cells acquire a metabolic strategy of aerobic glycolysis generally referred as to the War... | Introduction, Results, Discussion, Materials and methods | Kaposi’s sarcoma associated herpesvirus ( KSHV ) infection stabilizes hypoxia inducible factors ( HIFs ) ., The interaction between KSHV encoded factors and HIFs plays a critical role in KSHV latency , reactivation and associated disease phenotypes ., Besides modulation of large-scale signaling , KSHV infection also re... | Hypoxia inducible factors ( HIFs ) play a critical role in survival and growth of cancerous cells , in addition to modulating cellular metabolism ., Kaposi’s sarcoma associated herpesvirus ( KSHV ) infection stabilizes HIFs ., Several factors encoded by KSHV are known to interact with up or downstream targets of HIFs .... | sequencing techniques, cell physiology, carbohydrate metabolism, medicine and health sciences, pathology and laboratory medicine, oxygen, pathogens, microbiology, cell metabolism, glucose metabolism, viruses, dna viruses, hypoxia, molecular biology techniques, rna sequencing, herpesviruses, research and analysis method... | null |
journal.pcbi.1002737 | 2,012 | Next-Generation Sequencing of Human Mitochondrial Reference Genomes Uncovers High Heteroplasmy Frequency | The first complete human ‘genome’ sequenced was that of the mitochondrion in 1981 1 ., Since then , over 8 , 250 complete human and 3 , 220 complete non-human vertebrate mitochondrial genomes have been sequenced ( http://www . ncbi . nlm . nih . gov ) ., These contributions have come from numerous laboratories , where ... | Introduction, Results, Discussion, Materials and Methods | We describe methods for rapid sequencing of the entire human mitochondrial genome ( mtgenome ) , which involve long-range PCR for specific amplification of the mtgenome , pyrosequencing , quantitative mapping of sequence reads to identify sequence variants and heteroplasmy , as well as de novo sequence assembly ., Thes... | This manuscript details a novel algorithm to evaluate high-throughput DNA sequence data from whole mitochondrial genomes purified from genomic DNA , which also contains multiple fragmented nuclear copies of mtgenomes ( numts ) ., 40 samples were selected from 2 distinct reference ( HapMap ) populations of African ( YRI... | population genetics, sequence assembly tools, algorithms, genome sequencing, genome analysis tools, population biology, mitochondrial diseases, sequence analysis, genetic polymorphism, biology, computer science, genetics, genomics, computational biology, genetics and genomics, human genetics | null |
journal.pgen.1003807 | 2,013 | Natural Genetic Variation of Integrin Alpha L (Itgal) Modulates Ischemic Brain Injury in Stroke | Stroke is the second leading cause of death and the most common cause of acquired adult disability worldwide 1 , 2 ., Ischemic stroke is caused by disrupted blood flow within the territory of an occluded blood vessel that results in death of brain cells ( infarct ) ., The severity of cerebral infarction primarily depen... | Introduction, Results, Discussion, Materials and Methods | During ischemic stroke , occlusion of the cerebrovasculature causes neuronal cell death ( infarction ) , but naturally occurring genetic factors modulating infarction have been difficult to identify in human populations ., In a surgically induced mouse model of ischemic stroke , we have previously mapped Civq1 to dista... | Stroke is the second leading cause of death and the most common cause of acquired adult disability worldwide ., Ischemic stroke is caused by an interruption of blood flow in the cerebral arteries and results in neuronal damage ( infarct ) to the area of perfusion in the brain ., Although significant progress has been m... | null | null |
journal.pgen.1000672 | 2,009 | Genetic Determinants of Circulating Sphingolipid Concentrations in European Populations | Sphingolipids are essential components of plasma membranes and endosomes and are believed to play critical roles in cell surface protection , protein and lipid transport and sorting , and cellular signalling cascades ., They are known to have roles in both health and disease 1 , 2 ., Several rare monogenic diseases ass... | Introduction, Results, Discussion, Materials and Methods | Sphingolipids have essential roles as structural components of cell membranes and in cell signalling , and disruption of their metabolism causes several diseases , with diverse neurological , psychiatric , and metabolic consequences ., Increasingly , variants within a few of the genes that encode enzymes involved in sp... | Although several rare monogenic diseases are caused by defects in enzymes involved in sphingolipid biosynthesis and metabolism , little is known about the major variants that control the circulating levels of these important bioactive molecules ., As well as being essential components of plasma membranes and endosomes ... | neuroscience/motor systems, genetics and genomics/complex traits, genetics and genomics/genetics of disease, neuroscience/neurobiology of disease and regeneration, cardiovascular disorders/myocardial infarction, genetics and genomics/medical genetics, genetics and genomics/population genetics | null |
journal.pgen.1003068 | 2,012 | A Spatial and Temporal Gradient of Fgf Differentially Regulates Distinct Stages of Neural Development in the Zebrafish Inner Ear | Neurons of the VIIIth cranial ganglion , or the statoacoustic ganglion ( SAG ) , innervate sensory hair cells in the inner ear ., These bipolar neurons relay auditory and vestibular information to the hindbrain ., During development , SAG precursors ( neuroblasts ) originate in the floor of the otic vesicle during a re... | Introduction, Results, Discussion, Materials and Methods | Neuroblasts of the statoacoustic ganglion ( SAG ) initially form in the floor of the otic vesicle during a relatively brief developmental window ., They soon delaminate and undergo a protracted phase of proliferation and migration ( transit-amplification ) ., Neuroblasts eventually differentiate and extend processes bi... | Neurons of the statoacoustic ganglion ( SAG ) , which innervate the inner ear , are derived from neuroblasts originating from the floor of the otic vesicle ., Neuroblasts quickly delaminate from the otic vesicle to form dividing progenitors , which eventually differentiate into mature neurons of the SAG ., Fgf has been... | growth control, neurogenesis, neuroscience, cell differentiation, developmental biology, organism development, molecular development, morphogenesis, pattern formation, developmental neuroscience, biology, auditory system, neural stem cells, regeneration, signaling, sensory systems, cell fate determination | null |
journal.pcbi.1003319 | 2,013 | Cell-Based Multi-Parametric Model of Cleft Progression during Submandibular Salivary Gland Branching Morphogenesis | Branching morphogenesis is a specific type of tissue morphogenesis that is a crucial developmental process occurring in several organs , such as the mammary glands , lungs , kidney , and salivary glands to maximize epithelial surface area for secretion or absorption of fluids and gases 1 ., The process of branching mor... | Introduction, Material and Methods, Results, Discussion | Cleft formation during submandibular salivary gland branching morphogenesis is the critical step initiating the growth and development of the complex adult organ ., Previous experimental studies indicated requirements for several epithelial cellular processes , such as proliferation , migration , cell-cell adhesion , c... | Branching morphogenesis is a complex and dynamic embryonic process that creates the structure of many adult organs , including the salivary gland ., During this process , many cellular changes occur in the epithelial cells , including changes in cell-cell adhesions , cell-extracellular matrix ( matrix ) adhesions , cel... | null | null |
journal.pcbi.1002932 | 2,013 | A Protein Turnover Signaling Motif Controls the Stimulus-Sensitivity of Stress Response Pathways | Eukaryotic cells must constantly recycle their proteomes ., Of the approximately 109 proteins in a typical mouse L929 fibrosarcoma cell , 106 are degraded every minute 1 ., Assuming first-order degradation kinetics , this rate of constitutive protein turnover , or flux , imposes an average half-life of 24 hours ., Not ... | Introduction, Results, Discussion, Methods | Stimulus-induced perturbations from the steady state are a hallmark of signal transduction ., In some signaling modules , the steady state is characterized by rapid synthesis and degradation of signaling proteins ., Conspicuous among these are the p53 tumor suppressor , its negative regulator Mdm2 , and the negative fe... | Eukaryotic cells constantly synthesize new proteins and degrade old ones ., While most proteins are degraded within 24 hours of being synthesized , some proteins are short-lived and exist for only minutes ., Using mathematical models , we asked how rapid turnover , or flux , of signaling proteins might regulate the act... | cellular stress responses, signaling networks, mathematics, stress signaling cascade, regulatory networks, biology, nonlinear dynamics, systems biology, biochemical simulations, signal transduction, cell biology, computational biology, molecular cell biology, signaling cascades | null |
journal.ppat.1004665 | 2,015 | Recognition and Activation Domains Contribute to Allele-Specific Responses of an Arabidopsis NLR Receptor to an Oomycete Effector Protein | A critical step in the lifestyles of plant pathogens is the secretion of effectors—pathogen-encoded proteins that are translocated into the plant cell , where they manipulate the host and promote pathogen growth 1 ., Many effectors function to modulate basal immunity , but their presence in the plant cell may betray th... | Introduction, Results, Discussion, Materials and Methods | In plants , specific recognition of pathogen effector proteins by nucleotide-binding leucine-rich repeat ( NLR ) receptors leads to activation of immune responses ., RPP1 , an NLR from Arabidopsis thaliana , recognizes the effector ATR1 , from the oomycete pathogen Hyaloperonospora arabidopsidis , by direct association... | Plants defend themselves against pathogens using specific multi-domain immune receptors , which are able to recognize secreted “effector” proteins from the pathogen , and thus activate an immune response ., Variants of the Arabidopsis immune receptor RPP1 recognize different alleles of the oomycete effector ATR1 throug... | null | null |
journal.pcbi.1006637 | 2,018 | Dynamical anchoring of distant arrhythmia sources by fibrotic regions via restructuring of the activation pattern | Many clinically relevant cardiac arrhythmias are conjectured to be organized by rotors ., A rotor is an extension of the concept of a reentrant source of excitation into two or three dimensions with an area of functional block in its center , referred to as the core ., Rapid and complex reentry arrhythmias such as atri... | Introduction, Materials and methods, Results, Discussion | Rotors are functional reentry sources identified in clinically relevant cardiac arrhythmias , such as ventricular and atrial fibrillation ., Ablation targeting rotor sites has resulted in arrhythmia termination ., Recent clinical , experimental and modelling studies demonstrate that rotors are often anchored around fib... | Rotors are waves of cardiac excitation like a tornado causing cardiac arrhythmia ., Recent research shows that they are found in ventricular and atrial fibrillation ., Burning ( via ablation ) the site of a rotor can result in the termination of the arrhythmia ., Recent studies showed that rotors are often anchored to ... | dermatology, medicine and health sciences, diagnostic radiology, engineering and technology, cardiovascular anatomy, cardiac ventricles, fibrosis, magnetic resonance imaging, developmental biology, electrocardiography, bioassays and physiological analysis, cardiology, research and analysis methods, scars, arrhythmia, i... | null |
journal.pcbi.1004878 | 2,016 | Oscillations via Spike-Timing Dependent Plasticity in a Feed-Forward Model | It is generally believed that synaptic plasticity is the basis for learning and memory ., According to Hebbs rule 1 , which is considered the foundation for current views on learning and memory , the interaction strength between two neurons that are co-activated potentiates ., This rule has been extended to the tempora... | Introduction, Results, Discussion | Neuronal oscillatory activity has been reported in relation to a wide range of cognitive processes including the encoding of external stimuli , attention , and learning ., Although the specific role of these oscillations has yet to be determined , it is clear that neuronal oscillations are abundant in the central nervo... | Oscillatory activity in the brain has been described in relation to many cognitive states and tasks , including the encoding of external stimuli , attention , learning and consolidation of memory ., However , without tuning of synaptic weights with the preferred phase of firing the oscillatory signal may not be able to... | learning, medicine and health sciences, action potentials, nervous system, population dynamics, membrane potential, social sciences, electrophysiology, neuroscience, learning and memory, synaptic plasticity, cognitive psychology, population biology, neuronal plasticity, developmental neuroscience, animal cells, cellula... | null |
journal.ppat.1005045 | 2,015 | Dimerization-Induced Allosteric Changes of the Oxyanion-Hole Loop Activate the Pseudorabies Virus Assemblin pUL26N, a Herpesvirus Serine Protease | The family Herpesviridae is divided into the three subfamilies alpha- , beta- and gammaherpesviruses ., These infectious agents cause a variety of diseases in many different hosts including humans ., Pseudorabies virus ( PrV ) is a neurotropic porcine alphaherpesvirus 1 and the causative agent of Aujeszkys disease ., T... | Introduction, Results and Discussion, Materials and Methods | Herpesviruses encode a characteristic serine protease with a unique fold and an active site that comprises the unusual triad Ser-His-His ., The protease is essential for viral replication and as such constitutes a promising drug target ., In solution , a dynamic equilibrium exists between an inactive monomeric and an a... | Herpesviruses encode a unique serine protease , which is essential for herpesvirus capsid maturation and is therefore an interesting target for drug development ., In solution , this protease exists in an equilibrium of an inactive monomeric and an active dimeric form ., All currently available crystal structures of he... | null | null |
journal.pntd.0003284 | 2,014 | Improvements on Restricted Insecticide Application Protocol for Control of Human and Animal African Trypanosomiasis in Eastern Uganda | African trypanosomes transmitted by tsetse flies ( Diptera: Glossinidae ) pose one of the biggest constraints to animal and human health and livestock-crop integration in Sub-Saharan Africa 1 , 2 ., They cause a debilitating disease in domestic animals ( nagana ) and humans ( sleeping sickness ) 3–5 ., In the south-eas... | Introduction, Materials and Methods, Results, Discussion | African trypanosomes constrain livestock and human health in Sub-Saharan Africa , and aggravate poverty and hunger of these otherwise largely livestock-keeping communities ., To solve this , there is need to develop and use effective and cheap tsetse control methods ., To this end , we aimed at determining the smallest... | Poverty , hunger and human ill-health aggravated by trypanosomiasis in Sub-Saharan Africa can only be reduced by developing and using cheap and effective tsetse control methods ., To further reduce the cost of tsetse control by restricting insecticides to the legs , belly and ears ( RAP ) we set out to determine the lo... | biotechnology, research design, infectious diseases, electrophoretic techniques, veterinary science, medicine and health sciences, epidemiology, mathematical and statistical techniques, molecular biology techniques, biology and life sciences, tropical diseases, extraction techniques, parasitic diseases, molecular biolo... | null |
journal.pgen.1008273 | 2,019 | BCDIN3D regulates tRNAHis 3’ fragment processing | The 5’ ends of eukaryotic RNAs are vital for determining their processing and function 1 ., The most well-known 5’ end RNA modification is the m7G cap , which has multiple functions , including of protecting messenger RNAs from exonucleolytic degradation , and of marking them for nucleo-cytoplasmic export and translati... | Introduction, Results, Discussion, Methods | 5’ ends are important for determining the fate of RNA molecules ., BCDIN3D is an RNA phospho-methyltransferase that methylates the 5’ monophosphate of specific RNAs ., In order to gain new insights into the molecular function of BCDIN3D , we performed an unbiased analysis of its interacting RNAs by Thermostable Group I... | We previously identified an important modification of human microRNAs , written by BCDIN3D , an RNA phospho-methyltransferase linked to triple negative breast cancer , obesity and type II diabetes ., Here , we employed a powerful sequencing method that overcomes RNA secondary structure and RNA modifications , to unbias... | sequencing techniques, transfer rna, molecular probe techniques, natural antisense transcripts, gene regulation, enzymes, geographical locations, enzymology, phosphatases, northern blot, micrornas, methylation, molecular biology techniques, rna sequencing, gel electrophoresis, research and analysis methods, electrophor... | null |
journal.pgen.1001133 | 2,010 | Identification of Early Requirements for Preplacodal Ectoderm and Sensory Organ Development | Cranial placodes provide major contributions to the paired sensory organs of the head ., Examples include the anterior pituitary , the lens of the eye , the olfactory epithelium , the inner ear , and clusters of sensory neurons in the trigeminal and epibranchial ganglia 1–4 ., Though diverse in fate , all placodes are ... | Introduction, Results, Discussion, Materials and Methods | Preplacodal ectoderm arises near the end of gastrulation as a narrow band of cells surrounding the anterior neural plate ., This domain later resolves into discrete cranial placodes that , together with neural crest , produce paired sensory structures of the head ., Unlike the better-characterized neural crest , little... | Cranial placodes , which produce sensory structures in the head , arise from a contiguous band of preplacodal ectoderm surrounding the anterior neural plate during gastrulation ., Little is known about early regulation of preplacodal ectoderm , but modulation of signaling through Bone Morphogenetic Protein ( Bmp ) is c... | developmental biology/embryology, cell biology/cell signaling, cell biology/developmental molecular mechanisms, developmental biology/pattern formation, developmental biology/cell differentiation, genetics and genomics/gene function, developmental biology/neurodevelopment, neuroscience/neurodevelopment, developmental b... | null |
journal.pcbi.1000914 | 2,010 | Regression Analysis for Constraining Free Parameters in Electrophysiological Models of Cardiac Cells | Mathematical modeling has become an increasingly popular and important technique for gaining insight into biological systems , both in physiology , where models have a long history 1 , 2 , and in biochemistry and cell biology , where quantitative approaches have gained traction more recently 3 , 4 ., However , as new m... | Introduction, Results, Discussion, Methods | A major challenge in computational biology is constraining free parameters in mathematical models ., Adjusting a parameter to make a given model output more realistic sometimes has unexpected and undesirable effects on other model behaviors ., Here , we extend a regression-based method for parameter sensitivity analysi... | Mathematical models of biological processes generally contain many free parameters that are not known from experiments ., Choosing values for these parameters , although an important step in the construction of realistic computational models , is frequently performed using an ad hoc approach that is a combination of in... | cardiovascular disorders/arrhythmias, electrophysiology, and pacing, computational biology/systems biology, physiology/cardiovascular physiology and circulation | null |
journal.pcbi.1000127 | 2,008 | The Spatiotemporal Pattern of Src Activation at Lipid Rafts Revealed by Diffusion-Corrected FRET Imaging | Src is a protein tyrosine kinase which plays crucial roles in cell adhesion , migration and cancer invasion 1 ., In fact , epidermal growth factor ( EGF ) and its receptor EGFR has been well documented to couple with Src kinase to regulate cancer progression 2 ., Before stimulation , Src is localized at microtubule-ass... | Introduction, Results, Discussion, Materials and Methods | Genetically encoded biosensors based on fluorescence resonance energy transfer ( FRET ) have been widely applied to visualize the molecular activity in live cells with high spatiotemporal resolution ., However , the rapid diffusion of biosensor proteins hinders a precise reconstruction of the actual molecular activatio... | Fluorescence biosensors have been widely used to report the spatial and temporal activity of target molecules in live cells ., However , biosensors can move independently of the target molecule and carry its signal to other subcellular locations ., Therefore , the observed images appear to be the combination of the tar... | cell biology/cell signaling, biochemistry/bioinformatics, biotechnology/bioengineering, biophysics/cell signaling and trafficking structures, computational biology/systems biology | null |
journal.pcbi.1005566 | 2,017 | Chemomechanical regulation of myosin Ic cross-bridges: Deducing the elastic properties of an ensemble from single-molecule mechanisms | The myosin family includes at least 20 structurally and functionally distinct classes 1 , 2 ., Although they all exhibit a common chemomechanical cycle , myosin molecules have remarkably diverse functions-including intracellular transport , force production in muscles , and cellular migration-as well as important roles... | Introduction, Results, Discussion, Methods | Myosin Ic is thought to be the principal constituent of the motor that adjusts mechanical responsiveness during adaptation to prolonged stimuli by hair cells , the sensory receptors of the inner ear ., In this context myosin molecules operate neither as filaments , as occurs in muscles , nor as single or few molecules ... | Myosin molecules are biological nanomachines that transduce chemical energy into mechanical work and thus produce directed motion in living cells ., These molecules proceed through cyclic reactions in which they change their conformational states upon the binding and release of nucleotides while attaching to and detach... | stiffness, cell motility, mechanical properties, actin filaments, classical mechanics, chemical compounds, phosphates, nucleotides, mechanical energy, molecular motors, actin motors, mathematics, statistics (mathematics), materials science, motor proteins, research and analysis methods, contractile proteins, proteins, ... | null |
journal.ppat.1006702 | 2,017 | Estimating virus effective population size and selection without neutral markers | Evolution in isolated populations results from the interplay between several forces , including mutation , selection , and genetic drift ., Mutation creates genetic diversity within a population ., Subsequent selection and genetic drift drive the evolution of diversity within the population ., Selection is a determinis... | Introduction, Materials and methods, Results, Discussion | By combining high-throughput sequencing ( HTS ) with experimental evolution , we can observe the within-host dynamics of pathogen variants of biomedical or ecological interest ., We studied the evolutionary dynamics of five variants of Potato virus Y ( PVY ) in 15 doubled-haploid lines of pepper ., All plants were inoc... | A growing number of experimental evolution studies are using an “evolve-and-resequence” approach to observe the within-host dynamics of pathogen variants of biomedical or ecological interest ., The resulting data are particularly appropriate for studying the effects of evolutionary forces , such as selection and geneti... | organismal evolution, plant anatomy, population genetics, variant genotypes, microbiology, genetic mapping, plant science, effective population size, microbial evolution, population biology, leaves, evolutionary genetics, viral evolution, genetic drift, population metrics, population size, virology, heredity, genetics,... | null |
journal.pcbi.1003651 | 2,014 | The Effects of Theta Precession on Spatial Learning and Simplicial Complex Dynamics in a Topological Model of the Hippocampal Spatial Map | Considerable effort has been devoted over the years to understanding how the hippocampus is able to form an internal representation of the environment that enables an animal to efficiently navigate and remember the space 1 ., This internal map is made possible , in part , by the activity of pyramidal neurons in the hip... | Introduction, Results, Discussion, Materials and Methods | Learning arises through the activity of large ensembles of cells , yet most of the data neuroscientists accumulate is at the level of individual neurons; we need models that can bridge this gap ., We have taken spatial learning as our starting point , computationally modeling the activity of place cells using methods d... | One of the challenges in contemporary neuroscience is that we have few ways to connect data about the features of individual neurons with effects ( such as learning ) that emerge only at the scale of large cell ensembles ., We are tackling this problem using spatial learning as a starting point ., In previous work we c... | computational neuroscience, biology and life sciences, computational biology, neuroscience, learning and memory | null |
journal.pcbi.1006161 | 2,018 | Logistical constraints lead to an intermediate optimum in outbreak response vaccination | In applied epidemiology , models are increasingly used to inform management decisions on effective responses to a variety of outbreaking diseases , e . g . cholera 1 , smallpox 2 , influenza 3 , Ebola 4 , measles 5 , and Zika fever 6 ., In general , these epidemic dynamic models are designed with an emphasis on the tra... | Introduction, Methods, Results, Discussion | Dynamic models in disease ecology have historically evaluated vaccination strategies under the assumption that they are implemented homogeneously in space and time ., However , this approach fails to formally account for operational and logistical constraints inherent in the distribution of vaccination to the populatio... | It has long been recognized that an epidemic of infectious disease can be prevented if a sufficient proportion of the susceptible population is vaccinated in advance ., This logic also holds for vaccine-based outbreak response to stop an outbreak of a novel , or re-emerging pathogen , but with an important caveat ., If... | vaccines, public and occupational health, preventive medicine, population metrics, infectious diseases, medicine and health sciences, cholera vaccines, immunity, epidemiology, disease dynamics, biology and life sciences, immunology, population biology, vaccination and immunization, infectious disease control, populatio... | null |
journal.pntd.0005885 | 2,017 | Modeling the environmental suitability of anthrax in Ghana and estimating populations at risk: Implications for vaccination and control | Anthrax is a soil-borne , zoonotic disease found on nearly every continent ( except Antarctica ) that primarily infects herbivorous animals while secondarily infecting humans through the handling or ingestion of contaminated meat or animal by-products 1 , 2 ., The geographic distribution of the disease appears to be li... | Introduction, Methods, Results, Discussion | Anthrax is hyper-endemic in West Africa ., Despite the effectiveness of livestock vaccines in controlling anthrax , underreporting , logistics , and limited resources makes implementing vaccination campaigns difficult ., To better understand the geographic limits of anthrax , elucidate environmental factors related to ... | Anthrax is a soil-borne zoonotic disease found worldwide ., In the West African nation of Ghana , anthrax outbreaks occur annually with a high burden to livestock keepers and their animals ., To control anthrax in both humans and animals , annual livestock vaccination is recommended in endemic regions ., However , in r... | livestock, medicine and health sciences, immunology, geographical locations, vaccines, preventive medicine, bacterial diseases, infectious disease control, vaccination and immunization, africa, veterinary science, veterinary medicine, public and occupational health, infectious diseases, anthrax, veterinary diseases, zo... | null |
journal.ppat.0040037 | 2,008 | Nucleotide Biosynthesis Is Critical for Growth of Bacteria in Human Blood | Bacteremia , characterized by the presence of pathogenic bacteria in the bloodstream , is a major cause of morbidity and mortality worldwide ., Bacteremia often leads to sepsis and death 1 ., To survive in blood , bacterial pathogens must evade a multitude of host defense mechanisms such as complement-mediated lysis , ... | Introduction, Results, Discussion, Materials and Methods | Proliferation of bacterial pathogens in blood represents one of the most dangerous stages of infection ., Growth in blood serum depends on the ability of a pathogen to adjust metabolism to match the availability of nutrients ., Although certain nutrients are scarce in blood and need to be de novo synthesized by prolife... | Bacterial growth in the bloodstream is a common manifestation of a number of bacterial infections ., When growing in blood , bacteria not only have to evade the hosts immune response , but also adjust their metabolism to suit availability of nutrients ., Although the concentrations of various metabolites in human blood... | infectious diseases, microbiology, eubacteria | null |
journal.pgen.1002199 | 2,011 | Genome-Wide Association Analysis of Incident Coronary Heart Disease (CHD) in African Americans: A Short Report | Coronary heart disease ( CHD ) is the leading cause of death worldwide 1 ., In the United States , African Americans are the most vulnerable population with regard to CHD risk factors and mortality ., A recent American Heart Association report showed that African Americans are twice as likely to die from a heart-relate... | Introduction, Results/Discussion, Materials and Methods | African Americans have the highest rate of mortality due to coronary heart disease ( CHD ) ., Although multiple loci have been identified influencing CHD risk in European-Americans using a genome-wide association ( GWAS ) approach , no GWAS of incident CHD has been reported for African Americans ., We performed a GWAS ... | In the United States , African Americans are at high risk for coronary heart disease ( CHD ) ., Although environmental and social factors have a role , genetic factors also contribute to CHD risk and mortality ., Research to identify genetic factors for CHD susceptibility has been carried out mostly in Europeans and Eu... | medicine, biology | null |
Subsets and Splits
No community queries yet
The top public SQL queries from the community will appear here once available.