PLOS ONE

http://journals.plos.org/plosone/

List of Papers (Total 202,024)

Fetuin-A/Albumin-Mineral Complexes Resembling Serum Calcium Granules and Putative Nanobacteria: Demonstration of a Dual Inhibition-Seeding Concept

Serum-derived granulations and purported nanobacteria (NB) are pleomorphic apatite structures shown to resemble calcium granules widely distributed in nature. They appear to be assembled through a dual inhibitory-seeding mechanism involving proteinaceous factors, as determined by protease (trypsin and chymotrypsin) and heat inactivation studies. When inoculated into cell culture...

A Macaque Model to Study Vaginal HSV-2/Immunodeficiency Virus Co-Infection and the Impact of HSV-2 on Microbicide Efficacy

Background Herpes simplex virus type-2 (HSV-2) infection enhances the transmission and acquisition of human immunodeficiency virus (HIV). This occurs in symptomatic and asymptomatic stages of HSV-2 infection, suggesting that obvious herpetic lesions are not required to increase HIV spread. An animal model to investigate the underlying causes of the synergistic action of the two...

The Crystal Structures of Yeast Get3 Suggest a Mechanism for Tail-Anchored Protein Membrane Insertion

Tail-anchored (TA) proteins represent a unique class of membrane proteins that contain a single C-terminal transmembrane helix. The post-translational insertion of the yeast TA proteins into the ER membrane requires the Golgi ER trafficking (GET) complex which contains Get1, Get2 and Get3. Get3 is an ATPase that recognizes and binds the C-terminal transmembrane domain (TMD) of...

Structural Plasticity Can Produce Metaplasticity

Background Synaptic plasticity underlies many aspect of learning memory and development. The properties of synaptic plasticity can change as a function of previous plasticity and previous activation of synapses, a phenomenon called metaplasticity. Synaptic plasticity not only changes the functional connectivity between neurons but in some cases produces a structural change in...

Notch mRNA Expression in Drosophila Embryos Is Negatively Regulated at the Level of mRNA 3′ Processing

Notch receptor regulates differentiation of almost all tissues and organs during animal development. Many mechanisms function at the protein level to finely regulate Notch activity. Here we provide evidence for Notch regulation at an earlier step - mRNA 3′ processing. Processing at the Notch consensus polyadenylation site appears by default to be suppressed in Drosophila embryos...

Identifying Gene Interaction Enrichment for Gene Expression Data

Gene set analysis allows the inclusion of knowledge from established gene sets, such as gene pathways, and potentially improves the power of detecting differentially expressed genes. However, conventional methods of gene set analysis focus on gene marginal effects in a gene set, and ignore gene interactions which may contribute to complex human diseases. In this study, we propose...

Pluripotent Transcription Factors Possess Distinct Roles in Normal versus Transformed Human Stem Cells

Background Cancer and normal stem cells (SCs) share proliferative properties of self-renewal and expression of key transcription factors (TFs). Despite similar TF identities, the functional role of specific TFs responsible for retaining SC state has yet to be examined in cancer. Methodology/Principal Findings Here, we compare the role of Oct4 and Nanog, two-core pluripotent TFs...

Pathway Analysis of GWAS Provides New Insights into Genetic Susceptibility to 3 Inflammatory Diseases

Although the introduction of genome-wide association studies (GWAS) have greatly increased the number of genes associated with common diseases, only a small proportion of the predicted genetic contribution has so far been elucidated. Studying the cumulative variation of polymorphisms in multiple genes acting in functional pathways may provide a complementary approach to the more...

Maggot Secretions Skew Monocyte-Macrophage Differentiation Away from a Pro-Inflammatory to a Pro-Angiogenic Type

Background Maggots of the blowfly Lucilia sericata are used for the treatment of chronic wounds. Earlier we reported maggot secretions to inhibit pro-inflammatory responses of human monocytes. The aim of this study was to investigate the effect of maggot secretions on the differentiation of monocytes into pro-inflammatory (MØ-1) and anti-inflammatory/pro-angiogenic macrophages (M...

Cross Species Genomic Analysis Identifies a Mouse Model as Undifferentiated Pleomorphic Sarcoma/Malignant Fibrous Histiocytoma

Undifferentiated pleomorphic sarcoma/Malignant Fibrous Histiocytoma (MFH) is one of the most common subtypes of human soft tissue sarcoma. Using cross species genomic analysis, we define a geneset from the LSL-KrasG12D; Trp53Flox/Flox mouse model of soft tissue sarcoma that is highly enriched in human MFH. With this mouse geneset as a filter, we identify expression of the RAS...

Phosphatase-Dependent Regulation of Epithelial Mitogen-Activated Protein Kinase Responses to Toxin-Induced Membrane Pores

Diverse bacterial species produce pore-forming toxins (PFT) that can puncture eukaryotic cell membranes. Host cells respond to sublytic concentrations of PFT through conserved intracellular signaling pathways, including activation of mitogen-activated protein kinases (MAPK), which are critical to cell survival. Here we demonstrate that in respiratory epithelial cells p38 and JNK...

Identification of an Xiap-Like Pseudogene on Mouse Chromosome 7

The most thoroughly characterized mammalian IAP is XIAP/BIRC4, which can inhibit caspases 9, 3 and 7, but may also regulate apoptosis through interactions with other proteins such as Smac/DIABLO, HtrA2/Omi, XAF1, TAK1, cIAP1, and cIAP2. High throughput sequencing of the mouse genome revealed the existence of a gene resembling Xiap/Birc4 on mouse chromosome 7. To confirm the...

Toward the Discovery of Vaccine Adjuvants: Coupling In Silico Screening and In Vitro Analysis of Antagonist Binding to Human and Mouse CCR4 Receptors

Background Adjuvants enhance or modify an immune response that is made to an antigen. An antagonist of the chemokine CCR4 receptor can display adjuvant-like properties by diminishing the ability of CD4+CD25+ regulatory T cells (Tregs) to down-regulate immune responses. Methodology Here, we have used protein modelling to create a plausible chemokine receptor model with the aim of...

Comparison of Mantoux and Tine Tuberculin Skin Tests in BCG-Vaccinated Children Investigated for Tuberculosis

Background Tuberculin skin tests (TSTs) are long-established screening methods for tuberculosis (TB). We aimed to compare agreement between the intradermal Mantoux and multipuncture percutaneous Tine methods and to quantify risk factors for a positive test result. Methodology/Principal Findings 1512 South African children younger than 5 years of age who were investigated for...

Chromatin Regulation and Gene Centrality Are Essential for Controlling Fitness Pleiotropy in Yeast

Background There are a wide range of phenotypes that are due to loss-of-function or null mutations. Previously, the functions of gene products that distinguish essential from nonessential genes were characterized. However, the functions of products of non-essential genes that contribute to fitness remain minimally understood. Principal Findings Using data from Saccharomyces...

Influenza Morbidity and Mortality in Elderly Patients Receiving Statins: A Cohort Study

Background Statins possess immunomodulatory properties and have been proposed for reducing morbidity during an influenza pandemic. We sought to evaluate the effect of statins on hospitalizations and deaths related to seasonal influenza outbreaks. Methodology/Principal Findings We conducted a population-based cohort study over 10 influenza seasons (1996 to 2006) using linked...

Network Properties of Complex Human Disease Genes Identified through Genome-Wide Association Studies

Background Previous studies of network properties of human disease genes have mainly focused on monogenic diseases or cancers and have suffered from discovery bias. Here we investigated the network properties of complex disease genes identified by genome-wide association studies (GWAs), thereby eliminating discovery bias. Principal findings We derived a network of complex...

Mechanism for CCC DNA Synthesis in Hepadnaviruses

Hepadnavirus replication requires the synthesis of a covalently closed circular (CCC) DNA from the relaxed circular (RC) viral genome by an unknown mechanism. CCC DNA formation could require enzymatic activities of the viral reverse transcriptase (RT), or cellular DNA repair enzymes, or both. Physical mapping of the 5′ and 3′ ends of RC DNA and sequence analysis of CCC DNA...

Integrating In Silico and In Vitro Analysis of Peptide Binding Affinity to HLA-Cw*0102: A Bioinformatic Approach to the Prediction of New Epitopes

Background Predictive models of peptide-Major Histocompatibility Complex (MHC) binding affinity are important components of modern computational immunovaccinology. Here, we describe the development and deployment of a reliable peptide-binding prediction method for a previously poorly-characterized human MHC class I allele, HLA-Cw*0102. Methodology/Findings Using an in-house, flow...

Dlx5 Is a Cell Autonomous Regulator of Chondrocyte Hypertrophy in Mice and Functionally Substitutes for Dlx6 during Endochondral Ossification

The axial and appendicular skeleton of vertebrates develops by endochondral ossification, in which skeletogenic tissue is initially cartilaginous and the differentiation of chondrocytes via the hypertrophic pathway precedes the differentiation of osteoblasts and the deposition of a definitive bone matrix. Results from both loss-of-function and misexpression studies have...

Patients' Perception of Quality of Pre-Operative Informed Consent in Athens, Greece: A Pilot Study

Background We sought to perform a study to record and evaluate patients' views of the way surgeons communicate informed consent (IC) in Greece. Methodology/Principal Findings A prospective pilot study was carried out in Athens from 9/2007 to 4/2008. The study sample was extracted from patients, operated by eight different surgeons, who volunteered to fill in a post-surgery self...

Structures of KaiC Circadian Clock Mutant Proteins: A New Phosphorylation Site at T426 and Mechanisms of Kinase, ATPase and Phosphatase

Background The circadian clock of the cyanobacterium Synechococcus elongatus can be reconstituted in vitro by three proteins, KaiA, KaiB and KaiC. Homo-hexameric KaiC displays kinase, phosphatase and ATPase activities; KaiA enhances KaiC phosphorylation and KaiB antagonizes KaiA. Phosphorylation and dephosphorylation of the two known sites in the C-terminal half of KaiC subunits...

A Novel Enediynyl Peptide Inhibitor of Furin That Blocks Processing of proPDGF-A, B and proVEGF-C

Background Furin represents a crucial member of secretory mammalian subtilase, the Proprotein Convertase (PC) or Proprotein Convertase Subtilisin/Kexin (PCSK) superfamily. It has been linked to cancer, tumorgenesis, viral and bacterial pathogenesis. As a result it is considered a major target for intervention of these diseases. Methodology/Principal Findings Herein, we report...

Structure of an Odorant-Binding Protein from the Mosquito Aedes aegypti Suggests a Binding Pocket Covered by a pH-Sensitive “Lid”

Background The yellow fever mosquito, Aedes aegypti, is the primary vector for the viruses that cause yellow fever, mostly in tropical regions of Africa and in parts of South America, and human dengue, which infects 100 million people yearly in the tropics and subtropics. A better understanding of the structural biology of olfactory proteins may pave the way for the development...

Canine Uterine Bacterial Infection Induces Upregulation of Proteolysis-Related Genes and Downregulation of Homeobox and Zinc Finger Factors

Background Bacterial infection with the severe complication of sepsis is a frequent and serious condition, being a major cause of death worldwide. To cope with the plethora of occurring bacterial infections there is therefore an urgent need to identify molecular mechanisms operating during the host response, in order both to identify potential targets for therapeutic intervention...