PLOS ONE

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

List of Papers (Total 193,866)

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...

Visual Search Elicits the Electrophysiological Marker of Visual Working Memory

Background Although limited in capacity, visual working memory (VWM) plays an important role in many aspects of visually-guided behavior. Recent experiments have demonstrated an electrophysiological marker of VWM encoding and maintenance, the contralateral delay activity (CDA), which has been shown in multiple tasks that have both explicit and implicit memory demands. Here, we...

Hyperspectral and Physiological Analyses of Coral-Algal Interactions

Space limitation leads to competition between benthic, sessile organisms on coral reefs. As a primary example, reef-building corals are in direct contact with each other and many different species and functional groups of algae. Here we characterize interactions between three coral genera and three algal functional groups using a combination of hyperspectral imaging and oxygen...

Direct Activation of RhoA by Reactive Oxygen Species Requires a Redox-Sensitive Motif

Background Rho family GTPases are critical regulators of the cytoskeleton and affect cell migration, cell-cell adhesion, and cell-matrix adhesion. As with all GTPases, their activity is determined by their guanine nucleotide-bound state. Understanding how Rho proteins are activated and inactivated has largely focused on regulatory proteins such as guanine nucleotide exchange...

Sphingosine Kinase-1 Is Central to Androgen-Regulated Prostate Cancer Growth and Survival

Background Sphingosine kinase-1 (SphK1) is an oncogenic lipid kinase notably involved in response to anticancer therapies in prostate cancer. Androgens regulate prostate cancer cell proliferation, and androgen deprivation therapy is the standard of care in the management of patients with advanced disease. Here, we explored the role of SphK1 in the regulation of androgen-dependent...

Crop Diversity for Yield Increase

Traditional farming practices suggest that cultivation of a mixture of crop species in the same field through temporal and spatial management may be advantageous in boosting yields and preventing disease, but evidence from large-scale field testing is limited. Increasing crop diversity through intercropping addresses the problem of increasing land utilization and crop...

High-Efficient FLPo Deleter Mice in C57BL/6J Background

Conditional gene manipulation in mice becomes a routine for genetic studies of mammalian gene functions. Additional site-specific recombinases such as FLP or φ31 provide one more level of gene manipulation flexibility. The recombination activity of the currently available FLP deleter mice remains low. We generated a new FLP deleter mouse line with the mouse codon-optimized FLPo...

GD3 Synthase Overexpression Sensitizes Hepatocarcinoma Cells to Hypoxia and Reduces Tumor Growth by Suppressing the cSrc/NF-κB Survival Pathway

Background Hypoxia-mediated HIF-1α stabilization and NF-κB activation play a key role in carcinogenesis by fostering cancer cell survival, angiogenesis and tumor invasion. Gangliosides are integral components of biological membranes with an increasingly recognized role as signaling intermediates. In particular, ganglioside GD3 has been characterized as a proapoptotic lipid...