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Inhibition of Telomerase Activity by Human Immunodeficiency Virus (HIV) Nucleos(t)ide Reverse Transcriptase Inhibitors: A Potential Factor Contributing to HIV-Associated Accelerated Aging

Background. Human immunodeficiency virus (HIV)-infected patients on combination active antiretroviral therapy (cART) are at increased risk of age-related complications. We hypothesized that nucleos(t)ide reverse transcriptase inhibitors (NRTI) may contribute to accelerated aging in HIV-infected individuals on cART via inhibition of telomerase activity. Methods. Telomerase activity ...

Evolution of duplicated IgH loci in Atlantic salmon, Salmo salar

Background The Atlantic salmon (Salmo salar) immunoglobulin heavy chain (IgH) locus possesses two parallel IgH isoloci (IGH-A and IGH-B), that are related to the genomic duplication event in the family Salmonidae. These duplicated IgH loci in Atlantic salmon provide a unique opportunity to examine the mechanisms of genome diversity and genome evolution of the IgH loci in ...

EGF regulates survivin stability through the Raf-1/ERK pathway in insulin-secreting pancreatic β-cells

Background Postnatal expansion of the pancreatic β-cell mass is required to maintain glucose homeostasis immediately after birth. This β-cell expansion is regulated by multiple growth factors, including glucose, insulin, insulin-like growth factor (IGF-1) and epidermal growth factor (EGF). These mitogens signal through several downstream pathways (AKT, ERK, STAT3, and JNK) to ...

Finding signals that regulate alternative splicing in the post-genomic era

Alternative splicing of pre-mRNAs is central to the generation of diversity from the relatively small number of genes in metazoan genomes. Auxiliary cis elements and trans-acting factors are required for the recognition of constitutive and alternatively spliced exons and their inclusion in pre-mRNA. Here, we discuss the regulatory elements that direct alternative splicing and how ...

Intensification of Antiretroviral Therapy With Raltegravir or Addition of Hyperimmune Bovine Colostrum in HIV-Infected Patients With Suboptimal CD4+ T-Cell Response: A Randomized Controlled Trial

Background. Despite virally suppressive combination antiretroviral therapy (cART), some HIV-infected patients exhibit suboptimal CD4+ T-cell recovery. This study aimed to determine the effect of intensification of cART with raltegravir or addition of hyperimmune bovine colostrum (HIBC) on CD4+ T-cell count in such patients. Methods. We randomized 75 patients to 4 treatment groups ...

Expression, localization and tau exon 10 splicing activity of the brain RNA-binding protein TNRC4

Elucidating the mechanisms of alternative splicing in the brain is a prerequisite to the understanding of the pathogenesis of major neurological diseases linked to impairment of pre-mRNA alternative splicing. The gene trinucleotide repeat-containing 4 (TNRC4) is predicted to encode a member of the CELF (CUG-BP- and ETR-3-like factors) family of RNA-binding proteins containing a ...

The population of Milky Way satellites in the Λ cold dark matter cosmology

We present a model for the satellites of the Milky Way in which galaxy formation is followed using semi-analytic techniques applied to the six high-resolution N-body simulations of galactic haloes of the Aquarius project. The model, calculated using the galform code, incorporates improved treatments of the relevant physics in the Λ cold dark matter cosmogony, particularly a ...

Male circumcision for HIV prevention: current evidence and implementation in sub-Saharan Africa

Sokal 4 Jeffrey D Klausner 3 Ross Appleton Nelson Sewankambo David A Cooper John Bongaarts Guy de Bruyn Alex D Wodak Joya Banerjee 0 Department of African-American Studies, Northeastern University

Membrane Type-1 Matrix Metalloproteinases and Tissue Inhibitor of Metalloproteinases-2 RNA Levels Mimic Each Other during Xenopus laevis Metamorphosis

Matrix metalloproteinases (MMPs) and their endogenous inhibitors TIMPs (tissue inhibitors of MMPs), are two protein families that work together to remodel the extracellular matrix (ECM). TIMPs serve not only to inhibit MMP activity, but also aid in the activation of MMPs that are secreted as inactive zymogens. Xenopus laevis metamorphosis is an ideal model for studying MMP and TIMP ...

A hypomorphic allele of dab1 reveals regional differences in reelin-Dab1 signaling during brain development

Tara M. Herrick 0 Jonathan A. Cooper ) 0 0 Fred Hutchinson Cancer Research Center , 1100 Fairview Avenue N, Seattle, WA 98109 , USA signaling during brain development - The disabled 1 (Dab1) p80

Variants of ADRA2A are associated with fasting glucose, blood pressure, body mass index and type 2 diabetes risk: meta-analysis of four prospective studies

Aims/hypothesis We quantified the effect of ADRA2A (encoding α-2 adrenergic receptor) variants on metabolic traits and type 2 diabetes risk, as reported in four studies. Methods Genotype data for ADRA2A single nucleotide polymorphisms (SNPs) rs553668 and rs10885122 were analysed in >17,000 individuals (1,307 type 2 diabetes cases) with regard to metabolic traits and type 2 diabetes ...

ANGPTL4 variants E40K and T266M are associated with lower fasting triglyceride levels in Non-Hispanic White Americans from the Look AHEAD Clinical Trial

Background Elevated triglyceride levels are a risk factor for cardiovascular disease. Angiopoietin-like protein 4 (Angptl4) is a metabolic factor that raises plasma triglyceride levels by inhibiting lipoprotein lipase (LPL). In non-diabetic individuals, the ANGPTL4 coding variant E40K has been associated with lower plasma triglyceride levels while the T266M variant has been ...

Structural and Biochemical Characterization of SrcA, a Multi-Cargo Type III Secretion Chaperone in Salmonella Required for Pathogenic Association with a Host

Many Gram-negative bacteria colonize and exploit host niches using a protein apparatus called a type III secretion system (T3SS) that translocates bacterial effector proteins into host cells where their functions are essential for pathogenesis. A suite of T3SS-associated chaperone proteins bind cargo in the bacterial cytosol, establishing protein interaction networks needed for ...

The Diagnostic Sensitivity of Dengue Rapid Test Assays Is Significantly Enhanced by Using a Combined Antigen and Antibody Testing Approach

Background Serological tests for IgM and IgG are routinely used in clinical laboratories for the rapid diagnosis of dengue and can differentiate between primary and secondary infections. Dengue virus non-structural protein 1 (NS1) has been identified as an early marker for acute dengue, and is typically present between days 1–9 post-onset of illness but following seroconversion it ...

Low Bone Mineral Density, Renal Dysfunction, and Fracture Risk in HIV Infection: A Cross-Sectional Study

BackgroundReduced bone mineral density (BMD) is common in adults infected with human immunodeficiency virus (HIV). The role of proximal renal tubular dysfunction (PRTD) and alterations in bone metabolism in HIV-related low BMD are incompletely understood MethodsWe quantified BMD (dual-energy x-ray absorptiometry), blood and urinary markers of bone metabolism and renal function, and ...

Changes in symptom clusters in patients undergoing radiation therapy

Goals of work The goals of the study were to determine the occurrence rates for and the severity of symptoms at the middle, end, and 1 month after the completion of radiation therapy (RT), to determine the number and types of symptom clusters at these three time points, and to evaluate for changes over time in these symptom clusters. Materials and methods Symptom occurrence and ...

ETR‐3 and CELF4 protein domains required for RNA binding and splicing activity in vivo

Members of the CUG‐BP and ETR‐3 like factor (CELF) protein family bind within conserved intronic elements (called MSEs) flanking the cardiac troponin T (cTNT) alternative exon 5 and promote exon inclusion in vivo and in vitro. Here we use a comparative deletion analysis of two family members (ETR‐3 and CELF4) to identify separate domains required for RNA binding and splicing ...

Variation in the UCP2-UCP3 Gene Cluster Predicts the Development of Type 2 Diabetes in Healthy Middle-Aged Men

The impact of the UCP2 −866G>A and UCP3 −55C>T variants on prospective risk of type 2 diabetes was examined over 15 years in 2,936 healthy middle-aged men (mean age 56 years). Conversion to diabetes (n = 169) was associated with higher BMI, blood pressure, cholesterol, triglycerides and C-reactive protein. The hazard ratio (HR) for diabetes of a BMI >30 kg/m2 was 3.96 (95% CI ...

Efavirenz versus Boosted Atazanavir or Zidovudine and Abacavir in Antiretroviral Treatment-Naive, HIV-Infected Subjects: Week 48 Data from the Altair Study

Sanchez, Graciela Guaragna, Cristina Miglioranza, Stella Maris Oliva, Liliana Trape; Australia: Jonathan Anderson, David A Cooper, Nicholas Doong, Dominic Dwyer, Martyn French, Jennifer Hoy, Pam Konecny

AIDS Vaccine for Asia Network (AVAN): Expanding the Regional Role in Developing HIV Vaccines

Yiming Shao and colleagues describe the work of AVAN, the AIDS Vaccine for Asia Network, which aims to strengthen its regional efforts in finding an AIDS vaccine.