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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 ...

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 ...

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 ...

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 ...

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 ...

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

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 ...

Integrated Science Investigation of the Sun (ISIS): Design of the Energetic Particle Investigation

The Integrated Science Investigation of the Sun (ISIS) is a complete science investigation on the Solar Probe Plus (SPP) mission, which flies to within nine solar radii of the Sun’s surface. ISIS comprises a two-instrument suite to measure energetic particles over a very broad energy range, as well as coordinated management, science operations, data processing, and scientific ...

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 ...

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.

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 ...

A randomized controlled trial of interventions to enhance patient-physician partnership, patient adherence and high blood pressure control among ethnic minorities and poor persons: study protocol NCT00123045

Background Disparities in health and healthcare are extensively documented across clinical conditions, settings, and dimensions of healthcare quality. In particular, studies show that ethnic minorities and persons with low socioeconomic status receive poorer quality of interpersonal or patient-centered care than whites and persons with higher socioeconomic status. Strong evidence ...

Telomeres are shorter in myocardial infarction patients compared to healthy subjects: correlation with environmental risk factors

Shorter telomeres have been reported in premature myocardial infarction (MI) patients. Our work aimed at confirming the association of shorter telomere with MI in two case–control studies and in familial hypercholesterolemia (FH) patients with coronary heart disease (CHD). The HIFMECH study compared 598 white male patients (<60 years) who survived a first MI and 653 age-matched ...

Effect of Rosiglitazone on Peroxisome Proliferator-Activated Receptor γ Gene Expression in Human Adipose Tissue Is Limited by Antiretroviral Drug-Induced Mitochondrial Dysfunction

common conditions. ROSEY INVESTIGATORS Steering committee: Andrew Carr (St. Vincent’s Hospital, Sydney; coprincipal investigator); David A. Cooper (coprincipal investigator), Dianne Carey, Sean Emery ... ; 143 : 337 - 46 . 21. Mallon PW , Sedwell R , Unemori P , Kelleher A , Cooper DA , Carr A . Methodological considerations in human studies of gene expression in HIV-associated lipodystrophy . Antivir

EST and Mitochondrial DNA Sequences Support a Distinct Pacific Form of Salmon Louse, Lepeophtheirus salmonis

Nuclear deoxyribonucleic acid sequences from approximately 15,000 salmon louse expressed sequence tags (ESTs), the complete mitochondrial genome (16,148bp) of salmon louse, and 16S ribosomal ribonucleic acid (rRNA) and cytochrome oxidase subunit I (COI) genes from 68 salmon lice collected from Japan, Alaska, and western Canada support a Pacific lineage of Lepeophtheirus salmonis ...

Salmo salar and Esox lucius full-length cDNA sequences reveal changes in evolutionary pressures on a post-tetraploidization genome

Background Salmonids are one of the most intensely studied fish, in part due to their economic and environmental importance, and in part due to a recent whole genome duplication in the common ancestor of salmonids. This duplication greatly impacts species diversification, functional specialization, and adaptation. Extensive new genomic resources have recently become available for ...

Does Choice of Combination Antiretroviral Therapy (cART) Alter Changes in Cerebral Function Testing after 48 Weeks in Treatment-Naive, HIV-1–Infected Individuals Commencing cART? A Randomized, Controlled Study

Background. Neurocognitive impairment remains prevalent, despite combination antiretroviral therapy (cART). Differences between changes in cerebral function and alternative cARTs have not been prospectively assessed. Methods. Treatment-naive, HIV-1–infected individuals randomly allocated to commence cART (tenofovir-emtricitabine plus either efavirenz [arm 1], atazanavir-ritonavir ...