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233 papers found.
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Interleukin-10 regulates the inflammasome-driven augmentation of inflammatory arthritis and joint destruction

Introduction Activation of the inflammasome has been implicated in the pathology of various autoinflammatory and autoimmune diseases. While the NLRP3 inflammasome has been linked to arthritis progression, little is known about its synovial regulation or contribution to joint histopathology. Regulators of inflammation activation, such as interleukin (IL)-10, may have the potential ...

Molecular Analysis of Household Transmission of Giardia lamblia in a Region of High Endemicity in Peru

Background. Giardia lamblia is ubiquitous in multiple communities of nonindustrialized nations. Genotypes A1, A2, and B (Nash groups 1, 2, and 3, respectively) are found in humans, whereas genotypes C and D are typically found in dogs. However, genotypes A and B have occasionally been identified in dogs. Methods. Fecal Giardia isolates from 22 families and their dogs, living in ...

Clinical Profiling of BCL-2 Family Members in the Setting of BRAF Inhibition Offers a Rationale for Targeting De Novo Resistance Using BH3 Mimetics

While response rates to BRAF inhibitiors (BRAFi) are high, disease progression emerges quickly. One strategy to delay the onset of resistance is to target anti-apoptotic proteins such as BCL-2, known to be associated with a poor prognosis. We analyzed BCL-2 family member expression levels of 34 samples from 17 patients collected before and 10 to 14 days after treatment initiation ...

The Combination of BH3-Mimetic ABT-737 with the Alkylating Agent Temozolomide Induces Strong Synergistic Killing of Melanoma Cells Independent of p53

Metastatic melanoma has poor prognosis and is refractory to most conventional chemotherapies. The alkylating agent temozolomide (TMZ) is commonly used in treating melanoma but has a disappointing response rate. Agents that can act cooperatively with TMZ and improve its efficacy are thus highly sought after. The BH3 mimetic ABT-737, which can induce apoptosis by targeting ...

CUGBP1 overexpression in mouse skeletal muscle reproduces features of myotonic dystrophy type 1

The neuromuscular disease myotonic dystrophy type I (DM1) affects multiple organ systems with the major symptoms being severe muscle weakness, progressive muscle wasting and myotonia. The causative mutation in DM1 is a CTG repeat expansion in the 3′-untranslated region of the DM protein kinase (DMPK) gene. RNA transcribed from the expanded allele contains the expanded CUG repeats ...

Functional Analysis of Two PLA2G2A Variants Associated with Secretory Phospholipase A2-IIA Levels

Background Secretory phospholipase A2 group IIA (sPLA2-IIA) has been identified as a biomarker of atherosclerosis in observational and animal studies. The protein is encoded by the PLA2G2A gene and the aim of this study was to test the functionality of two PLA2G2A non-coding SNPs, rs11573156 C>G and rs3767221 T>G where the rare alleles have been previously associated with higher ...

Identification of CELF splicing activation and repression domains in vivo

CUG-BP and ETR-3 like factor (CELF) proteins are regulators of pre-mRNA alternative splicing. We created a series of truncation mutants to identify the regions of CELF proteins that are required to activate and to repress alternative splicing of different exons. This analysis was performed in parallel on two CELF proteins, ETR-3 (CUG-BP2, NAPOR, BRUNOL3) and CELF4 (BRUNOL4). We ...

Longitudinal change in energy expenditure and effects on energy requirements of the elderly

Background Very little is known about the longitudinal changes in energy requirements in late life. The purposes of this study were to: (1) determine the energy requirements in late life and how they changed during a 7 year time-span, (2) determine whether changes in fat free mass (FFM) were related to changes in resting metabolic rate (RMR), and (3) determine the accuracy of ...

The adaptor protein Dab2 sorts LDL receptors into coated pits independently of AP-2 and ARH

Meghan E. Maurer 1 Jonathan A. Cooper ) 0 0 Division of Basic Sciences, Fred Hutchinson Cancer Research Center , 1100 Fairview Avenue N, Seattle, WA 98109, USA 1 Molecular and Cellular Biology

High gene expression of inflammatory markers and IL-17A correlates with severity of injection site reactions of Atlantic salmon vaccinated with oil-adjuvanted vaccines

Background Two decades after the introduction of oil-based vaccines in the control of bacterial and viral diseases in farmed salmonids, the mechanisms of induced side effects manifested as intra-abdominal granulomas remain unresolved. Side effects have been associated with generation of auto-antibodies and autoimmunity but the underlying profile of inflammatory and immune response ...

The Energetic Particle Detector (EPD) Investigation and the Energetic Ion Spectrometer (EIS) for the Magnetospheric Multiscale (MMS) Mission

The Energetic Particle Detector (EPD) Investigation is one of 5 fields-and-particles investigations on the Magnetospheric Multiscale (MMS) mission. MMS comprises 4 spacecraft flying in close formation in highly elliptical, near-Earth-equatorial orbits targeting understanding of the fundamental physics of the important physical process called magnetic reconnection using Earth’s ...

Heart-specific overexpression of CUGBP1 reproduces functional and molecular abnormalities of myotonic dystrophy type 1

Myotonic dystrophy type 1 (DM1) is caused by a CTG expansion within the 3′-untranslated region of the DMPK gene. The predominant mechanism of pathogenesis is a toxic gain of function of CUG repeat containing RNA transcribed from the expanded allele. The molecular mechanisms by which the RNA containing expanded repeats produce pathogenic effects include: sequestration of ...

Switching Virally Suppressed, Treatment-Experienced Patients to a Raltegravir-Containing Regimen Does Not Alter Levels of HIV-1 DNA

Background Current HIV-1 antiretroviral therapy (ART) greatly reduces virus replication but does not significantly affect the viral reservoir. Raltegravir, a recently introduced integrase inhibitor, could, at least theoretically, reduce residual viremia in patients on ART and affect the viral reservoir size. The aim of this study was to assess whether switching therapy in ...

Disease Progression and Fatal Outcomes in HIV-Infected Patients during Interruption of Antiretroviral Treatment

0 David A. Cooper, Sean Emery, and Damien V. Cordery National Centre in HIV Epidemiology and Clinical Research, University of New South Wales , Sydney, Australia - To the EditorSeveral recent

Identification of Stk25 as a Genetic Modifier of Tau Phosphorylation in Dab1-Mutant Mice

Hyperphosphorylation of the microtubule binding protein Tau is a feature of a number of neurodegenerative diseases, including Alzheimer's disease. Tau is hyperphosphorylated in the hippocampus of dab1-null mice in a strain-dependent manner; however, it has not been clear if the Tau phosphorylation phenotype is a secondary effect of the morbidity of these mutants. The dab1 gene ...

Progressive Activation of CD127+132− Recent Thymic Emigrants into Terminally Differentiated CD127−132+ T-Cells in HIV-1 Infection

Aim HIV infection is associated with distortion of T-cell homeostasis and the IL-7/IL7R axis. Progressive infection results in loss of CD127+132− and gains in CD127−132+ CD4+ and CD8+ T-cells. We investigated the correlates of loss of CD127 from the T-cell surface to understand mechanisms underlying this homeostatic dysregulation. Methods Peripheral and cord blood mononuclear cells ...

Genetic Variation at Nuclear Loci Fails to Distinguish Two Morphologically Distinct Species of Aquilegia

Aquilegia formosa and pubescens are two closely related species belonging to the columbine genus. Despite their morphological and ecological differences, previous studies have revealed a large degree of intercompatibility, as well as little sequence divergence between these two taxa [1], [2]. We compared the inter- and intraspecific patterns of variation for 9 nuclear loci, and ...

Distinct Roles for Arp2/3 Regulators in Actin Assembly and Endocytosis

The Arp2/3 complex is essential for actin assembly and motility in many cell processes, and a large number of proteins have been found to bind and regulate it in vitro. A critical challenge is to understand the actions of these proteins in cells, especially in settings where multiple regulators are present. In a systematic study of the sequential multicomponent actin assembly ...

Endocytosis of megalin by visceral endoderm cells requires the Dab2 adaptor protein

Meghan E. Maurer 0 Jonathan A. Cooper ) 0 0 Division of Basic Sciences and Molecular and Cellular Biology Program, Fred Hutchinson Cancer Research Center , 1100 Fairview Ave N, Seattle, WA, 98109