The α-subunits of hypoxia-inducible factors (HIF1α and HIF2α) promote transcription of genes that regulate glycolysis and cell survival and growth. Sprouty2 (Spry2) is a modulator of receptor tyrosine kinase signaling and inhibits cell proliferation by a number of different mechanisms. Because of the seemingly opposite actions of HIFα subunits and Spry2 on cellular processes, we investigated whether Spry2 regulates the levels of HIF1α and HIF2α proteins.
View Article and Find Full Text PDFWe aimed to evaluate the pharmacodynamics, efficacy, safety and tolerability of the JAK1 inhibitor GSK2586184 in adults with systemic lupus erythematosus (SLE). In this adaptive, randomized, double-blind, placebo-controlled study, patients received oral GSK2586184 50-400 mg, or placebo twice daily for 12 weeks. Primary endpoints included interferon-mediated messenger RNA transcription over time, changes in Safety of Estrogen in Lupus National Assessment-SLE Disease Activity Index score, and number/severity of adverse events.
View Article and Find Full Text PDFTargeting CD3 antigens on human T lymphocytes with monoclonal antibodies has been shown to reduce the rate of decline of C-peptides in recent-onset type 1 diabetes mellitus patients. However, effective doses are associated with infusion reactions typical of "cytokine release syndrome" and appear to be dose-limiting when administered as short-duration infusions. A possible alternative approach, which may reduce the rate of T cell activation and consequent systemic cytokine release, is to inject subcutaneously.
View Article and Find Full Text PDFThe onset of developmental stuttering typically occurs between 2 to 4 years of age, coinciding with a period of rapid development in speech, language, motor and cognitive domains. Previous studies have reported generally poorer performance and uneven, or "dissociated" development across speech and language domains in children who stutter (CWS) relative to children who do not stutter (CWNS) (Anderson, Pellowski, & Conture, 2005). The aim of this study was to replicate and expand previous findings by examining whether CWS exhibit dissociated development across speech-language, cognitive, and motor domains that are also reflected in measures of neuroanatomical development.
View Article and Find Full Text PDFAim: To investigate whether there is a sex difference in exercise induced muscle damage.
Materials And Method: Vastus Lateralis and patella tendon properties were measured in males and females using ultrasonography. During maximal voluntary eccentric knee extensions (12 reps x 6 sets), Vastus Lateralis fascicle lengthening and maximal voluntary eccentric knee extensions torque were recorded every 10° of knee joint angle (20-90°).
It is generally agreed upon that the mechanisms underlying task switching heavily depend on working memory, yet numerous studies have failed to show a strong relationship between working memory capacity (WMC) and task-switching ability. We argue that this relationship does indeed exist but that the dependent variable used to measure task switching is problematic. To support our claim, we reanalyzed data from two studies with a new scoring procedure that combines reaction time (RT) and accuracy into a single score.
View Article and Find Full Text PDFBackground: GSK2586184 is a selective oral Janus kinase (JAK)1 inhibitor being evaluated as a treatment for moderate-to-severe plaque-type psoriasis.
Objectives: To assess the relationship between dose of GSK2586184 and clinical response, primarily by the Psoriasis Area Severity Index (PASI).
Methods: Sixty patients with moderate-to-severe plaque psoriasis were randomized to cohort A: 100 mg, 200 mg or 400 mg GSK2586184 twice daily or placebo; and eight were randomized to open-label cohort B, a small exploratory cohort treated with 400 mg GSK2586184 twice daily, to explore differential gene expression.
Unintentional injury is a significant public health burden for American Indians and Alaska Natives and was the leading cause of death among those aged 1 to 44 years between 1999 and 2004. Of those deaths, motor vehicle-related deaths cause the most mortality, justifying the need for intervention at an American Indian Reservation in Arizona (United States). We describe motor vehicle injury prevention program operations from 2004 through 2013.
View Article and Find Full Text PDFUnpolarized and beam-polarized fourfold cross sections (d^{4}σ/dQ^{2}dx_{B}dtdϕ) for the ep→e^{'}p^{'}γ reaction were measured using the CLAS detector and the 5.75-GeV polarized electron beam of the Jefferson Lab accelerator, for 110 (Q^{2},x_{B},t) bins over the widest phase space ever explored in the valence-quark region. Several models of generalized parton distributions (GPDs) describe the data well at most of our kinematics.
View Article and Find Full Text PDFBoth barley hulls and straw contain valuable arabinoxylans and other useful carbohydrate and non-carbohydrate components. The functional water soluble non-caloric arabinoxylan (hemicellulose B) fraction was isolated from hot water-extracted and de-starched barley hulls and straws by an alkaline hydrogen peroxide extraction followed by ethanol precipitation. Barley hulls contained comparatively more Hemi.
View Article and Find Full Text PDFIntroduction: Almost a decade on from the New Zealand Primary Health Care Strategy and amidst concerns about funding of health promotion, we undertook a nationwide survey of health promotion providers.
Aim: To identify trends in recruitment and turnover in New Zealand's health promotion workforce.
Methods: Surveys were sent to 160 organisations identified as having a health focus and employing one or more health promoter.
Salmonella PhoQ is a histidine kinase with a periplasmic sensor domain (PD) that promotes virulence by detecting the macrophage phagosome. PhoQ activity is repressed by divalent cations and induced in environments of acidic pH, limited divalent cations, and cationic antimicrobial peptides (CAMP). Previously, it was unclear which signals are sensed by salmonellae to promote PhoQ-mediated virulence.
View Article and Find Full Text PDFThe paper describes the inhalation nickel (Ni) exposure of humans via the environment for the regional scale in the EU, together with a tiered approach for assessing additional local exposure from industrial emissions. The approach was designed, in the context of REACH, for the purpose of assessing and controlling emissions and air quality in the neighbourhood of Ni producers and downstream users. Two Derived No Effect Level (DNEL) values for chronic inhalation exposure to total Ni in PM10 (20 and 60ngNi/m(3)) were considered.
View Article and Find Full Text PDFThere is a significant discrepancy between the values of the proton electric form factor, G(E)(p), extracted using unpolarized and polarized electron scattering. Calculations predict that small two-photon exchange (TPE) contributions can significantly affect the extraction of G(E)(p) from the unpolarized electron-proton cross sections. We determined the TPE contribution by measuring the ratio of positron-proton to electron-proton elastic scattering cross sections using a simultaneous, tertiary electron-positron beam incident on a liquid hydrogen target and detecting the scattered particles in the Jefferson Lab CLAS detector.
View Article and Find Full Text PDFIntroduction: The incidence rate of end-stage renal disease (ESRD) is highest among African-American (AA) males. The reason for this disparity in ESRD for AA males remains unclear, but it is well established that diabetes is the leading risk factor. Prediabetes may also be a risk for kidney disease since prediabetics have increased risk for cardiovascular disease and often do not receive drug interventions unless their hemoglobin A1c (A1c) level is above 6%.
View Article and Find Full Text PDFIntroduction: Falls and fall-related injuries are a serious cause of morbidity and cost to society. Foot problems and inappropriate footwear may increase the risk of falls; therefore podiatric interventions may play a role in reducing falls. Two Cochrane systematic reviews identified only one study of a podiatry intervention aimed to reduce falls, which was undertaken in Australia.
View Article and Find Full Text PDFWheat bran arabinoxylan (WBAX) gels entrapping standard model proteins at different mass ratios were formed. The entrapment of protein affected the gel elasticity and viscosity values, which decreased from 177 to 138 Pa. The presence of protein did not modify the covalent cross-links content of the gel.
View Article and Find Full Text PDFThe atomic nucleus is composed of two different kinds of fermions: protons and neutrons. If the protons and neutrons did not interact, the Pauli exclusion principle would force the majority of fermions (usually neutrons) to have a higher average momentum. Our high-energy electron-scattering measurements using (12)C, (27)Al, (56)Fe, and (208)Pb targets show that even in heavy, neutron-rich nuclei, short-range interactions between the fermions form correlated high-momentum neutron-proton pairs.
View Article and Find Full Text PDFBackground: Most people referred to rapid access chest pain clinics have non-cardiac chest pain, and in those diagnosed with stable coronary heart disease, guidance recommends that first-line treatment is usually medication rather than revascularisation. Consequently, many patients are not reassured they have the correct diagnosis or treatment. A previous trial reported that, in people with non-cardiac chest pain, a brief discussion with a health psychologist before the tests about the meaning of potential results led to people being significantly more reassured.
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