Agrin-induced acetylcholine receptor clustering in mammalian muscle requires tyrosine phosphorylation.

Agrin is thought to be the nerve-derived factor that initiates acetylcholine receptor (AChR) clustering at the developing neuromuscularjunction. We have investigated the signaling pathway in mouse C2 myotubes and report that agrin induces a rapid but transient tyrosine phosphorylation of the AChR beta subunit. As the beta-subunit tyrosine phosphorylation occurs before the formation of AChR clusters, it may serve as a precursor step in the clustering mechanism. Consistent with this, we observed that tyrosine phosphorylation of the beta subunit correlated precisely with the presence or absence of clustering under several experimental conditions. Moreover, two tyrosine kinase inhibitors, herbimycin and staurosporine, that blocked beta-subunit phosphorylation also blocked agrin-induced clustering. Surprisingly, the inhibitors also dispersed preformed AChR clusters, suggesting that the tyrosine phosphorylation of other proteins may be required for the maintenance of receptor clusters. These findings indicate that in mammalian muscle, agrin-induced AChR clustering occurs through a mechanism that requires tyrosine phosphorylation and may involve tyrosine phosphorylation of the AChR itself

Heavy Metal Poisoning and Cardiovascular Disease

Cardiovascular disease (CVD) is an increasing world health problem. Traditional risk factors fail to account for all deaths from CVD. It is mainly the environmental, dietary and lifestyle behavioral factors that are the control keys in the progress of this disease. The potential association between chronic heavy metal exposure, like arsenic, lead, cadmium, mercury, and CVD has been less well defined. The mechanism through which heavy metals act to increase cardiovascular risk factors may act still remains unknown, although impaired antioxidants metabolism and oxidative stress may play a role. However, the exact mechanism of CVD induced by heavy metals deserves further investigation either through animal experiments or through molecular and cellular studies. Furthermore, large-scale prospective studies with follow up on general populations using appropriate biomarkers and cardiovascular endpoints might be recommended to identify the factors that predispose to heavy metals toxicity in CVD. In this review, we will give a brief summary of heavy metals homeostasis, followed by a description of the available evidence for their link with CVD and the proposed mechanisms of action by which their toxic effects might be explained. Finally, suspected interactions between genetic, nutritional and environmental factors are discussed

Relationship Between Vitamin D and Cardio-Metabolic Biomarkers Among Saudi Postmenopausal Women

Vitamin D deficiency is prevalent worldwide, and in Saudi Arabia in particular. There is growing evidence that hypovitaminosis D is involved in the pathogenesis of cardiovascular diseases. We determined concentrations of serum 25 hydroxy 25(OH) vitamin D in relation to several metabolic biomarkers including total cholesterol (TC), low density lipoprotein-cholesterol (LDL-C), high density lipoprotein-cholesterol, triglycerides (TG), atherogenic index (AI), glucose, C-reactive protein (CRP), adiposity, and blood pressure in a cross-sectional analysis in 300 Saudi postmenopausal women. Participants completed a detailed questionnaire and fasting blood samples were collected. Vitamin D deficiency was common, affecting 89% of individuals. Higher serum 25(OH) vitamin D levels were consistently found among subjects with no prevalent cardiovascular risk factors (p>0.05) except for those subjects with serum CRP level ≥3mg/dl, HDL-C <1.04mmol/L, AI≥5, exercising ≥3times/week, and those with 4 or more pregnancies. Hypovitaminosis D was inversely correlated with DBP (r=-0.118, p=0.042), TC (r=-0.165, p=0.004), TG (r=-0.119, p=0.040), LDL-C (r=-0.138, p=0.017), AI (r=-0.125, p=0.031), and veiling type (r=-0.127, p=0.028). No significant impact of hypovitaminosis D on CRP, levels of which were similar among vitamin D sufficient and deficient subjects. However, hypovitaminosis D was significantly related to dyslipidemia and diastolic blood pressure in a group of Saudi postmenopausal women

Columbia River Rhyolites: Age-Distribution Patterns and Their Implications for Arrival, Location, and Dispersion of Continental Flood Basalt Magmas in the Crust

Columbia River province magmatism is now known to include abundant and widespread rhyolite centers even though the view that the earliest rhyolites erupted from the McDermitt Caldera and other nearby volcanic fields along the Oregon–Nevada state border has persisted. Our study covers little-studied or unknown rhyolite occurrences in eastern Oregon that show a much wider distribution of older centers. With our new data on distribution of rhyolite centers and ages along with literature data, we consider rhyolites spanning from 17.5 to 14.5 Ma of eastern Oregon, northern Nevada, and western Idaho to be a direct response to flood basalts of the Columbia River Basalt Group (CRBG) and collectively categorize them as Columbia River Rhyolites. The age distribution patterns of Columbia River Rhyolites have implications for the arrival, location, and dispersion of flood basalt magmas in the crust. We consider the period from 17.5 to 16.4 Ma to be the waxing phase of rhyolite activity and the period from 15.3 to 14.5 Ma to be the waning phase. The largest number of centers was active between 16.3–15.4 Ma. The existence of crustal CRBG magma reservoirs beneath rhyolites seems inevitable, and hence, rhyolites suggest the following. The locations of centers of the waxing phase imply the arrival of CRBG magmas across the distribution area of rhyolites and are thought to correspond to the thermal pulses of arriving Picture Gorge Basalt and Picture-Gorge-Basalt-like magmas of the Imnaha Basalt in the north and to those of Steens Basalt magmas in the south. The earlier main rhyolite activity phase corresponds with Grande Ronde Basalt and evolved Picture Gorge Basalt and Steens Basalt. The later main phase rhyolite activity slightly postdated these basalts but is contemporaneous with icelanditic magmas that evolved from flood basalts. Similarly, centers of the waning phase span the area distribution of earlier phases and are similarly contemporaneous with icelanditic magmas and with other local basalts. These data have a number of implications for long-held notions about flood basalt migration through time and the age-progressive Snake River Plain Yellowstone rhyolite trend. There is no age progression in rhyolite activity from south-to-north, and this places doubt on the postulated south-to-north progression in basalt activity, at least for main-phase CRBG lavas. Furthermore, we suggest that age-progressive rhyolite activity of the Snake River Plain–Yellowstone trend starts at ~12 Ma with activity at the Bruneau Jarbidge center, and early centers along the Oregon–Nevada border, such as McDermitt, belong to the early to main phase rhyolites identified here

The effects of curcumin on weight loss among patients with metabolic syndrome and related disorders: A systematic review and meta-analysis of randomized controlled trials

Background and objective: The current systematic review and meta-analysis of randomized controlled trials (RCTs) was carried out to assess the influence of curcumin intake on weight among patients with metabolic syndrome and related disorders. Methods: We searched the following databases up until January 2018: MEDLINE, EMBASE, Web of Science, and Cochrane Central Register of Controlled Trials. The relevant data were extracted and evaluated for quality of the studies in accordance with the Cochrane risk of bias tool. Data were pooled using the inverse variance method and expressed as standardized mean difference (SMD) with 95 confidence intervals (95 CI). Results: Eighteen articles (21 studies) that comprised a total of 1,604 individuals were finally included in the meta-analysis. Curcumin intake significantly reduced body mass index (BMI) (SMD �0.37; 95 CI, �0.61, �0.13; P < 0.01), weight (SMD �0.23; 95 CI, �0.39, �0.06; P < 0.01), waist-circumference (WC) (SMD �0.25; 95 CI, �0.44, �0.05; P = 0.01), leptin levels (SMD �0.97; 95 CI, �1.18, �0.75; P < 0.001) and increased adiponectin levels (SMD 1.05; 95 CI, 0.23, 1.87; P = 0.01). We found no significant effect of curcumin intake on hip ratio (HR) (SMD �0.17; 95 CI, �0.42, 0.08; P = 0.18). Conclusions: Overall, we have found that curcumin intake among patients with metabolic syndrome and related disorders was correlated with a significant reduction in BMI, weight, WC, and leptin, and a significant increase in adiponectin levels, but did not affect HR. Copyright © 2019 Akbari, Lankarani, Tabrizi, Ghayour-Mobarhan, Peymani, Ferns, Ghaderi and Asemi. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms

The effects of vitamin D supplementation on expanded disability status scale in people with multiple sclerosis: A critical, systematic review and metaanalysis of randomized controlled trials

In this meta-analysis of randomized controlled trials (RCTs), the effects of vitamin D supplementation on the scores for the expanded disability status scale (EDSS) in people with multiple sclerosis (MS) are assessed. The following databases were search up to January 2018: MEDLINE, EMBASE, Web of Science, and Cochrane Central Register of Controlled Trials. The quality of the relevant extracted data was assessed according to the Cochrane risk of bias tool. Data were pooled by the use of the inverse variance method and expressed as mean difference with 95 Confidence Intervals (95 CI). Six studies were included in this meta-analysis. The findings demonstrated that supplementation with vitamin D alone and vitamin D plus calcium did not affect the EDSS score (WMD -0.11 (-0.33, 0.11); P = 0.32). In addition, subgroup analysis showed that vitamin D supplementation alone, when compared to the use of a placebo, and vitamin D plus calcium supplementation compared with the control did not affect EDSS (WMD -0.13 (-0.30, 0.11); P = 0.29) and (WMD -0.08 (-0.57, 0.41); P = 0.29), respectively. Overall, this meta-analysis indicated that taking vitamin D in people with MS had no significant effect on EDSS. © 2019 Elsevier B.V

Aligning assessment with the needs of work-integrated learning: the challenges of authentic assessment in a complex context

Work-integrated learning (WIL) is a feature of university courses, both in professional areas, where it is commonplace, but also across many different disciplines. Assessment of WIL can be complex as it involves parties and settings external to the university, and it can be problematic because of difficulties in aligning learning activities during placements with what is or can be assessed by the university. This paper explores the relationship between students’ placement experiences and accompanying assessments in contexts where activities are tightly coupled with the curriculum, and in those where it is not. It draws on a qualitative analysis of student interviews and drawings by the interviewees of their WIL experiences, supplemented with analysis of unit guides. Our findings highlight that students’ perceptions of authenticity of assessment were undermined by misalignments between the student, university and industry. Assessment authenticity was perceived by students as based on alignment between their current and future selves in the assessment process, involvement of industry supervisors and relevance of placement activities to assessment activities. The paper discusses the complexity of coordination of educational activities with external partners, especially when one party drives assessment. It then suggests a reframing of WIL assessment to promote alignment and authenticity

Protein kinase D enzymes are dispensable for proliferation, survival and antigen receptor-regulated NFκB activity in vertebrate B-cells

To investigate the importance of protein kinase D (PKD) enzymes we generated a PKD-null DT40 B-lymphocyte cell line. Previously we have shown that PKDs have an essential role in regulating class II histone deacetylases in DT40 B-cells [Matthews, S.A., Liu, P., Spitaler, M., Olson, E.N., McKinsey, T.A., Cantrell, D.A. and Scharenberg, A.M. (2006) Essential role for protein kinase D family kinases in the regulation of class II histone deacetylases in B lymphocytes. Mol. Cell Biol. 26, 1569–1577]. We now show that PKDs are also required to regulate HSP27 phosphorylation in DT40 B-cells. However, in contrast to previous observations in other cell types, PKD enzymes do not regulate basic cellular processes such as proliferation or survival responses, nor NFκB transcriptional activity downstream of the B cell antigen receptor. Thus, PKDs have a selective role in DT40 B-cell biology