Activating transcription factor 6 (ATF6) is one of three principle endoplasmic reticulum (ER) stress response proteins and becomes activated when ER homeostasis is perturbed. ATF6 functions to increase ER capacity by stimulating transcription of ER-resident chaperone genes such as GRP78. Using an antibody that recognizes active ATF6α-p50, we found that active ATF6α was detected in insulinoma cells and rodent islets even under basal conditions and the levels were further increased by ER stress. To examine the function of ATF6α-p50, we depleted endogenous ATF6α-p50 levels using small interfering RNA in insulinoma cells. Knockdown of endogenous ATF6α-p50 levels by ∼60% resulted in a reduction in the steady-state levels of GRP78 mRNA and protein levels in nonstressed cells. Furthermore, ATF6α knockdown resulted in an apoptotic phenotype. We hypothesized that removal of the ATF6α branch of the unfolded protein response (UPR) would result in ER stress. However, neither the PKR-like endoplasmic reticulum kinase (PERK), nor the inositol requiring enzyme 1 (IRE1) pathways of the UPR were significantly activated in ATF6α knockdown cells, although these cells were more sensitive to ER stress-inducing compounds. Interestingly, phosphorylation of JNK, p38, and c-Jun were elevated in ATF6α knockdown cells and inhibition of JNK or p38 kinases prevented apoptosis. These results suggest that ATF6α may have a role in maintaining β-cell survival even in the absence of ER stress.
Rett syndrome is a pediatric neurological condition that affects primarily girls. Approximately 30% of Rett syndrome cases arise from point mutations that introduce a premature stop codon into the MECP2 gene. Several studies have now shown that certain aminoglycosides can facilitate read-through of some types of nonsense mutations in a context-dependent manner and allow the generation of a full-length protein. It remains mostly unclear whether different nonsense mutations of MECP2 will be responsive to aminoglycoside treatment. In this study, we tested whether the common premature terminating mutations of MECP2 seen in Rett syndrome cases can be partially suppressed by aminoglycoside administration. Our results show that aminoglycosides allow different mutant forms of MECP2 to be overcome in transiently transfected HEK293 cells, but with differing levels of efficiency. In addition, we also show that aminoglycosides increased the prevalence of full-length MeCP2 protein in a dose-dependent manner in a lymphocyte cell line derived from a Rett syndrome girl with the R255X mutation. This study helps to establish the "proof of principle" that some nonsense mutations causing Rett syndrome can be at least partially suppressed by drug treatment.
Comparative characteristics of induced sputum cellular composition in 11mild and 12 moderate stable COPD patients, 30 patients with chronic bronchitis and 13 smokers have been studied. Patients with mild stable COPD were found to have increased absolute number of all cells, including neutrophils and macrophages in the induced sputum in comparison with patients with chronic bronchitis. The inflammatory process in the lungs increases along with airflow limitation degree.
Вероятно, в первую очередь это связано с тем, что наибольшее количество женщин в пери-и постменопаузальном возрасте изначально было именно в группе вегетарианцев. Исключение лиц, регулярно принимавших добавки витамина D, не сказалось радикально на результатах исследования. При анализе выборки, куда вошли лица, удовлетворявшие обоим исключающим критериям, не обнаружено существенных различий в показателях. Заключение. Полученные данные свидетельствуют о том, что показатели МПКТ у российских веганов и вегетарианцев не отличаются от таковых у лиц со смешанным рационом, однако требуются дальнейшие более крупные исследования. Ключевые слова: остеопения; остеопороз; минеральной плотности костной ткани, Т-критерий, Z-критерий, растительное происхождение The number of vegetarians and vegans is increasing each year. In this regard, studies of the quality of diets that exclude slaughter foods, as well as their impact on human health, are becoming more and more relevant. The main purpose of the study was to assess the bone mineral density (BMD) in Russian vegetarians and vegans, as well as in omnivores. Material and methods. Design -cross-sectional study. On an outpatient basis, we examined 103 conditionally healthy people aged 18 to 77 years with different diets: 36 vegans, 38 vegetarians and 29 omnivores. X-ray two energy absorptiometry was used to assess BMD. The density of the lumbar vertebrae (L I -L IV ) and femoral neck was measured. Results; Osteopenia in the lumbar spine was diagnosed in 27.8% of vegans, 39.5% of vegetarians, and 31.0% of omnivores. In the femoral neck, BMD corresponding to osteopenia was detected in 19.4, 26.3, and 17.2% of cases, respectively. 18.4% of vegetarians and 6.9% of omnivores had BMD corresponding to osteoporosis in the lumbar spine. Osteoporosis was not diagnosed in the femoral neck. No significant differences were observed after exclusion of people over 50 years of age. This was probably due primarily to the fact that the largest number of peri and postmenopausal women were in the vegetarian group. Excluding people who had took vitamin D supplements regularly did not drastically change the results of the study. When taking into account both exclusion criteria, no significant differences were observed. Conclusion. The findings suggest that BMD in vegans and vegetarians in Russia does not differ from that in omnivores. However, further larger studies are required.
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