Palmitate-induced ER stress and inhibition of protein synthesis in cultured myotubes does not require Toll-like receptor 4

Saturated fatty acids, such as palmitate, are elevated in metabolically dysfunctional condi- tions like type 2 diabetes mellitus. Palmitate has been shown to impair insulin sensitivity and suppress protein synthesis while upregulating proteolytic systems in skeletal muscle. Increased sarco/endoplasmic reticulum (ER) stress and subsequent activation of the unfolded protein response may contribute to the palmitate-induced impairment of muscle protein synthesis. In some cell types, ER stress occurs through activation of the Toll-like receptor 4 (TLR4). Given the link between ER stress and suppression of protein synthesis, we investigated whether palmitate induces markers of ER stress and protein synthesis by activating TLR4 in cultured mouse C2C12 myotubes. Myotubes were treated with vehicle, a TLR4-specific ligand (lipopolysaccharides), palmitate, or a combination of palmitate plus a TLR4-specific inhibitor (TAK-242). Inflammatory indicators of TLR4 activation (IL-6 and TNFα) and markers of ER stress were measured, and protein synthesis was assessed using puromycin incorporation. Palmitate substantially increased the levels of IL-6, TNF-α, CHOP, XBP1s, and ATF 4 mRNAs and augmented the levels of CHOP, XBP1s, phospho- PERK and phospho-eIF2α proteins. The TLR4 antagonist attenuated both acute palmitate and LPS-induced increases in IL-6 and TNFα, but did not reduce ER stress signaling with either 6 h or 24 h palmitate treatment. Similarly, treating myotubes with palmitate for 6 h caused a 43% decline in protein synthesis consistent with an increase in phospho-eIF2α, and the TLR4 antagonist did not alter these responses. These results suggest that palmitate does not induce ER stress through TLR4 in muscle, and that palmitate impairs protein syn- thesis in skeletal muscle in part by induction of ER stress

The problem of information transparency of managing the state programs implementation in the region

В статье обсуждаются вопросы информационной открытости управления государственными программами субъекта Российской Федерации, которые сегодня являются одним из основных стратегических документов. Приведены отдельные результаты анализа официальных сайтов, на которых представлена информация о государственных программах региона. В настоящее время во всех регионах завершен процесс нормативно-правового закрепления механизмов управления государственными программами, разработаны и утверждены основные, а в ряде регионов и дополнительные, нормативно-правовые документы. Но при этом сохраняется средний уровень информационной открытости субъектов Российской Федерации, что проявляется как в качестве размещения материалов, так и в возможности доступа к ним.The article discusses the issues of information transparency of management of state programs of the Russian Federation, which today are one of the key strategic documents. Some results of official websites analysis of that provides information about state programs in the region are shown. Currently all regions completed the process of legal fixation of the public programs governance; the principles, and in some regions and the additional legal documents, are developed and approved. But an average level of information transparency of the Russian Federation subjects remains, which manifests itself both in the quality of the materials and in access to them

Highlights of the Customs Union

The authors summarize the main results of two years of the operation of the Customs Union in Belarus, Kazakhstan and Russia, which is hardly impressive in the aftermath of the global financial crisis and economic instability in Belarus. However, the authors stressed that it is too early to jump to conclusions about the effectiveness of the Customs Union. In addition, the structure of trade, working arrangements and the list of goods are changed. Separately it is analyzed the changing economic situation in Kazakhstan, where the increased influx of Russian investments are after joining the Customs Union fully operational. In different sectors of the domestic economy are active joint Kazakh-Russian companies because Kazakhstan has more attractive business environment, compared to Russia. Russian companies are interested in Kazakhstan and produce this product to sell back to Russia or Belarus. For Kazakhstan benefit is job creation, expansion of production base, increasing tax revenues, new investments