726 research outputs found

    Sestrins Link Tumor Suppressors with the AMPK-TOR Signaling Network

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    Upgrading Russian enterprises from the value chain perspective: the case study of tube & pipe, and furniture sectors

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    The paper is the first analysis of the competitiveness of Russian enterprises from the perspective of value chains, with a focus on the example of tube & pipe and furniture producers. In both industries, Russian firms enjoy an advantage on the raw material side. Nevertheless, the overall competitiveness level of Russian producers remains modest. Domestic industries primarily owe decreased competitiveness to the inadequate operation of the final links in the value chain: from end-product production to the end-user. In addition, the competitiveness of domestic producers is limited to the ability of key players in the chain to redistribute additional gains in their own favor. Study shows that any non-selective methods of supporting enterprises (such as tax reductions) exert extremely limited influence on the status of players in those chains where one of the links is characterized by serious entry barriers and related opportunities of rent redistribution in favor of a particular player. Paper suggests several policy measures which aim to improve the ability of the producers to reposition themselves along the chain or to modify the chain itself

    Low-frequency (ELF–VLF) radio atmospherics study at the Ukrainian Antarctic Akademik Vernadsky station

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    This paper describes the results of the atmospherics measurements in the extremely low-frequency (ELF) and very low-frequency (VLF) frequency ranges performed at the Akademik Vernadsky station (64.26W; 65.25S) during February–April 2019. The main objective of the study was the implementation of a single-site technique for monitoring the lower ionosphere parameters and locating globally distributed powerful lightning discharges.У даній статті описано результати вимірювань атмосфериків в діапазонах наднизькочастотних (ННЧ) і дуже низькочастотних (ДНЧ), виконаних на Українській антарктичній станції (УАС) «Академік Вернадський» (64.26 W; 65.25 S) протягом лютого—квітня 2019 року. Основною метою дослідження була реалізація однопозиційного методу для моніторингу параметрів нижньої іоносфери та локації потужних грозових розрядів, розподілених по всій планеті

    Sestrin2 Modulates AMPK Subunit Expression and Its Response to Ionizing Radiation in Breast Cancer Cells

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    Background: The sestrin family of stress-responsive genes (SESN1-3) are suggested to be involved in regulation of metabolism and aging through modulation of the AMPK-mTOR pathway. AMP-activated protein kinase (AMPK) is an effector of the tumour suppressor LKB1, which regulates energy homeostasis, cell polarity, and the cell cycle. SESN1/2 can interact directly with AMPK in response to stress to maintain genomic integrity and suppress tumorigenesis. Ionizing radiation (IR), a widely used cancer therapy, is known to increase sestrin expression, and acutely activate AMPK. However, the regulation of AMPK expression by sestrins in response to IR has not been studied in depth. Methods and Findings: Through immunoprecipitation we observed that SESN2 directly interacted with the AMPKa1b1c1 trimer and its upstream regulator LKB1 in MCF7 breast cancer cells. SESN2 overexpression was achieved using a Flag-tagged SESN2 expression vector or a stably-integrated tetracycline-inducible system, which also increased AMPKa1 and AMPKb1 subunit phosphorylation, and co-localized with phosphorylated AMPKa-Thr127 in the cytoplasm. Furthermore, enhanced SESN2 expression increased protein levels of LKB1 and AMPKa1b1c1, as well as mRNA levels of LKB1, AMPKa1, and AMPKb1. Treatment of MCF7 cells with IR elevated AMPK expression and activity, but this effect was attenuated in the presence of SESN2 siRNA. In addition, elevated SESN2 inhibited IR-induced mTOR signalling and sensitized MCF7 cells to IR through an AMPK-dependent mechanism

    Sestrin2 is induced by glucose starvation via the unfolded protein response and protects cells from non-canonical necroptotic cell death

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    Sestrin2 is a member of a family of stress responsive proteins, which controls cell viability via antioxidant activity and regulation of the mammalian target of rapamycin protein kinase (mTOR). Sestrin2 is induced by different stress insults, which diminish ATP production and induce energetic stress in the cells. Glucose is a critical substrate for ATP production utilized via glycolysis and mitochondrial respiration as well as for glycosylation of newly synthesized proteins in the endoplasmic reticulum (ER) and Golgi. Thus, glucose starvation causes both energy deficiency and activation of ER stress followed by the unfolding protein response (UPR). Here, we show that UPR induces Sestrin2 via ATF4 and NRF2 transcription factors and demonstrate that Sestrin2 protects cells from glucose starvation-induced cell death. Sestrin2 inactivation sensitizes cells to necroptotic cell death that is associated with a decline in ATP levels and can be suppressed by Necrostatin 7. We propose that Sestrin2 protects cells from glucose starvation-induced cell death via regulation of mitochondrial homeostasis
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