340 research outputs found

    Determination of cellular glutathione: glutathione disulphide ratio in prostate cancer cells by high performance liquid chromatography with electrochemical detection

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    A validated method has been developed for the simultaneous measurement of reduced and oxidized glutathione in de-proteinised cellular extracts. This has been used to compare models of malignant and non-malignant human prostate cell lines. Analysis of LNCaP and DU145 cells showed a glutathione to glutathione disulfide ratio of 8:1 and 32:1 respectively, whilst the control cell line, PZ-HPV7 displayed a ratio of 93:1. Results indicate that the more aggressive phenotype displays adaptation to increased oxidative stress via up regulation of glutathione turnover. It was also noted that in the LNCaP and DU145 cell line, glutathione was only responsible for ca. 60% and 79% respectively, of the total cellular reduced thiol; indicating the presence of other biological thiols

    Information exchange networks at the climate science-policy interface : Evidence from the Czech Republic, Finland, Ireland, and Portugal

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    Scientifically informed climate policymaking starts with the exchange of credible, salient, and legitimate scientific information between scientists and policymakers. It is therefore important to understand what explains the exchange of scientific information in national climate policymaking processes. This article applies exponential random graph models to network data from the Czech Republic, Finland, Ireland, and Portugal to investigate which types of organizations are favored sources of scientific information and whether actors obtain scientific information from those with similar beliefs as their own. Results show that scientific organizations are favored sources in all countries, while only in the Czech Republic do actors obtain scientific information from those with similar policy beliefs. These findings suggest that actors involved in climate policymaking mostly look to scientific organizations for information, but that in polarized contexts where there is a presence of influential denialists overcoming biased information exchange is a challenge.Peer reviewe

    Vaspin Is an Adipokine Ameliorating ER Stress in Obesity as a Ligand for Cell-Surface GRP78/MTJ-1 Complex

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    It is unknown whether adipokines derived from adipose tissues modulate endoplasmic reticulum (ER) stress induced in obesity. Here, we show that visceral adipose tissue-derived serine protease inhibitor (vaspin) binds to cell-surface 78-kDa glucose-regulated protein (GRP78), which is recruited from ER to plasma membrane under ER stress. Vaspin transgenic mice were protected from diet-induced obesity, glucose intolerance, and hepatic steatosis, while vaspin-deficient mice developed glucose intolerance associated with upregulation of ER stress markers. With tandem affinity tag purification using HepG2 cells, we identified GRP78 as an interacting molecule. The complex formation of vaspin, GRP78, and murine tumor cell DnaJ-like protein 1 (MTJ-1) (DnaJ homolog, subfamily C, member 1) on plasma membrane was confirmed by cell-surface labeling with biotin and immunoprecipitation in liver tissues and H-4-II-E-C3 cells. The addition of recombinant human vaspin in the cultured H-4-II-E-C3 cells also increased the phosphorylation of Akt and AMP-activated protein kinase (AMPK) in a dose-dependent manner, and anti-GRP78 antibodies completely abrogated the vaspin-induced upregulation of pAkt and pAMPK Vaspin is a novel ligand for cell-surface GRP78/MTJ-1 complex, and its subsequent signals exert beneficial effects on ER stress-induced metabolic dysfunctions. Diabetes 61:2823-2832, 201

    What is consumption, where has it been going, and does it still matter?

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    This article considers the relationships between consumption, the environment, and wider sociological endeavour. The current vogue for applying theories of practice to the policy domain of ‘sustainable consumption’ has been generative of conceptual renewal, however the field now sits closer to the applied environmental social sciences than to the sociology of consumption. The analysis proceeds via a close reading of the intellectual currents that have given rise to this situation, and it identifies a number of interrelated issues concerning conceptual slippage and the exclusion of core disciplinary concerns. Accordingly a more suitable definition of consumption is offered, an agenda for re-engaging with foundational approaches to consumer culture is established, and a renewal and reorientation of critique is proposed. Working through and building on the contributions of practice theoretical repertoires, this article suggests that consumption scholarship offers a distinctive set of resources to discussions of current ecological crises and uncertain social futures. These are briefly described and the conclusion argues that consumption still matters

    Retargeted adenoviruses for radiation-guided gene delivery

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    The combination of radiation with radiosensitizing gene delivery or oncolytic viruses promises to provide an advantage that could improve the therapeutic results for glioblastoma. X-rays can induce significant molecular changes in cancer cells. We isolated the GIRLRG peptide that binds to radiation-inducible 78 kDa glucose-regulated protein (GRP78), which is overexpressed on the plasma membranes of irradiated cancer cells and tumor-associated microvascular endothelial cells. The goal of our study was to improve tumor-specific adenovirus-mediated gene delivery by selectively targeting the adenovirus binding to this radiation-inducible protein. We employed an adenoviral fiber replacement approach to conduct a study of the targeting utility of GRP78-binding peptide. We have developed fiber-modified adenoviruses encoding the GRP78-binding peptide inserted into the fiber-fibritin. We have evaluated the reporter gene expression of fiber-modified adenoviruses in vitro using a panel of glioma cells and a human D54MG tumor xenograft model. The obtained results demonstrated that employment of the GRP78-binding peptide resulted in increased gene expression in irradiated tumors following infection with fiber-modified adenoviruses, compared with untreated tumor cells. These studies demonstrate the feasibility of adenoviral retargeting using the GRP78-binding peptide that selectively recognizes tumor cells responding to radiation treatment
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