Expression parameters of the metabolic pathway genes pyruvate dehydrogenase kinase-1 (PDK-1) and DJ-1/PARK7 in renal cell carcinoma (RCC).

PURPOSE: Metabolic adaptations, such as increases in glucose and energy metabolism, play a pivotal role in the biology of RCC. PDK-1 and DJ-1/PARK7 are thought to control metabolic pathways in cancer. We investigated the expression of PDK-1 and DJ-1/PARK7 in RCC and their prognostic relevance. METHODS: RCC tumor tissue and corresponding normal parenchyma samples were obtained from 91 patients with clear cell RCC. Expression of PDK-1 and DJ-1/PARK7 was determined on the mRNA and protein levels using quantitative RT-PCR and immunohistochemistry. Expression ratios tumor/normal were analyzed for associations with pathological stage and grade (Kruskal-Wallis ANOVA, chi-square test). Potential associations with progression-free and overall survival were analyzed using Cox regression models. RESULTS: PDK-1 mRNA expression was up-regulated as compared to normal tissue (p < 0.001). Differences were observed by tumor stage (p < 0.05) with a trend toward lower expression with increasing stage (p > 0.01). Expression ratio tumor/normal also showed differences by tumor stage with the lowest ratio observed in advanced (pT3) disease. MRNA expression data were confirmed on the protein level with the lowest protein expression in pT3 tumors. PDK-1 expression ratio tumor/normal was inversely associated with outcome after adjustment for stage and grade (HR, 0.54; 95 % CI, 0.31-0.94). No associations observed for DJ-1/PARK7 expression. CONCLUSIONS: PDK is up-regulated in RCC, but down-regulation may be associated with progression toward a metastasizing behavior. Given the role of PDK-1 in the control of glucose metabolism, aerobic glycolysis via up-regulation of PDK-1 may be an early event in RCC development, but less relevant for the progression toward an aggressive phenotype.

Genetic and environmental contributions to the subjective burden of social isolation during the COVID-19 pandemic.

BACKGROUND: Feelings of loneliness and the burden of social isolation were among the most striking consequences of widespread containment measures, such as "social distancing", during the COVID-19 pandemic. Because of the potential impact on people's health, there has been increased interest in understanding the mechanisms and factors that contributed to feelings of loneliness and the burdens of social isolation. However, in this context, genetic predisposition has been largely ignored as an important factor. This is problematic because some of the phenotypic associations observed to date may in fact be genetic. The aim of this study is, therefore, to examine the genetic and environmental contributions to the burden of social isolation at two time points during the pandemic. In addition, we examine whether risk factors identified in previous studies explain genetic or environmental contributions to the burden of social isolation. METHODS: The present study is based on a genetically sensitive design using data from the TwinLife panel study, which surveyed a large sample of adolescent and young adult twins during the first (N = 798) and the second (N = 2520) lockdown in Germany. RESULTS: We find no substantive differences in genetic and environmental contributions to social isolation burden over the course of the pandemic. However, we find the determinants highlighted as important in previous studies can explain only a small proportion of the observed variance in the burden of social isolation and mainly explained genetic contributions. CONCLUSIONS: While some of the observed associations appear to be genetic, our findings underscore the need for further research, as the causes of individual differences in burden of social isolation remain unclear.

Sequential information processing in persuasion.

We present a theory of sequential information processing in persuasion (SIP). It extends assumptions of the heuristic-systematic model, in particular the idea that information encountered early in a persuasion situation may affect the processing of subsequent information. SIP also builds on the abstraction from content-related dichotomies in accord with the parametric unimodel of social judgment. SIP features one constitutional axiom and three main postulates: (A) Persuasion is the sequential processing of information that is relevant to judgment formation. (1) Inferences drawn from initial information may bias the processing of subsequent information if they are either activated rules or valence expectations that are relevant to the subsequent information. (2) Inferences drawn from initial information are resistant to change. Thus, the interpretation of subsequent information is assimilated to inferences drawn from the initial information. Or, if assimilation is impossible, contrast effects occur. (3) The overall effect of a persuasion attempt corresponds to the recipient's judgment at the moment the processing of information is terminated. We illustrate how our predictions for assimilation and contrast effects may be tested by presenting results from an experiment (N = 216) in which we presented exactly the same arguments but varied the processing sequence. We discuss theoretical and applied implications of sequence effects for persuasion phenomena, as well as challenges for further research developing and testing the theory.