Alcohol has been shown to affect performance on tasks associated with executive functioning. However, studies in this area have generally been limited to a single dose or gender or have used small sample sizes. The purpose of this study was to provide a more nuanced and systematic examination of alcohol's effects on commonly used tests of executive functioning at multiple dosages in both men and women. Research volunteers (91 women and 94 men) were randomly assigned to one of four drink conditions (alcohol doses associated with target blood alcohol concentrations of .000%, .050%, .075% and .100%). Participants then completed three tasks comprising two domains of executive functioning: two set shifting tasks, the Trail Making Test and a computerized version of the Wisconsin Card Sorting Task, and a response inhibition task, the GoStop Impulsivity Paradigm. Impaired performance on set shifting tasks was found at the .100% and .075% dosages, but alcohol intoxication did not impair performance on the GoStop. No gender effects emerged. Thus, alcohol negatively affects set shifting at moderately high levels of intoxication in both men and women, likely due to alcohol's interference with prefrontal cortex function. Although it is well-established that alcohol negatively affects response inhibition as measured by auditory stop-signal tasks, alcohol does not appear to exert a negative effect on response inhibition as measured by the GoStop, a visual stop-signal task.
One of the requirements for tumor development is blood supply, most often driven by hypoxia-induced angiogenesis. Hypoxia induces the stabilization of hypoxia-inducible factor-1 alpha (HIF-1α), which induces expression of an angiogenic factor, vascular endothelial growth factor (VEGF). The purpose of this study is to validate a new screening platform combined with orthogonal assays to rapidly identify HIF-1 inhibitors and to evaluate the effectiveness of approved drugs on modulating HIF-1 signaling.We generated an endogenous HIF-1α–NanoLuc luciferase reporter allele in the human HCT116 colon cancer cell line using genome editing and screened a panel of small interfering RNAs (siRNAs) to 960 druggable targets and approximately 2,500 drugs on a quantitative high-throughput screening (qHTS) platform. Selected compounds were further investigated with secondary assays to confirm their anti-HIF activity and to study their mode of action. The qHTS assay identified over 300 drugs that inhibited HIF-1α-NanoLuc expression. The siRNA screening results supported the effectiveness of several target-specific inhibitors. Moreover, the identified HIF-1 inhibitors, such as mycophenolate mofetil, niclosamide, and trametinib, were able to suppress cancer cell proliferation and angiogenesis. Our study indicates that blocking the mitogen-activated protein kinase (MAPK) and phosphoinositol 3-kinase (PI3K) pathways effectively inhibits hypoxia-induced HIF-1α accumulation and HIF-1α transactivation and that proteasome inhibitors induce accumulation and decrease transcriptional activity of HIF-1α. These findings underline the importance of developing a battery of robust assay platforms and confirmation studies that focus on endogenous protein targets so that only relevant and reliable data will be taken into pre-clinical and clinical studies.
Objective Non-experimental survey and field research support the notion that alcohol use may be associated with deliberate self-harm (DSH) across the spectrum of lethality, from non-suicidal self-injury (NSSI) through suicide. Non-experimental studies, however, provide limited information about potential causal relationships between alcohol consumption and DSH. Two previous experiments showed that a relatively high-dose of alcohol increases the likelihood of engaging in DSH in the laboratory, defined by the self-administration of a “painful” shock (the Self-Aggression Paradigm: SAP; Berman & Walley, 2003; McCloskey & Berman, 2003). In this study, we examined whether (a) lower doses of alcohol also elicit DSH, (b) this effect occurs for women as well as men, and (c) individual differences in past non-suicidal self-injury (NSSI) moderate alcohol’s effects on DSH. Method Non-alcohol dependent men and women (N = 210) were assigned either to .00%, .05%, .075%, or .100% blood alcohol concentration (BAC) drink conditions and completed a self-rating scale of NSSI (the Deliberate Self-Harm Inventory: DSHI; Gratz, 2001). As in previous SAP studies, DSH was operationalized by shock setting behavior during a competitive reaction-time game. Results Overall, a greater proportion of participants in the .075% and .100% (but not .050%) alcohol conditions self-selected a “painful” shock to administer compared to participants in the placebo condition. NSSI predicted self- administration of painful shocks, but did not moderate the alcohol effect. Conclusions Results provide experimental evidence to support the notion that interventions for self-harm should include processes to monitor and limit alcohol intake.
No abstract
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.