Deceived,Disgusted, and Defensive: Motivated Processing of Anti-Tobacco Advertisements

A 2 × 2 experiment was conducted, where participants watched anti-tobacco messages that varied in deception (content portraying tobacco companies as dishonest) and disgust (negative graphic images) content. Psychophysiological measures, self-report, and a recognition test were used to test hypotheses generated from the motivated cognition framework. The results of this study indicate that messages containing both deception and disgust push viewers into a cascade of defensive responses reflected by increased self-reported unpleasantness, reduced resources allocated to encoding, worsened recognition memory, and dampened emotional responses compared to messages depicting one attribute or neither. Findings from this study demonstrate the value of applying a motivated cognition theoretical framework in research on responses to emotional content in health messages and support previous research on defensive processing and message design of anti-tobacco messages.     

Loss of ATE1-mediated arginylation leads to impaired platelet myosin phosphorylation,clot retraction,and in vivo thrombosis formation

Protein arginylation by arginyl–transfer RNA protein transferase (ATE1) is emerging as a regulator protein function that is reminiscent of phosphorylation. For example, arginylation of β-actin has been found to regulate lamellipodial formation at the leading edge in fibroblasts. This finding suggests that similar functions of β-actin in other cell types may also require arginylation. Here, we have tested the hypothesis that ATE1 regulates the cytoskeletal dynamics essential for in vivo platelet adhesion and thrombus formation. To test this hypothesis, we generated conditional knockout mice specifically lacking ATE1 in their platelets and in their megakaryocytes and analyzed the role of arginylation during platelet activation. Surprisingly, rather than finding an impairment of the actin cytoskeleton structure and its rearrangement during platelet activation, we observed that the platelet-specific ATE1 knockout led to enhanced clot retraction and in vivo thrombus formation. This effect might be regulated by myosin II contractility since it was accompanied by enhanced phosphorylation of the myosin regulatory light chain on Ser19, which is an event that activates myosin in vivo. Furthermore, ATE1 and myosin co-immunoprecipitate from platelet lysates. This finding suggests that these proteins directly interact within platelets. These results provide the first evidence that arginylation is involved in phosphorylation-dependent protein regulation, and that arginylation affects myosin function in platelets during clot retraction.     

Posttraumatic Stress Disorder and One‐Year Outcome in Methadone Maintenance Treatment

Background: Although opiate use may be associated with posttraumatic stress disorder (PTSD), it is not clear whether PTSD is associated with retention in methadone maintenance. Objectives: To evaluate among those receiving methadone maintenance at an urban methadone maintenance clinic the frequency of life‐time traumatic experiences, the predictors and prevalence of current PTSD, and whether PTSD affects retention at 1 year. Methods: Eighty‐nine people participated in the study. The Post Traumatic Diagnostic Scale was used to determine the prevalence of PTSD. The Life Stressor Checklist Revised was used to evaluate trauma history. Logistic regression analyses examined associations between demographic characteristics, substance use, trauma‐related variables, and PTSD. Similar logistic regression analyses were used to examine retention in methadone maintenance at 1 year. Results: The mean number of reported lifetime stressful events was 8.0 (SD = 3.7). Twenty‐seven percent were diagnosed with PTSD. Nearly 92% of those with PTSD had co‐occurring depressive symptoms. Female gender (adjusted odds ratio [AOR][95% CI]; 3.89 [1.07–14.01]), number of traumatic events (AOR [95% CI]; 1.34 [1.13–1.61]), and less education (AOR [95% CI]; 4.13 [1.14–14.98]) were significantly associated with PTSD. Those with a toxicology positive screen were 80% less likely to remaine in methadone maintenance at 1 year (OR [95% CI]; 0.20 [0.07–0.52]). PTSD diagnosis was not significantly associated with treatment retention at 1 year (OR [95% CI]; 0.61 [0.23–1.64]). Conclusions and Scientific Significance: Future studies are needed to determine if treatment of PTSD that is integrated into methadone maintenance programs may impact continued substance abuse use and thereby improve retention in care. (Am J Addict 2012;21:524–530)     

Evaluation of 5-(Trifluoromethyl)-1,2,4-oxadiazole-Based Class IIa HDAC Inhibitors for Huntington’s Disease

Using an iterative structure–activity relationship driven approach, we identified a CNS-penetrant 5-(trifluoromethyl)-1,2,4-oxadiazole (TFMO, 12) with a pharmacokinetic profile suitable for probing class IIa histone deacetylase (HDAC) inhibition in vivo. Given the lack of understanding of endogenous class IIa HDAC substrates, we developed a surrogate readout to measure compound effects in vivo, by exploiting the >100-fold selectivity compound 12 exhibits over class I/IIb HDACs. We achieved adequate brain exposure with compound 12 in mice to estimate a class I/IIb deacetylation EC₅₀, using class I substrate H4K12 acetylation and global acetylation levels as a pharmacodynamic readout. We observed excellent correlation between the compound 12 in vivo pharmacodynamic response and in vitro class I/IIb cellular activity. Applying the same relationship to class IIa HDAC inhibition, we estimated the compound 12 dose required to inhibit class IIa HDAC activity, for use in preclinical models of Huntington’s disease.