5-HT1A receptor blockade reverses GABAA receptor α3 subunit-mediated anxiolytic effects on stress-induced hyperthermia

Stress-related disorders are associated with dysfunction of both serotonergic and GABAergic pathways, and clinically effective anxiolytics act via both neurotransmitter systems. As there is evidence that the GABA(A) and the serotonin receptor system interact, a serotonergic component in the anxiolytic actions of benzodiazepines could be present. The main aim of the present study was to investigate whether the anxiolytic effects of (non-)selective alpha subunit GABA(A) receptor agonists could be reversed with 5-HT1A receptor blockade using the stress-induced hyperthermia (SIH) paradigm. The 5-HT1A receptor antagonist WAY-100635 (0.1-1 mg/kg) reversed the SIH-reducing effects of the non-alpha-subunit selective GABA(A) receptor agonist diazepam (1-4 mg/kg) and the GABA(A) receptor alpha(3)-subunit selective agonist TP003 (1 mg/kg), whereas WAY-100635 alone was without effect on the SIH response or basal body temperature. At the same time, co-administration of WAY-100635 with diazepam or TP003 reduced basal body temperature. WAY-100635 did not affect the SIH response when combined with the preferential alpha(1)-subunit GABA(A) receptor agonist zolpidem (10 mg/kg), although zolpidem markedly reduced basal body temperature. The present study suggests an interaction between GABA(A) receptor alpha-subunits and 5-HT1A receptor activation in the SIH response. Specifically, our data indicate that benzodiazepines affect serotonergic signaling via GABA(A) receptor alpha(3)-subunits. Further understanding of the interactions between the GABA(A) and serotonin system in reaction to stress may be valuable in the search for novel anxiolytic drugs

The SOCS-Box of HIV-1 Vif Interacts with ElonginBC by Induced-Folding to Recruit Its Cul5-Containing Ubiquitin Ligase Complex

The HIV-1 viral infectivity factor (Vif) protein recruits an E3 ubiquitin ligase complex, comprising the cellular proteins elongin B and C (EloBC), cullin 5 (Cul5) and RING-box 2 (Rbx2), to the anti-viral proteins APOBEC3G (A3G) and APOBEC3F (A3F) and induces their polyubiquitination and proteasomal degradation. In this study, we used purified proteins and direct in vitro binding assays, isothermal titration calorimetry and NMR spectroscopy to describe the molecular mechanism for assembly of the Vif-EloBC ternary complex. We demonstrate that Vif binds to EloBC in two locations, and that both interactions induce structural changes in the SOCS box of Vif as well as EloBC. In particular, in addition to the previously established binding of Vif's BC box to EloC, we report a novel interaction between the conserved Pro-Pro-Leu-Pro motif of Vif and the C-terminal domain of EloB. Using cell-based assays, we further show that this interaction is necessary for the formation of a functional ligase complex, thus establishing a role of this motif. We conclude that HIV-1 Vif engages EloBC via an induced-folding mechanism that does not require additional co-factors, and speculate that these features distinguish Vif from other EloBC specificity factors such as cellular SOCS proteins, and may enhance the prospects of obtaining therapeutic inhibitors of Vif function

Associação entre estágios de mudança de comportamento relacionados à atividade física e estado nutricional em universitários Association between stages of behavior change related to physical activity and nutritional status in university students

Este estudo objetivou verificar a associação entre os estágios de mudança de comportamento e o estado nutricional junto a 862 universitários. Para a classificação do estado nutricional, utilizaram-se pontos de corte para o índice de massa corporal, segundo padronização internacional. Os estágios de mudança de comportamento foram analisados individualmente e agrupados em ativos (ação, manutenção) e inativos (pré-contemplação, contemplação, preparação). Proporção mais elevada de universitários foi encontrada nos estágios contemplação (32%) e preparação (29,5%). Observou-se que 68,4% dos universitários eram inativos. As prevalências de baixo peso, sobrepeso e obesidade foram, respectivamente, de 9,5%, 12,4% e 1,7%. Os universitários do estágio Pré-contemplação apresentaram, respectivamente, 5,99 (IC95%: 2,29-15,68) e 7,98 (IC95%: 1,41-45,32) vezes mais chance de terem baixo peso e sobrepeso. Os resultados encontrados no presente estudo sugerem que a universidade tem papel fundamental na adoção de planos e ações voltados para o meio acadêmico, promovendo modificação no estilo de vida mediante programas de atividade física.<br>This study aimed to verify the association between stages of behavior change related to physical activity and nutritional status among 862 university students. Body mass index cut-off values were used to classify nutritional status. Stages of behavior change were analyzed individually and classified into active (action, maintenance) and inactive (pre-contemplation, contemplation, preparation). The most prevalent stages of behavior change were contemplation (32%) and preparation (29.5%). Among the entire sample of students, 68.4% were inactive. Prevalence rates for underweight, overweight, and obesity were 9.5%, 12.4%, and 1.7%, respectively. Students classified in the pre-contemplation stage were 5.99 times (CI95%: 2.29-15.68) and 7.98 times (CI95%: 1.41-45.32) more likely to be underweight and overweight, respectively. The university plays a fundamental role in adopting plans and actions targeting the academic community, promoting lifestyle changes through physical activity programs