GABA(A) receptor composition is determined by distinct assembly signals within alpha and beta subunits.

Key to understanding how receptor diversity is achieved and controlled is the identification of selective assembly signals capable of distinguishing between other subunit partners. We have identified that the beta1-3 subunits exhibit distinct assembly capabilities with the gamma2L subunit. Similarly, analysis of an assembly box in alpha1-(57-68) has revealed an absolute requirement for this region in the assembly of alphabeta receptors. Furthermore, a selective requirement for a single amino acid (Arg-66), previously shown to be essential for the formation of the low affinity GABA binding site, is observed. This residue is critical for the assembly of alpha1beta2 but not alpha1beta1 or alpha1beta3 receptors. We have confirmed the ability of the previously identified GKER signal in beta3 to direct the assembly of betagamma receptors. The GKER signal is also involved in driving assembly with the alpha1 subunit, conferring the ability to assemble with alpha1(R66A) on the beta2 subunit. Although this signal is sufficient to permit the formation of beta2gamma2 receptors, it is not necessary for beta3gamma2 receptor formation, suggesting the existence of alternative assembly signals. These findings support the belief that GABA(A) receptor assembly occurs via defined pathways to limit the receptor diversity.

Turning point: rethinking violence--evaluation of program efficacy in reducing adolescent violent crime recidivism.

BACKGROUND: The link between medicine and violence prevention is self-evident, yet the literature reveals few studies that scientifically document effective interventions. The Turning Point: Rethinking Violence (TPRV) program is a unique multiagency program developed to expose, educate, and remediate first-time violent offenders and their parents regarding the real-world consequences of violence. Four key components are integrated into a 6-week, court-ordered program (14 total contact hours): the Trauma Experience (tour, video, discussions), the Victim Impact Panel (presented by parent survivors), Group Process, and Community Networking (individualized mental health referral). We hypothesize that TPRV delivers lower outcomes regarding violence recidivism (VR) when compared with standard court sentencing options (100 hours of community service) for first-time violent offenders. METHODS: The study group subjects (n = 38) met inclusion criteria and were blindly and randomly sentenced to attend the TPRV program. The control group (n = 38) were pulled from a subject pool of first-time offenders who received standard sentencing options, met the same inclusion criteria with regard to age and types of offenses, and were matched by race to the study group. Both groups were studied for VR within the year after the first violent conviction, and comparison was performed by a (2 analysis of recidivism rates. RESULTS: Results reveal a statistically significant difference between the study group and the control group for VR (p