Anti-BSND (aa 211-260) polyclonal antibody

Hearing depends on functional ClC-K-type chloride channels composed of barttin with ClC-Ka or ClC-Kb. Loss-of-function mutations of the barttin gene BSND or of both, the ClC-Ka gene CLNKA and the ClC-Kb gene CLNKB lead to congenital deafness and renal salt wasting. Recently, we identified the gain-of-function mutation ClC-Kb(T411S) which is associated with increased blood pressure. To explore the impact of ClC-Kb(T411S) on hearing, healthy volunteers (n = 329) and individuals suffering from tinnitus (n = 246) volunteered for hearing tests (n = 348) and genetic analysis (n = 575). 19.1% of the individuals were heterozygote (ClC-Kb(T41IS)/ClC-Kb) and 1.7% homozygote carriers. Pure tone average hearing threshold (PTAt) for air conduction was significantly (p < 0.033) lower in ClC-Kb(T481S) carriers (13.2 +/- 1.2 dB) than in wild-type individuals (17.1 +/- 0.9 dB). The prevalence of ClC-Kb(T411S) carriers was significantly increased (29.7%) in individuals with PTAt < 15 dB (p < 0.05) and significantly decreased (13.2%) in individuals with PTAt > 30 dB (P < 0.017). The difference was largely due to the female population. Bone conduction was less affected pointing to an effect of the mutation on middle ear function. Tinnitus tended to be more frequent in ClC-Kb(T411S) carriers, a difference, however, not statistically significant. In conclusion, hearing thresholds are slightly lower in carriers of ClC-Kb(T411S), i.e., the gain-of-function polymorphism ClC-Kb(T481S) exerts a subtle but significant protective effect against hearing loss. (c) 2006 Elsevier B.V. All rights reserved.

We present ab initio multiconfiguration self consistent field calculations, using a polarized basis set, of equilibrium and transition-state structures relevant to the two competing mechanisms for the unimolecular decomposition of acetic acid. Single-point calculations using a modified Gaussian-2 method indicate that the lowest energy decomposition pathway for acetic acid is decarboxylation through a four-center transition state leading to methane and carbon dioxide, with a barrier of 71.8 kcal/mol. Dehydration, leading to ketene and water, has a calculated overall activation energy of 73.1 kcal/mol and occurs most easily through a two-step mechanism: 1,3 hydrogen migration to an enediol followed by elimination of water via a four-center transition state. The direct (one-step) dehydration of acetic acid has a calculated barrier of 76.4 kcal/mol. Transition state theory calculations indicate that all three decomposition routes are competitive at high temperatures: the predicted branching between decarboxylation, one-step dehydration, and two-step dehydration is 1.00:0.34:0.28 at 900 K and 1.00:1.11:0.31 at 1500 K. The hydration of ketene to acetic acid in the gas phase is predicted to occur competitively at high temperature by addition of water to the CO pi-bond followed by a 1,3 hydrogen migration and by one-step addition to the CC pi-bsnd.