Loss of auditory sensitivity from inner hair cell synaptopathy can be centrally compensated in the young but not old brain

AbstractA dramatic shift in societal demographics will lead to rapid growth in the number of older people with hearing deficits. Poorer performance in suprathreshold speech understanding and temporal processing with age has been previously linked with progressing inner hair cell (IHC) synaptopathy that precedes age-dependent elevation of auditory thresholds. We compared central sound responsiveness after acoustic trauma in young, middle-aged, and older rats. We demonstrate that IHC synaptopathy progresses from middle age onward and hearing threshold becomes elevated from old age onward. Interestingly, middle-aged animals could centrally compensate for the loss of auditory fiber activity through an increase in late auditory brainstem responses (late auditory brainstem response wave) linked to shortening of central response latencies. In contrast, old animals failed to restore central responsiveness, which correlated with reduced temporal resolution in responding to amplitude changes. These findings may suggest that cochlear IHC synaptopathy with age does not necessarily induce temporal auditory coding deficits, as long as the capacity to generate neuronal gain maintains normal sound-induced central amplitudes

New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms

Abstracts from the 8th International Conference on cGMP Generators, Effectors and Therapeutic Implications

This work was supported by a restricted research grant of Bayer AG

Role of calcium ions in the pressure control of renin secretion from the kidneys

In this study we examined the role of calcium ions in the control of renin release by the renal artery pressure. For this purpose renin secretion rates (RSR) were measured in isolated rat kidneys perfused at pressures of 140, 100, 80 and 40 mmHg (19, 13, 11, 5 kPa) with media containing either 1.5 mmol/l ("normal") or zero calcium concentrations (calcium-free perfusate with 0.5 mmol/l EGTA). At normal calcium the RSR was inversely related to the renal artery pressure, whereas calcium withdrawal resulted in an almost linear and proportional relationship between RSR and perfusion pressure. As a consequence, RSR at 140 mm Hg (19 kPa) with a calcium-free medium was similar to renin release at 40 mm Hg (5 kPa) with normal calcium. The nitric oxide (NO) donor sodium nitroprusside (1 mumol/l) stimulated RSR in a pressure-dependent fashion at a calcium concentration of 1.5 mmol/l. With a calcium-free perfusate, sodium nitroprusside did not restore the inverse pressure dependence of RSR seen with normal calcium but almost doubled the RSR across the whole pressure range. Whilst RSR was significantly reduced by angiotensin II (1 nmol/l) in the range between 40 mmHg and 140 mmHg (5-19 kPa) with normal calcium, withdrawal of extracellular calcium ions practically abolished the inhibitory action of angiotensin II. Since angiotensin II attenuated RSR especially at low renal perfusion pressure, our results indicate that renin release in this pressure range is still inhibitable by calcium mobilization in renal juxtaglomerular cells. Thus, the enhancement of renin secretion at lower pressures cannot be explained by a decreased sensitivity of renin release towards calcium ions.(ABSTRACT TRUNCATED AT 250 WORDS

Musikwirtschaft: Gutachten im Auftrag des Ministeriums fuer Wirtschaft, Mittelstand und Technologie des Landes Nordrhein-Westfalen

SIGLEAvailable from Bibliothek des Instituts fuer Weltwirtschaft, ZBW, Duesternbrook Weg 120, D-24105 Kiel A 188496 / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekDEGerman