Subtype-selective GABAA receptor mimetics—novel antihyperalgesic agents?

Agonists at the benzodiazepine-binding site of ionotropic γ-aminobutyric acid (GABAA) receptors are in clinical use as hypnotics, anxiolytics, and anticonvulsants since the early 1960. Analgesic effects of classical benzodiazepines have occasionally been reported in certain subgroups of patients suffering from chronic pain or after spinal delivery through intrathecal catheters. However, these drugs are generally not considered as analgesics but should in fact be avoided in patients with chronic pain. Recent evidence from genetically modified mice now indicates that agents targeting only a subset of benzodiazepine (GABAA) receptors should provide pronounced antihyperalgesic activity against inflammatory and neuropathic pain. Several such compounds have been developed recently, which exhibit significant antihyperalgesia in mice and rats and appear to be devoid of the typical side-effects of classical benzodiazepine

Dmrt1 polymorphism covaries with sex-determination patterns in Rana temporaria.

Patterns of sex-chromosome differentiation and gonadal development have been shown to vary among populations of Rana temporaria along a latitudinal transect in Sweden. Frogs from the northern-boreal population of Ammarnäs displayed well-differentiated X and Y haplotypes, early gonadal differentiation, and a perfect match between phenotypic and genotypic sex. In contrast, no differentiated Y haplotypes could be detected in the southern population of Tvedöra, where juveniles furthermore showed delayed gonadal differentiation. Here, we show that Dmrt1, a gene that plays a key role in sex determination and sexual development across all metazoans, displays significant sex differentiation in Tvedöra, with a Y-specific haplotype distinct from Ammarnäs. The differential segment is not only much shorter in Tvedöra than in Ammarnäs, it is also less differentiated and associates with both delayed gonadal differentiation and imperfect match between phenotypic and genotypic sex. Whereas Tvedöra juveniles with a local Y haplotype tend to ultimately develop as males, those without it may nevertheless become functional XX males, but with strongly female-biased progeny. Our findings suggest that the variance in patterns of sex determination documented in common frogs might result from a genetic polymorphism within a small genomic region that contains Dmrt1. They also substantiate the view that recurrent convergences of sex determination toward a limited set of chromosome pairs may result from the co-option of small genomic regions that harbor key genes from the sex-determination pathway

Amelioration of bleomycin-induced lung fibrosis in hamsters by dietary supplementation with taurine and niacin: biochemical mechanisms.

Interstitial pulmonary fibrosis induced by intratracheal instillation of bleomycin (BL) involves an excess production of reactive oxygen species, unavailability of adequate levels of NAD and ATP to repair the injured pulmonary epithelium, and an overexuberant lung collagen reactivity followed by deposition of highly cross-linked mature collagen fibrils resistant to enzymatic degradation. In the present study, we have demonstrated that dietary supplementation with taurine and niacin offered almost complete protection against the lung fibrosis in a multidose BL hamster model. The mechanisms for the protective effect of taurine and niacin are multifaceted. These include the ability of taurine to scavenge HOCl and stabilize the biomembrane; niacin's ability to replenish the BL-induced depletion of NAD and ATP; and the combined effect of taurine and niacin to suppress all aspects of BL-induced increases in the lung collagen reactivity, a hallmark of interstitial pulmonary fibrosis. It was concluded from the data presented at this Conference that the combined treatment with taurine and niacin, which offers a multipronged approach, will have great therapeutic potential in the intervention of the development of chemically induced interstitial lung fibrosis in animals and humans

Seasonal Variation in Birds

Wild birds show cyclical alternation between breeding seasons and seasons of sexual inactivity. During the latter the sex glands are at rest and are very small. With the approach of the breeding season they start to grow rapidly, -- increasing in volume up to one thousand times. Accompanying this growth of the gonads many secondary sex characters also show a characteristic development. This is true in first respect for the sperm- and oviducts, but also external secondary sex characters often show striking changes. The bill color of the sparrow is light brown during the resting period and becomes blue black in the breeding season. In some birds, as the Rose-breasted Grosbeak, a remarkable change also takes place in the plumage. Experiments have been performed and will be presented to show the external and hormonal factors that control these seasonal changes

A survey to determine general music activities in selected elementary schools of Massachusetts

Thesis (M.M.)--Boston Universit

Alonzo Old Block Delano

When Alonzo Delano died on 8 September 1874, newspapers throughout the Northern California region lamented the passing of a favorite local celebrity. A death notice issued by the Sacramento Union on 10 September (reprinted a day later by San Francisco’s Daily Alta California), observed that Delano “was known by reputation throughout the State as an author and a man of integrity. [. . .] He was a writer of much native humor and plainness of speech, abounding in facts, anxious to do justice to all and injury to none.” The San Francisco Chronicle echoed this sentiment, adding that he “was a writer of considerable ability.” A longer obituary from the Grass Valley Union, the newspaper in Delano’s adopted hometown, observed that he “was known all over the State as a writer for the papers, and for books which he published. [. . .] ‘Old Block,’ under which name he wrote, is as familiar on this coast as any household word” (10 September, reprinted by the Sacramento Union on 11 September). Even the New York Times, in which a few years earlier Delano had published a series of correspondence about life in California, carried on 23 September a five-sentence obituary that noted, in accord with the others, that upon “Arriving in California without capital, he speedily became one of the most active men in the State, as a writer displaying talent of a peculiar order, over the signature of‘Old Block.’