Sirtuin 2 inhibitors rescue alpha-synuclein-mediated toxicity in models of Parkinson's disease

The sirtuins are members of the histone deacetylase family of proteins that participate in a variety of cellular functions and play a role in aging. We identified a potent inhibitor of sirtuin 2 (SIRT2) and found that inhibition of SIRT2 rescued alpha-synuclein toxicity and modified inclusion morphology in a cellular model of Parkinson's disease. Genetic inhibition of SIRT2 via small interfering RNA similarly rescued alpha-synuclein toxicity. Furthermore, the inhibitors protected against dopaminergic cell death both in vitro and in a Drosophila model of Parkinson's disease. The results suggest a link between neurodegeneration and aging.     

Yeast genes that enhance the toxicity of a mutant huntingtin fragment or alpha-synuclein

Genome-wide screens were performed in yeast to identify genes that enhance the toxicity of a mutant huntingtin fragment or of alpha-synuclein. Of 4850 haploid mutants containing deletions of nonessential genes, 52 were identified that were sensitive to a mutant huntingtin fragment, 86 that were sensitive to alpha-synuclein, and only one mutant that was sensitive to both. Genes that enhanced toxicity of the mutant huntingtin fragment clustered in the functionally related cellular processes of response to stress, protein folding, and ubiquitin-dependent protein catabolism, whereas genes that modified alpha-synuclein toxicity clustered in the processes of lipid metabolism and vesicle-mediated transport. Genes with human orthologs were overrepresented in our screens, suggesting that we may have discovered conserved and nonoverlapping sets of cell-autonomous genes and pathways that are relevant to Huntington's disease and Parkinson's disease.     

Evaluation of a regimen using a progesterone releasing intravaginal device (CIDR) and PMSG as a treatment for post partum anoestrus in dairy cattle

Anoestrous dairy cows in seasonally calving herds in the Macalister Irrigation District of Gippsland, Victoria were treated at the start of the mating period with a progesterone releasing intravaginal device (CIDR). The CIDR was inserted for 7 days and 400 IU of PMSG was injected intramuscularly at removal. There was no clinically useful difference among cows receiving the CIDR, a placebo and untreated cows in the interval from treatment to either first oestrus or conception, the conception rate to first service or percent pregnant by the end of mating. Analyses of data from 2-year-old cows, older cattle, cows calved at least 45 days or cows calved at least 55 days and cows treated 3 weeks after the start of mating did not show improved reproductive performance following treatment with the CIDR.     

The north‐west of the Iberian Peninsula is crucial for conservation of Margaritifera margaritifera (L.) in Europe

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Survival and fertility after uterine prolapse in dairy cows

Sixty-eight cases of uterine prolapase in pastured dairy cows were treated in 2 consecutive spring calving seasons in East Gippsland, Victoria. Fifty cows survived (73.5%). Of 43 cows available for followup, 36 (84%) conceived in the mating period following the prolapse, taking 10 d longer to conceive than herd mates that calved on the same day. Three of the 36 cows (8%) that conceived, aborted, this occurring in the middle trimester of pregnancy. No prolapses occurred at the following calving but one case had suffered uterine prolapse 2 years previously. The conclusions drawn from these observations are that cows with uterine prolapse have a good chance of surviving if treated, that treatment is cost-effective, that uterine prolapse is unlikely to reoccur and treated cows have a good chance of conceiving. The veterinarians involved in this investigation were reasonably accurate in their ability to predict long term survival but not as good in predicting ability to conceive again.     

Black soil blindness: A new mycotoxicosis of cattle grazing Corallocytostroma-infected Mitchell grass (Astrebla spp)

A new, fatal mycotoxicosis of cattle has been recognised in north-western Australia. A feeding trial confirmed the toxicity of a previously unknown species of Corallocytostroma that grows on Mitchell grass (Astrebla spp). The disease has been colloquially named ‘black soil blindness’ because its most prominent features are its confinement to pastures on black soil, and blindness and death of affected animals. Over 500 cattle have died and considerable subclinical disease is present. Above average wet season rainfall and extended growing seasons may explain the emergence of the fungus. The disease is important because cattle production in large areas of Australia utilise Mitchell grass pastures.