IDH-mutant glioma specific association of rs55705857 located at 8q24.21 involves MYC deregulation

The single nucleotide polymorphism rs55705857, located in a non-coding but evolutionarily conserved region at 8q24.21, is strongly associated with IDH-mutant glioma development and was suggested to be a causal variant. However, the molecular mechanism underlying this association has remained unknown. With a case control study in 285 gliomas, 316 healthy controls, 380 systemic cancers, 31 other CNS-tumors, and 120 IDH-mutant cartilaginous tumors, we identified that the association was specific to IDH-mutant gliomas. Odds-ratios were 9.25 (5.17–16.52; 95% CI) for IDH-mutated gliomas and 12.85 (5.94–27.83; 95% CI) for IDH-mutated, 1p/19q co-deleted gliomas. Decreasing strength with increasing anaplasia implied a modulatory effect. No somatic mutations were noted at this locus in 114 blood-tumor pairs, nor was there a copy number difference between risk-allele and only-ancestral allele carriers. CCDC26 RNA-expression was rare and not different between the two groups. There were only minor subtype-specific differences in common glioma driver genes. RNA sequencing and LC-MS/MS comparisons pointed to significantly altered MYC-signaling. Baseline enhancer activity of the conserved region specifically on the MYC promoter and its further positive modulation by the SNP risk-allele was shown in vitro. Our findings implicate MYC deregulation as the underlying cause of the observed association

Genetics of randomly bred cats support the cradle of cat domestication being in the Near East

Cat domestication likely initiated as a symbiotic relationship between wildcats (Felis silvestris subspecies) and the peoples of developing agrarian societies in the Fertile Crescent. As humans transitioned from hunter-gatherers to farmers ~12,000 years ago, bold wildcats likely capitalized on increased prey density (i.e., rodents). Humans benefited from the cats’ predation on these vermin. To refine the site(s) of cat domestication, over 1000 random-bred cats of primarily Eurasian descent were genotyped for single-nucleotide variants and short tandem repeats. The overall cat population structure suggested a single worldwide population with significant isolation by the distance of peripheral subpopulations. The cat population heterozygosity decreased as genetic distance from the proposed cat progenitor’s (F.s. lybica) natural habitat increased. Domestic cat origins are focused in the eastern Mediterranean Basin, spreading to nearby islands, and southernly via the Levantine coast into the Nile Valley. Cat population diversity supports the migration patterns of humans and other symbiotic species

The ascent of cat breeds : genetic evaluations of breeds and worldwide random-bred populations

The diaspora of the modern cat was traced with microsatellite markers from the presumed site of domestication to distant regions of the world. Genetic data were derived from over 1100 individuals, representing 17 random-bred populations from five continents and 22 breeds. The Mediterranean was reconfirmed to be the probable site of domestication. Genetic diversity has remained broad throughout the world, with distinct genetic clustering in the Mediterranean basin, Europe/America, Asia and Africa. However, Asian cats appeared to have separated early and expanded in relative isolation. Most breeds were derived from indigenous cats of their purported regions of origin. However, the Persian and Japanese bobtail were more aligned with European/American than with Mediterranean basin or Asian clusters. Three recently derived breeds were not distinct from their parental breeds of origin. Pure breeding was associated with a loss of genetic diversity; however, this loss did not correlate with breed popularity or age

Erucic acid, a nutritional PPAR delta-ligand may influence Huntington's disease pathogenesis

Increasing recent evidence suggests a key role of oligodendroglial injury and demyelination in the pathophysiology of Huntington's Disease (HD) and the transcription factor PPAR delta is critical for oligodendroglial regeneration and myelination. PPAR delta directly involves in the pathogenesis of HD and treatment with a brain-permeable PPAR delta-agonist (KD3010) alleviates its severity in mice. Erucic acid (EA) is also a PPAR delta-ligand omega 9 fatty acid which is highly consumed in Asian countries through ingesting cruciferous vegetables such as rapeseed (Brassica napus) and indian mustard (Brassica juncea). EA is also an ingredient of Lorenzo's oil employed in the medical treatment of adrenoleukodystrophy and can be converted to nervonic acid, a component of myelin. HD pathogenesis also involves oxidative and inflammatory injury and EA exerts antioxidative and antiinflammatory efficacies including inhibition of thrombin and elastase. Consumption of rapeseed, indian mustard, and Canola oils (containing EA) improves cognitive parameters in animal models, as well as treatment with pure EA. Moreover, erucamide, an endogenous EA-amide derivative regulating angiogenesis and water balance, exerts antidepressive and anxiolytic effects in mice. Hitherto, no study has investigated the therapeutic potential of EA in HD and we believe that it strongly merits to be studied in animal models of HD as a potential therapeutic.</p

Metabolic profile of pre-pregnancy, pregnancy and early lactation in multiple lambing Sakiz ewes 1. Changes in plasma glucose, 3-hydroxybutyrate and cortisol levels

Twenty synchronized Sakiz ewes aged 3-4 years were used in the study. Blood samples were taken once in pre-pregnancy and at the 100th day of pregnancy. At the 120th day of pregnancy and on the 10th day of lactation, blood samples were collected every 2 h for 24 h from only 10 ewes. Plasma cortisol levels were analyzed by radioimmunoassay. Plasma glucose and 3-hydroxybutyrate levels were determined spectrophotometrically. Plasma cortisol level slightly increased at the 100th day of pregnancy, decreased during late pregnancy and continued to decrease during lactation. Plasma glucose and 3-hydroxybutyrate levels were not significantly different during pre-pregnancy, pregnancy and the early lactation periods. In conclusion, the results showed that metabolic disorders such as pregnancy toxaemia did not occur in ewes fed a balanced ration sufficient in energy and protein levels even in a multiple lambing breed of ewes. Copyright (C) 2002 S. Karger AG, Basel