Multiple recurrent genetic events converge on control of histone lysine methylation in medulloblastoma

We used high-resolution SNP genotyping to identify regions of genomic gain and loss in the genomes of 212 medulloblastomas, malignant pediatric brain tumors. We found focal amplifications of 15 known oncogenes and focal deletions of 20 known tumor suppressor genes (TSG), most not previously implicated in medulloblastoma. Notably, we identified previously unknown amplifications and homozygous deletions, including recurrent, mutually exclusive, highly focal genetic events in genes targeting histone lysine methylation, particularly that of histone 3, lysine 9 (H3K9). Post-translational modification of histone proteins is critical for regulation of gene expression, can participate in determination of stem cell fates and has been implicated in carcinogenesis. Consistent with our genetic data, restoration of expression of genes controlling H3K9 methylation greatly diminishes proliferation of medulloblastoma in vitro. Copy number aberrations of genes with critical roles in writing, reading, removing and blocking the state of histone lysine methylation, particularly at H3K9, suggest that defective control of the histone code contributes to the pathogenesis of medulloblastoma.

The Genome Sequence of Taurine Cattle: A Window to Ruminant Biology and Evolution

To understand the biology and evolution of ruminants, the cattle genome was sequenced to about sevenfold coverage. The cattle genome contains a minimum of 22,000 genes, with a core set of 14,345 orthologs shared among seven mammalian species of which 1217 are absent or undetected in noneutherian (marsupial or monotreme) genomes. Cattle-specific evolutionary breakpoint regions in chromosomes have a higher density of segmental duplications, enrichment of repetitive elements, and species-specific variations in genes associated with lactation and immune responsiveness. Genes involved in metabolism are generally highly conserved, although five metabolic genes are deleted or extensively diverged from their human orthologs. The cattle genome sequence thus provides a resource for understanding mammalian evolution and accelerating livestock genetic improvement for milk and meat production.

Presence of MRI-detected joint effusion and synovitis increases the risk of cartilage loss in knees without osteoarthritis at 30-month follow-up: the MOST study

Objective To evaluate if two different measures of synovial activation, baseline Hoffa synovitis and effusion synovitis, assessed by MRI, predict cartilage loss in the tibiofemoral joint at 30 months follow-up in subjects with neither cartilage damage nor tibiofemoral radiographic osteoarthritis of the knee. Methods Non-contrast-enhanced MRI was performed using proton density-weighted fat-suppressed sequences in the axial and sagittal planes and a short tau inversion recovery sequence in the coronal plane. Hoffa synovitis, effusion synovitis and cartilage status were assessed semiquantitatively according to the WORMS scoring system. Included were knees that had neither radiographic osteoarthritis nor MRI-detected tibiofemoral cartilage damage at the baseline visit. The presence of Hoffa synovitis was defined as any grade = 2 (range 0-3) and effusion synovitis as any grade = 2 (range 0-3). Logistic regression was performed to examine the relation of the presence of either measure to the risk of cartilage loss at 30 months adjusting for other potential confounders. Results Of 514 knees included in the analysis, the prevalence of Hoffa synovitis and effusion synovitis at the baseline visit was 8.4% and 10.3%, respectively. In the multivariable analysis, baseline effusion synovitis was associated with an increased risk of cartilage loss. No such association was observed for baseline Hoffa synovitis. Conclusions Baseline effusion synovitis, but not Hoffa synovitis, predicted cartilage loss. The findings suggest that effusion synovitis, a reflection of inflammatory activity including joint effusion and synovitic thickening, may play a role in the future development of cartilage lesions in knees without osteoarthritis.

Social-conservatism, Australian politics and cricket: The triumvirate of Prime Minister John Howard, Sir Robert Menzies and Sir Donald Bradman

This Article does not have an abstract.

James Parkinson (1755-1824): A pioneer of child care

James Parkinson (1755-1824) of Parkinson's disease, is well recognized as a pioneer of clinical neurology; and is even more famous as a founder of modem palaeontology. We have reviewed from primary sources his extensive contributions to clinical child care and his pioneering advocacy for child welfare, protection and safety. His writings, outreach and advocacy for children's health characterizes him as one whose influence was an important springboard from which evolved the modern specialty of paediatrics. Parkinson was one of the first to write on child-rearing practices and in this context antedated Benjamin Spock by 150 years. Parkinson was a pioneer of child safety and the prevention of childhood trauma. He wrote of the resuscitation of near-drowned children and of first aid for injured children. This critical analysis reviews his pioneering description of child abuse and the development of post-abuse hydrocephalus. He wrote the datum description (in English) of the pathophysiology and pathology of appendicitis in children, of fatal rabies in children and highlighted the risk of death even when the biting dog was not clinically rabid. His advocacy for social reform for children's welfare was courageous and pioneering. James Parkinson, hitherto unacknowledged, was a significant founder of the evolving discipline of paediatrics and child health.

Cultural frictions: John Romeril's The 'Floating World'

Hailed as an 'unruly masterpiece', John Romeril's The Floating World is one of the few 'new wave' Australian plays representing Australians and their Asian 'others' to be restaged periodically since its premiere in 1974. Paying particular attention to production of the play that have used Japanese theatre forms such as kabuki and bunraku, this article focuses primarily on the ways in which the significations of race have been interpreted by the critical establishment. The fascinating stage history of The Floating World is treated as a barometer of Australian theatre's response to the challenge of representing cultural conflict, during a period marked by public debate about the desirability, and inevitability, of Australia's political, economic and cultural 'enmeshment' with Asia.