Mutation signatures of carcinogen exposure: Genome-wide detection and new opportunities for cancer prevention

10.1186/gm541Genome Medicine63

VHL substrate transcription factor ZHX2 as an oncogenic driver in clear cell renal cell carcinoma

Inactivation of the von Hippel-Lindau (VHL) E3 ubiquitin ligase protein is a hallmark of clear cell renal cell carcinoma (ccRCC). Identifying how pathways affected by VHL loss contribute to ccRCC remains challenging. We used a genome-wide in vitro expression strategy to identify proteins that bind VHL when hydroxylated. Zinc fingers and homeoboxes 2 (ZHX2) was found as a VHL target, and its hydroxylation allowed VHL to regulate its protein stability. Tumor cells from ccRCC patients with VHL loss-of-function mutations usually had increased abundance and nuclear localization of ZHX2. Functionally, depletion of ZHX2 inhibited VHL-deficient ccRCC cell growth in vitro and in vivo. Mechanistically, integrated chromatin immunoprecipitation sequencing and microarray analysis showed that ZHX2 promoted nuclear factor κB activation. These studies reveal ZHX2 as a potential therapeutic target for ccRCC

Trans-ancestry genome-wide association study identifies 12 genetic loci influencing blood pressure and implicates a role for DNA methylation

We carried out a trans-ancestry genome-wide association and replication study of blood pressure phenotypes among up to 320,251 individuals of East Asian, European and South Asian ancestry. We find genetic variants at 12 new loci to be associated with blood pressure (P = 3.9 × 10-11 to 5.0 × 10-21). The sentinel blood pressure SNPs are enriched for association with DNA methylation at multiple nearby CpG sites, suggesting that, at some of the loci identified, DNA methylation may lie on the regulatory pathway linking sequence variation to blood pressure. The sentinel SNPs at the 12 new loci point to genes involved in vascular smooth muscle (IGFBP3, KCNK3, PDE3A and PRDM6) and renal (ARHGAP24, OSR1, SLC22A7 and TBX2) function. The new and known genetic variants predict increased left ventricular mass, circulating levels of NT-proBNP, and cardiovascular and all-cause mortality (P = 0.04 to 8.6 × 10-6). Our results provide new evidence for the role of DNA methylation in blood pressure regulation

Neural logic programming

485-49

Temporary cardiopulmonary bypass and isolated lung ventilation for tracheal stenosis and reconstruction.

A 27-yr-old lady with a past history of prolonged ventilation presented with worsening respiratory distress caused by tracheal stenosis. She required urgent tracheal resection and reconstruction. Because of the risk of an acute respiratory obstruction, spinal anaesthesia was used to establish cardiopulmonary bypass by cannulating the femoral artery and femoral vein. Adequate gas exchange was possible with full flow rate. Thoracotomy was then carried out to mobilize the left main bronchus. After successfully securing an airway by intubation of the left main bronchus, cardiopulmonary bypass was discontinued and tracheal resection and anastomosis was done under conventional one lung anaesthesia

Machine translation for financial news

International Journal of Computer Applications in Technology4153-61IJCT

Connectionist expert system with adaptive learning capability

10.1109/69.88000IEEE Transactions on Knowledge and Data Engineering32200-207ITKE

Tussive effect of a fentanyl bolus

Canadian Journal of Anaesthesia383330-334CJOA

Comparative gene expression profiling analysis of urothelial carcinoma of the renal pelvis and bladder

10.1186/1755-8794-3-58BMC Medical Genomics35