Multiple newly identified loci associated with prostate cancer susceptibility

Prostate cancer is the most common cancer affecting males in developed countries. It shows consistent evidence of familial aggregation, but the causes of this aggregation are mostly unknown. To identify common alleles associated with prostate cancer risk, we conducted a genome-wide association study (GWAS) using blood DNA samples from 1,854 individuals with clinically detected prostate cancer diagnosed at 相似文献   

Comparative analysis of phospholamban phosphorylation in crude membranes of vertebrate hearts

Summary Phospholamban, a sarcoplasmic reticulum phosphoprotein, is present in the hearts of mammalian, avian, amphibian, and fish species. Phylogenetic changes are indicated by marked differences among species in cardiac phospholamban content and by the absence of Ca²⁺/calmodulin-dependent phospholamban phosphorylation at an early developmental stage.     

Forecasting volatility in commodity markets

This paper uses recent advances in time-series modeling to derive long-horizon forecasts of commodity price volatility which incorporate investors' expectations of volatility. Our results are promising. We compare several different forecasts of commodity price volatility, which we divide into three categories: (1) forecasts using only expectations derived from options prices; (2) forecasts using only time-series modeling; and (3) forecasts which combine market expectations and time-series methods. The forecasts in (1) and (2) are used extensively in the literature, while those in (3) are new in this paper. On comparing these different forecasts, we find that our proposed forecasts from category (3) outperform both market expectations forecasts and time-series forecasts. This result holds both in and out of sample for virtually all commodities considered.     

Forecasting with an econometric model: The ‘ragged edge’ problem

In practical econometric forecasting exercises, incomplete data on current and immediate past values of endogenous variables are available. This paper considers various approaches to this ‘ragged edge’ problem, including the common device of treating as ‘temporarily exogenous’ an endogenous variable whose value is known, by deleting it from the set of endogenous variables for whose forecast values the model is solved and suppressing the corresponding structural equation. It is seen that this forecast can be adjusted to coincide with the optimal forecast. The initial discussion concerns the textbook linear simultaneous equation model; extensions to non-linear dynamic models are described.     

Pre-training Assessment Through the Web

Web-based training is growing quickly in popularit y for professionals in industrial organizations and large enterprises. The savings in cost and time are significant. The instructor-led trainings are bounded by time and place, not to mention the cost involved in traveling, accommodation and training venue. However, in the most online training courses, all trainees are given same training materials and teaching paradigms. The problem of differentia ting the trainees‘ abilities is the main concern. We n...     

Identification of mutations in CUL7 in 3-M syndrome

Intrauterine growth retardation is caused by maternal, fetal or placental factors that result in impaired endovascular trophoblast invasion and reduced placental perfusion. Although various causes of intrauterine growth retardation have been identified, most cases remain unexplained. Studying 29 families with 3-M syndrome (OMIM 273750), an autosomal recessive condition characterized by severe pre- and postnatal growth retardation, we first mapped the underlying gene to chromosome 6p21.1 and then identified 25 distinct mutations in the gene cullin 7 (CUL7). CUL7 assembles an E3 ubiquitin ligase complex containing Skp1, Fbx29 (also called Fbw8) and ROC1 and promotes ubiquitination. Using deletion analysis, we found that CUL7 uses its central region to interact with the Skp1-Fbx29 heterodimer. Functional studies indicated that the 3-M-associated CUL7 nonsense and missense mutations R1445X and H1464P, respectively, render CUL7 deficient in recruiting ROC1. These results suggest that impaired ubiquitination may have a role in the pathogenesis of intrauterine growth retardation in humans.     

DNMT1 and DNMT3b cooperate to silence genes in human cancer cells

Inactivation of tumour suppressor genes is central to the development of all common forms of human cancer. This inactivation often results from epigenetic silencing associated with hypermethylation rather than intragenic mutations. In human cells, the mechanisms underlying locus-specific or global methylation patterns remain unclear. The prototypic DNA methyltransferase, Dnmt1, accounts for most methylation in mouse cells, but human cancer cells lacking DNMT1 retain significant genomic methylation and associated gene silencing. We disrupted the human DNMT3b gene in a colorectal cancer cell line. This deletion reduced global DNA methylation by less than 3%. Surprisingly, however, genetic disruption of both DNMT1 and DNMT3b nearly eliminated methyltransferase activity, and reduced genomic DNA methylation by greater than 95%. These marked changes resulted in demethylation of repeated sequences, loss of insulin-like growth factor II (IGF2) imprinting, abrogation of silencing of the tumour suppressor gene p16INK4a, and growth suppression. Here we demonstrate that two enzymes cooperatively maintain DNA methylation and gene silencing in human cancer cells, and provide compelling evidence that such methylation is essential for optimal neoplastic proliferation.     

Nanometre-size products of uranium bioreduction

One strategy that is being pursued to tackle the international problem of actinide contamination of soils, sediments and water is to use microbial activity to 'fix' these radionuclides into an insoluble form that cannot be readily dispersed. Here we show that uraninite (UO(2)) particles formed from uranium in sediments by bacterial reduction are typically less than 2 nanometres across and that the small size has important implications for uraninite reactivity and fate. Because these tiny particles may still be transported in an aqueous environment, precipitation of uranium as insoluble uraninite cannot be presumed to immobilize it.     

Colorectal cancer: mutations in a signalling pathway

Protein kinases are enzymes that are important for controlling cellular growth and invasion, and their malfunction is implicated in the development of some tumours. We analysed human colorectal cancers for genetic mutations in 340 serine/threonine kinases and found mutations in eight genes, including in three members of the phosphatidylinositol-3-OH kinase (PI(3)K) pathway. The discovery of this mutational activation of a key cell-signalling pathway may provide new targets for therapeutic intervention.