Haplotype-based analysis of common variation in the acetyl-CoA carboxylase α gene and breast cancer risk: A case-control study nested within the European Prospective Investigation into Cancer and Nutrition

A key fatty acid synthesis enzyme, acetyl-CoA carboxylase α. (ACC-α), has been shown to be highly expressed in human breast cancer and other tumor types and also to specifically interact with the protein coded by one of two major breast cancer susceptibility genes BRCA1. We used a comprehensive haplotype analysis to examine the contribution of the ACC-α common genetic variation (allele frequency >5%) to breast cancer in a case-control study (1,588 cases/2,600 controls) nested within the European Prospective Investigation into Cancer and Nutrition. We identified 21 haplotype-tagging polymorphisms efficiently capturing common variation within 325 kb of ACC-α and surrounding sequences using genotype data from the HapMap project and our resequencing data. We found an effect on overall risk of breast cancer in homozygous carriers of one common haplotype [odds ratio (OR), 1.74; 95% confidence interval (95% CI), 1.03-2.94]. When the data were subdivided by menopausal status, we found statistical evidence of heterogeneity for two other common haplotypes (P value for heterogeneity = 0.016 and 0.045). In premenopausal women, the carriers of these haplotypes, compared with noncarriers, had an altered risk of breast cancer (OR, 0.70; 95% CI, 0.53-0.92 and OR, 1.35; 95% CI, 1.04-1.76). These findings were not significant after adjustment for multiple testing and therefore should be considered as preliminary and evaluated in larger independent studies. However, they suggest a possible role of the ACC-α common sequence variants in susceptibility to breast cancer and encourage studies of other genes involved in fatty acid synthesis. Copyright © 2007 American Association for Cancer Research

Role of interleukin-2 in superantigen-induced T-cell anergy

T-cell anergy is a state of immunological tolerance characterized by unresponsiveness to antigenic stimulation. Previous studies have shown that anergy is induced in T cells following stimulation in the absence of adequate costimulatory signals. These cells fail to respond to stimulation via the T-cell receptor (TCR), and fail to produce normal levels of interleukin-2 (IL-2). We present results here which show that low concentrations of the superantigen staphylococcal enterotoxin A (SEA) in the absence of antigen-presenting cells induced both proliferation and anergy in the A.E7 T-cell clone. Furthermore, under these conditions, the A.E7 clone remained responsive to exogenous IL-2. Fluorescence-activated cellular cytometry analysis revealed unaltered expression of the TCR/CD3 complex in the anergized clone; however, both CD4 and CD25 expression increased after 24 hr of stimulation by SEA under these conditions. Interestingly, a low level of IL-2 production was measured during the induction of anergy. Most strikingly, stimulation of the A.E7 clone by SEA in combination with exogenous IL-2 resulted in a more pronounced state of anergy. These results suggest that the induction of anergy is a process that is essentially independent of the production of IL-2

Fusion Energy-Production from a Deuterium-Tritium Plasma in the Jet Tokamak

The paper describes a series of experiments in the Joint European Torus (JET), culminating in the first tokamak discharges in deuterium-tritium fuelled mixtures. The experiments were undertaken within limits imposed by restrictions on vessel activation and tritium usage. The objectives were: (i) to produce more than one megawatt of fusion power in a controlled way; (ii) to validate transport codes and provide a basis for accurately predicting the performance of deuterium-tritium plasma from measurements made in deuterium plasmas; (iii) to determine tritium retention in the torus systems and to establish the effectiveness of discharge cleaning techniques for tritium removal; (iv) to demonstrate the technology related to tritium usage; and (v) to establish safe procedures for handling tritium in compliance with the regulatory requirements. A single-null X-point magnetic configuration, diverted onto the upper carbon target, with reversed toroidal magnetic field was chosen. Deuterium plasmas were heated by high power, long duration deuterium neutral beams from fourteen sources and fuelled also by up to two neutral beam sources injecting tritium. The results from three of these high performance hot ion H-mode discharges are described: a high performance pure deuterium discharge; a deuterium-tritium discharge with a 1% mixture of tritium fed to one neutral beam source; and a deuterium-tritium discharge with 100% tritium fed to two neutral beam sources. The TRANSP code was used to check the internal consistency of the measured data and to determine the origin of the measured neutron fluxes. In the best deuterium-tritium discharge, the tritium concentration was about 11% at the time of peak performance, when the total neutron emission rate was 6.0 x 10(17) neutrons/s. The integrated total neutron yield over the high power phase, which lasted about 2 s, was 7.2 x 10(17) neutrons, with an accuracy of +/- 7%. The actual fusion amplification factor, Q(DT), was about 0.15. With an optimum tritium concentration, this pulse would have produced a fusion power of almost-equal-to 5 MW and a nominal Q(DT) almost-equal-to 0.46. The same extrapolation for the pure deuterium discharge would have given almost-equal-to 11 MW and a nominal Q(DT) = 1.14, so that the total fusion power (neutrons and alpha-particles) would have exceeded the total losses in the equivalent deuterium-tritium discharge in these transient conditions. Techniques for introducing, tracking, monitoring and recovering tritium were demonstrated to be highly effective: essentially all of the tritium introduced into the neutral beam system and, so far, about two thirds of that introduced into the torus have been recovered