Allelic variation in HLA-B and HLA-C sequences and the evolution of the HLA-B alleles

Several new HLA-B (B8, B51, Bw62)- and HLA-C (Cw6, Cw7)-specific genes were isolated either as genomic cosmid or cDNA clones to study the diversity of HLA antigens. The allele specificities were identified by sequence analysis in comparison with published HLAB and -C sequences, by transfection experiments, and Southern and northern blot analysis using oligonucleotide probes. Comparison of the classical HLA-A, -B, and -C sequences reveals that allele-specific substitutions seem to be rare events. HLA-B51 codes only for one allelespecific residue: arginine at position 81 located on the cd helix, pointing toward the antigen binding site. HLA-B8 contains an acidic substitution in amino acid position 9 on the first central/3 sheet which might affect antigen binding capacity, perhaps in combination with the rare replacement at position 67 (F) on the Alpha-l helix. HLA-B8 shows greatest homology to HLA-Bw42, -Bw41, -B7, and -Bw60 antigens, all of which lack the conserved restriction sites Pst I at position 180 and Sac I at position 131. Both sites associated with amino acid replacements seem to be genetic markers of an evolutionary split of the HLA-B alleles, which is also observed in the leader sequences. HLA-Cw7 shows 98% sequence identity to the JY328 gene. In general, the HLA-C alleles display lower levels of variability in the highly polymorphic regions of the Alpha 1 and Alpha 2 domains, and have more distinct patterns of locusspecific residues in the transmembrane and cytoplasmic domains. Thus we propose a more recent origin for the HLA-C locus

An evaluation of the impact of 'Lifeskills' training on road safety, substance use and hospital attendance in adolescence

AbstractPurposeTo evaluate if attendance at Lifeskills, a safety education centre for children in Year 6 (10–11 years), is associated with engagement in safer behaviours, and with fewer accidents and injuries, in adolescence.MethodsThe sample are participants in the Avon Longitudinal Study of Parents and Children who attended school in the Lifeskills catchment area in Year 6; 60% attended Lifeskills. At 14–15 years, participants (n approximately 3000, varies by outcome) self-reported road safety behaviours and accidents, and perceived health effects and use of alcohol, cannabis, and tobacco. Additional outcomes from linkage to Hospital Episodes Statistics were available for a sub-sample (n=1768): hospital admittance (for accident-related reason, from 11–16 years) and A&E attendance (for any reason, from approximately 14–16 years).ResultsChildren who attended Lifeskills were more likely to report using pedestrian crossings on their way to school than children who did not attend (59% versus 52%). Lifeskills attendance was unrelated to the ownership of cycle helmets, or the use of cycle helmets, seat belts, or reflective/fluorescent clothing, or to A&E attendance. Use of cycle helmets (37%) and reflective/fluorescent clothing (<4%) on last cycle was low irrespective of Lifeskills attendance. Lifeskills attendance was associated with less reported smoking and cannabis use, but was generally unrelated to perceptions of the health impact of substance use.ConclusionsLifeskills attendance was associated with some safer behaviours in adolescence. The overall low use of cycle helmets and reflective/fluorescent clothing evidences the need for powerful promotion of some safer behaviours at Lifeskills and at follow-up in schools

Argonne National Laboratory Reports

Test data from an in-pile failure experiment of high-power LMFBR-type fuel pins in a simulated $3/s transient-overpower (TOP) accident are reported and analyzed. Major conclusions are that (1) a series of cladding ruptures during the 100-ms period preceding fuel release injected small bursts of fission gas into the flow stream; (2) gas release influenced subsequent cladding melting and fuel release (there were no measurable FCI's (fuel-coolant interactions), and all fuel motion observed by the hodoscope was very slow); (3) the predominant post-failure fuel motion appears to be radial swelling that left a spongy fuel crust on the holder wall; (4) less than 4 to 6 percent of the fuel moved axially out of the original fuel zone, and most of this froze within a 10-cm region above the original top of the fuel zone to form the outlet blockage. An inlet blockage approximately 1 cm long was formed and consisted of large interconnected void regions. Both blockages began just beyond the ends of the fuel pellets

Dissociative recombination and electron-impact de-excitation in CH photon emission under ITER divertor-relevant plasma conditions

For understanding carbon erosion and redeposition in nuclear fusion devices, it is important to understand the transport and chemical break-up of hydrocarbon molecules in edge plasmas, often diagnosed by emission of the CH A^2\Delta - X^2\Pi Ger\"o band around 430 nm. The CH A-level can be excited either by electron-impact or by dissociative recombination (D.R.) of hydrocarbon ions. These processes were included in the 3D Monte Carlo impurity transport code ERO. A series of methane injection experiments was performed in the high-density, low-temperature linear plasma generator Pilot-PSI, and simulated emission intensity profiles were benchmarked against these experiments. It was confirmed that excitation by D.R. dominates at T_e < 1.5 eV. The results indicate that the fraction of D.R. events that lead to a CH radical in the A-level and consequent photon emission is at least 10%. Additionally, quenching of the excited CH radicals by electron impact de-excitation was included in the modeling. This quenching is shown to be significant: depending on the electron density, it reduces the effective CH emission by a factor of 1.4 at n_e=1.3*10^20 m^-3, to 2.8 at n_e=9.3*10^20 m^-3. Its inclusion significantly improved agreement between experiment and modeling

Over-expression of Adenine Nucleotide Translocase 1 (ANT1) Induces Apoptosis and Tumor Regression in vivo

Background: Adenine nucleotide translocase (ANT) is located in the inner mitochondrial membrane and catalyzes the exchange of mitochondrial ATP for cytosolic ADP. ANT has been known to be a major component of the permeability transition pore complex of mitochondria and contributes to mitochondria-mediated apoptosis. Human ANT has four isoforms (ANT1, ANT2, ANT3, and ANT4), and the expression of the ANT isoforms is variable depending on the tissue and cell type, developmental stage, and proliferation status. Among the isoforms, ANT1 is highly expressed in terminally-differentiated tissues, but expressed in low levels in proliferating cells, such as cancer cells. In particular, over-expression of ANT1 induces apoptosis in cultured tumor cells. Methods: We applied an ANT1 gene transfer approach to induce apoptosis and to evaluate the anti-tumor effect of ANT1 in a nude mouse model. Results: We demonstrated that ANT1 transfection induced apoptosis of MDA-MB-231 cells, inactivated NF-κB activity, and increased Bax expression. ANT1-inducing apoptosis was accompanied by the disruption of mitochondrial membrane potential, cytochrome c release and the activation of caspases-9 and -3. Moreover, ANT1 transfection significantly suppressed tumor growth in vivo. Conclusion: Our results suggest that ANT1 transfection may be a useful therapeutic modality for the treatment of cancer

Sexual health of ethnic minority MSM in Britain (MESH project): design and methods

Background: Men who have sex with men (MSM) remain the group most at risk of acquiring HIV infection in Britain. HIV prevalence appears to vary widely between MSM from different ethnic minority groups in this country for reasons that are not fully understood. The aim of the MESH project was to examine in detail the sexual health of ethnic minority MSM living in Britain. Methods/Design: The main objectives of the MESH project were to explore among ethnic minority MSM living in Britain: (i) sexual risk behaviour and HIV prevalence; (ii) their experience of stigma and discrimination; (iii) disclosure of sexuality; (iv) use of, and satisfaction with sexual health services; (v) the extent to which sexual health services (for treatment and prevention) are aware of the needs of ethnic minority MSM. The research was conducted between 2006 and 2008 in four national samples: (i) ethnic minority MSM living in Britain; (ii) a comparison group of white British MSM living in Britain; (iii) NHS sexual health clinic staff in 15 British towns and cities with significant ethnic minority communities and; (iv) sexual health promotion/HIV prevention service providers. We also recruited men from two “key migrant” groups living in Britain: MSM born in Central or Eastern Europe and MSM born in Central or South America. Internet-based quantitative and qualitative research methods were used. Ethnic minority MSM were recruited through advertisements on websites, in community venues, via informal networks and in sexual health clinics. White and “key migrant” MSM were recruited mostly through Gaydar, one of the most popular dating sites used by gay men in Britain. MSM who agreed to take part completed a questionnaire online. Ethnic minority MSM who completed the online questionnaire were asked if they would be willing to take part in an online qualitative interview using email. Service providers were identified through the British Association of Sexual Health and HIV (BASHH) and the Terrence Higgins Trust (THT) CHAPS partnerships. Staff who agreed to take part were asked to complete a questionnaire online. The online survey was completed by 1241 ethnic minority MSM, 416 men born in South and Central America or Central and Eastern Europe, and 13,717 white British MSM; 67 ethnic minority MSM took part in the online qualitative interview. In addition 364 people working in sexual health clinics and 124 health promotion workers from around Britain completed an online questionnaire. Discussion: The findings from this study will improve our understanding of the sexual health and needs of ethnic minority MSM in Britain

Migration of Artificially Introduced Micron Size Carbon Dust in the DIII-D Divertor

Migration of pre-characterized carbon dust in a tokamak environment was studied by introducing about 30 milligrams of dust flakes 5-10 {micro}m in diameter in the lower divertor of DIII-D using the DiMES sample holder. The dust was exposed to high power ELMing Hmode discharges in lower-single-null magnetic configuration with the strike points swept across the divertor floor. When the outer strike point (OSP) passed over the dust holder exposing it to high particle and heat fluxes, part of the dust was injected into the plasma. In about 0.1 sec following the OSP pass over the dust, 1-2% of the total dust carbon content (2-4 x 10{sup 19} carbon atoms, equivalent to a few million dust particles) penetrated the core plasma, raising the core carbon density by a factor of 2-3. When the OSP was inboard of the dust holder, the dust injection continued at a lower rate. Individual dust particles were observed moving at velocities of 10-100 m/s, predominantly in the toroidal direction for deuteron flow to the outer divertor target, consistent with the ion drag force. The observed behavior of the dust is in qualitative agreement with modeling by the 3D DustT code

TRPA1 Is a Polyunsaturated Fatty Acid Sensor in Mammals

Fatty acids can act as important signaling molecules regulating diverse physiological processes. Our understanding, however, of fatty acid signaling mechanisms and receptor targets remains incomplete. Here we show that Transient Receptor Potential Ankyrin 1 (TRPA1), a cation channel expressed in sensory neurons and gut tissues, functions as a sensor of polyunsaturated fatty acids (PUFAs) in vitro and in vivo. PUFAs, containing at least 18 carbon atoms and three unsaturated bonds, activate TRPA1 to excite primary sensory neurons and enteroendocrine cells. Moreover, behavioral aversion to PUFAs is absent in TRPA1-null mice. Further, sustained or repeated agonism with PUFAs leads to TRPA1 desensitization. PUFAs activate TRPA1 non-covalently and independently of known ligand binding domains located in the N-terminus and 5th transmembrane region. PUFA sensitivity is restricted to mammalian (rodent and human) TRPA1 channels, as the drosophila and zebrafish TRPA1 orthologs do not respond to DHA. We propose that PUFA-sensing by mammalian TRPA1 may regulate pain and gastrointestinal functions