Cellular Plasticity of CD4+ T Cells in the Intestine

Barrier sites such as the gastrointestinal tract are in constant contact with the environment which contains both beneficial and harmful components. The immune system at the epithelia must make the distinction between these components to balance tolerance, protection and immunopathology. This is achieved via multifaceted immune recognition, highly organised lymphoid structures and the interaction of many types of immune cells. The adaptive immune response in the gut is orchestrated by CD4+ helper T (Th) cells which are integral to gut immunity. In recent years it has become apparent that the functional identity of these Th cells is not as fixed as initially thought. Plasticity in differentiated T cell subsets has now been firmly established, in both health and disease. The gut, in particular, utilises CD4+ T cell plasticity to mould CD4+ T cell phenotypes to maintain its finely poised balance of tolerance and inflammation and to encourage biodiversity within the enteric microbiome. In this review we will discuss intestinal helper T cell plasticity and our current understanding of its mechanisms, including our growing knowledge of an evolutionarily ancient symbiosis between microbiota and malleable CD4+ T cell effectors

The tissue distribution of Se 75 -selenouracil and Se 75 -selenourea

With the development of photoscanning clinical medicine now possesses a diagnostic technique in which further advances will depend heavily upon pharmacologic investigations of structure-distribution relations. In the present study the distribution of the selenium analogs of thiouracil and thiourea, labeled with Selenium-75, was studied in rabbits. After administration of either compound, high concentrations of Se 75 were found in the lung, liver and kidney. The concentration of Se 75 in the lungs after administration of these compounds, especially Se 75 -selenouracil, permitted visualization of the lungs in the living, intact animal by photoscanning. However, neither Se 75 -selenouracil nor Se 75 -selenourea permit pulmonary scans of high quality and these particular compounds are not recommended for trial in man. The possible relation of labelled compounds of this type, as well as certain other series of labeled compounds, to the problem of adrenal scanning is also discussed.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/46301/1/210_2004_Article_BF00246346.pd

Survey of sediment quality in Sabine Lake, Texas and vicinity

The toxicity of sediments in Sabine Lake, Texas, and adjoining Intracoastal Waterway canals was determined as part of bioeffects assessment studies managed by NOAA’s National Status and Trends Program. The objectives of the survey were to determine: (1) the incidence and degree of toxicity of sediments throughout the study area; (2) the spatial patterns (or gradients) in chemical contamination and toxicity, if any, throughout the study area; (3) the spatial extent of chemical contamination and toxicity; and (4) the statistical relationships between measures of toxicity and concentrations of chemicals in the sediments. Surficial sediment samples were collected during August, 1995 from 66 randomly-chosen locations. Laboratory toxicity tests were performed as indicators of potential ecotoxicological effects in sediments. A battery of tests was performed to generate information from different phases (components) of the sediments. Tests were selected to represent a range in toxicological endpoints from acute to chronic sublethal responses. Toxicological tests were conducted to measure: reduced survival of adult amphipods exposed to solid-phase sediments; impaired fertilization success and abnormal morphological development in gametes and embryos, respectively, of sea urchins exposed to pore waters; reduced metabolic activity of a marine bioluminescent bacteria exposed to organic solvent extracts; and induction of a cytochrome P-450 reporter gene system in exposures to solvent extracts of the sediments. Chemical analyses were performed on portions of each sample to quantify the concentrations of trace metals, polynuclear aromatic hydrocarbons, and chlorinated organic compounds. Correlation analyses were conducted to determine the relationships between measures of toxicity and concentrations of potentially toxic substances in the samples. Based upon the compilation of results from chemical analyses and toxicity tests, the quality of sediments in Sabine Lake and vicinity did not appear to be severely degraded. Chemical concentrations rarely exceeded effects-based numerical guidelines, suggesting that toxicant-induced effects would not be expected in most areas. None of the samples was highly toxic in acute amphipod survival tests and a minority (23%) of samples were highly toxic in sublethal urchin fertilization tests. Although toxic responses occurred frequently (94% of samples) in urchin embryo development tests performed with 100% pore waters, toxicity diminished markedly in tests done with diluted pore waters. Microbial bioluminescent activity was not reduced to a great degree (no EC50 <0.06 mg/ml) and cytochrome P-450 activity was not highly induced (6 samples exceeded 37.1 ug/g benzo[a]pyrene equivalents) in tests done with organic solvent extracts. Urchin embryological development was highly correlated with concentrations of ammonia and many trace metals. Cytochrome P450 induction was highly correlated with concentrations of a number of classes of organic compounds (including the polynuclear aromatic hydrocarbons and chlorinated compounds). (PDF contains 51 pages

Confirmation of the genetic association of CTLA4 and PTPN22 with ANCA-associated vasculitis.

BACKGROUND: The genetic contribution to the aetiology of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is not well defined. Across different autoimmune diseases some genes with immunomodulatory roles, such as PTPN22, are frequently associated with multiple diseases, whereas specific HLA associations, such as HLA-B27, tend to be disease restricted. We studied ten candidate loci on the basis of their immunoregulatory role and prior associations with type 1 diabetes (T1D). These included PTPN22, CTLA4 and CD226, which have previously been associated with AAV. METHODS: We genotyped the following 11 SNPs, from 10 loci, in 641 AAV patients using TaqMan genotyping: rs2476601 in PTPN22, rs1990760 in IFIH1, rs3087243 in CTLA4, rs2069763 in IL2, rs10877012 in CYP27B1, rs2292239 in ERBB3, rs3184504 in SH2B3, rs12708716 in CLEC16A, rs1893217 and rs478582 in PTPN2 and rs763361 in CD226. Where possible, we performed a meta-analysis with previous analyses. RESULTS: Both CTLA4 rs3087243 and PTPN22 rs2476601 showed association with AAV, P = 6.4 x 10-3 and P = 1.4 x 10-4 respectively. The minor allele (A) of CTLA4 rs3087243 is protective (odds ratio = 0.84), whereas the minor allele (A) of PTPN22 rs2476601 confers susceptibility (odds ratio = 1.40). These results confirmed previously described associations with AAV. After meta-analysis, the PTPN22 rs2476601 association was further strengthened (combined P = 4.2 x 10-7, odds ratio of 1.48 for the A allele). The other 9 SNPs, including rs763361 in CD226, showed no association with AAV. CONCLUSION: Our study of T1D associated SNPs in AAV has confirmed CTLA4 and PTPN22 as susceptibility loci in AAV. These genes encode two key regulators of the immune response and are associated with many autoimmune diseases, including T1D, autoimmune thyroid disease, celiac disease, rheumatoid arthritis, and now AAV

Searching for stellar mass black holes in the solar neighborhood

We propose a strategy for searching for isolated stellar mass black holes in the solar neighborhood with the Sloan Digital Sky Survey. Due to spherical accretion of the inter-stellar medium and the ambient magnetic field, an isolated black hole is expected to emit a blended, thermal synchrotron spectrum with a roughly flat peak from the optical down to the far infra-red. We find that the Sloan Survey will be able to detect isolated black holes, in the considered mass range of 1--100$M_{\odot}$, out to a few hundred parsecs, depending on the local conditions of the ISM. We also find that the black holes are photmetrically distinguishable from field stars and they have a photometry similar to QSOs. They can be further singled out from QSO searches because they have a featureless spectrum with no emission lines. The Sloan Survey will likely find hundreds of objects that meet these criteria, and to further reduce the number of candidates, we suggest other selection criteria such as infra-red searches and proper motion measurements. Estimates indicate that dozens of black holes may exist out to a few hundred parsecs. If no black hole candidates are found in this survey, important limits can be placed on the local density of black holes and the halo fraction in black holes, especially for masses greater than about $20 M_{\odot}$.Comment: Latex, 7 pages, 3 postscript figures, submitted to ApJ Letters. Also available at http://fnas08.fnal.gov

Cleaner Fuels for Ships Provide Public Health Benefits with Climate Tradeoffs

We evaluate public health and climate impacts of low-sulphur fuels in global shipping. Using high-resolution emissions inventories, integrated atmospheric models, and health risk functions, we assess ship-related PM 2.5 pollution impacts in 2020 with and without the use of low-sulphur fuels. Cleaner marine fuels will reduce ship-related premature mortality and morbidity by 34 and 54%, respectively, representing a ~ 2.6% global reduction in PM 2.5 cardiovascular and lung cancer deaths and a ~3.6% global reduction in childhood asthma. Despite these reductions, low-sulphur marine fuels will still account for ~250k deaths and ~6.4 M childhood asthma cases annually, and more stringent standards beyond 2020 may provide additional health benefits. Lower sulphur fuels also reduce radiative cooling from ship aerosols by ~80%, equating to a ~3% increase in current estimates of total anthropogenic forcing. Therefore, stronger international shipping policies may need to achieve climate and health targets by jointly reducing greenhouse gases and air pollution

Contrasting genetic association of IL2RA with SLE and ANCA-associated vasculitis.

BACKGROUND: Autoimmune diseases are complex and have genetic and environmental susceptibility factors. The objective was to test the genetic association of systemic lupus erythematosus (SLE) and anti-neutrophil cytoplasmic antibody (ANCA) - associated systemic vasculitis (AAV) with SNPs in the IL2RA region and to correlate genotype with serum levels of IL-2RA. METHODS: Using a cohort of over 700 AAV patients, two SLE case-control studies and an SLE trio collection (totalling over 1000 SLE patients), and a TaqMan genotyping approach, we tested 3 SNPs in the IL2RA locus, rs11594656, rs2104286 & rs41295061, each with a prior association with autoimmune disease; rs11594656 and rs41295061 with type 1 diabetes (T1D) and rs2104286 with multiple sclerosis (MS) and T1D. RESULTS: We show that SLE is associated with rs11594656 (P = 3.87 x 10-7) and there is some evidence of association of rs41295061 with AAV (P = 0.0122), which both have prior association with T1D. rs2104286, an MS and T1D - associated SNP in the IL2RA locus, is not associated with either SLE or AAV. CONCLUSION: We have confirmed a previous suggestion that the IL2RA locus is associated with SLE and showed some evidence of association with AAV. Soluble IL-2RA concentrations correlate with rs11594656 genotype in quiescent disease in both AAV and SLE. Differential association of autoimmune diseases and SNPs within the IL2RA locus suggests that the IL2RA pathway may prove to play differing, as yet undefined, roles in each disease

Central obesity as a precursor to the metabolic syndrome in the AusDiab study and Mauritius

Evidence from epidemiologic studies that central obesity precedes future metabolic change and does not occur concurrently with the appearance of the blood pressure, glucose, and lipid abnormalities that characterize the metabolic syndrome (MetS) has been lacking. Longitudinal surveys were conducted in Mauritius in 1987, 1992, and 1998, and in Australia in 2000 and 2005 (AusDiab). This analysis included men and women (aged 25 years) in three cohorts: AusDiab 2000&ndash;2005 (n = 5,039), Mauritius 1987&ndash;1992 (n = 2,849), and Mauritius 1987&ndash;1998 (n = 1,999). MetS components included waist circumference, systolic blood pressure, fasting and 2-h postload plasma glucose, high-density lipoprotein (HDL) cholesterol, triglycerides, and homeostasis model assessment of insulin sensitivity (HOMA-S) (representing insulin sensitivity). Linear regression was used to determine which baseline components predicted deterioration in other MetS components over 5 years in AusDiab and 5 and 11 years in Mauritius, adjusted for age, sex, and ethnic group. Baseline waist circumference predicted deterioration (P &lt; 0.01) in four of the other six MetS variables tested in AusDiab, five of six in Mauritius 1987&ndash;1992, and four of six in Mauritius 1987&ndash;1998. In contrast, an increase in waist circumference between baseline and follow-up was only predicted by insulin sensitivity (HOMA-S) at baseline, and only in one of the three cohorts. These results suggest that central obesity plays a central role in the development of the MetS and appears to precede the appearance of the other MetS components.<br /

Four-shooter: a large format charge-coupled-device camera for the Hale telescope

We describe an astronomical camera for the 200-in. Hale telescope using four 800 X800 Texas Instruments CCDs in an optical arrangement that allows imaging of a contiguous 1600-pixel-square region of sky. The system employs reimaging optics to yield a scale of 0.33 arcsec per pixel, a good match to the best seeing conditions at Palomar Observatory. Modern high-efficiency coatings are used in the complex optical system to yield a throughput at peak efficiency of nearly 50% (including the losses in the telescope), corresponding to a quantum efficiency on the sky of about 30%. The system uses a fifth CCD in a spectroscopic channel, and it is possible to obtain simultaneous imaging and spectroscopic observations with the system. The camera may also be used in a scanning mode, in which the telescope tracking rate is offset, and the charge is clocked in the chips in such a manner as to keep the charge image aligned with the optical image. In this way, a survey for high-redshift quasars has been carried out over a large area of sky. The instrument has produced images for the most distant clusters of galaxies yet discovered as well as spectra of the most distant galaxies yet observed