Genetic variants alter T-bet binding and gene expression in mucosal inflammatory disease

The polarization of CD4+ T cells into distinct T helper cell lineages is essential for protective immunity against infection, but aberrant T cell polarization can cause autoimmunity. The transcription factor T-bet (TBX21) specifies the Th1 lineage and represses alternative T cell fates. Genome-wide association studies have identified single nucleotide polymorphisms (SNPs) that may be causative for autoimmune diseases. The majority of these polymorphisms are located within non-coding distal regulatory elements. It is considered that these genetic variants contribute to disease by altering the binding of regulatory proteins and thus gene expression, but whether these variants alter the binding of lineage-specifying transcription factors has not been determined. Here, we show that SNPs associated with the mucosal inflammatory diseases Crohn’s disease, ulcerative colitis (UC) and celiac disease, but not rheumatoid arthritis or psoriasis, are enriched at T-bet binding sites. Furthermore, we identify disease-associated variants that alter T-bet binding in vitro and in vivo. ChIP-seq for T-bet in individuals heterozygous for the celiac disease-associated SNPs rs1465321 and rs2058622 and the IBD-associated SNPs rs1551398 and rs1551399, reveals decreased binding to the minor disease-associated alleles. Furthermore, we show that rs1465321 is an expression quantitative trait locus (eQTL) for the neighboring gene IL18RAP, with decreased T-bet binding associated with decreased expression of this gene. These results suggest that genetic polymorphisms may predispose individuals to mucosal autoimmune disease through alterations in T-bet binding. Other disease-associated variants may similarly act by modulating the binding of lineage-specifying transcription factors in a tissue-selective and disease-specific manner

Accelerator system for the PRISM based muon to electron conversion experiment

The next generation of lepton flavor violation experiments need high intensity and high quality muon beams. Production of such beams requires sending a short, high intensity proton pulse to the pion production target, capturing pions and collecting the resulting muons in the large acceptance transport system. The substantial increase of beam quality can be obtained by applying the RF phase rotation on the muon beam in the dedicated FFAG ring, which was proposed for the PRISM project.This allows to reduce the momentum spread of the beam and to purify from the unwanted components like pions or secondary protons. A PRISM Task Force is addressing the accelerator and detector issues that need to be solved in order to realize the PRISM experiment. The parameters of the required proton beam, the principles of the PRISM experiment and the baseline FFAG design are introduced. The spectrum of alternative designs for the PRISM FFAG ring are shown. Progress on ring main systems like injection and RF are presented. The current status of the study and its future directions are discussed.Comment: Studies performed within the PRISM Task Force initiativ

Parental perspectives on negotiations over diet and physical activity: how do we involve parents in adolescent health interventions?

OBJECTIVE: To identify the ways in which parental involvement can be incorporated into interventions to support adolescent health behaviour change. DESIGN: Data from semi-structured interviews were analysed using inductive thematic analysis. SETTING: Southampton, Hampshire, UK. PARTICIPANTS: A convenience sample of twenty-four parents of adolescents. RESULTS: Parents consider themselves to play an important role in supporting their adolescents to make healthy choices. Parents saw themselves as gatekeepers of the household and as role models to their adolescents but recognised this could be both positive and negative in terms of health behaviours. Parents described the changing dynamics of the relationships they have with their adolescents because of increased adolescent autonomy. Parents stated that these changes altered their level of influence over adolescents' health behaviours. Parents considered it important to promote independence in their adolescents; however, many described this as challenging because they believed their adolescents were likely to make unhealthy decisions if not given guidance. Parents reported difficulty in supporting adolescents in a way that was not viewed as forceful or pressuring. CONCLUSIONS: When designing adolescent health interventions that include parental components, researchers need to be aware of the disconnect between public health recommendations and the everyday reality for adolescents and their parents. Parental involvement in adolescent interventions could be helpful but needs to be done in a manner that is acceptable to both adolescents and parents. The findings of this study may be useful to inform interventions which need to consider the transitions and negotiations which are common in homes containing adolescents

Genetic characterization of influenza virus circulating in Brazilian pigs during

Background Influenza A viruses circulating in pigs in Brazil are still not characterized, and only limited data are available about swine influenza epidemiology in the country. Therefore, we characterized the hemagglutinin (HA) and neuraminidase (NA) genes of influenza viruses isolated from Brazilian pigs. We also evaluated one case of probable swine-to-human transmission. Methods Twenty influenza viruses isolated from pigs during 2009-2010 in five Brazilian states (Minas Gerais, Sao Paulo, Parana, Rio Grande do Sul, and Mato Grosso) were used. One human isolate, from a technician who became ill after visiting a swineherd going through a respiratory disease outbreak, was also used in the study. Phylogenetic analysis for the HA and NA genes and hemagglutinin amino acid sequence alignment were performed. Results All isolates clustered with pandemic H1N1 2009 (pH1N1) viruses and appeared to have a common ancestor. Genetic diversity was higher in the HA than in the NA gene, and the amino acid substitution S203T in one of HA's antigenic sites was found in most of the samples. The human isolate was more related to swine isolates from the same herd visited by the technician than to other human isolates, suggesting swine-to-human transmission. Conclusion Our results show that pH1N1 was disseminated and the predominant subtype in Brazilian pigs in 2009-2010

The impacts of environmental warming on Odonata: a review

Climate change brings with it unprecedented rates of increase in environmental temperature, which will have major consequences for the earth's flora and fauna. The Odonata represent a taxon that has many strong links to this abiotic factor due to its tropical evolutionary history and adaptations to temperate climates. Temperature is known to affect odonate physiology including life-history traits such as developmental rate, phenology and seasonal regulation as well as immune function and the production of pigment for thermoregulation. A range of behaviours are likely to be affected which will, in turn, influence other parts of the aquatic ecosystem, primarily through trophic interactions. Temperature may influence changes in geographical distributions, through a shifting of species' fundamental niches, changes in the distribution of suitable habitat and variation in the dispersal ability of species. Finally, such a rapid change in the environment results in a strong selective pressure towards adaptation to cope and the inevitable loss of some populations and, potentially, species. Where data are lacking for odonates, studies on other invertebrate groups will be considered. Finally, directions for research are suggested, particularly laboratory studies that investigate underlying causes of climate-driven macroecological patterns

A Study of Muon Neutrino Disappearance Using the Fermilab Main Injector Neutrino Beam

We report the results of a search for muon-neutrino disappearance by the Main Injector Neutrino Oscillation Search. The experiment uses two detectors separated by 734 km to observe a beam of neutrinos created by the Neutrinos at the Main Injector facility at Fermi National Accelerator Laboratory. The data were collected in the first 282 days of beam operations and correspond to an exposure of 1.27e20 protons on target. Based on measurements in the Near Detector, in the absence of neutrino oscillations we expected 336 +/- 14 muon-neutrino charged-current interactions at the Far Detector but observed 215. This deficit of events corresponds to a significance of 5.2 standard deviations. The deficit is energy dependent and is consistent with two-flavor neutrino oscillations according to delta m-squared = 2.74e-3 +0.44/-0.26e-3 eV^2 and sin^2(2 theta) > 0.87 at 68% confidence level.Comment: In submission to Phys. Rev.

Measurement of the Atmospheric Muon Charge Ratio at TeV Energies with MINOS

The 5.4 kton MINOS far detector has been taking charge-separated cosmic ray muon data since the beginning of August, 2003 at a depth of 2070 meters-water-equivalent in the Soudan Underground Laboratory, Minnesota, USA. The data with both forward and reversed magnetic field running configurations were combined to minimize systematic errors in the determination of the underground muon charge ratio. When averaged, two independent analyses find the charge ratio underground to be 1.374 +/- 0.004 (stat.) +0.012 -0.010(sys.). Using the map of the Soudan rock overburden, the muon momenta as measured underground were projected to the corresponding values at the surface in the energy range 1-7 TeV. Within this range of energies at the surface, the MINOS data are consistent with the charge ratio being energy independent at the two standard deviation level. When the MINOS results are compared with measurements at lower energies, a clear rise in the charge ratio in the energy range 0.3 -- 1.0 TeV is apparent. A qualitative model shows that the rise is consistent with an increasing contribution of kaon decays to the muon charge ratio.Comment: 16 pages, 17 figure

Measurement of neutrino velocity with the MINOS detectors and NuMI neutrino beam

The velocity of a ~3 GeV neutrino beam is measured by comparing detection times at the near and far detectors of the MINOS experiment, separated by 734 km. A total of 473 far detector neutrino events was used to measure (v-c)/c=5.12.910-5 (at 68% C.L.). By correlating the measured energies of 258 charged-current neutrino events to their arrival times at the far detector, a limit is imposed on the neutrino mass of mnu<50 MeV/c2 (99% C.L.)

Past and present distribution, densities and movements of blue whales <i>Balaenoptera musculus</i> in the Southern Hemisphere and northern Indian Ocean

1Blue whale locations in the Southern Hemisphere and northern Indian Ocean were obtained from catches (303 239), sightings (4383 records of =8058 whales), strandings (103), Discovery marks (2191) and recoveries (95), and acoustic recordings.2Sighting surveys included 7 480 450 km of effort plus 14 676 days with unmeasured effort. Groups usually consisted of solitary whales (65.2%) or pairs (24.6%); larger feeding aggregations of unassociated individuals were only rarely observed. Sighting rates (groups per 1000 km from many platform types) varied by four orders of magnitude and were lowest in the waters of Brazil, South Africa, the eastern tropical Pacific, Antarctica and South Georgia; higher in the Subantarctic and Peru; and highest around Indonesia, Sri Lanka, Chile, southern Australia and south of Madagascar.3Blue whales avoid the oligotrophic central gyres of the Indian, Pacific and Atlantic Oceans, but are more common where phytoplankton densities are high, and where there are dynamic oceanographic processes like upwelling and frontal meandering.4Compared with historical catches, the Antarctic (‘true’) subspecies is exceedingly rare and usually concentrated closer to the summer pack ice. In summer they are found throughout the Antarctic; in winter they migrate to southern Africa (although recent sightings there are rare) and to other northerly locations (based on acoustics), although some overwinter in the Antarctic.5Pygmy blue whales are found around the Indian Ocean and from southern Australia to New Zealand. At least four groupings are evident: northern Indian Ocean, from Madagascar to the Subantarctic, Indonesia to western and southern Australia, and from New Zealand northwards to the equator. Sighting rates are typically much higher than for Antarctic blue whales.6South-east Pacific blue whales have a discrete distribution and high sighting rates compared with the Antarctic. Further work is needed to clarify their subspecific status given their distinctive genetics, acoustics and length frequencies.7Antarctic blue whales numbered 1700 (95% Bayesian interval 860–2900) in 1996 (less than 1% of original levels), but are increasing at 7.3% per annum (95% Bayesian interval 1.4–11.6%). The status of other populations in the Southern Hemisphere and northern Indian Ocean is unknown because few abundance estimates are available, but higher recent sighting rates suggest that they are less depleted than Antarctic blue whales.</li