2,732 research outputs found

    Leukotrienes provide an NFAT-dependent signal that synergizes with IL-33 to activate ILC2s.

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    Group 2 innate lymphoid cells (ILC2s) and type 2 helper T cells (Th2 cells) are the primary source of interleukin 5 (IL-5) and IL-13 during type 2 (allergic) inflammation in the lung. In Th2 cells, T cell receptor (TCR) signaling activates the transcription factors nuclear factor of activated T cells (NFAT), nuclear factor κB (NF-κB), and activator protein 1 (AP-1) to induce type 2 cytokines. ILC2s lack a TCR and respond instead to locally produced cytokines such as IL-33. Although IL-33 induces AP-1 and NF-κB, NFAT signaling has not been described in ILC2s. In this study, we report a nonredundant NFAT-dependent role for lipid-derived leukotrienes (LTs) in the activation of lung ILC2s. Using cytokine reporter and LT-deficient mice, we find that complete disruption of LT signaling markedly diminishes ILC2 activation and downstream responses during type 2 inflammation. Type 2 responses are equivalently attenuated in IL-33- and LT-deficient mice, and optimal ILC2 activation reflects potent synergy between these pathways. These findings expand our understanding of ILC2 regulation and may have important implications for the treatment of airways disease

    Nuclear alpha-clustering, superdeformation, and molecular resonances

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    Nuclear alpha-clustering has been the subject of intense study since the advent of heavy-ion accelerators. Looking back for more than 40 years we are able today to see the connection between quasimolecular resonances in heavy-ion collisions and extremely deformed states in light nuclei. For example superdeformed bands have been recently discovered in light N=Z nuclei such as 36^{36}Ar, 40^{40}Ca, 48^{48}Cr, and 56^{56}Ni by γ\gamma-ray spectroscopy. The search for strongly deformed shapes in N=Z nuclei is also the domain of charged-particle spectroscopy, and our experimental group at IReS Strasbourg has studied a number of these nuclei with the charged particle multidetector array {\sc Icare} at the {\sc Vivitron} Tandem facility in a systematical manner. Recently the search for γ\gamma-decays in 24^{24}Mg has been undertaken in a range of excitation energies where previously nuclear molecular resonances were found in 12^{12}C+12^{12}C collisions. The breakup reaction 24^{24}Mg+12+^{12}C has been investigated at Elab_{lab}(24^{24}Mg) = 130 MeV, an energy which corresponds to the appropriate excitation energy in 24^{24}Mg for which the 12^{12}C+12^{12}C resonance could be related to the breakup resonance. Very exclusive data were collected with the Binary Reaction Spectrometer in coincidence with {\sc Euroball IV} installed at the {\sc Vivitron}.Comment: 10 pages, 4 eps figures included. Invited Talk 10th Nuclear Physics Workshop Marie and Pierre Curie, Kazimierz Dolny Poland, Sep. 24-28, 2003; To be published in International Journal of Modern Physics

    Socio-economic variations in anticipated adverse reactions to testing HPV positive: Implications for the introduction of primary HPV-based cervical screening

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    Some cervical cancer screening programmes are replacing cytology with human papillomavirus (HPV) DNA testing as the primary screening test. Concerns have been previously raised around the potential psychosocial impact of testing positive for HPV. We analysed socio-economic variations in anticipated adverse reactions to testing positive for HPV in women of screening age in the general population. A questionnaire was mailed to a random sample of 5553 women aged 20-64 in 2010, selected through primary care in Ireland. This included questions on: socio-economics; HPV knowledge; and women's anticipated adverse psychosocial responses to testing HPV positive (shame, anxiety, stigma and worry). Multivariable linear regression was used to identify socio-economic factors significantly associated with each anticipated adverse reaction. The response rate was 62% (n = 3470). In multivariate analyses, having only attained primary level education were significantly associated with higher mean scores for all four adverse outcomes. Religion was significantly associated with all four adverse outcomes. Age was associated with anxiety and worry; younger women (<30 years) had the highest mean scores. Being married/cohabiting was significantly associated with significantly lower shame and worry scores. Not working was significantly associated with higher mean anxiety and worry scores. Our large population-based survey found significant socio-economic variations in anticipated adverse reactions to testing HPV positive. In order to minimise possible negative impacts on screening uptake and alleviate potential adverse psychological effects of HPV-based screening on women, screening programmes may need to develop specific messages around HPV infection and HPV screening that target certain subgroups of women

    Shot-noise-limited spin measurements in a pulsed molecular beam

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    Heavy diatomic molecules have been identified as good candidates for use in electron electric dipole moment (eEDM) searches. Suitable molecular species can be produced in pulsed beams, but with a total flux and/or temporal evolution that varies significantly from pulse to pulse. These variations can degrade the experimental sensitivity to changes in spin precession phase of an electri- cally polarized state, which is the observable of interest for an eEDM measurement. We present two methods for measurement of the phase that provide immunity to beam temporal variations, and make it possible to reach shot-noise-limited sensitivity. Each method employs rapid projection of the spin state onto both components of an orthonormal basis. We demonstrate both methods using the eEDM-sensitive H state of thorium monoxide (ThO), and use one of them to measure the magnetic moment of this state with increased accuracy relative to previous determinations.Comment: 12 pages, 6 figure

    Transcription-translation coupling: direct interactions of RNA polymerase with ribosomes and ribosomal subunits.

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    In prokaryotes, RNA polymerase and ribosomes can bind concurrently to the same RNA transcript, leading to the functional coupling of transcription and translation. The interactions between RNA polymerase and ribosomes are crucial for the coordination of transcription with translation. Here, we report that RNA polymerase directly binds ribosomes and isolated large and small ribosomal subunits. RNA polymerase and ribosomes form a one-to-one complex with a micromolar dissociation constant. The formation of the complex is modulated by the conformational and functional states of RNA polymerase and the ribosome. The binding interface on the large ribosomal subunit is buried by the small subunit during protein synthesis, whereas that on the small subunit remains solvent-accessible. The RNA polymerase binding site on the ribosome includes that of the isolated small ribosomal subunit. This direct interaction between RNA polymerase and ribosomes may contribute to the coupling of transcription to translation

    Conus : First comprehensive conservation red list assessment of a marine gastropod mollusc genus

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    Marine molluscs represent an estimated 23% of all extant marine taxa, but research into their conservation status has so far failed to reflect this importance, with minimal inclusion on the authoritative Red List of the International Union for the Conservation of Nature (IUCN). We assessed the status of all 632 valid species of the tropical marine gastropod mollusc, Conus (cone snails), using Red List standards and procedures to lay the groundwork for future decadal monitoring, one of the first fully comprehensive global assessments of a marine taxon. Three-quarters (75.6%) of species were not currently considered at risk of extinction owing to their wide distribution and perceived abundance. However, 6.5% were considered threatened with extinction with a further 4.1% near threatened. Data deficiency prevented 13.8% of species from being categorised although they also possess characteristics that signal concern. Where hotspots of endemism occur, most notably in the Eastern Atlantic, 42.9% of the 98 species from that biogeographical region were classified as threatened or near threatened with extinction. All 14 species included in the highest categories of Critically Endangered and Endangered are endemic to either Cape Verde or Senegal, with each of the three Critically Endangered species restricted to single islands in Cape Verde. Threats to all these species are driven by habitat loss and anthropogenic disturbance, in particular from urban pollution, tourism and coastal development. Our findings show that levels of extinction risk to which cone snails are exposed are of a similar magnitude to those seen in many fully assessed terrestrial taxa. The widely held view that marine species are less at risk is not upheld

    Massive open star clusters using the VVV survey III: A young massive cluster at the far edge of the Galactic bar

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    Context: Young massive clusters are key to map the Milky Way's structure, and near-IR large area sky surveys have contributed strongly to the discovery of new obscured massive stellar clusters. Aims: We present the third article in a series of papers focused on young and massive clusters discovered in the VVV survey. This article is dedicated to the physical characterization of VVV CL086, using part of its OB-stellar population. Methods: We physically characterized the cluster using JHKSJHK_S near-infrared photometry from ESO public survey VVV images, using the VVV-SkZ pipeline, and near-infrared KK-band spectroscopy, following the methodology presented in the first article of the series. Results: Individual distances for two observed stars indicate that the cluster is located at the far edge of the Galactic bar. These stars, which are probable cluster members from the statistically field-star decontaminated CMD, have spectral types between O9 and B0V. According to our analysis, this young cluster (1.01.0 Myr << age <5.0< 5.0 Myr) is located at a distance of 11−6+511^{+5}_{-6} kpc, and we estimate a lower limit for the cluster total mass of (2.8−1.4+1.6)⋅103M⊙(2.8^{+1.6}_{-1.4})\cdot10^3 {M}_{\odot}. It is likely that the cluster contains even earlier and more massive stars.Comment: Accepted for publication as a Letter in A&
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