4,947 research outputs found

    Asymmetric thymocyte death underlies the CD4:CD8 T-cell ratio in the adaptive immune system

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    It has long been recognized that the T-cell compartment has more CD4 helper than CD8 cytotoxic T cells, and this is most evident looking at T-cell development in the thymus. However, it remains unknown how thymocyte development so favors CD4 lineage development. To identify the basis of this asymmetry, we analyzed development of synchronized cohorts of thymocytes in vivo and estimated rates of thymocyte death and differentiation throughout development, inferring lineage-specific efficiencies of selection. Our analysis suggested that roughly equal numbers of cells of each lineage enter selection and found that, overall, a remarkable ∼75% of cells that start selection fail to complete the process. Importantly it revealed that class I-restricted thymocytes are specifically susceptible to apoptosis at the earliest stage of selection. The importance of differential apoptosis was confirmed by placing thymocytes under apoptotic stress, resulting in preferential death of class I-restricted thymocytes. Thus, asymmetric death during selection is the key determinant of the CD4:CD8 ratio in which T cells are generated by thymopoiesis

    Knudsen gas provides nanobubble stability

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    We provide a model for the remarkable stability of surface nanobubbles to bulk dissolution. The key to the solution is that the gas in a nanobubble is of Knudsen type. This leads to the generation of a bulk liquid flow which effectively forces the diffusive gas to remain local. Our model predicts the presence of a vertical water jet immediately above a nanobubble, with an estimated speed of 3.3m/s\sim3.3\,\mathrm{m/s}, in good agreement with our experimental atomic force microscopy measurement of 2.7m/s\sim2.7\,\mathrm{m/s}. In addition, our model also predicts an upper bound for the size of nanobubbles, which is consistent with the available experimental data

    From Reintroduction to Assisted Colonization: Moving along the Conservation Translocation Spectrum

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    Translocation, the intentional movement of living organisms from one area to another is increasingly being used as a conservation tool to overcome barriers to dispersal. A dichotomy exists for conservation-oriented translocations: on one hand there are those that release plants or animals into known historic ranges, on the other hand there are releases outside historic distributions. Misuse of or attempts to redefine established terms, and a proliferation of variants of new terms such as assisted colonization, confuse and hamper communication. The aim of this opinion paper is to describe and define a conservation translocation spectrum, from species re-introductions through to assisted colonization, and beyond, and in so doing provide a standard framework and terminology for discussing translocation options. I suggest that we are moving along this spectrum, away from the dictates of historical species distribution records, towards the inclusion of more risky interventions that will be required to respond to habitat shifts due to anthropogenic impacts. To some extent rapid climate change changes everything, including how we should view introductions versus reintroductions. We need seriously to consider adding other approaches to our conservation toolbox. Assisted colonization will start us along this path, acknowledging as it does the accelerated rate of habitat change and the problems of attempting to preserve dynamic systems. The next step along the conservation translocation spectrum may be for reintroduction biology and restoration ecology to more comprehensively join forces on carefully selected projects to use species introductions to create novel ecosystems through active ecological community constructio

    Models of self-peptide sampling by developing T cells identify candidate mechanisms of thymic selection

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    Conventional and regulatory T cells develop in the thymus where they are exposed to samples of self-peptide MHC (pMHC) ligands. This probabilistic process selects for cells within a range of responsiveness that allows the detection of foreign antigen without excessive responses to self. Regulatory T cells are thought to lie at the higher end of the spectrum of acceptable self-reactivity and play a crucial role in the control of autoimmunity and tolerance to innocuous antigens. While many studies have elucidated key elements influencing lineage commitment, we still lack a full understanding of how thymocytes integrate signals obtained by sampling self-peptides to make fate decisions. To address this problem, we apply stochastic models of signal integration by T cells to data from a study quantifying the development of the two lineages using controllable levels of agonist peptide in the thymus. We find two models are able to explain the observations; one in which T cells continually re-assess fate decisions on the basis of multiple summed proximal signals from TCR-pMHC interactions; and another in which TCR sensitivity is modulated over time, such that contact with the same pMHC ligand may lead to divergent outcomes at different stages of development. Neither model requires that T and T are differentially susceptible to deletion or that the two lineages need qualitatively different signals for development, as have been proposed. We find additional support for the variable-sensitivity model, which is able to explain apparently paradoxical observations regarding the effect of partial and strong agonists on T and T development

    Drink wise, age well; reducing alcohol related harm among people over 50: a study protocol

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    Background: Evidence suggests that the use of alcohol among older adults (defined as those aged 50+) has increased in recent years, with people aged 55-64 now more likely to exceed the recommended weekly guidelines than any other age group. Methods/ design: This is a quasi-experimental study with a before-after design. A postal questionnaire will be sent to 76,000 people aged 50 and over registered with a general practice in five different 'demonstration' (intervention) and control areas in the UK. Multiple interventions will then be delivered in demonstration areas across the UK. At the end of the programme, a postal questionnaire will be sent to the same individuals who completed it pre-programme to establish if there has been a reduction in alcohol use, at-risk drinking and alcohol related problems. Qualitative interviews with clients and staff will explore how the interventions were experienced; how they may work to bring about change and to identify areas for practice improvements. Discussion: This study protocol describes a multi-level, multi-intervention prevention-to-treatment programme which aims to reduce alcohol-related harm in people aged 50 and over

    Entropy-driven formation of the gyroid cubic phase

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    We show, by computer simulation, that tapered or pear-shaped particles, interacting through purely repulsive interactions, can freely self-assemble to form the three-dimensionally periodic, gyroid cubic phase. The Ia3d gyroid cubic phase is formed by these particles both on compression of an isotropic configuration and on expansion of a smectic A bilayer arrangement. For the latter case, it is possible identify the steps by which the topological transformation from non-intersecting planes to fully interpenetrating, periodic networks takes place</p

    Sporadic-E As Observed with Rockets

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    Data obtained with rockets flown over New Mexico, U.S.A. and Manitoba, Canada have always shown the sporadic-E layer to be a thin layer with a large electron density gradient. The vertical electron density profiles and the horizontal uniformity of the sporadic-E layer are discussed herein. These layers have a strong tendency to form at preferential altitudes separated by approximately 6 km, and a striking correlation exists with wind- shears and magnetic field variations. In two cases where comparisons with ionograms were possible, the minimum frequency of the F-region echoes was found approximately equal to the plasma frequency of the sporadic-E layer reduced by half the gyrofrequency. On the other hand, the maximum frequency of the sporadic-E echoes as noted on ionograms was sometimes as much as 1 to 2 Mc greater than the plasma frequency

    Evidence for polarised boron in Co-B and Fe-B alloys

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    By exploiting the tunability of synchrotron radiation in measurements of spin-resolved photoemission it has proved possible to obtain information on the polarisation of the valence electrons of Co-B and Fe-B amorphous magnetic alloys, Both the spin-integrated and spin-resolved energy distribution curves show a marked dependence on photon energy indicating that the p states of boron hybridise with the d states of the transition metals giving rise to mixed states in the binding energy range 1 to 5 eV, The observed polarisation and spin-resolved densities of states imply that in the above restricted energy range there is a net negative polarisation of the boron states
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