82 research outputs found

    CD103 Deficiency Prevents Graft-versus-Host Disease but Spares Graft-versus-Tumor Effects Mediated by Alloreactive CD8 T Cells

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    Graft-versus-host disease (GVHD) remains the main barrier to broader application of allogeneic hematopoietic stem cell transplantation (alloSCT) as a curative therapy for host malignancy. GVHD is mediated by allogeneic T cells directed against histocompatibility antigens expressed by host tissues. Based on previous studies, we postulated that the integrin CD103 is required for CD8-mediated GVHD, but not for graft-versus-tumor effects (GVT).We herein provide evidence in support of this hypothesis. To circumvent the potentially confounding influence of donor CD4 T cells, we developed an alloSCT model in which GVHD mortality is mediated by purified CD8 T cells. In this model, host-reactive CD8 T cells receive CD4 T cell help at the time of initial activation but not in the effector phase in which mature CD8 T effectors migrate into host tissues. We show that donor CD8 T cells from wild-type BALB/c mice primed to host alloantigens induce GVHD pathology and eliminate tumors of host origin in the absence of host CD4 T cells. Importantly, CD103 deficiency dramatically attenuated GVHD mortality, but had no detectable impact on the capacity to eliminate a tumor line of host origin. We provide evidence that CD103 is required for accumulation of donor CD8 T cells in the host intestinal epithelium but not in the tumor or host lymphoid compartments. Consistent with these data, CD103 was preferentially expressed by CD8 T cells infiltrating the host intestinal epithelium but not by those infiltrating the tumor, lamina propria, or lymphoid compartments. We further demonstrate that CD103 expression is not required for classic CD8 effector activities including cytokine production and cytotoxicity.These data indicate that CD103 deficiency inhibits GVHD pathology while sparing anti-tumor effects mediated by CD8 T cells, identifying CD103 blockade as an improved strategy for GVHD prophylaxis

    Multi-band analyses of the bright GRB~230812B and the associated SN2023pel

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    GRB~230812B is a bright and relatively nearby (z=0.36z =0.36) long gamma-ray burst that has generated significant interest in the community and therefore has been subsequently observed over the entire electromagnetic spectrum. We report over 80 observations in X-ray, ultraviolet, optical, infrared, and sub-millimeter bands from the GRANDMA (Global Rapid Advanced Network for Multi-messenger Addicts) network of observatories and from observational partners. Adding complementary data from the literature, we then derive essential physical parameters associated with the ejecta and external properties (i.e. the geometry and environment) and compare with other analyses of this event (e.g. Srinivasaragavan et al. 2023). We spectroscopically confirm the presence of an associated supernova, SN2023pel, and we derive a photospheric expansion velocity of v \sim 17×103\times10^3 km s1s^{-1}. We analyze the photometric data first using empirical fits of the flux and then with full Bayesian Inference. We again strongly establish the presence of a supernova in the data, with an absolute peak r-band magnitude Mr=19.41±0.10M_r = - 19.41 \pm 0.10. We find a flux-stretching factor or relative brightness kSN=1.04±0.09k_{\rm SN}=1.04 \pm 0.09 and a time-stretching factor sSN=0.68±0.05s_{\rm SN}=0.68 \pm 0.05, both compared to SN1998bw. Therefore, GRB 230812B appears to have a clear long GRB-supernova association, as expected in the standard collapsar model. However, as sometimes found in the afterglow modelling of such long GRBs, our best fit model favours a very low density environment (log10(nISM/cm3)=2.161.30+1.21\log_{10}({n_{\rm ISM}/{\rm cm}^{-3}}) = -2.16^{+1.21}_{-1.30}). We also find small values for the jet's core angle θcore=1.700.71+1.00 deg\theta_{\rm core}={1.70^{+1.00}_{-0.71}} \ \rm{deg} and viewing angle. GRB 230812B/SN2023pel is one of the best characterized afterglows with a distinctive supernova bump

    From gut dysbiosis to altered brain function and mental illness: mechanisms and pathways

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    The human body hosts an enormous abundance and diversity of microbes, which perform a range of essential and beneficial functions. Our appreciation of the importance of these microbial communities to many aspects of human physiology has grown dramatically in recent years. We know, for example, that animals raised in a germ-free environment exhibit substantially altered immune and metabolic function, while the disruption of commensal microbiota in humans is associated with the development of a growing number of diseases. Evidence is now emerging that, through interactions with the gut-brain axis, the bidirectional communication system between the central nervous system and the gastrointestinal tract, the gut microbiome can also influence neural development, cognition and behaviour, with recent evidence that changes in behaviour alter gut microbiota composition, while modifications of the microbiome can induce depressive-like behaviours. Although an association between enteropathy and certain psychiatric conditions has long been recognized, it now appears that gut microbes represent direct mediators of psychopathology. Here, we examine roles of gut microbiome in shaping brain development and neurological function, and the mechanisms by which it can contribute to mental illness. Further, we discuss how the insight provided by this new and exciting field of research can inform care and provide a basis for the design of novel, microbiota-targeted, therapies.GB Rogers, DJ Keating, RL Young, M-L Wong, J Licinio, and S Wesseling

    High-gain Broadband Printed Yagi Antenna For Applications In ISM Bands

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    High-gain Slot Antenna on a Grooved Structure with à Frequency Selective Surface

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    International audienceThis paper presents a high-gain antenna for non-contact measurement systems around the frequency ~26GHz. The proposed antenna consists of a slot antenna on a metallic grooved structure with a single frequency selective surface. A small size and improved gain performance are the key objectives of this design. To achieve these two objectives, we use an optimization procedure based on a global algorithm. Both simulation and optimization are carried out by means of a full-wave electromagnetic simulation tool. Afterward, a prototype of the proposed antenna has been manufactured in order to verify their performances. More than 15dB of gain is obtained over the operating frequency range, with approximately 17dB at the frequency 25.5GHz. the small size and high-gain characteristics make this antenna very suitable for non-contact measurement, especially for short-range radar sensors
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