The scientific payload of the Ultraviolet Transient Astronomy Satellite (ULTRASAT)

The Ultraviolet Transient Astronomy Satellite (ULTRASAT) is a space-borne near UV telescope with an unprecedented large field of view (200 sq. deg.). The mission, led by the Weizmann Institute of Science and the Israel Space Agency in collaboration with DESY (Helmholtz association, Germany) and NASA (USA), is fully funded and expected to be launched to a geostationary transfer orbit in Q2/3 of 2025. With a grasp 300 times larger than GALEX, the most sensitive UV satellite to date, ULTRASAT will revolutionize our understanding of the hot transient universe, as well as of flaring galactic sources. We describe the mission payload, the optical design and the choice of materials allowing us to achieve a point spread function of ~10arcsec across the FoV, and the detector assembly. We detail the mitigation techniques implemented to suppress out-of-band flux and reduce stray light, detector properties including measured quantum efficiency of scout (prototype) detectors, and expected performance (limiting magnitude) for various objects.Comment: Presented in the SPIE Astronomical Telescopes + Instrumentation 202

Tr1 cell–dependent active tolerance blunts the pathogenic effects of determinant spreading

Experimental autoimmune encephalomyelitis (EAE) is a T cell–mediated autoimmune disease of the CNS. The current study shows that even in an acute episode of disease the autoimmune response spreads from one determinant on myelin basic protein (MBP) to the other linked determinant and that this spread plays a functional role in the pathogenesis of disease. The soluble form of each determinant could be used to induce Ag-specific T cell tolerance and reverse an ongoing disease. We show that the rapid effect of soluble peptide therapy is due to repolarization of autoimmune T cells undergoing activation. We suggest that at least two different types of regulatory T cells participate in the induction of active tolerance. The first, yet to be fully characterized, functions in an IL-4–dependent manner. The second produces high levels of IL-10 and low levels of IL-4 (Tr1). We bring about completing evidence showing that these Tr1 cells play a pivotal role in the regulation of T cell tolerance during determinant spread and that soluble peptide therapy with the determinant to which the autoimmune response spreads amplifies a de novo regulatory mechanism aimed to reduce the pathological consequences of determinant spreading

Mitigation of Lethal Radiation Syndrome in Mice by Intramuscular Injection of 3D Cultured Adherent Human Placental Stromal Cells.

Exposure to high lethal dose of ionizing radiation results in acute radiation syndrome with deleterious systemic effects to different organs. A primary target is the highly sensitive bone marrow and the hematopoietic system. In the current study C3H/HeN mice were total body irradiated by 7.7 Gy. Twenty four hrs and 5 days after irradiation 2×10(6) cells from different preparations of human derived 3D expanded adherent placental stromal cells (PLX) were injected intramuscularly. Treatment with batches consisting of pure maternal cell preparations (PLX-Mat) increased the survival of the irradiated mice from ∼27% to 68% (P<0.001), while cell preparations with a mixture of maternal and fetal derived cells (PLX-RAD) increased the survival to ∼98% (P<0.0001). The dose modifying factor of this treatment for both 50% and 37% survival (DMF50 and DMF37) was∼1.23. Initiation of the more effective treatment with PLX-RAD injection could be delayed for up to 48 hrs after irradiation with similar effect. A delayed treatment by 72 hrs had lower, but still significantly effect (p<0.05). A faster recovery of the BM and improved reconstitution of all blood cell lineages in the PLX-RAD treated mice during the follow-up explains the increased survival of the cells treated irradiated mice. The number of CD45+/SCA1+ hematopoietic progenitor cells within the fast recovering population of nucleated BM cells in the irradiated mice was also elevated in the PLX-RAD treated mice. Our study suggests that IM treatment with PLX-RAD cells may serve as a highly effective "off the shelf" therapy to treat BM failure following total body exposure to high doses of radiation. The results suggest that similar treatments may be beneficial also for clinical conditions associated with severe BM aplasia and pancytopenia

Human PLacental eXpanded (PLX) mesenchymal-like adherent stromal cells confer neuroprotection to nerve growth factor (NGF)-differentiated PC12 cells exposed to ischemia by secretion of IL-6 and VEGF

AbstractMesenchymal stem cells are potent candidates in stroke therapy due to their ability to secrete protective anti-inflammatory cytokines and growth factors. We investigated the neuroprotective effects of human placental mesenchymal-like adherent stromal cells (PLX) using an established ischemic model of nerve growth factor (NGF)-differentiated pheochromocytoma PC12 cells exposed to oxygen and glucose deprivation (OGD) followed by reperfusion. Under optimal conditions, 2×105 PLX cells, added in a trans-well system, conferred 30–60% neuroprotection to PC12 cells subjected to ischemic insult. PC12 cell death, measured by LDH release, was reduced by PLX cells or by conditioned medium derived from PLX cells exposed to ischemia, suggesting the active release of factorial components. Since neuroprotection is a prominent function of the cytokine IL-6 and the angiogenic factor VEGF165, we measured their secretion using selective ELISA of the cells under ischemic or normoxic conditions. IL-6 and VEGF165 secretion by co-culture of PC12 and PLX cells was significantly higher under ischemic compared to normoxic conditions. Exogenous supplementation of 10ng/ml each of IL-6 and VEGF165 to insulted PC12 cells conferred neuroprotection, reminiscent of the neuroprotective effect of PLX cells or their conditioned medium. Growth factors as well as co-culture conditioned medium effects were reduced by 70% and 20% upon pretreatment with 240ng/ml Semaxanib (anti VEGF165) and/or 400ng/ml neutralizing anti IL-6 antibody, respectively. Therefore, PLX-induced neuroprotection in ischemic PC12 cells may be partially explained by IL-6 and VEGF165 secretion. These findings may also account for the therapeutic effects seen in clinical trials after treatment with these cells

RNA binding targets aminoacyl-tRNA synthetases to translating ribosomes.

International audienceHere, we examine tRNA-aminoacyl synthetase (ARS) localization in protein synthesis. Proteomics reveals that ten of the twenty cytosolic ARSs associate with ribosomes in sucrose gradients: phenylalanyl-RS (FRS), and the 9 ARSs that form the multi-ARS complex (MSC). Using the ribopuromycylation method (RPM) for localizing intracellular translation, we show that FRS and the MSC, and to a lesser extent other ARSs, localize to translating ribosomes, most strikingly when translation is restricted to poxvirus or alphavirus factories in infected cells. Immunoproximity fluorescence indicates close proximity between MSC and the ribosome. Stress induced-translational shutdown recruits the MSC to stress-granules, a depot for mRNA and translation components. MSC binding to mRNA provides a facile explanation for its delivery to translating ribosomes and stress granules. These findings, along with the abundance of the MSC (9 × 10(6) copies per cell, roughly equimolar with ribosomes), is consistent with the idea that MSC specificity, recently reported to vary with cellular stress (Netzer, N., Goodenbour, J. M., David, A., Dittmar, K. A., Jones, R. B., Schneider, J. R., Boone, D., Eves, E. M., Rosner, M. R., Gibbs, J. S., Embry, A., Dolan, B., Das, S., Hickman, H. D., Berglund, P., Bennink, J. R., Yewdell, J. W., and Pan, T. (2009) Nature 462, 522-526) can be modulated at the level of individual mRNAs to modify decoding of specific gene products