First Constraints from DAMIC-M on Sub-GeV Dark-Matter Particles Interacting with Electrons

We report constraints on sub-GeV dark matter particles interacting with electrons from the first underground operation of DAMIC-M detectors. The search is performed with an integrated exposure of 85.23 g days, and exploits the subelectron charge resolution and low level of dark current of DAMIC-M charge-coupled devices (CCDs). Dark-matter-induced ionization signals above the detector dark current are searched for in CCD pixels with charge up to 7e−. With this dataset we place limits on dark matter particles of mass between 0.53 and 1000  MeV/c2, excluding unexplored regions of parameter space in the mass ranges [1.6,1000]  MeV/c2 and [1.5,15.1]  MeV/c2 for ultralight and heavy mediator interactions, respectively

Search for daily modulation of MeV dark matter signals with DAMIC-M

Dark matter (DM) particles with sufficiently large cross sections may scatter as they travel through Earth’s bulk. The corresponding changes in the DM flux give rise to a characteristic daily modulation signal in detectors sensitive to DM-electron interactions. Here, we report results obtained from the first underground operation of the DAMIC-M prototype detector searching for such a signal from DM with MeV-scale mass. A model-independent analysis finds no modulation in the rate of 1 e− events with sidereal period, where a DM signal would appear. We then use these data to place exclusion limits on DM in the mass range ½0.53; 2.7 MeV=c2 interacting with electrons via a dark photon mediator. Taking advantage of the time-dependent signal we improve by ∼2 orders of magnitude on our previous limit obtained from the total rate of 1 e− events, using the same dataset. This daily modulation search represents the current strongest limit on DM-electron scattering via ultralight mediators for DM masses around 1 MeV=c².I. F. C. A. was supported by Project No. PID2019–109829 GB-I00 funded by MCIN/AEI/10.13039/501100011033. B. J. K. acknowledges funding from the Ramón y Cajal Grant No. RYC2021-034757-I, financed by MCIN/AEI/10.13039/501100011033 and by the European Union “NextGenerationEU”/PRTR

The Cherenkov Telescope Array Large Size Telescope

The two arrays of the Very High Energy gamma-ray observatory Cherenkov Telescope Array (CTA) will include four Large Size Telescopes (LSTs) each with a 23 m diameter dish and 28 m focal distance. These telescopes will enable CTA to achieve a low-energy threshold of 20 GeV, which is critical for important studies in astrophysics, astroparticle physics and cosmology. This work presents the key specifications and performance of the current LST design in the light of the CTA scientific objectives.Comment: 4 pages, 5 figures, In Proceedings of the 33rd International Cosmic Ray Conference (ICRC2013), Rio de Janeiro (Brazil). All CTA contributions at arXiv:1307.223

Humans Lack iGb3 Due to the Absence of Functional iGb3-Synthase: Implications for NKT Cell Development and Transplantation

The glycosphingolipid isoglobotrihexosylceramide, or isogloboside 3 (iGb3), is believed to be critical for natural killer T (NKT) cell development and self-recognition in mice and humans. Furthermore, iGb3 may represent an important obstacle in xenotransplantation, in which this lipid represents the only other form of the major xenoepitope Galα(1,3)Gal. The role of iGb3 in NKT cell development is controversial, particularly with one study that suggested that NKT cell development is normal in mice that were rendered deficient for the enzyme iGb3 synthase (iGb3S). We demonstrate that spliced iGb3S mRNA was not detected after extensive analysis of human tissues, and furthermore, the iGb3S gene contains several mutations that render this product nonfunctional. We directly tested the potential functional activity of human iGb3S by expressing chimeric molecules containing the catalytic domain of human iGb3S. These hybrid molecules were unable to synthesize iGb3, due to at least one amino acid substitution. We also demonstrate that purified normal human anti-Gal immunoglobulin G can bind iGb3 lipid and mediate complement lysis of transfected human cells expressing iGb3. Collectively, our data suggest that iGb3S is not expressed in humans, and even if it were expressed, this enzyme would be inactive. Consequently, iGb3 is unlikely to represent a primary natural ligand for NKT cells in humans. Furthermore, the absence of iGb3 in humans implies that it is another source of foreign Galα(1,3)Gal xenoantigen, with obvious significance in the field of xenotransplantation

The Liganding of Glycolipid Transfer Protein Is Controlled by Glycolipid Acyl Structure

Glycosphingolipids (GSLs) play major roles in cellular growth and development. Mammalian glycolipid transfer proteins (GLTPs) are potential regulators of cell processes mediated by GSLs and display a unique architecture among lipid binding/transfer proteins. The GLTP fold represents a novel membrane targeting/interaction domain among peripheral proteins. Here we report crystal structures of human GLTP bound to GSLs of diverse acyl chain length, unsaturation, and sugar composition. Structural comparisons show a highly conserved anchoring of galactosyl- and lactosyl-amide headgroups by the GLTP recognition center. By contrast, acyl chain chemical structure and occupancy of the hydrophobic tunnel dictate partitioning between sphingosine-in and newly-observed sphingosine-out ligand-binding modes. The structural insights, combined with computed interaction propensity distributions, suggest a concerted sequence of events mediated by GLTP conformational changes during GSL transfer to and/or from membranes, as well as during GSL presentation and/or transfer to other proteins

Structure of a Classical MHC Class I Molecule That Binds “Non-Classical” Ligands

The chicken MHC YF1*7.1 X-ray structures reveal that this protein binds lipids and thus represents a "hybrid" class I complex with features of classical as well as non-classical MHC molecules

Search for Daily Modulation of MeV Dark Matter Signals with DAMIC-M

Dark Matter (DM) particles with sufficiently large cross sections may scatter as they travel through Earth's bulk. The corresponding changes in the DM flux give rise to a characteristic daily modulation signal in detectors sensitive to DM-electron interactions. Here, we report results obtained from the first underground operation of the DAMIC-M prototype detector searching for such a signal from DM with MeV-scale mass. A model-independent analysis finds no modulation in the rate of 1$e^-$ events with periods in the range 1-48 h. We then use these data to place exclusion limits on DM in the mass range [0.53, 2.7] MeV/c$^2$ interacting with electrons via a dark photon mediator. Taking advantage of the time-dependent signal we improve by $\sim$2 orders of magnitude on our previous limit obtained from the total rate of 1$e^-$ events, using the same data set. This daily modulation search represents the current strongest limit on DM-electron scattering via ultralight mediators for DM masses around 1 MeV/c$^2$

Linking Inflammation to Natural Killer T Cell Activation

Immune activation is often associated with inflammation, but inflammation's role in the expansion of antigen-specific immune responses remains unclear. This primer focuses on recent findings that show how specific natural killer T cells are activated by inflammatory messengers, thus illuminating the cellular and molecular links between immunity and inflammation

DOCK8 deficiency impairs CD8 T cell survival and function in humans and mice

As shown by analysis of mice and humans bearing DOCK8-inactivating mutations, DOCK8 plays a cell-autonomous role in survival of naive CD8 T cells, LFA-1 polarization toward the immune synapse, and CD8 T cell memory and recall responses following viral infection

EBV Promotes Human CD8+ NKT Cell Development

The reports on the origin of human CD8+ Vα24+ T-cell receptor (TCR) natural killer T (NKT) cells are controversial. The underlying mechanism that controls human CD4 versus CD8 NKT cell development is not well-characterized. In the present study, we have studied total 177 eligible patients and subjects including 128 healthy latent Epstein-Barr-virus(EBV)-infected subjects, 17 newly-onset acute infectious mononucleosis patients, 16 newly-diagnosed EBV-associated Hodgkin lymphoma patients, and 16 EBV-negative normal control subjects. We have established human-thymus/liver-SCID chimera, reaggregated thymic organ culture, and fetal thymic organ culture. We here show that the average frequency of total and CD8+ NKT cells in PBMCs from 128 healthy latent EBV-infected subjects is significantly higher than in 17 acute EBV infectious mononucleosis patients, 16 EBV-associated Hodgkin lymphoma patients, and 16 EBV-negative normal control subjects. However, the frequency of total and CD8+ NKT cells is remarkably increased in the acute EBV infectious mononucleosis patients at year 1 post-onset. EBV-challenge promotes CD8+ NKT cell development in the thymus of human-thymus/liver-SCID chimeras. The frequency of total (3% of thymic cells) and CD8+ NKT cells (∼25% of NKT cells) is significantly increased in EBV-challenged chimeras, compared to those in the unchallenged chimeras (<0.01% of thymic cells, CD8+ NKT cells undetectable, respectively). The EBV-induced increase in thymic NKT cells is also reflected in the periphery, where there is an increase in total and CD8+ NKT cells in liver and peripheral blood in EBV-challenged chimeras. EBV-induced thymic CD8+ NKT cells display an activated memory phenotype (CD69+CD45ROhiCD161+CD62Llo). After EBV-challenge, a proportion of NKT precursors diverges from DP thymocytes, develops and differentiates into mature CD8+ NKT cells in thymus in EBV-challenged human-thymus/liver-SCID chimeras or reaggregated thymic organ cultures. Thymic antigen-presenting EBV-infected dendritic cells are required for this process. IL-7, produced mainly by thymic dendritic cells, is a major and essential factor for CD8+ NKT cell differentiation in EBV-challenged human-thymus/liver-SCID chimeras and fetal thymic organ cultures. Additionally, these EBV-induced CD8+ NKT cells produce remarkably more perforin than that in counterpart CD4+ NKT cells, and predominately express CD8αα homodimer in their co-receptor. Thus, upon interaction with certain viruses, CD8 lineage-specific NKT cells are developed, differentiated and matured intrathymically, a finding with potential therapeutic importance against viral infections and tumors