Event-horizon-scale structure in the supermassive black hole candidate at the Galactic Centre

The cores of most galaxies are thought to harbour supermassive black holes, which power galactic nuclei by converting the gravitational energy of accreting matter into radiation (ref 1). Sagittarius A*, the compact source of radio, infrared and X-ray emission at the centre of the Milky Way, is the closest example of this phenomenon, with an estimated black hole mass that is 4 million times that of the Sun (refs. 2,3). A long-standing astronomical goal is to resolve structures in the innermost accretion flow surrounding Sgr A* where strong gravitational fields will distort the appearance of radiation emitted near the black hole. Radio observations at wavelengths of 3.5 mm and 7 mm have detected intrinsic structure in Sgr A*, but the spatial resolution of observations at these wavelengths is limited by interstellar scattering (refs. 4-7). Here we report observations at a wavelength of 1.3 mm that set a size of 37 (+16, -10; 3-sigma) microarcseconds on the intrinsic diameter of Sgr A*. This is less than the expected apparent size of the event horizon of the presumed black hole, suggesting that the bulk of SgrA* emission may not be not centred on the black hole, but arises in the surrounding accretion flow.Comment: 12 pages including 2 figure

A Random Walk through Star and Planet Formation

This thesis explores selected questions in several active areas of research in star and planet formation. Chapter 2 constrains the star formation history and initial mass function of the old stellar population in the Galactic Center nuclear star cluster. Preliminary results suggest an initial mass function for this region that differs significantly from the standard mass function observed in other parts of the Galaxy. Chapter 3 derives stellar and planetary properties for an extraordinary planetary system that surrounds an unusually low-mass star and includes the closest, smallest, and least massive planet known to date. The data presented in this chapter were valuable in enabling a follow-up transit detection of this planet that placed strong constraints on its internal structure and composition. Chapters 4 and 5 analyze observations of extrasolar debris disks in an effort to infer global characteristics of the underlying planetary systems, including the location and properties of planetesimals and planets. Specifically, Chapter 4 presents multi-wavelength imaging observations of a debris disk that potentially point to the existence of an unseen exoplanet. In contrast, Chapter 5 considers substructure in a different debris disk that is unlikely to be gravitational in origin. The results suggest that debris disk interactions with the interstellar medium may create asymmetries that mimic the presence of an exoplanet at short, scattered-light wavelengths

CD8+ T Cell Recognition of Cryptic Epitopes Is a Ubiquitous Feature of AIDS Virus Infection▿ †

Vaccines designed to elicit AIDS virus-specific CD8+ T cells should engender broad responses. Emerging data indicate that alternate reading frames (ARFs) of both human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) encode CD8+ T cell epitopes, termed cryptic epitopes. Here, we show that SIV-specific CD8+ T cells from SIV-infected rhesus macaques target 14 epitopes in eight ARFs during SIV infection. Animals recognized up to five epitopes, totaling nearly one-quarter of the anti-SIV responses. The epitopes were targeted by high-frequency responses as early as 2 weeks postinfection and in the chronic phase. Hence, previously overlooked ARF-encoded epitopes could be important components of AIDS vaccines

A novel L1CAM isoform with angiogenic activity generated by NOVA2-mediated alternative splicing

The biological players involved in angiogenesis are only partially defined. Here, we report that endothelial cells (ECs) express a novel isoform of the cell-surface adhesion molecule L1CAM, termed L1-ΔTM. The splicing factor NOVA2, which binds directly to L1CAM pre-mRNA, is necessary and sufficient for the skipping of L1CAM transmembrane domain in ECs, leading to the release of soluble L1-ΔTM. The latter exerts high angiogenic function through both autocrine and paracrine activities. Mechanistically, L1-ΔTM-induced angiogenesis requires fibroblast growth factor receptor-1 signaling, implying a crosstalk between the two molecules. NOVA2 and L1-ΔTM are overexpressed in the vasculature of ovarian cancer, where L1-ΔTM levels correlate with tumor vascularization, supporting the involvement of NOVA2-mediated L1-ΔTM production in tumor angiogenesis. Finally, high NOVA2 expression is associated with poor outcome in ovarian cancer patients. Our results point to L1-ΔTM as a novel, EC-derived angiogenic factor which may represent a target for innovative antiangiogenic therapies.This work was supported by grants from the Associazione Italiana per la Ricerca sul Cancro (AIRC, projects IG-17395 to CG, IG-14622 to UC, IG-18683 to ED and IG-18853 to RG, IG-19919 to DG), Worldwide Cancer Research (formerly known as Association for International Cancer Research; AICR 10–0091 to UC), the European Research Council (ERC) under the European Union's Horizon 2020 program (ERC-StG-LS2-637591 to MI) and the Spanish Ministerio de Economía y Competitividad (BFU2017-89201-P to MI). EB, FA and ADM were supported by AIRC - FIRC ITALY postdoctoral fellowships. MG was supported by a fellowship from Fondazione IEO-CCM. Research in FF laboratory is supported by The Giovanni Armenise-Harvard Foundation, and by the Italian Ministry for Education, University and Research (MIUR): Programma Giovani Ricercatori "Rita Levi-Montalcini" and Dipartimenti di Eccellenza Program (2018–2022) - Dept. of Biology and Biotechnology "L. Spallanzani", University of Pavia. AC is supported by a Marie Curie Individual Fellowship from the Horizon 2020 EU Program (Grant agreement n. 745934 – COTETHERS)