Gaia Early Data Release 3: Structure and properties of the Magellanic Clouds

We compare the Gaia DR2 and Gaia EDR3 performances in the study of the Magellanic Clouds and show the clear improvements in precision and accuracy in the new release. We also show that the systematics still present in the data make the determination of the 3D geometry of the LMC a difficult endeavour; this is at the very limit of the usefulness of the Gaia EDR3 astrometry, but it may become feasible with the use of additional external data. We derive radial and tangential velocity maps and global profiles for the LMC for the several subsamples we defined. To our knowledge, this is the first time that the two planar components of the ordered and random motions are derived for multiple stellar evolutionary phases in a galactic disc outside the Milky Way, showing the differences between younger and older phases. We also analyse the spatial structure and motions in the central region, the bar, and the disc, providing new insights into features and kinematics. Finally, we show that the Gaia EDR3 data allows clearly resolving the Magellanic Bridge, and we trace the density and velocity flow of the stars from the SMC towards the LMC not only globally, but also separately for young and evolved populations. This allows us to confirm an evolved population in the Bridge that is slightly shift from the younger population. Additionally, we were able to study the outskirts of both Magellanic Clouds, in which we detected some well-known features and indications of new ones

The Gaia mission

Gaia is a cornerstone mission in the science programme of the EuropeanSpace Agency (ESA). The spacecraft construction was approved in 2006, following a study in which the original interferometric concept was changed to a direct-imaging approach. Both the spacecraft and the payload were built by European industry. The involvement of the scientific community focusses on data processing for which the international Gaia Data Processing and Analysis Consortium (DPAC) was selected in 2007. Gaia was launched on 19 December 2013 and arrived at its operating point, the second Lagrange point of the Sun-Earth-Moon system, a few weeks later. The commissioning of the spacecraft and payload was completed on 19 July 2014. The nominal five-year mission started with four weeks of special, ecliptic-pole scanning and subsequently transferred into full-sky scanning mode. We recall the scientific goals of Gaia and give a description of the as-built spacecraft that is currently (mid-2016) being operated to achieve these goals. We pay special attention to the payload module, the performance of which is closely related to the scientific performance of the mission. We provide a summary of the commissioning activities and findings, followed by a description of the routine operational mode. We summarise scientific performance estimates on the basis of in-orbit operations. Several intermediate Gaia data releases are planned and the data can be retrieved from the Gaia Archive, which is available through the Gaia home page. http://www.cosmos.esa.int/gai

The IgM Response to Modified LDL in Experimental Atherosclerosis Hypochlorite-modified LDL IgM Antibodies versus Classical Natural T15 IgM Antibodies

Introduction: It is hypothesized that IgM antibodies to oxidized LDL are anti-atherogenic. Myeloperoxidase from plaque-infiltrating neutrophils catalyzes the production of hypochlorite (HOCl), which oxidizes LDL. Here we study the IgM response to HOCl-modified LDL in comparison to titers of T15 clonotypic natural antibodies. Methods: Plasma of LDLR-/- mice fed a normal chow or high-fat diet was obtained after 6 and 16 weeks. The IgM responses to HOCl-modified LDL and T15 clonotypic natural IgM antibodies were measured by ELISA. Results: The IgM levels in response to HOCl-modified LDL increased dramatically in the atherosclerotic group after introduction of the high-fat diet, but not in mice on normal chow. The natural IgM T15 clonotypic antibody titers revealed a more moderate increase during atherogenesis. Conclusion: Our results show that during atherogenesis there is a strong induction of IgM antibodies to HOCl-modified LDL particles. Whether these induced IgM antibodies are pro- or anti-atherogenic remains to be established

Accumulation of myeloperoxidase-positive neutrophils in atherosclerotic lesions in LDLR-/- mice

Objective-Atherosclerosis is a chronic inflammatory disease in which the immune system plays an important role. Neutrophils have not been thoroughly studied in the context of atherogenesis. Here, we investigated neutrophils in the development of murine atherosclerotic lesions. Methods and Results-LDLR-/- mice were given a high-fat diet for different time periods and subsequently atherosclerotic lesions were studied by immunohistochemistry. Staining with anti-Ly-6G monoclonal antibody, a specific marker for neutrophils, revealed a marked accumulation of neutrophils during atherosclerosis development. Neutrophils were observed in the lesion, attached to the cap, and in the arterial adventitia. In addition, at some sites, neutrophil accumulation colocalized with endothelial E-selectin expression. Immunofluorescence double staining with anti-myeloperoxidase and anti-Ly-6G antibodies demonstrated the presence of myeloperoxidase in atherosclerotic lesions and its colocalization with neutrophils. After introducing the high-fat diet, levels of circulating myeloperoxidase in plasma strongly increased, with a peak at 6 weeks and a subsequent decrease to almost normal levels after 16 weeks of diet. Conclusions-We here demonstrate for the first time the presence of neutrophils and myeloperoxidase in murine atherosclerotic lesions. As a major cell type in inflammatory responses the neutrophil may also be an important mediator in the development of atherosclerosis

Passive Immunization with Hypochlorite-oxLDL Specific Antibodies Reduces Plaque Volume in LDL Receptor-Deficient Mice

<p>Aims: New strategies to overcome complications of cardiovascular diseases are needed. Since it has been demonstrated that atherosclerosis is an inflammatory disease, modulation of the immune system may be a promising approach. Previously, it was suggested that antibodies may confer protective effects on the development of atherosclerosis. In this study, we hypothesised that passive immunization with anti-oxLDL IgM antibodies specific for hypochlorite (HOCl) may be athero-protective in mice.</p><p>Methods and Results: Monoclonal mouse IgM antibodies were produced and the antibody with specificity for hypochlorite-oxLDL (HOCl-oxLDL) (Moab A7S8) was selected. VH sequence determination revealed that Moab A7S8 is a natural IgM antibody. Atherosclerosis in LDLr-/- mice was induced by a perivascular collar placement around the right carotid artery in combination with feeding a high-fat diet. Subsequently, the mice were treated every six days with 500 mu g Moab A7S8, non-relevant IgM or with PBS and the carotid arteries and aortic roots were studied for atherosclerosis. Passive immunization with this Moab A7S8 resulted in a significant reduced plaque volume formation in LDLr-/- mice when compared with PBS treatment (P = 0.002 and P = 0.035). Cholesterol levels decreased by 20% when mice were treated with Moab A7S8 compared to PBS. Furthermore, anti-oxLDL specific IgM and IgG antibody production increased significantly in the Moab A7S8 treated mice in comparison with PBS treated mice.</p><p>Conclusion: Our data show that passive immunization with a natural IgM antibody, directed to HOCl-oxLDL, can reduce atherosclerotic plaque development. We postulate that specific antibody therapy may be developed for use in human cardiovascular diseases.</p>

Cu-anti-oxLDL IgM titers, T15/EO6 IgM antibodies and IgM-apoB immune complexes.

<p>A. Anti-Cu-oxLDL IgM titers, B. T15/EO6 IgM antibodies and C. IgM-apoB immune complexes expressed as IgM/apoB. Mice treated with PBS (▪), control IgM treated mice (o) and in mice treated with Moab A7S8 (□).</p

Cholesterol levels.

<p>Serum cholesterol levels are expressed as mM (± SEM). Closed bars: PBS treated mice. Grey bars: control IgM treated mice. Open bars: Moab A7S8 treated mice.</p

IgM Monoclonal antibody (Moab A7S8).

<p>A. Reactivity to native, HOCL-oxLDL and MDA-oxLDL. Measured by ELISA, OD 405 at different concentrations (100, 50, 25, 10 and 1 µg/ml IgM concentration). B. Sequence IgM hybridoma. The sequence of Moab A7S8 was compared with germline VH genes by using the international ImMunoGeneTics information system/−QUEry and Standardization (IMGT/V-Quest). Moab A7S8 is composed of IgHV1–78*01, IGHJ3*01 and IGHD1-1*02 alleles, with 100% identity and no gaps. Except for the N-addition, the alleles are in frame germline sequences.</p

Schematic representation of the collar model and the experimental design.

<p>A. Atherosclerotic lesions develop caudal to the collar, cross-sections were made of the common right carotid artery in a caudal direction from the collar and collected in a parallel series of slides, B. Time schedule of the experiment to study the effect of passive immunization using Moab A7S8 or PBS on atherosclerotic plaque development.</p