Gaia Data Release 3 Creevey, O. L.; Sordo, R.; Pailler, F. ...
Astronomy and astrophysics (Berlin),
06/2023, Volume:
674
Journal Article
Peer reviewed
Open access
Gaia
Data Release 3 contains a wealth of new data products for the community. Astrophysical parameters are a major component of this release, and were produced by the Astrophysical parameters ...inference system (Apsis) within the
Gaia
Data Processing and Analysis Consortium (DPAC). The aim of this paper is to describe the overall content of the astrophysical parameters in
Gaia
DR3 and how they were produced. In Apsis, we use the mean BP/RP and mean RVS spectra along with astrometry and photometry, and we derive the following parameters: source classification and probabilities for 1.6 billion objects; interstellar medium characterisation and distances for up to 470 million sources, including a 2D total Galactic extinction map; 6 million redshifts of quasar candidates; 1.4 million redshifts of galaxy candidates; and an analysis of 50 million outlier sources through an unsupervised classification. The astrophysical parameters also include many stellar spectroscopic and evolutionary parameters for up to 470 million sources. These comprise
T
eff
, log
g
, and M/H (470 million using BP/RP, 6 million using RVS), radius (470 million), mass (140 million), age (120 million), chemical abundances (up to 5 million), diffuse interstellar band analysis (0.5 million), activity indices (2 million), H
α
equivalent widths (200 million), and further classification of spectral types (220 million) and emission-line stars (50 000). This paper is the first in a series of three papers, and focusses on describing the global content of the parameters in
Gaia
DR3. The accompanying Papers II and III focus on the validation and use of the stellar and non-stellar products, respectively. This catalogue is the most extensive homogeneous database of astrophysical parameters to date, and is based uniquely on
Gaia
data. It will only be superseded by
Gaia
Data Release 4, and will therefore remain a key reference over the next four years, providing astrophysical parameters independent of other ground- and space-based data.
Gaia Data Release 3 contains a wealth of new data products for the community. Astrophysical parameters are a major component of this release. They were produced by the Astrophysical parameters ...inference system (Apsis) within the Gaia Data Processing and Analysis Consortium. The aim of this paper is to describe the overall content of the astrophysical parameters in Gaia Data Release 3 and how they were produced. In Apsis we use the mean BP/RP and mean RVS spectra along with astrometry and photometry, and we derive the following parameters: source classification and probabilities for 1.6 billion objects, interstellar medium characterisation and distances for up to 470 million sources, including a 2D total Galactic extinction map, 6 million redshifts of quasar candidates and 1.4 million redshifts of galaxy candidates, along with an analysis of 50 million outlier sources through an unsupervised classification. The astrophysical parameters also include many stellar spectroscopic and evolutionary parameters for up to 470 million sources. These comprise Teff, logg, and m_h (470 million using BP/RP, 6 million using RVS), radius (470 million), mass (140 million), age (120 million), chemical abundances (up to 5 million), diffuse interstellar band analysis (0.5 million), activity indices (2 million), H-alpha equivalent widths (200 million), and further classification of spectral types (220 million) and emission-line stars (50 thousand). This catalogue is the most extensive homogeneous database of astrophysical parameters to date, and it is based uniquely on Gaia data.
The chemo-physical parametrisation of stellar spectra is essential for understanding the nature and evolution of stars and of Galactic stellar populations. Gaia DR3 contains the parametrisation of ...RVS data performed by the General Stellar Parametriser-spectroscopy, module. Here we describe the parametrisation of the first 34 months of RVS observations. GSP-spec estimates the chemo-physical parameters from combined RVS spectra of single stars. The main analysis workflow described here, MatisseGauguin, is based on projection and optimisation methods and provides the stellar atmospheric parameters; the individual chemical abundances of N, Mg, Si, S, Ca, Ti, Cr, FeI, FeII, Ni, Zr, Ce and Nd; the differential equivalent width of a cyanogen line; and the parameters of a DIB feature. Another workflow, based on an artificial neural network, provides a second set of atmospheric parameters that are useful for classification control. We implement a detailed quality flag chain considering different error sources. With about 5.6 million stars, the Gaia DR3 GSP-spec all-sky catalogue is the largest compilation of stellar chemo-physical parameters ever published and the first one from space data. Internal and external biases have been studied taking into account the implemented flags. In some cases, simple calibrations with low degree polynomials are suggested. The homogeneity and quality of the estimated parameters enables chemo-dynamical studies of Galactic stellar populations, interstellar extinction studies from individual spectra, and clear constraints on stellar evolution models. We highly recommend that users adopt the provided quality flags for scientific exploitation . The Gaia DR3 GSP-spec catalogue is a major step in the scientific exploration of Milky Way stellar populations, confirming the Gaia promise of a new Galactic vision (abridged).
Nonalcoholic fatty liver disease (NAFLD) is linked to obesity and diabetes, suggesting an important role of adipose tissue in the pathogenesis of NAFLD. Here, we aimed to investigate the interaction ...between adipose tissue and liver in NAFLD and identify potential early plasma markers that predict nonalcoholic steatohepatitis (NASH).
C57Bl/6 mice were chronically fed a high-fat diet to induce NAFLD and compared with mice fed a low-fat diet. Extensive histological and phenotypical analyses coupled with a time course study of plasma proteins using multiplex assay were performed.
Mice exhibited pronounced heterogeneity in liver histological scoring, leading to classification into four subgroups: low-fat low (LFL) responders displaying normal liver morphology, low-fat high (LFH) responders showing benign hepatic steatosis, high-fat low (HFL) responders displaying pre-NASH with macrovesicular lipid droplets, and high fat high (HFH) responders exhibiting overt NASH characterized by ballooning of hepatocytes, presence of Mallory bodies, and activated inflammatory cells. Compared with HFL responders, HFH mice gained weight more rapidly and exhibited adipose tissue dysfunction characterized by decreased final fat mass, enhanced macrophage infiltration and inflammation, and adipose tissue remodeling. Plasma haptoglobin, IL-1β, TIMP-1, adiponectin, and leptin were significantly changed in HFH mice. Multivariate analysis indicated that in addition to leptin, plasma CRP, haptoglobin, eotaxin, and MIP-1α early in the intervention were positively associated with liver triglycerides. Intermediate prognostic markers of liver triglycerides included IL-18, IL-1β, MIP-1γ, and MIP-2, whereas insulin, TIMP-1, granulocyte chemotactic protein 2, and myeloperoxidase emerged as late markers.
Our data support the existence of a tight relationship between adipose tissue dysfunction and NASH pathogenesis and point to several novel potential predictive biomarkers for NASH.
The objective of this work was to assess the consequences of repeated intra-articular injection of monosodium urate (MSU) crystals with inflammasome priming by lipopolysaccharide (LPS) in order to ...simulate recurrent bouts of gout in rats. Translational imaging was applied to simultaneously detect and quantify injury in different areas of the knee joint. MSU/LPS induced joint swelling, synovial membrane thickening, fibrosis of the infrapatellar fat pad, tidemark breaching, and cartilage invasion by inflammatory cells. A higher sensitivity to mechanical stimulus was detected in paws of limbs receiving MSU/LPS compared to saline-injected limbs. In MSU/LPS-challenged joints, magnetic resonance imaging (MRI) revealed increased synovial fluid volume in the posterior region of the joint, alterations in the infrapatellar fat pad reflecting a progressive decrease of fat volume and fibrosis formation, and a significant increase in the relaxation time T
in femoral cartilage, consistent with a reduction of proteoglycan content. MRI also showed cyst formation in the tibia, femur remodeling, and T
reductions in extensor muscles consistent with fibrosis development. Repeated intra-articular MSU/LPS injections in the rat knee joint induced pathology in multiple tissues and may be a useful means to investigate the relationship between urate crystal deposition and the development of degenerative joint disease.
A key to enhance the low translatability of preclinical drug discovery are in vitro human three-dimensional (3D) microphysiological systems (MPS). Here, we show a new method for automated engineering ...of 3D human skeletal muscle models in microplates and functional compound screening to address the lack of muscle wasting disease medication. To this end, we adapted our recently described 24-well plate 3D bioprinting platform with a printhead cooling system to allow microvalve-based drop-on-demand printing of cell-laden Matrigel containing primary human muscle precursor cells. Mini skeletal muscle models develop within a week exhibiting contractile, striated myofibers aligned between two attachment posts. As an in vitro exercise model, repeated high impact stimulation of contractions for 3 h by a custom-made electrical pulse stimulation (EPS) system for 24-well plates induced interleukin-6 myokine expression and Akt hypertrophy pathway activation. Furthermore, the known muscle stimulators caffeine and Tirasemtiv acutely increase EPS-induced contractile force of the models. This validated new human muscle MPS will benefit development of drugs against muscle wasting diseases. Moreover, our Matrigel 3D bioprinting platform will allow engineering of non-self-organizing complex human 3D MPS.
Assessment of myelin integrity in peripheral nerve injuries and pathologies has largely been limited to post-mortem analysis owing to the difficulty in obtaining biopsies without affecting nerve ...function. This is further encumbered by the small size of the tissue and its location. Therefore, the development of robust, non-invasive methods is highly attractive. In this study, we used magnetic resonance imaging (MRI) techniques, including magnetization transfer ratio (MTR), to longitudinally and non-invasively characterize both the sciatic nerve crush and lysolecithin (LCP) demyelination models of peripheral nerve injury in rodents. Electrophysiological, gene expression and histological assessments complemented the extensive MRI analyses in young and aged animals. In the nerve crush model, MTR analysis indicated a slower recovery in regions distal to the site of injury in aged animals, as well as incomplete recovery at six weeks post-crush when analyzing across the entire nerve surface. Similar regional impairments were also found in the LCP demyelination model. This research underlines the power of MTR for the study of peripheral nerve injury in small tissues such as the sciatic nerve of rodents and contributes new knowledge to the effect of aging on recovery after injury. A particular advantage of the approach is the translational potential to human neuropathies.
Musculoskeletal diseases are a leading contributor to mobility disability worldwide. Since the majority of patients with musculoskeletal diseases present with associated muscle weakness, treatment ...approaches typically comprise an element of resistance training to restore physical strength. The health-promoting effects of resistance exercise are mediated
via
complex, multifarious mechanisms including modulation of systemic and local inflammation. Here we investigated whether targeted inhibition of the chemerin pathway, which largely controls inflammatory processes
via
chemokine-like receptor 1 (CMKLR1), can improve skeletal muscle function. Using genetically modified mice, we demonstrate that blockade of CMKLR1 transiently increases maximal strength during growth, but lastingly decreases strength endurance. In-depth analyses of the underlying long-term adaptations revealed microscopic alterations in the number of Pax7-positive satellite cells, as well as molecular changes in genes governing myogenesis and calcium handling. Taken together, these data provide evidence of a critical role for CMKLR1 in regulating skeletal muscle function by modulating the regenerative and contractile properties of muscle tissue. CMKLR1 antagonists are increasingly viewed as therapeutic modalities for a variety of diseases (e.g., psoriasis, metabolic disorders, and multiple sclerosis). Our findings thus have implications for the development of novel drug substances that aim at targeting the chemerin pathway for musculoskeletal or other diseases.
The 3Rs principles-reduction, refinement, replacement-are at the core of preclinical research within drug discovery, which still relies to a great extent on the availability of models of disease in ...animals. Minimizing their distress, reducing their number as well as searching for means to replace them in experimental studies are constant objectives in this area. Due to its non-invasive character
imaging supports these efforts by enabling repeated longitudinal assessments in each animal which serves as its own control, thereby enabling to reduce considerably the animal utilization in the experiments. The repetitive monitoring of pathology progression and the effects of therapy becomes feasible by assessment of quantitative biomarkers. Moreover, imaging has translational prospects by facilitating the comparison of studies performed in small rodents and humans. Also, learnings from the clinic may be potentially back-translated to preclinical settings and therefore contribute to refining animal investigations. By concentrating on activities around the application of magnetic resonance imaging (MRI) and ultrasound elastography to small rodent models of disease, we aim to illustrate how
imaging contributes primarily to reduction and refinement in the context of pharmacological research.
Multiple sclerosis (MS) is a chronic inflammatory disease affecting the central nervous system (CNS). While multiple effective immunomodulatory therapies for MS exist today, they lack the scope of ...promoting CNS repair, in particular remyelination. Microglia play a pivotal role in regulating myelination processes, and the colony-stimulating factor 1 (CSF-1) pathway is a key regulator for microglia differentiation and survival. Here, we investigated the effects of the CSF-1 receptor kinase inhibitor, BLZ945, on central myelination processes in the 5-week murine cuprizone model by non-invasive and longitudinal magnetic resonance imaging (MRI) and histology. Therapeutic 2-week BLZ945 treatment caused a brain region-specific enhancement of remyelination in the striatum/cortex, which was absent in the corpus callosum/external capsule. This beneficial effect correlated positively with microglia reduction, increased oligodendrocytes and astrogliosis. Prophylactic BLZ945 treatment prevented excessive demyelination in the corpus callosum by reducing microglia and increasing oligondendrocytes. In the external capsule oligodendrocytes were depleted but not microglia and a buildup of myelin debris and axonal damage was observed. A similar microglial dysfunction in the external capsule with an increase of myelin debris was obvious in triggering receptor expressed on myeloid cells 2 (TREM2) knock-out mice treated with cuprizone. Finally, therapeutic BLZ945 treatment did not change the disease course in experimental autoimmune encephalomyelitis mice, a peripherally driven neuroinflammation model. Taken together, our data suggest that a short-term therapeutic inhibition of the CSF-1 receptor pathway by BLZ945 in the murine cuprizone model enhances central remyelination by modulating neuroinflammation. Thus, microglia-modulating therapies could be considered clinically for promoting myelination in combination with standard-of-care treatments in MS patients.
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