103 research outputs found

    A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)

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    Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)1.

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    In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field

    Search for strongly interacting massive particles generating trackless jets in proton-proton collisions at s = 13 TeV

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    A search for dark matter in the form of strongly interacting massive particles (SIMPs) using the CMS detector at the LHC is presented. The SIMPs would be produced in pairs that manifest themselves as pairs of jets without tracks. The energy fraction of jets carried by charged particles is used as a key discriminator to suppress efficiently the large multijet background, and the remaining background is estimated directly from data. The search is performed using proton-proton collision data corresponding to an integrated luminosity of 16.1 fb - 1 , collected with the CMS detector in 2016. No significant excess of events is observed above the expected background. For the simplified dark matter model under consideration, SIMPs with masses up to 100 GeV are excluded and further sensitivity is explored towards higher masses

    Neuronal hyperactivity disturbs ATP microgradients, impairs microglial motility, and reduces phagocytic receptor expression triggering apoptosis/microglial phagocytosis uncoupling

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    Phagocytosis is essential to maintain tissue homeostasis in a large number of inflammatory and autoimmune diseases, but its role in the diseased brain is poorly explored. Recent findings suggest that in the adult hippocampal neurogenic niche, where the excess of newborn cells undergo apoptosis in physiological conditions, phagocytosis is efficiently executed by surveillant, ramified microglia. To test whether microglia are efficient phagocytes in the diseased brain as well, we confronted them with a series of apoptotic challenges and discovered a generalized response. When challenged with excitotoxicity in vitro (via the glutamate agonist NMDA) or inflammation in vivo (via systemic administration of bacterial lipopolysaccharides or by omega 3 fatty acid deficient diets), microglia resorted to different strategies to boost their phagocytic efficiency and compensate for the increased number of apoptotic cells, thus maintaining phagocytosis and apoptosis tightly coupled. Unexpectedly, this coupling was chronically lost in a mouse model of mesial temporal lobe epilepsy (MTLE) as well as in hippocampal tissue resected from individuals with MTLE, a major neurological disorder characterized by seizures, excitotoxicity, and inflammation. Importantly, the loss of phagocytosis/apoptosis coupling correlated with the expression of microglial proinflammatory, epileptogenic cytokines, suggesting its contribution to the pathophysiology of epilepsy. The phagocytic blockade resulted from reduced microglial surveillance and apoptotic cell recognition receptor expression and was not directly mediated by signaling through microglial glutamate receptors. Instead, it was related to the disruption of local ATP microgradients caused by the hyperactivity of the hippocampal network, at least in the acute phase of epilepsy. Finally, the uncoupling led to an accumulation of apoptotic newborn cells in the neurogenic niche that was due not to decreased survival but to delayed cell clearance after seizures. These results demonstrate that the efficiency of microglial phagocytosis critically affects the dynamics of apoptosis and urge to routinely assess the microglial phagocytic efficiency in neurodegenerative disorders

    Gaia Data Release 3 The extragalactic content⋆

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    The Gaia Galactic survey mission is designed and optimized to obtain astrometry, photometry, and spectroscopy of nearly two billion stars in our Galaxy. Yet as an all-sky multi-epoch survey, Gaia also observes several million extragalactic objects down to a magnitude of G ∌ 21 mag. Due to the nature of the Gaia onboard-selection algorithms, these are mostly point-source-like objects. Using data provided by the satellite, we have identified quasar and galaxy candidates via supervised machine learning methods, and estimate their redshifts using the low resolution BP/RP spectra. We further characterise the surface brightness profiles of host galaxies of quasars and of galaxies from pre-defined input lists. Here we give an overview of the processing of extragalactic objects, describe the data products in Gaia DR3, and analyse their properties. Two integrated tables contain the main results for a high completeness, but low purity (50−70%), set of 6.6 million candidate quasars and 4.8 million candidate galaxies. We provide queries that select purer sub-samples of these containing 1.9 million probable quasars and 2.9 million probable galaxies (both ∌95% purity). We also use high quality BP/RP spectra of 43 thousand high probability quasars over the redshift range 0.05−4.36 to construct a composite quasar spectrum spanning restframe wavelengths from 72−1000 nm

    Gaia Data Release 3: Chemical cartography of the Milky Way

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    Context. The motion of stars has been used to reveal details of the complex history of the Milky Way, in constant interaction with its environment. Nevertheless, to reconstruct the Galactic history puzzle in its entirety, the chemo-physical characterisation of stars is essential. Previous Gaia data releases were supported by a smaller, heterogeneous, and spatially biased mixture of chemical data from ground-based observations. Aims. Gaia Data Release 3 opens a new era of all-sky spectral analysis of stellar populations thanks to the nearly 5.6 million stars observed by the Radial Velocity Spectrometer (RVS) and parametrised by the GSP-Spec module. In this work, we aim to demonstrate the scientific quality of Gaia’s Milky Way chemical cartography through a chemo-dynamical analysis of disc and halo populations. Methods. Stellar atmospheric parameters and chemical abundances provided by Gaia DR3 spectroscopy are combined with DR3 radial velocities and EDR3 astrometry to analyse the relationships between chemistry and Milky Way structure, stellar kinematics, and orbital parameters. Results. The all-sky Gaia chemical cartography allows a powerful and precise chemo-dynamical view of the Milky Way with unprecedented spatial coverage and statistical robustness. First, it reveals the strong vertical symmetry of the Galaxy and the flared structure of the disc. Second, the observed kinematic disturbances of the disc – seen as phase space correlations – and kinematic or orbital substructures are associated with chemical patterns that favour stars with enhanced metallicities and lower [α/Fe] abundance ratios compared to the median values in the radial distributions. This is detected both for young objects that trace the spiral arms and older populations. Several α, iron-peak elements and at least one heavy element trace the thin and thick disc properties in the solar cylinder. Third, young disc stars show a recent chemical impoverishment in several elements. Fourth, the largest chemo-dynamical sample of open clusters analysed so far shows a steepening of the radial metallicity gradient with age, which is also observed in the young field population. Finally, the Gaia chemical data have the required coverage and precision to unveil galaxy accretion debris and heated disc stars on halo orbits through their [α/Fe] ratio, and to allow the study of the chemo-dynamical properties of globular clusters. Conclusions. Gaia DR3 chemo-dynamical diagnostics open new horizons before the era of ground-based wide-field spectroscopic surveys. They unveil a complex Milky Way that is the outcome of an eventful evolution, shaping it to the present day

    Gaia Data Release 3 Exploring and mapping the diffuse interstellar band at 862 nm

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    Context. Diffuse interstellar bands (DIBs) are common interstellar absorption features in spectroscopic observations but their origins remain unclear. DIBs play an important role in the life cycle of the interstellar medium (ISM) and can also be used to trace Galactic structure. Aims. Here, we demonstrate the capacity of the Gaia-Radial Velocity Spectrometer (RVS) in Gaia DR3 to reveal the spatial distribution of the unknown molecular species responsible for the most prominent DIB at 862 nm in the RVS passband, exploring the Galactic ISM within a few kiloparsecs from the Sun. Methods. The DIBs are measured within the GSP-Spec module using a Gaussian profile fit for cool stars and a Gaussian process for hot stars. In addition to the equivalent widths and their uncertainties, Gaia DR3 provides their characteristic central wavelength, width, and quality flags. Results. We present an extensive sample of 476 117 individual DIB measurements obtained in a homogeneous way covering the entire sky. We compare spatial distributions of the DIB carrier with interstellar reddening and find evidence that DIB carriers are present in a local bubble around the Sun which contains nearly no dust. We characterised the DIB equivalent width with a local density of 0.19 ± 0.04 Å kpc−1 and a scale height of 98.60−8.46+11.10 pc. The latter is smaller than the dust scale height, indicating that DIBs are more concentrated towards the Galactic plane. We determine the rest-frame wavelength with unprecedented precision (λ0 = 8620.86  ± 0.019 Å in air) and reveal a remarkable correspondence between the DIB velocities and the CO gas velocities, suggesting that the 862 nm DIB carrier is related to macro-molecules. Conclusions. We demonstrate the unique capacity of Gaia to trace the spatial structure of the Galactic ISM using the 862 nm DIB

    Gaia Data Release 3 Stellar multiplicity, a teaser for the hidden treasure

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    Context. The Gaia DR3 catalogue contains, for the first time, about 800 000 solutions with either orbital elements or trend parameters for astrometric, spectroscopic, and eclipsing binaries, and combinations of these three.Aims. With this paper, we aim to illustrate the huge potential of this large non-single-star catalogue. Methods. Using the orbital solutions and models of the binaries, we have built a catalogue of tens of thousands of stellar masses or lower limits thereof, some with consistent flux ratios. Properties concerning the completeness of the binary catalogues are discussed, statistical features of the orbital elements are explained, and a comparison with other catalogues is performed. Results. Illustrative applications are proposed for binaries across the Hertzsprung-Russell Diagram (HRD). Binarity is studied in the giant branch and a search for genuine spectroscopic binaries among long-period variables is performed. The discovery of new EL CVn systems illustrates the potential of combining variability and binarity catalogues. Potential compact object companions are presented, mainly white dwarf companions or double degenerates, but one candidate neutron star is also found. Towards the bottom of the main sequence, the orbits of previously suspected binary ultracool dwarfs are determined and new candidate binaries are discovered. The long awaited contribution of Gaia to the analysis of the substellar regime shows the brown dwarf desert around solar-type stars using true rather than minimum masses, and provides new important constraints on the occurrence rates of substellar companions to M dwarfs. Several dozen new exoplanets are proposed, including two with validated orbital solutions and one super-Jupiter orbiting a white dwarf, all being candidates requiring confirmation. Besides binarity, higher order multiple systems are also found
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