201 research outputs found
Small critical RNAs in the scrapie agent
Unconventional infectious agents cause transmissible spongiform encephalopathy (TSE) diseases including scrapie and bovine spongiform encephalopathy (BSE) in animals and Creutzfeldt-Jakob disease in humans. The protein only hypothesis claims that the TSE agent is composed solely of the protein called prion (PrP^sc^)^1^. This protein is the misfolded form of a host-encoded cellular protein, PrP^c^ exerting presumably a vital role at the synapse^2^. Even though now widely accepted, the prion concept fails to provide in certain circumstances^3-6^, a satisfying interpretation of the infectious phenomenon. Using the 263K scrapie-hamster model, we conducted a transmission study to search for a putative prion-associated factor indispensable for infectivity. Here we show that innocuous recombinant prion protein (recPrP) was capable, in a reproducible manner, of transmitting scrapie disease when the protein was [beta]–sheet converted in a solution containing PrP^sc^-derived RNA material. Analysis of the PrP-RNA mixture revealed the association of recPrP with two prominent populations of small RNA molecules having an average length of about ~27 and ~55 nucleotides. We conclude that the nature of the TSE agent seems to be composed of a nucleoprotein molecular complex, in which informative RNA molecules of small sizes are associated with the misfolded prion protein (PrP^sc^)
In Vitro and In Vivo Neurotoxicity of Prion Protein Oligomers
The mechanisms underlying prion-linked neurodegeneration remain to be elucidated, despite several recent advances in this field. Herein, we show that soluble, low molecular weight oligomers of the full-length prion protein (PrP), which possess characteristics of PrP to PrPsc conversion intermediates such as partial protease resistance, are neurotoxic in vitro on primary cultures of neurons and in vivo after subcortical stereotaxic injection. Monomeric PrP was not toxic. Insoluble, fibrillar forms of PrP exhibited no toxicity in vitro and were less toxic than their oligomeric counterparts in vivo. The toxicity was independent of PrP expression in the neurons both in vitro and in vivo for the PrP oligomers and in vivo for the PrP fibrils. Rescue experiments with antibodies showed that the exposure of the hydrophobic stretch of PrP at the oligomeric surface was necessary for toxicity. This study identifies toxic PrP species in vivo. It shows that PrP-induced neurodegeneration shares common mechanisms with other brain amyloidoses like Alzheimer disease and opens new avenues for neuroprotective intervention strategies of prion diseases targeting PrP oligomers
LINGO1 Variants in the French-Canadian Population
Essential tremor (ET) is a complex genetic disorder for which no causative gene has been found. Recently, a genome-wide association study reported that two variants in the LINGO1 locus were associated to this disease. The aim of the present study was to test if this specific association could be replicated using a French-Canadian cohort of 259 ET patients and 479 ethnically matched controls. Our genotyping results lead us to conclude that no association exists between the key variant rs9652490 and ET (Pcorr = 1.00)
Innovation et développement dans les systèmes agricoles et alimentaires
L’innovation est souvent présentée comme l’un des principaux leviers pour promouvoir un développement plus durable et plus inclusif. Dans les domaines de l’agriculture et de l’alimentation, l’innovation est marquée par des spécificités liées à sa relation à la nature, mais aussi à la grande diversité d’acteurs concernés, depuis les agriculteurs jusqu’aux consommateurs, en passant par les services de recherche et de développement. L’innovation émerge des interactions entre ces acteurs, qui mobilisent des ressources et produisent des connaissances dans des dispositifs collaboratifs, afin de générer des changements. Elle recouvre des domaines aussi variés que les pratiques de production, l’organisation des marchés, ou les pratiques alimentaires. L’innovation est reliée aux grands enjeux de développement : innovation agro-écologique, innovation sociale, innovation territoriale, etc. Cet ouvrage porte un regard sur l’innovation dans les systèmes agricoles et alimentaires. Il met un accent particulier sur l’accompagnement de l’innovation, en interrogeant les méthodes et les organisations, et sur l’évaluation de l’innovation au regard de différents critères. Il s’appuie sur des réflexions portées par différentes disciplines scientifiques, sur des travaux de terrain conduits tant en France que dans de nombreux pays du Sud, et enfin sur les expériences acquises en accompagnant des acteurs qui innovent. Il combine des synthèses sur l’innovation et des études de cas emblématiques pour illustrer les propos. L’ouvrage est destiné aux enseignants, professionnels, étudiants et chercheurs
Recommended from our members
Gaia Early Data Release 3: The celestial reference frame (Gaia-CRF3)
Context. Gaia-CRF3 is the celestial reference frame for positions and proper motions in the third release of data from the Gaia mission, Gaia DR3 (and for the early third release, Gaia EDR3, which contains identical astrometric results). The reference frame is defined by the positions and proper motions at epoch 2016.0 for a specific set of extragalactic sources in the (E)DR3 catalogue. Aims. We describe the construction of Gaia-CRF3 and its properties in terms of the distributions in magnitude, colour, and astrometric quality. Methods. Compact extragalactic sources in Gaia DR3 were identified by positional cross-matching with 17 external catalogues of quasi-stellar objects (QSO) and active galactic nuclei (AGN), followed by astrometric filtering designed to remove stellar contaminants. Selecting a clean sample was favoured over including a higher number of extragalactic sources. For the final sample, the random and systematic errors in the proper motions are analysed, as well as the radio-optical offsets in position for sources in the third realisation of the International Celestial Reference Frame (ICRF3). Results. Gaia-CRF3 comprises about 1.6 million QSO-like sources, of which 1.2 million have five-parameter astrometric solutions in Gaia DR3 and 0.4 million have six-parameter solutions. The sources span the magnitude range G = 13-21 with a peak density at 20.6 mag, at which the typical positional uncertainty is about 1 mas. The proper motions show systematic errors on the level of 12 μas yr-1 on angular scales greater than 15 deg. For the 3142 optical counterparts of ICRF3 sources in the S/X frequency bands, the median offset from the radio positions is about 0.5 mas, but it exceeds 4 mas in either coordinate for 127 sources. We outline the future of Gaia-CRF in the next Gaia data releases. Appendices give further details on the external catalogues used, how to extract information about the Gaia-CRF3 sources, potential (Galactic) confusion sources, and the estimation of the spin and orientation of an astrometric solution
Pulsations in main sequence OBAF-type stars
CONTEXT: The third Gaia data release provides photometric time series covering 34 months for about 10 million stars. For many of those stars, a characterisation in Fourier space and their variability classification are also provided. This paper focuses on intermediate- to high-mass (IHM) main sequence pulsators (M ≥ 1.3 M⊙) of spectral types O, B, A, or F, known as β Cep, slowly pulsating B (SPB), δ Sct, and γ Dor stars. These stars are often multi-periodic and display low amplitudes, making them challenging targets to analyse with sparse time series. AIMS: We investigate the extent to which the sparse Gaia DR3 data can be used to detect OBAF-type pulsators and discriminate them from other types of variables. We aim to probe the empirical instability strips and compare them with theoretical predictions. The most populated variability class is that of the δ Sct variables. For these stars, we aim to confirm their empirical period-luminosity (PL) relation, and verify the relation between their oscillation amplitude and rotation. METHODS: All datasets used in this analysis are part of the Gaia DR3 data release. The photometric time series were used to perform a Fourier analysis, while the global astrophysical parameters necessary for the empirical instability strips were taken from the Gaia DR3 gspphot tables, and the v sin i data were taken from the Gaia DR3 esphs tables. The δ Sct PL relation was derived using the same photometric parallax method as the one recently used to establish the PL relation for classical Cepheids using Gaia data. RESULTS: We show that for nearby OBAF-type pulsators, the Gaia DR3 data are precise and accurate enough to pinpoint them in the Hertzsprung-Russell (HR) diagram. We find empirical instability strips covering broader regions than theoretically predicted. In particular, our study reveals the presence of fast rotating gravity-mode pulsators outside the strips, as well as the co-existence of rotationally modulated variables inside the strips as reported before in the literature. We derive an extensive period–luminosity relation for δ Sct stars and provide evidence that the relation features different regimes depending on the oscillation period. We demonstrate how stellar rotation attenuates the amplitude of the dominant oscillation mode of δ Sct stars. CONCLUSIONS: The Gaia DR3 time-series photometry already allows for the detection of the dominant (non-)radial oscillation mode in about 100 000 intermediate- and high-mass dwarfs across the entire sky. This detection capability will increase as the time series becomes longer, allowing the additional delivery of frequencies and amplitudes of secondary pulsation modes
Gaia Data Release 3: Mapping the asymmetric disc of the Milky Way
With the most recent Gaia data release the number of sources with complete 6D
phase space information (position and velocity) has increased to well over 33
million stars, while stellar astrophysical parameters are provided for more
than 470 million sources, in addition to the identification of over 11 million
variable stars. Using the astrophysical parameters and variability
classifications provided in Gaia DR3, we select various stellar populations to
explore and identify non-axisymmetric features in the disc of the Milky Way in
both configuration and velocity space. Using more about 580 thousand sources
identified as hot OB stars, together with 988 known open clusters younger than
100 million years, we map the spiral structure associated with star formation
4-5 kpc from the Sun. We select over 2800 Classical Cepheids younger than 200
million years, which show spiral features extending as far as 10 kpc from the
Sun in the outer disc. We also identify more than 8.7 million sources on the
red giant branch (RGB), of which 5.7 million have line-of-sight velocities,
allowing the velocity field of the Milky Way to be mapped as far as 8 kpc from
the Sun, including the inner disc. The spiral structure revealed by the young
populations is consistent with recent results using Gaia EDR3 astrometry and
source lists based on near infrared photometry, showing the Local (Orion) arm
to be at least 8 kpc long, and an outer arm consistent with what is seen in HI
surveys, which seems to be a continuation of the Perseus arm into the third
quadrant. Meanwhile, the subset of RGB stars with velocities clearly reveals
the large scale kinematic signature of the bar in the inner disc, as well as
evidence of streaming motions in the outer disc that might be associated with
spiral arms or bar resonances. (abridged
Use of anticoagulants and antiplatelet agents in stable outpatients with coronary artery disease and atrial fibrillation. International CLARIFY registry
Gaia Data Release 3: reflectance spectra of Solar System small bodies
Stars and planetary system
- …