301 research outputs found
The cellular prion protein beyond prion diseases
No full textThe cellular prion protein (PrPC), a cell surface glycoprotein originally identified for its central role in prion diseases (also called transmissible spongiform encephalopathies), has recently been implicated in the pathogenesis of other neurodegenerative disorders, such as Alzheimer’s and Parkinson’s diseases, by acting as a toxicity-transducing receptor for different misfolded protein isoforms, or in some case by exerting neuroprotective effects. Interestingly, PrPC has also been reported to play unexpected functions outside the nervous system, for example by contributing to myelin homeostasis, regulating specific processes of the immune system and participating in various aspects of cancer progression. Collectively, these observations point to a much broader role for PrPC in physiological and disease processes than originally assumed. In this manuscript, we provide an overview of what is known about the role of PrPC beyond prion disorders and discuss the potential implications of targeting this protein in different diseases
Structures in the AU Mic disk are still moving fast …
No full textObservations of AU Mic in 2014 with SPHERE, once combined with former HST data, revealed a series of five arch-like structures of which localization and speed are at odd with keplerian motions. Rather, a complex star/disk interaction is considered. We will present new results from a follow up program in 2015 (intensity and polarimetry), which confirms fast motion of individual structures.C. Thalmann, A.M. Lagrange, M. Janson, J.C. Augereau, G. Schneider, J. Milli, C. Grady, J. Debes, M. Langlois, D. Mouillet, T. Henning, C. Dominik, A.L. Maire, J.L. Beuzit, J. Carson, K. Dohlen, M. Feldt, T. Fusco, C. Ginski, J.H. Girard,
D. Hines, M. Kasper, D. Mawet, F. Ménard, M. Meyer, C. Moutou, J. Olofsson,
T. Rodigas, J.F. Sauvage, J. Schlieder, H.M. Schmid, M. Turatto, S. Udry,
F. Vakili, A. Vigan, Z. Wahhaj, J. Wisniewski
SPHERE-team + US-team Collaboratio
Predicting loss in magnetic steels under arbitrary induction waveform and with minor hysteresis loops
No full textWe have studied ways of predicting power losses in soft magnetic laminations for generic time dependence of the periodic magnetic polarization J(t). We found that, whatever the frequency and the induction waveform, the loss behavior can be quantitatively assessed within the theoretical framework of the statistical loss model. The prediction requires a limited set of preemptive experimental data, depending on whether or not the arbitrary J(t) waveform is endowed with local slope inversions (i.e., minor hysteresis loops) in its periodic time behavior. In the absence of minor loops, such data reduce, for any peak polarization value Jp, to the loss figures obtained under sinusoidal J(t) at two different frequency values. In the presence of minor loops of semiamplitude Jm, the two-frequency loss experiment should be carried out for both peak polarization values Jp and Jm. Additional knowledge of the quasi-static major loop, to be used for modeling hysteresis loss, does improve the accuracy of the prediction method. A more general approach to loss in soft magnetic laminations is obtained in this way, the only limitation apparently being the onset of skin effect at high frequencie
Proline-rich tyrosine kinase 2 mediates gonadotropin-releasing hormone signaling to a specific extracellularly regulated kinase-sensitive transcriptional locus in the luteinizing hormone beta-subunit gene
No full textG protein-coupled receptor regulation of gene transcription primarily occurs through the phosphorylation of transcription factors by MAPKs. This requires transduction of an activating signal via scaffold proteins that can ultimately determine the outcome by binding signaling kinases and adapter proteins with effects on the target transcription factor and locus of activation. By investigating these mechanisms, we have elucidated how pituitary gonadotrope cells decode an input GnRH signal into coherent transcriptional output from the LH beta-subunit gene promoter. We show that GnRH activates c-Src and multiple members of the MAPK family, c-Jun NH2-terminal kinase 1/2, p38MAPK, and ERK1/2. Using dominant-negative point mutations and chemical inhibitors, we identified that calcium-dependent proline-rich tyrosine kinase 2 specifically acts as a scaffold for a focal adhesion/cytoskeleton-dependent complex comprised of c-Src, Grb2, and mSos that translocates an ERK-activating signal to the nucleus. The locus of action of ERK was specifically mapped to early growth response-1 (Egr-1) DNA binding sites within the LH beta-subunit gene proximal promoter, which was also activated by p38MAPK, but not c-Jun NH2-terminal kinase 1/2. Egr-1 was confirmed as the transcription factor target of ERK and p38MAPK by blockade of protein expression, transcriptional activity, and DNA binding. We have identified a novel GnRH-activated proline-rich tyrosine kinase 2-dependent ERK-mediated signal transduction pathway that specifically regulates Egr-1 activation of the LH beta-subunit proximal gene promoter, and thus provide insight into the molecular mechanisms required for differential regulation of gonadotropin gene expression
Discovery of concentric broken rings at sub-arcsec separations in the HD 141569A gas-rich, debris disk with VLT/SPHERE
No full textObservations with SPHERE of HD141569A revealed a series of concentric ringlets located at 116-46AU and matching the formerly detected extended emission in the mid-IR and visible, although finer details are detected here. The brightest ring at 46AU has sharp edges and presents an unusual strong north/south asymmetry. Such structures may result from planet sheperding or gas/dust interactions.A. Boccaletti, E. Pantin, J-C. Augereau, A-M. Lagrange, R. Galicher, A-L. Maire, J. Mazoyer, J. Milli, G. Rousset, R. Gratton, M. Bonnefoy, W. Brandner, E. Buenzli, M. Langlois, J. Lannier, D. Mesa, S. Peretti, G. Salter, E. Sissa, G. Chauvin, S. Desidera, M. Feldt, A. Vigan, E. Di Folco, A. Dutrey, J. Pércaud, P. Baudoz, M. Benisty, J. De Boer, A. Garufi, J. H. Girard, F. Menard, J. Olofsson, S. P. Quanz, D. Mouillet, V. Christiaens, 17, S. Casassus, J.-L. Beuzit, P. Blanchard, M. Carle, T. Fusco, E. Giro, N. Hubin, D. Maurel, O. Moeller-Nilsson, A. Sevin, L. Webe
Dust disks around old Pre Main-Sequence stars: HST/NICMOS2 scattered light images and modeling
No full text6 pagesWe present recent near-infrared detections of circumstellar disks around the two old PMS Herbig stars HD 141569 and HD 100546 obtained with the HST/NICMOS2 camera. They reveal extended structures larger than 350-400 AU in radius. While the HD 100546 disk appears as a continuous disk down to 40 AU, the HD 141569 environment seems more complex, splitted at least into two dust populations. As a convincing example, the full modeling of the disk surrounding HR 4796, another old PMS star, is detailed and confronted with more recent observations
Timing of aortic valve replacement in high-gradient severe aortic stenosis: impact of left ventricular ejection fraction
No full textBackground: Patients with high-gradient (HG) severe aortic stenosis (AS) and left ventricular (LV) dysfunction are at high risk of death. The optimal timing for aortic valve replacement (AVR) is not defined by guidelines. The objective was to define the optimal timing to perform isolated AVR in patients with HG-AS and severe LV dysfunction. Methods: We retrospectively included 233 consecutive patients admitted for severe HG-AS (aortic valve area <1cm2 and mean gradient ≥40mmHg). Severe LV dysfunction was defined by LV ejection fraction ≤35% (LVEF). All-cause mortality while waiting for AVR and after the intervention (30 days) was compared in patients with (n = 28) and without (n = 205) LVEF ≤35%. Results: Patients with HG-AS and severe LV dysfunction had a higher risk profile than those with LVEF >35%. AVR was performed in 93% (218/233) of patients, 41% by surgery (SAVR) and 53% by transcatheter (TAVR). TAVR was the preferred method to treat HG-AS patients with LVEF ≤35%. All-cause mortality while waiting for AVR was higher in patients with severe LV dysfunction (22% vs. 2.0%, p < 0.001) and occurred within a shorter time (12 [8–26] days vs. 63 [58–152] days, p = 0.010) compared to those with LVEF >35%. All death in HG-AS patients with a severe LV dysfunction occurred within the first month. Postoperative mortality was low (1.3%), irrespective of LVEF. Conclusions: AVR should be performed promptly after Heart Team decision in patients with HG severe AS and LVEF ≤35% because of a very high and premature risk of death while waiting for intervention
Contribution à l'étude des variations de la teneur en sels minéraux du lait de vache dans différentes régions françaises
No full textInternational audienc
Is ecdysone involved in the moult cycle of the terrestrial crustacean<i>Orchestia cavimana</i>(Amphipoda)?
No full textLaboratory verification of 'Fast & Furious' phase diversity: Towards controlling the low wind effect in the SPHERE instrument
No full text13 pages, 7 figures: accepted for publication in Astronomy & AstrophysicsInternational audienceThe low wind effect (LWE) refers to a characteristic set of quasi-static wavefront aberrations seen consistently by the SPHERE instrument when dome-level wind speeds drop below 3 m/s. This effect produces bright low-order speckles in the stellar PSF, which severely limit the contrast performance of SPHERE under otherwise optimal observing conditions. In this paper we propose the Fast & Furious (F&F) phase diversity algorithm as a viable software-only solution for real-time LWE compensation, which would utilise image sequences from the SPHERE differential tip-tilt sensor (DTTS). We evaluated the closed-loop performance of F&F on the MITHIC high-contrast test-bench under a variety of conditions emulating LWE-affected DTTS images, in order to assess the expected performance of an on-sky implementation of F&F in SPHERE. The algorithm was found to be capable of returning such LWE-affected images to Strehl ratios of greater than 90% within five iterations, for all appropriate laboratory test cases. These results are highly representative of predictive simulations, and demonstrate the stability of the algorithm against a wide range of factors including low image signal-to-noise ratio (S/N), small image field of view, and amplitude errors. It was also found in simulation that closed-loop stability can be preserved down to image S/N as low as five while still improving overall wavefront quality, allowing for reliable operation even on faint targets. The Fast & Furious algorithm is an extremely promising solution for real-time compensation of the LWE, which can operate simultaneously with science observations and may be implemented in SPHERE without requiring additional hardware. The robustness and relatively large effective dynamic range of F&F also make it suitable for general wavefront optimisation applications, including the co-phasing of segmented ELT-class telescopes
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