Optimizing filter trap assay for the detection of aggregated alpha-synuclein in brain samples

No abstract availabl

Spatio-temporal expression patterns of aurora kinases a, B, and C and cytoplasmic polyadenylation-element-binding protein in bovine oocytes during meiotic maturation.

International audienceMaturation of immature bovine oocytes requires cytoplasmic polyadenylation and synthesis of a number of proteins involved in meiotic progression and metaphase-II arrest. Aurora serine-threonine kinases--localized in centrosomes, chromosomes, and midbody--regulate chromosome segregation and cytokinesis in somatic cells. In frog and mouse oocytes, Aurora A regulates polyadenylation-dependent translation of several mRNAs such as MOS and CCNB1, presumably by phosphorylating CPEB, and Aurora B phosphorylates histone H3 during meiosis. We analyzed the expression of three Aurora kinase genes--AURKA, AURKB, and AURKC--in bovine oocytes during meiosis by reverse transcription followed by quantitative real-time PCR and immunodetection. Aurora A was the most abundant form in oocytes, both at mRNA and protein levels. AURKA protein progressively accumulated in the oocyte cytoplasm during antral follicle growth and in vitro maturation. AURKB associated with metaphase chromosomes. AURKB, AURKC, and Thr-phosphorylated AURKA were detected at a contractile ring/midbody during the first polar body extrusion. CPEB, localized in oocyte cytoplasm, was hyperphosphorylated during prophase/metaphase-I transition. Most CPEB degraded in metaphase-II oocytes and remnants remained localized in a contractile ring. Roscovitine, U0126, and metformin inhibited meiotic divisions; they all induced a decrease of CCNB1 and phospho-MAPK3/1 levels and prevented CPEB degradation. However, only metformin depleted AURKA. The Aurora kinase inhibitor VX680 at 100 nmol/L did not inhibit meiosis but led to multinuclear oocytes due to the failure of the polar body extrusion. Thus, in bovine oocyte meiosis, massive destruction of CPEB accompanies metaphase-I/II transition, and Aurora kinases participate in regulating segregation of the chromosomes, maintenance of metaphase-II, and formation of the first polar body

Natural History of Cardiac and Respiratory Involvement, Prognosis and Predictive Factors for Long-Term Survival in Adult Patients with Limb Girdle Muscular Dystrophies Type 2C and 2D

International audienceBackgroundType 2C and 2D limb girdle muscular dystrophies (LGMD) are a group of autosomal recessive limb girdle muscular dystrophies manifested by proximal myopathy, impaired respiratory muscle function and cardiomyopathy. The correlation and the prognostic impact of respiratory and heart impairment are poorly described. We aimed to describe the long-term cardiac and respiratory follow-up of these patients and to determine predictive factors of cardio-respiratory events and mortality in LGMD 2C and 2D.MethodsWe reviewed the charts of 34 LGMD patients, followed from 2005 to 2015, to obtain echocardiographic, respiratory function and sleep recording data. We considered respiratory events (acute respiratory failure, pulmonary sepsis, atelectasis or pneumothorax), cardiac events (acute heart failure, significant cardiac arrhythmia or conduction block, ischemic stroke) and mortality as outcomes of interest for the present analysis.ResultsA total of 21 patients had type 2C LGMD and 13 patients had type 2D. Median age was 30 years [IQR 24–38]. At baseline, median pulmonary vital capacity (VC) was 31% of predicted value [20–40]. Median maximal inspiratory pressure (MIP) was 31 cmH2O [IQR 20.25–39.75]. Median maximal expiratory pressure (MEP) was 30 cm H2O [20–36]. Median left ventricular ejection fraction (LVEF) was 55% [45–64] with 38% of patients with LVEF <50%. Over a median follow-up of 6 years, we observed 38% respiratory events, 14% cardiac events and 20% mortality. Among baseline characteristics, LVEF and left ventricular end diastolic diameter (LVEDD) were associated with mortality, whilst respiratory parameters (VC, MIP, MEP) and the need for home mechanical ventilation (HMV) were associated with respiratory events.ConclusionIn our cohort of severely respiratory impaired type 2C and 2D LGMD, respiratory morbidity was high. Cardiac dysfunction was frequent in particular in LGMD 2C and had an impact on long-term mortality

Status of the SOLEIL femtosecond X-ray source

http://accelconf.web.cern.ch/AccelConf/FEL2012/papers/wepd04.pdfInternational audienceAn electron bunch slicing setup is presently under construction on the SOLEIL storage ring for delivering 100 fs (rms) long photon pulses to two undulator-based beamlines providing soft (TEMPO) and hard X-rays (CRISTAL). Thanks to the non-zero dispersion function present in all straight sections of the storage ring, the sliced bunches can be easily separated from the core bunches. The modulator is a wiggler composed of 20 periods of 164.4 mm. It produces a magnetic field of 1.8 T at a minimum gap of 14.5 mm. To modulate the kinetic energy of the electrons in the wiggler, a Ti:Sa laser will be used, which produces 50 fs pulses at 800 nm with a repetition rate of 2.5 kHz. The laser beam is splitted into two branches in order to provide 2 mJ to the modulator and 0.5 mJ as pump pulse for the CRISTAL and TEMPO end stations. Focusing optics and beam path, from the laser hutch to the inside of the storage ring tunnel are presently under finalization. In this paper, we will report on the specificities of the SOLEIL setup, the status of its installation and the expected performances

Polychromatic guide star: feasibility study

International audienceAdaptive optics at astronomical telescopes aims at correcting in real time the phase corrugations of incoming wavefronts caused by the turbulent atmosphere, as early proposed by Babcock. Measuring the phase errors requires a bright source located within the isoplanatic patch of the program source. The probability that such a reference source exists is a function of the wavelength, of the required image quality (Strehl ratio), of the turbulence optical properties, and of the direction of the observation. It turns out that the sky coverage is disastrously low in particular in the visible wavelength range where, unfortunately, the gain in spatial resolution brought by adaptive optics is the largest. Foy and Labeyrie have proposed to overcome this difficulty by creating an artificial point source in the sky in the direction of the observation relying on the backscattered light due to a laser beam. This laser guide star (hereinafter referred to as LGS) can be bright enough to allow us to accurately measure the wavefront phase errors, except for two modes which are the piston (not relevant in this case) and the tilt. Pilkington has emphasized that the round trip time of the laser beam to the mesosphere, where the LGS is most often formed, is significantly shorter than the typical tilt coherence time; then the inverse-return-of-light principle causes deflections of the outgoing and the ingoing beams to cancel. The apparent direction of the LGS is independent of the tilt. Therefore the tilt cannot be measured only from the LGS. Until now, the way to overcome this difficulty has been to use a natural guide star to sense the tilt. Although the tilt is sensed through the entire telescope pupil, one cannot use a faint source because $APEX 90% of the variance of the phase error is in the tilt. Therefore, correcting the tilt requires a higher accuracy of the measurements than for higher orders of the wavefront. Hence current adaptive optics devices coupled with a LGS face low sky coverage. Several methods have been proposed to get a partial sky coverage for the tilt. The only one providing us with a full sky coverage is the polychromatic LGS (hereafter referred to as PLGS). We present here a progress report of the R&D; program Etoile Laser Polychromatique et Optique Adaptative (ELP-OA) carried out in France to develop the PLGS concept. After a short recall of the principles of the PLGS, we will review the goal of ELP-OA and the steps to get over to bring it into play. We finally shortly described the effort in Europe to develop the LGS

Polychromatic guide star: feasibility study

International audienceAdaptive optics at astronomical telescopes aims at correcting in real time the phase corrugations of incoming wavefronts caused by the turbulent atmosphere, as early proposed by Babcock. Measuring the phase errors requires a bright source located within the isoplanatic patch of the program source. The probability that such a reference source exists is a function of the wavelength, of the required image quality (Strehl ratio), of the turbulence optical properties, and of the direction of the observation. It turns out that the sky coverage is disastrously low in particular in the visible wavelength range where, unfortunately, the gain in spatial resolution brought by adaptive optics is the largest. Foy and Labeyrie have proposed to overcome this difficulty by creating an artificial point source in the sky in the direction of the observation relying on the backscattered light due to a laser beam. This laser guide star (hereinafter referred to as LGS) can be bright enough to allow us to accurately measure the wavefront phase errors, except for two modes which are the piston (not relevant in this case) and the tilt. Pilkington has emphasized that the round trip time of the laser beam to the mesosphere, where the LGS is most often formed, is significantly shorter than the typical tilt coherence time; then the inverse-return-of-light principle causes deflections of the outgoing and the ingoing beams to cancel. The apparent direction of the LGS is independent of the tilt. Therefore the tilt cannot be measured only from the LGS. Until now, the way to overcome this difficulty has been to use a natural guide star to sense the tilt. Although the tilt is sensed through the entire telescope pupil, one cannot use a faint source because $APEX 90% of the variance of the phase error is in the tilt. Therefore, correcting the tilt requires a higher accuracy of the measurements than for higher orders of the wavefront. Hence current adaptive optics devices coupled with a LGS face low sky coverage. Several methods have been proposed to get a partial sky coverage for the tilt. The only one providing us with a full sky coverage is the polychromatic LGS (hereafter referred to as PLGS). We present here a progress report of the R&D; program Etoile Laser Polychromatique et Optique Adaptative (ELP-OA) carried out in France to develop the PLGS concept. After a short recall of the principles of the PLGS, we will review the goal of ELP-OA and the steps to get over to bring it into play. We finally shortly described the effort in Europe to develop the LGS

II Congrés Internacional sobre Traducció : abril 1994 : actes

Machine learning-based approach unravels distinct pathological signatures induced by patient-derived α-synuclein seeds in monkeys. Dopaminergic neuronal cell death, associated with intracellular α-synuclein (α-syn)-rich protein aggregates [termed "Lewy bodies" (LBs)], is a well-established characteristic of Parkinson's disease (PD). Much evidence, accumulated from multiple experimental models, has suggested that α-syn plays a role in PD pathogenesis, not only as a trigger of pathology but also as a mediator of disease progression through pathological spreading. Here, we have used a machine learning-based approach to identify unique signatures of neurodegeneration in monkeys induced by distinct α-syn pathogenic structures derived from patients with PD. Unexpectedly, our results show that, in nonhuman primates, a small amount of singular α-syn aggregates is as toxic as larger amyloid fibrils present in the LBs, thus reinforcing the need for preclinical research in this species. Furthermore, our results provide evidence supporting the true multifactorial nature of PD, as multiple causes can induce a similar outcome regarding dopaminergic neurodegeneratio

Altimetry for the future: Building on 25 years of progress

In 2018 we celebrated 25 years of development of radar altimetry, and the progress achieved by this methodology in the fields of global and coastal oceanography, hydrology, geodesy and cryospheric sciences. Many symbolic major events have celebrated these developments, e.g., in Venice, Italy, the 15th (2006) and 20th (2012) years of progress and more recently, in 2018, in Ponta Delgada, Portugal, 25 Years of Progress in Radar Altimetry. On this latter occasion it was decided to collect contributions of scientists, engineers and managers involved in the worldwide altimetry community to depict the state of altimetry and propose recommendations for the altimetry of the future. This paper summarizes contributions and recommendations that were collected and provides guidance for future mission design, research activities, and sustainable operational radar altimetry data exploitation. Recommendations provided are fundamental for optimizing further scientific and operational advances of oceanographic observations by altimetry, including requirements for spatial and temporal resolution of altimetric measurements, their accuracy and continuity. There are also new challenges and new openings mentioned in the paper that are particularly crucial for observations at higher latitudes, for coastal oceanography, for cryospheric studies and for hydrology. The paper starts with a general introduction followed by a section on Earth System Science including Ocean Dynamics, Sea Level, the Coastal Ocean, Hydrology, the Cryosphere and Polar Oceans and the ‘‘Green” Ocean, extending the frontier from biogeochemistry to marine ecology. Applications are described in a subsequent section, which covers Operational Oceanography, Weather, Hurricane Wave and Wind Forecasting, Climate projection. Instruments’ development and satellite missions’ evolutions are described in a fourth section. A fifth section covers the key observations that altimeters provide and their potential complements, from other Earth observation measurements to in situ data. Section 6 identifies the data and methods and provides some accuracy and resolution requirements for the wet tropospheric correction, the orbit and other geodetic requirements, the Mean Sea Surface, Geoid and Mean Dynamic Topography, Calibration and Validation, data accuracy, data access and handling (including the DUACS system). Section 7 brings a transversal view on scales, integration, artificial intelligence, and capacity building (education and training). Section 8 reviews the programmatic issues followed by a conclusion

Altimetry for the future: building on 25 years of progress

In 2018 we celebrated 25 years of development of radar altimetry, and the progress achieved by this methodology in the fields of global and coastal oceanography, hydrology, geodesy and cryospheric sciences. Many symbolic major events have celebrated these developments, e.g., in Venice, Italy, the 15th (2006) and 20th (2012) years of progress and more recently, in 2018, in Ponta Delgada, Portugal, 25 Years of Progress in Radar Altimetry. On this latter occasion it was decided to collect contributions of scientists, engineers and managers involved in the worldwide altimetry community to depict the state of altimetry and propose recommendations for the altimetry of the future. This paper summarizes contributions and recommendations that were collected and provides guidance for future mission design, research activities, and sustainable operational radar altimetry data exploitation. Recommendations provided are fundamental for optimizing further scientific and operational advances of oceanographic observations by altimetry, including requirements for spatial and temporal resolution of altimetric measurements, their accuracy and continuity. There are also new challenges and new openings mentioned in the paper that are particularly crucial for observations at higher latitudes, for coastal oceanography, for cryospheric studies and for hydrology. The paper starts with a general introduction followed by a section on Earth System Science including Ocean Dynamics, Sea Level, the Coastal Ocean, Hydrology, the Cryosphere and Polar Oceans and the “Green” Ocean, extending the frontier from biogeochemistry to marine ecology. Applications are described in a subsequent section, which covers Operational Oceanography, Weather, Hurricane Wave and Wind Forecasting, Climate projection. Instruments’ development and satellite missions’ evolutions are described in a fourth section. A fifth section covers the key observations that altimeters provide and their potential complements, from other Earth observation measurements to in situ data. Section 6 identifies the data and methods and provides some accuracy and resolution requirements for the wet tropospheric correction, the orbit and other geodetic requirements, the Mean Sea Surface, Geoid and Mean Dynamic Topography, Calibration and Validation, data accuracy, data access and handling (including the DUACS system). Section 7 brings a transversal view on scales, integration, artificial intelligence, and capacity building (education and training). Section 8 reviews the programmatic issues followed by a conclusion

Multi scale approach of high temperature corrosion mechanisms of ceramic refractories : thermo chemical wear processes of silicon carbide by salts

Les processus de dégradation chimique des céramiques réfractaires sont des phénomènes complexes. Atravers des exemples concrets issus de la littérature et de travaux de recherche, les notions et les propriétésfondamentales permettant d’expliquer les différents modes de dégradation des matériaux réfractaires sontprésentées. A l’issu de cet état de l’art, une méthodologie adaptée à l’étude de la corrosion des réfractaires,prenant en compte une approche multi-échelle allant du macroscopique au microscopique, est proposée.Cette méthodologie, permettant de déterminer les mécanismes responsables de la corrosion en fonction del’environnement des matériaux, a été appliquée à la corrosion des réfractaires à base de SiC utilisés dans lesunités de valorisation énergétique (UVED). L’analyse post-mortem des échantillons a permis de constater laformation de para-wollastonite, dans la porosité et autour des grains de SiC, en face chaude. D’autresphases telles que la cristobalite et la microline ont également été observées jusqu’à mi-épaisseur desréfractaires. A travers une modélisation thermochimique, la nature des agents d’agression a été déterminéeet correspond essentiellement à une condensation d’espèces sulfatées (CaSO4, K2SO4 et Na2SO4) en facechaude et dans la porosité des matériaux. Les essais de corrosion en laboratoire par les sulfates, ont permisde mettre en évidence une dégradation similaire à celle rencontrée dans les UVED.L’ensemble des résultats permet d’envisager deux voies d’amélioration qui sont :- la voie matériaux par une modification de la matrice et notamment une diminution de la porosité et/ou l’ajoutd’une couche protectrice en face chaude imperméable aux gaz ;- une voie procédé en modifiant les isothermes de condensation des matériaux (réduire la température enface chaude afin d’éviter la condensation des espèces dans la porosité des matériaux).The chemical wear processes of ceramic refractories are complex phenomena. Relying on real applicationsand research works, notions and fundamental properties, which describe different wear mechanisms ofrefractory materials, are introduced. Then, a methodology adapted to the study of refractory corrosion,including a multi-scale approach (macroscopic and microscopic), is offered.This methodology, which makes it possible to define main mechanisms of corrosion according to theenvironment of refractories, was applied to the corrosion of silicon carbide refractories used in municipal solidwaste-to-energy facilities (WtE). The post-mortem analyses showed the formation of para-wollastonite, in theporosity and around the SiC grains, on the hot face of materials. Other phases such as cristobalite andmicroline were also formed down to the core of the refractories. From thermo-chemical modelling, the natureof the corrosive agents was calculated and corresponds to the condensation of sulphates (CaSO4, K2SO4 andNa2SO4) on the hot face and into the porosity of materials. The in-lab corrosion tests by sulphates, inconditions close to those met in WtE, are in accordance with the autopsy of corroded samples taken fromincinerator plants.All results suggest two axes of improvement:- a material way by a modification of the matrix and particularly the reduction of the porosity and/or theaddition of protective layer on the hot face ;- a technical way by a modification of condensation isotherms of refractories (reducing the temperature on thehot face to avoid the condensation of sulphate species in the porosity of materials)