Severe hereditary spherocytosis and distal renal tubular acidosis associated with the total absence of band 3

Absence of band 3, associated with the mutation Coimbra (V488M) in the homozygous state, caused severe hereditary spherocytosis in a young child. Although prenatal testing was made available to the parents, it was declined. Because the fetus stopped moving near term, an emergency cesarean section was performed and a severely anemic, hydropic female baby was delivered. She was resuscitated and initially kept alive with respiratory assistance and hypertransfusion therapy. Cord blood smears revealed erythroblastosis, poikilocytosis, and red cells with stalk-like elongations. Band 3 and protein 4.2 were absent; spectrin, ankyrin, and glycophorin A were significantly reduced. Renal tubular acidosis was detected by the age of 3 months. Nephrocalcinosis appeared soon thereafter. After 3 years of follow-up the child is doing reasonably well on a regimen that includes regular blood transfusions and daily bicarbonate supplements. The long-term prognosis remains uncertain given the potential for hematologic and renal complications

Phase stability of Fe-5at%Cr and Fe-10at%Cr films under Fe+ ion irradiation

This work is within the objective of understanding the effects caused to Fe–Cr alloys by fast Fe ion irradiation. As the penetration length of Fe ion is of the order of hundreds of nanometers, 70 nm Fe-5at%C and Fe-10at%Cr films were irradiated at room temperature with 490 keV Fe+ ions at increasing fluence corresponding to a maximum damage of 50 displacements per atom (dpa). In Fe-5at%Cr alloy the Cr solute concentration remains unaltered even after a damage of 50 dpa. In the 10at%Cr the Cr solute concentration is reduced, with the increase of damage, asymptotically to a value of 7.2 at%

Defective endoplasmic reticulum-mitochondria contacts and bioenergetics in SEPN1-related myopathy

SEPN1-related myopathy (SEPN1-RM) is a muscle disorder due to mutations of the SEPN1 gene, which is characterized by muscle weakness and fatigue leading to scoliosis and life-threatening respiratory failure. Core lesions, focal areas of mitochondria depletion in skeletal muscle fibers, are the most common histopathological lesion. SEPN1-RM underlying mechanisms and the precise role of SEPN1 in muscle remained incompletely understood, hindering the development of biomarkers and therapies for this untreatable disease. To investigate the pathophysiological pathways in SEPN1-RM, we performed metabolic studies, calcium and ATP measurements, super-resolution and electron microscopy on in vivo and in vitro models of SEPN1 deficiency as well as muscle biopsies from SEPN1-RM patients. Mouse models of SEPN1 deficiency showed marked alterations in mitochondrial physiology and energy metabolism, suggesting that SEPN1 controls mitochondrial bioenergetics. Moreover, we found that SEPN1 was enriched at the mitochondria-associated membranes (MAM), and was needed for calcium transients between ER and mitochondria, as well as for the integrity of ER-mitochondria contacts. Consistently, loss of SEPN1 in patients was associated with alterations in body composition which correlated with the severity of muscle weakness, and with impaired ER-mitochondria contacts and low ATP levels. Our results indicate a role of SEPN1 as a novel MAM protein involved in mitochondrial bioenergetics. They also identify a systemic bioenergetic component in SEPN1-RM and establish mitochondria as a novel therapeutic target. This role of SEPN1 contributes to explain the fatigue and core lesions in skeletal muscle as well as the body composition abnormalities identified as part of the SEPN1-RM phenotype. Finally, these results point out to an unrecognized interplay between mitochondrial bioenergetics and ER homeostasis in skeletal muscle. They could therefore pave the way to the identification of biomarkers and therapeutic drugs for SEPN1-RM and for other disorders in which muscle ER-mitochondria cross-talk are impaired

Disrupted autophagy undermines skeletal muscle adaptation and integrity

This review assesses the importance of proteostasis in skeletal muscle maintenance with a specific emphasis on autophagy. Skeletal muscle appears to be particularly vulnerable to genetic defects in basal and induced autophagy, indicating that autophagy is co-substantial to skeletal muscle maintenance and adaptation. We discuss emerging evidence that tension-induced protein unfolding may act as a direct link between mechanical stress and autophagic pathways. Mechanistic links between protein damage, autophagy and muscle hypertrophy, which is also induced by mechanical stress, are still poorly understood. However, some mouse models of muscle disease show ameliorated symptoms upon effective targeting of basal autophagy. These findings highlight the importance of autophagy as therapeutic target and suggest that elucidating connections between protein unfolding and mTOR-dependent or mTOR-independent hypertrophic responses is likely to reveal specific therapeutic windows for the treatment of muscle wasting disorders

Understanding of radiation effects and damage in nuclear reactors materials using JANNuS ion beams

International audienceIon accelerators have been used by material scientists for decades to investigate radiation damage formation in nuclear materials and thus to emulate neutron-induced changes. The versatility of conditions in terms of particle energy, dose rate, fluence is a key asset of ion beams allowing for well-controlled analytical studies. In addition, very short irradiation times and handling of non-radioactive samples dramatically curtail the global cost and duration as compared to in-reactor testing. Coupling of two or more beams, use of heated/cooled sample holders, and implementation of in situ characterization and microscopy pave the way to real time observation of microstructural and property evolution in various extreme radiation conditions more closely mimicking the nuclear environments. For these reasons, multiple ion beam facilities have been commissioned worldwide.In France, under the auspices of the Universite Paris-Saclay, the JANNuS platform for Joint Accelerators for Nanosciences and Nuclear Simulation comprises five ion implanter and accelerators with complementary performances. At CSNSM Orsay, a 200 kV Transmission Electron Microscope is coupled to an accelerator and an implanter for in situ observation of microstructure modifications induced by ion beams. At CEA Saclay, the unique triple beam facility in Europe allows the simultaneous irradiation with ions (Fe, Xe, W) for nuclear recoil damage and implantation of a large array of ions including gasses for well-controlled modelling-oriented experiments.Examples are given to illustrate the use of JANNuS ion beams in investigating the radiation resistance of structural materials for Generation IV reactors as well as GenII/III and fusion reactors. Materials of interest are ODS steels, model ferritic alloys, austenitic steels and metallic coatings. The main focus of this presentation is on studies pairing in situ microscopy at low to intermediate doses to elucidate the initial steps of damage formation and irradiation at JANNuS Saclay to characterize degradation up to high doses

Etude de l'endommagement induit par rayonnement dans des matériaux d'intérêt nucléaire à l'aide des faisceaux d'ions multiples de JANNuS

International audienceIon accelerators have been used by material scientists for decades to investigate radiation damage formation in nuclear materials and thus to emulate neutron-induced changes. The versatility of conditions in terms of particle energy, dose rate, fluence, etc., is a key asset of ion beams allowing for fully instrumented analytical studies. In addition, very short irradiation times and handling of non-radioactive samples dramatically curtail the global cost and duration as compared to in-reactor testing. Coupling of two or more beams, use of heated/cooled sample holders, and implementation of in situ characterization and microscopy pave the way to real time observation of microstructural and property evolution in various extreme radiation conditions more closely mimicking the nuclear environments. For these reasons, multiple ion beam facilities have been commissioned worldwide. In France, under the auspices of the Université Paris-Saclay, the JANNuS platform for 'Joint Accelerators for Nanosciences and Nuclear Simulation' comprises five ion implanter and electrostatic accelerators with complementary performances. At CSNSM (CNRS & Univ Paris-Sud, Orsay), a 200 kV Transmission Electron Microscope is coupled to an accelerator and an implanter for in situ observation of microstructure modifications induced by ion beams in a material, making important contribution to the understanding of physical phenomena at the nanoscale. At CEA Paris-Saclay, the unique triple beam facility in Europe allows the simultaneous irradiation with heavy ions (like Fe, W) for nuclear recoil damage and implantation of a large array of ions including gasses for well-controlled modelling-oriented experiments. Several classes of materials are of interest for the nuclear industry ranging from metals and alloys, to oxides or glasses and carbides. This paper gives selected examples that illustrate the use of JANNuS ion beams in investigating the radiation resistance of structural materials for today's and tomorrow's nuclear reactors

Thermodynamical behaviour of domain walls in ordered alloys : an experimental study by transmission electron microscopy

No abstract availabl

Recherche du mécanisme d’oxydation d’un alliage Ni-Cr par la vapeur d’eau

Pour une application dans les Réacteurs à Caloporteur Gaz, le comportement en oxydation de l’alliage Ni-22Cr-14W-1Mo a été étudié à 850 °C sous hélium avec des teneurs en vapeur d’eau de 20–80 Pa et en hydrogène de 20–4000 Pa. Il est admis que le pouvoir oxydant du gaz peut influer sur la croissance de l’oxyde de chrome superficiel des matériaux chromino-formeurs. Une étude paramétrique par thermogravimétrie a montré que les cinétiques d’oxydation de l’alliage Ni-22Cr-14W-1Mo sont paraboliques sur 250 h. La pression partielle d’oxygène n’a pas d’effet direct sur la constante de vitesse; par contre, la constante dépend à la fois de la pression partielle en hydrogène et de la pression partielle en vapeur d’eau. La surface des échantillons, caractérisée après exposition par microscopie électronique, diffraction des rayons X et analyse dispersive en énergie, est couverte d’une couche d’oxyde de chrome associé au manganèse. Des analyses plus poussées par photo-électrochimie et spectroscopie de masse d’ions secondaires révèlent que cet oxyde pourrait comporter simultanément deux types de défauts cationiques. Une description mécaniste de la croissance de la couche à partir des deux défauts offre une approche qualitative de l’influence couplée des pressions partielles en hydrogène et en vapeur