El asentamiento orientalizante e ibérico antiguo de "La Rábita", Guardamar del Segura (Alicante). Avance de las excavaciones 1996-1998

[es] Al sur de la desembocadura del río Segura, la excavación de La Rábita califal ha revelado la existencia, en el mismo lugar, de un establecimiento de época Orientalizante/Protoibérica e Ibérica Antigua. El hábitat, cuya historia empieza probablemente a finales del siglo VIII o en tomo al 700 a.C., en un momento que se puede fijar hacia el 600 a.C., fue rodeado de una potente muralla que incluye una superficie de 1,5 Ha. El asentamiento ha sido un lugar de intercambios intensos con el mundo orientalizante y fenicio-occidental. [fr] L´établissement orientalisant et ibérique ancien de "La Rábita", Guardamar del Segura (Alicante, Espagne). Campagnes de fouilles, 1996-1998. Au sud de l´embouchure du Segura, la fouille de La Rábita califale a révélé l´existence, au même emplacement, d'un établissement d'époque Orientalisante/Protoibérique et Ibérique Ancienne. L'habitat dont l'histoire commence probablement à la fin du VIIIe siècle ou aux environ de 700 avant J.-C.a été, à un moment que l´on peut situer autour de 600, entouré d'une puissante enceinte; il est alors vaste de 1,5 hectares. L'établissement a été un lieu d'échanges actifs avec le monde orientalisant et phénicien d'Occident

Increased Prevalence of Alloimmunization in Sickle Cell Disease? Should We Restore Blood Donation in French Guiana?

Patients with sickle cell disease often undergo frequent blood transfusions. This increases their exposure to red blood cell alloantigens of donor units, thus making it more likely that they produce alloantibodies. This cross-sectional study aimed to describe the prevalence of allo-immunization in patients with sickle cell disease who were monitored at Cayenne Hospital in 2016. Of the 451 patients recruited during the study period, 238 (52.8%) were female. There were 262 (58.1%) homozygous sickle cell and 151 (33.5%) compound heterozygous sickle cell patients. The median age of the participants was 23.09 years (range, 0.5–68). We noted different red blood cell extended phenotypes: -in the Duffy system, the Fya- Fyb–profile was found in 299 patients (66%);—for the Kidd system, the most represented profile was Jka+ Jkb-, with 213 patients (47%). The Jka antigen was present in 355 patients;—in the MNS system, the S-s+ profile was found in 297 patients (66%);—the Lea antigen of the Lewis system was absent in 319 patients. The most frequent Rh phenotype in our patients was D+ C- E- c+ e+ K-, representing 51% of the patients. A total of 6,834 transfused packed red blood cell units were recorded. Sixty-eight patients (23%; 95% confidence interval, 20–25%) had detectable RBC alloantibodies. In multivariate logistic regression, only the mean number of single transfusions was statistically higher for the alloimmunized patients (p < 0.04). Thirteen (19%) of the patients with alloimmunization developed a delayed hemolytic transfusion reaction, thus representing 4.4% of the total number of transfused patients. Whether differences between donors from France vs. recipients from French Guiana could explain this high prevalence of alloimmunization to be examined. In conclusion, careful transfusion strategies for patients with RBC alloantibodies should allow further reduction of the rate of alloimmunization

Light-driven processes: key players of the functional biodiversity in microalgae

International audienc

Omecamtiv mecarbil in chronic heart failure with reduced ejection fraction, GALACTIC‐HF: baseline characteristics and comparison with contemporary clinical trials

Aims: The safety and efficacy of the novel selective cardiac myosin activator, omecamtiv mecarbil, in patients with heart failure with reduced ejection fraction (HFrEF) is tested in the Global Approach to Lowering Adverse Cardiac outcomes Through Improving Contractility in Heart Failure (GALACTIC‐HF) trial. Here we describe the baseline characteristics of participants in GALACTIC‐HF and how these compare with other contemporary trials. Methods and Results: Adults with established HFrEF, New York Heart Association functional class (NYHA) ≥ II, EF ≤35%, elevated natriuretic peptides and either current hospitalization for HF or history of hospitalization/ emergency department visit for HF within a year were randomized to either placebo or omecamtiv mecarbil (pharmacokinetic‐guided dosing: 25, 37.5 or 50 mg bid). 8256 patients [male (79%), non‐white (22%), mean age 65 years] were enrolled with a mean EF 27%, ischemic etiology in 54%, NYHA II 53% and III/IV 47%, and median NT‐proBNP 1971 pg/mL. HF therapies at baseline were among the most effectively employed in contemporary HF trials. GALACTIC‐HF randomized patients representative of recent HF registries and trials with substantial numbers of patients also having characteristics understudied in previous trials including more from North America (n = 1386), enrolled as inpatients (n = 2084), systolic blood pressure < 100 mmHg (n = 1127), estimated glomerular filtration rate < 30 mL/min/1.73 m2 (n = 528), and treated with sacubitril‐valsartan at baseline (n = 1594). Conclusions: GALACTIC‐HF enrolled a well‐treated, high‐risk population from both inpatient and outpatient settings, which will provide a definitive evaluation of the efficacy and safety of this novel therapy, as well as informing its potential future implementation

Les glutathion peroxydases et protéine disulfure isomérases de peuplier (potentialités du repliement thiorédoxine pour la catalyse des réactions redox)

La formation de ponts disulfure constitue une modification post-traductionnelle des protéines importante pour de nombreux processus physiologiques, jouant un rôle particulier dans le repliement, la catalyse et la régulation de leur activité. Ce travail concerne l'étude des relations structure-fonction d'oxydoréductases de peuplier appartenant à deux familles de la superfamille des thiorédoxines, les glutathion peroxydases (Gpxs) et les protéine disulfure isomérases (PDIs).L'étude biochimique fine de la Gpx5 a permis de montrer que cette peroxydase réduit le peroxynitrite, propriété inconnue pour ce type de Gpx et de détailler plusieurs étapes du mécanisme catalytique (formation de l'acide sulfénique, changement structural entre formes réduites et oxydées, régénération par les Trxs). La dimérisation de la Gpx5 n'est pas requise pour son activité mais pourrait jouer un rôle dans la reconnaissance de certains substrats. Enfin, l'inactivation de la cystéine peroxydatique par suroxydation suggère que les Gpxs pourraient également avoir une fonction dans la signalisation en réponse aux peroxydes.Concernant les PDIs, suite à une analyse phylogénétique détaillée amenant à proposer une nouvelle classification en 9 classes chez les organismes photosynthétiques, la caractérisation biochimique de plusieurs isoformes présentant des organisations modulaires distinctes et appartenant à trois classes de PDIs a été entreprise. Aucune activité enzymatique typique n'a été identifiée pour la PDI-A, alors que les PDI-L1a et -M possèdent à la fois une activité oxydase et réductase. Les deux modules a de la PDI-M catalysent des réactions spécifiques, de réduction ou d'oxydation.Protein activity and folding can be regulated by post-translational modifications that can impact on their physiological functions. One of these is the formation/reduction of disulfide bridges. The aim of the present work is to study the structure-function relationship of protein members of the thioredoxin superfamily, the protein disulfide isomerases (PDI) and the glutathione peroxidases (Gpx).A precise biochemical study has allowed us to demonstrate that this enzyme is an efficient peroxynitrite scavenger, a new finding for this type of protein and allowed investigating several steps of the Gpx5 catalytic mechanism (i.e. sulfenic acid formation, structural changes between reduce dand oxidized forms, Trx-mediated recycling). We also demonstrate that the dimer form of Gpx5 is not absolutely required for peroxide reduction but probably involved in peroxide specificity. Finally, the capability of the peroxidatic cysteine to be overoxidized brings some new clues in favor of an additional signaling function for Gpx5.Concerning PDIs, a detailed phylogenetic analysis of photosynthetic organisms allowed us to identify 9 classes of PDIs and to propose a new nomenclature that fits all these organisms. The biochemical characterization of isoforms of interest has allowed us to highlight some specificity of PDI-L1a and PDI-M in terms of reduction or oxidation reactions catalyzed. A detailed analysis of PDI-M isoform also indicates that the two Trx modules of this protein show differential oxidation or reduction capacities. We could not detect any activity for PDI-A isoforms, leaving us to wonder whether this enzyme is simply active or possesses highly specific protein partners.NANCY1-Bib. numérique (543959902) / SudocSudocFranceF

El asentamiento orientalizante e ibérico antiguo de "La Rábita", Guardamar del Segura (Alicante). Avance de las excavaciones 1996-1998

[es] Al sur de la desembocadura del río Segura, la excavación de La Rábita califal ha revelado la existencia, en el mismo lugar, de un establecimiento de época Orientalizante/Protoibérica e Ibérica Antigua. El hábitat, cuya historia empieza probablemente a finales del siglo VIII o en tomo al 700 a.C., en un momento que se puede fijar hacia el 600 a.C., fue rodeado de una potente muralla que incluye una superficie de 1,5 Ha. El asentamiento ha sido un lugar de intercambios intensos con el mundo orientalizante y fenicio-occidental. [fr] L´établissement orientalisant et ibérique ancien de "La Rábita", Guardamar del Segura (Alicante, Espagne). Campagnes de fouilles, 1996-1998. Au sud de l´embouchure du Segura, la fouille de La Rábita califale a révélé l´existence, au même emplacement, d'un établissement d'époque Orientalisante/Protoibérique et Ibérique Ancienne. L'habitat dont l'histoire commence probablement à la fin du VIIIe siècle ou aux environ de 700 avant J.-C.a été, à un moment que l´on peut situer autour de 600, entouré d'une puissante enceinte; il est alors vaste de 1,5 hectares. L'établissement a été un lieu d'échanges actifs avec le monde orientalisant et phénicien d'Occident

The chloroplastic thiol reducing systems: Dual functions in the regulation of carbohydrate metabolism and regeneration of antioxidant enzymes, emphasis on the poplar redoxin equipment

International audienceThe post-translational modification consisting in the formation/reduction of disulfide bonds has been the subject of intense research in plants since the discovery in the 1970s that many chloroplastic enzymes are regulated by light through dithiol–disulfide exchange reactions catalyzed by oxidoreductases called thioredoxins (Trxs). Further biochemical and proteomic studies have considerably increased the number of target enzymes and processes regulated by these mechanisms in many sub-cellular compartments. Recently, glutathionylation, a modification consisting in the reversible formation of a glutathione adduct on cysteine residues, was proposed as an alternative redox regulation mechanism. Glutaredoxins (Grxs), proteins related to Trxs, are efficient catalysts for deglutathionylation, the opposite reaction. Hence, the Trxs- and Grxs-dependent pathways might constitute complementary and not only redundant regulatory processes. This article focuses on these two multigenic families and associated protein partners in poplar and on their involvement in the regulation of some major chloroplastic processes such as stress response, carbohydrate and heme/chlorophyll metabolism

Peroxide detoxification systems in poplar

International audienc