Evaluation de l'irradiation reçue par l'entourage familial des patients traités par l'iode 131 pour un cancer de la thyroïde

A la sortie de l hôpital, les patients traités par l iode 131 pour un cancer de la thyroïde sont une source d irradiation pour leurs proches. Cette étude a pour objectif d évaluer cette exposition afin d améliorer la pertinence des recommandations de radioprotection données lors du retour au domicile.Pour mesurer la dose reçue, les membres de la famille ont été munis de dosimètres opérationnels pendant une semaine permettant un suivi en temps réel de l exposition. 27 sujets âgés de 4 à 70 ans issus de l entourage familial de 21 patients traités par l iode 131 pour un cancer de la thyroïde ont été inclus depuis avril 2008. La dose cumulée moyenne sur un intervalle de temps de 7 jours était de 39,1 +-32,1 microsieverts.Les résultats obtenus montrent des valeurs situées très en dessous des contraintes de dose européennes. Ils fournissent au médecin nucléaire les données permettant de renseigner le patient sur l exposition de ses proches suite à son traitement.CHATENAY M.-PARIS 11-BU Pharma. (920192101) / SudocSudocFranceF

A New Miniaturized Gas Sensor Based on Zener Diode Network Covered by Metal Oxide

International audienceThe development of “portable, low cost and low consumption” gas microsensors is one of the strong needs for embedded portable devices in many fields such as public domain. In this paper, a new approach is presented on making, on the same chip, a network of head-to-tail facing PN junctions in order to miniaturize the sensor network and considerably reduce the required power for heating each cell independently. This paper is about recognizing a device that integrates both sensing and self-heating. This first study aims to evaluate the possibilities of this type of diode network for use as a gas sensor. The first part concerns the description of the technological process that is based on a doped polysilicon wafer in which a thin layer of metal oxide (a gallium-doped zinc oxide in our case) is deposited by RF sputtering. An electrical model will be proposed to explain the operation and advantage of this approach. We will show the two types of tests that have been carried out (static and dynamic) as well as the first encouraging results of these electrical characterizations under variable atmospheres

Structural determinants of DNA recognition by the NO sensor NsrR and related Rrf2-type [FeS]-transcription factors

International audienceAbstract Several transcription factors of the Rrf2 family use an iron-sulfur cluster to regulate DNA binding through effectors such as nitric oxide (NO), cellular redox status and iron levels. [4Fe-4S]-NsrR from Streptomyces coelicolor ( Sc NsrR) modulates expression of three different genes via reaction and complex formation with variable amounts of NO, which results in detoxification of this gas. Here, we report the crystal structure of Sc NsrR complexed with an hmpA1 gene operator fragment and compare it with those previously reported for [2Fe-2S]-RsrR/ rsrR and apo-IscR/ hyA complexes. Important structural differences reside in the variation of the DNA minor and major groove widths. In addition, different DNA curvatures and different interactions with the protein sensors are observed. We also report studies of NsrR binding to four hmpA1 variants, which indicate that flexibility in the central region is not a key binding determinant. Our study explores the promotor binding specificities of three closely related transcriptional regulators

Probing the Reactivity of [4Fe-4S] Fumarate and Nitrate Reduction (FNR) Regulator with O2 and NO: Increased O2 Resistance and Relative Specificity for NO of the [4Fe-4S] L28H FNR Cluster

The Escherichia coli fumarate and nitrate reduction (FNR) regulator acts as the cell’s master switch for the transition between anaerobic and aerobic respiration, controlling the expression of >300 genes in response to O2 availability. Oxygen is perceived through a reaction with FNR’s [4Fe-4S] cluster cofactor. In addition to its primary O2 signal, the FNR [4Fe-4S] cluster also reacts with nitric oxide (NO). In response to physiological concentrations of NO, FNR de-represses the transcription of hmp, which encodes a principal NO-detoxifying enzyme, and fails to activate the expression of the nitrate reductase (nar) operon, a significant source of endogenous cellular NO. Here, we show that the L28H variant of FNR, which is much less reactive towards O2 than wild-type FNR, remains highly reactive towards NO. A high resolution structure and molecular dynamics (MD) simulations of the closely related L28H-FNR from Aliivibrio fischeri revealed decreased conformational flexibility of the Cys20-Cys29 cluster-binding loop that is suggested to inhibit outer-sphere O2 reactivity, but only partially impair inner-sphere NO reactivity. Our data provide new insights into the mechanistic basis for how iron–sulfur cluster regulators can distinguish between O2 and NO

DHR51, the Drosophila melanogaster Homologue of the Human Photoreceptor Cell-Specific Nuclear Receptor, Is a Thiolate Heme-Binding Protein

International audienceHeme has been recently described as a regulating ligand for the activity of the human nuclear receptors (NR) REV-ERB alpha and REV-ERB beta and their Drosophila homologue E75. Here, we report the cloning, expression in Escherichia coli, purification, and screening for the heme-binding ability of 11 NR ligand-binding domains of Drosophila melanogaster (DHR3, DHR4, DHR39, DHR51, DHR78, DHR83, HNF4, TLL, ERR, FTZ-F1, and E78), of unknown structure. One of these NRs, DHR51, homologous to the human photoreceptor cell-specific nuclear receptor (PNR), specifically binds heme and exhibits a UV-visible spectrum identical to that of heme-bound E75-LBD. EPR and UV-visible absorption spectroscopy indicates that, like in E75, the heme contains a hexa-coordinated low spin ferric iron. One of its axial ligands is a tightly bound cysteine, while the other one is a histidine. A dissociation constant of 0.5 mu M for the heme was measured by isothermal titration calorimetry. We show that DHR51 binds NO and CO and discuss the possibility that DHR51 may be either a gas or a heme sensor

Crystal structure of the ligand-binding domain of the retinoid X receptor from the ascidian polyandrocarpa misakiensis

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Crystal structure of a novel tetrameric complex of agonist-bound ligand-binding domain of Biomphalaria glabrata retinoid X receptor

International audienc

Use of anti-CMV immunoglobulins in lung transplant recipients: The French experience

International audienceRational: Pending the authorization of new anti-CMV drugs with fewer adverse effects, exploring the possibilities offered by CMV immunoglobulins (CMVIG) seems necessary. In France, access to CMVIG requires official authorization by the national Health authority and is restricted to second line rescue therapy for CMV infection/disease. The aim of this multicenter retrospective study is to describe the indications and clinical situations that justified its use in France. Methods: A multicenter retrospective study included 22 lung transplant patients over a 3-year period. Data on clinical indication, tolerance and efficacy were collected. Results: The main indication for CMVIG initiation, which was documented in 17 of them (82%) was complex clinical situations resulting from side effects to antiviral drug. CMVIG indication was documented as treatment for 15 patients (68%) and as a secondary prophylaxis for 7 patients (32%). Only one side effect (pruritus during infusion with no anaphylactic symptoms) attributable to CMVIG was reported. After CMVIG initiation, no recurrence of infection or disease was observed during a median follow-up of 174 (12–682) days after treatment initiation for respectively 68% and 66% of the patients. Conclusion: This study describes an unusual indication of CMVIG use as a last resort treatment in complex situations, based on clinical needs. CMVIG could be useful to change the course of CMV infection with minimal adverse effects or comorbidity

An Immunogenicity Report for the Comparison between Heterologous and Homologous Prime-Boost Schedules with ChAdOx1-S and BNT162b2 Vaccines

Background: There is a small amount of immunological data on COVID-19 heterologous vaccination schedules in humans. We assessed the immunogenicity of BNT162b2 (Pfizer/BioNTech) administered as a second dose in healthcare workers primed with ChAdOx1-S (Vaxzevria, AstraZeneca). Methods: 197 healthcare workers were included in a monocentric observational study in Foch hospital, France, between June and July 2021. The main outcome was the immunogenicity measured by serum SARS-CoV-2 IgG antibodies. Results: 130 participants received the ChAdOx1-S/BNT vaccine and 67 received the BNT/BNT vaccine. The geometric mean of IgG antibodies was significantly higher in the BNT/BNT vaccine group compared to the ChAdOx1-S/BNT vaccine group, namely 10,734.9, 95% CI (9141.1–12,589.3) vs. 7268.6, 95% CI (6501.3–8128.3), respectively (p < 0.001). However, after adjustment for time duration between the prime and second vaccinations, no significant difference was observed (p = 0.181). A negative correlation between antibody levels and time duration between second dose and serology test was observed for the BNT/BNT vaccine (p < 0.001), which remained significant after adjustment for all covariates (p < 0.001), but not for the ChAdOx1-S/BNT vaccine (p = 0.467). Conclusions: Heterologous and homologous schedules of ChAdOx1-S and BNT vaccines present robust immune responses after the second vaccination. The results observed were equivalent after adjustment for covariates and emphasize the importance of flexibility in deploying mRNA and viral vectored vaccines. Nevertheless, applying the ChAdOx1-S schedule vaccination for the heterologous second dose of BNT was associated with decreased IgG antibody levels compared to the homologous BNT/BNT vaccination