Chemo-enzymatic synthesis of a series of 2,4-syn-functionalized (S)-glutamate analogues: new insight into the structure-activity relation of ionotropic glutamate receptor subtypes 5, 6, and 7.

International audience(S)-Glutamic acid (Glu) is the major excitatory neurotransmitter in the central nervous system (CNS) activating the plethora of ionotropic Glu receptors (iGluRs) and metabotropic Glu receptors (mGluRs). In this paper, we present a chemo-enzymatic strategy for the enantioselective synthesis of five new Glu analogues 2a−f (2d is exempt) holding a functionalized substituent in the 4-position. Nine Glu analogues 2a−j are characterized pharmacologically at native 2-amino-3-(3-hydroxy-5-methyl-4-isoxazolyl)propionic acid (AMPA), kainic acid (KA), and N-methyl-D-aspartic acid (NMDA) receptors in rat synaptosomes as well as in binding assays at cloned rat iGluR5−7 subtypes. A detailed in silico study address as to why 2h is a high-affinity ligand at iGluR5−7 (Ki = 3.81, 123, 57.3 nM, respectively), while 2e is only a high affinity ligand at iGluR5 (Ki = 42.8 nM). Furthermore, a small series of commercially available iGluR ligands are characterized in iGluR5−7 bindin

Aminotransferases for the stereospecific synthesis of glutamic acid analogues

Poste

Dernières avancées dans les fontaines atomiques

Nous décrivons le travail réalisé au LNE-SYRTE (Observatoire de Paris) ces dernières années, en vue de l'amélioration et de l'utilisation d'étalons de fréquence micro-onde fondés sur l'utilisation d'atomes refroidis par laser. Nous exposons les améliorations récentes des fontaines atomiques à $^{133}$Cs et $^{87}$Rb. La précision atteinte sur la réalisation de la seconde avec de tels systèmes (une exactitude relative de $7.10^{-16}$) permet de mener des expériences de physique fondamentale poussées et ouvre un champ d'applications dans les domaines de la navigation et des télécommunications

Dernières avancées dans les fontaines atomiques

National audienceNous décrivons le travail réalisé au LNE-SYRTE (Observatoire de Paris) ces dernières années, en vue de l'amélioration et de l'utilisation d'étalons de fréquence micro-onde fondés sur l'utilisation d'atomes refroidis par laser. Nous exposons les améliorations récentes des fontaines atomiques à <SUP>133</SUP>Cs et <SUP>87</SUP>Rb. La précision atteinte sur la réalisation de la seconde avec de tels systèmes (une exactitude relative de 7.10<SUP>-16</SUP>) permet de mener des expériences de physique fondamentale poussées et ouvre un champ d'applications dans les domaines de la navigation et des télécommunications

Low incidence of SARS-CoV-2, risk factors of mortality and the course of illness in the French national cohort of dialysis patients

International audienceThe aim of this study was to estimate the incidence of COVID-19 disease in the French national population of dialysis patients, their course of illness and to identify the risk factors associated with mortality. Our study included all patients on dialysis recorded in the French REIN Registry in April 2020. Clinical characteristics at last follow-up and the evolution of COVID-19 illness severity over time were recorded for diagnosed cases (either suspicious clinical symptoms, characteristic signs on the chest scan or a positive reverse transcription polymerase chain reaction) for SARS-CoV-2. A total of 1,621 infected patients were reported on the REIN registry from March 16th, 2020 to May 4th, 2020. Of these, 344 died. The prevalence of COVID-19 patients varied from less than 1% to 10% between regions. The probability of being a case was higher in males, patients with diabetes, those in need of assistance for transfer or treated at a self-care unit. Dialysis at home was associated with a lower probability of being infected as was being a smoker, a former smoker, having an active malignancy, or peripheral vascular disease. Mortality in diagnosed cases (21%) was associated with the same causes as in the general population. Higher age, hypoalbuminemia and the presence of an ischemic heart disease were statistically independently associated with a higher risk of death. Being treated at a selfcare unit was associated with a lower risk. Thus, our study showed a relatively low frequency of COVID-19 among dialysis patients contrary to what might have been assumed