Retrospective study of COVID-19 seroprevalence among tissue donors at the onset of the outbreak before implementation of strict lockdown measures in France

Cell and Tissue Banking - Background The COVID-19 pandemic has altered organ and tissue donations as well as transplantation practices. SARS-CoV-2 serological tests could help in the selection of...     

A 5-HT4 receptor transmembrane network implicated in the activity of inverse agonists but not agonists

Activation of G protein-coupled receptors is thought to involve disruption of intramolecular interactions that stabilize their inactive conformation. Such disruptions are induced by agonists or by constitutively active mutations. In the present study, novel potent inverse agonists are described to inhibit the constitutive activity of 5-HT(4) receptors. Using these compounds and specific receptor mutations, we investigated the mechanisms by which inverse agonists may reverse the disruption of intramolecular interactions that causes constitutive activation. Two mutations (D100(3.32)A in transmembrane domain (TMD)-III and F275(6.51)A in TMD-VI) were found to completely block inverse agonist effects without impairing their binding properties nor the molecular activation switches induced by agonists. Based on the rhodopsin model, we propose that these mutated receptors are in equilibrium between two states R and R* but are unable to reach a third "silent" state stabilized by inverse agonists. We also found another mutation in TMD-VI (W272(6.48)A) that stabilized this silent state. This mutant remained fully activated by agonists. Molecular modeling indicated that Asp-100, Phe-275, and Trp-272 might constitute a network required for stabilization of the silent state by the described inverse agonists. However, this network is not necessary for agonist activity.     

Life expectancy estimates as a key factor in over-treatment: The case of prostate cancer

Objective: To estimate the magnitude of over-diagnosis and of potential and actual over-treatment regarding prostate cancer, taking comorbidities into account. Materials and methods: We used a sample collected by the French cancer registries of 1840 cases (T1: 583; T2: 1257) diagnosed in 2001. The proportion of over-diagnosed and over-treated patients was estimated by comparing life expectancy (LE), including or not comorbidities, with natural LE with cancer, using several assumptions from the literature. We distinguished potential and actual over-treatment according to the treatment that patients actually received. Results: Among patients with T1 tumors the proportion of potential over-treatment using LE adjusted for comorbidity varied from 29.5% to 53.5%, using LE adjusted on comorbidities, and varied from 9.3% to 22.2% regarding actual over-treatment. Between 7.7% and 24.4% of patient's receiving a radical prostatectomy, and between 30.8% and 62.5% of those receiving radiotherapy, were over-treated. Among patients with T2 tumors, the proportions of potential and actual over-treatment were 0.9% and 2.0%. Two per cent of patients receiving a radical prostatectomy and 4.9% of those receiving radiotherapy were over-treated. Comorbidities dramatically increased these proportions to nearly 100% of patients, with more than two comorbidities being potentially over-treated and around 33% actually over-treated. Conclusions: According to the French incidence, 3200–4800 French patients may be over-treated, among whom a large proportion of patients had comorbidities. The real issue is to offer the most appropriate treatment to people with low-grade tumors and comorbidities.     

An IDH1-vitamin C crosstalk drives human erythroid development by inhibiting pro-oxidant mitochondrial metabolism

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Expression of S100B during embryonic development of the mouse cerebellum

Background  

In the cerebellum of newborn S100B-EGFP mice, we had previously noted the presence of a large population of S100B-expressing cells, which we assumed to be immature Bergmann glial cells. In the present study, we have drawn on this observation to establish the precise spatio-temporal pattern of S100B gene expression in the embryonic cerebellum.