Multimodal nanogels combining ZW800-1 as an optical absorber and gadolinium chelates for multispectral optoacoustic tomography (MSOT) and magnetic resonance imaging (MRI) »

peer reviewe

Automatisation des mesures cinétiques en dynamique dans le cas de la réaction catalytique gaz-solide d'oxydation ménagée du propène

We have developed an apparatus to study the kinetics of the catalytic reaction of propylene soft oxdation in a flowing system. Following a preestablished program, the apparatus is able to execute a series of measurements without the need for operator interference. In this way we have collected a significantly increased volume of experimental values and we can now envisage a statistical treatment of these values. This development has led us to co nceive of and realize several new types of apparatus.Nous avons réalisé un appareil pour l'étude cinétique en dynamique de la réaction catalytique d'oxydation ménagée du propène, pouvant effectuer des séries de mesures sans l'intervention d'un opérateur et suivant un programme préétabli. Le nombre de valeurs expérimentales obtenues s'en trouve considérablement accru, ce qui rend plus sûre l'interprétation des résultats et permet d'envisager un dépouillement statistique. Cette réalisation nous a conduit à concevoir et mettre au point un certain nombre de systèmes originaux que nous décrivons dans ce texte

Fluconazole in hypercalciuric patients with increased 1,25(OH)(2)D levels: the prospective, randomized, placebo-controlled, double-blind FLUCOLITH trial

International audienceBACKGROUND: Hypercalciuria is one of the most frequent metabolic disorders associated with nephrolithiasis and/or nephrocalcinosis possibly leading to chronic kidney disease (CKD) and bone complications in adults. Orphan diseases with different underlying primary pathophysiology share inappropriately increased 1,25(OH)(2)D levels and hypercalciuria, e.g., hypersensitivity to vitamin D and renal phosphate wasting. Their management is challenging, typically based on hyperhydration and dietary advice. The antifungal azoles are known to inhibit the 1α-hydroxylase and therefore decrease 1,25(OH)(2)D levels; they are commonly used, with well described pharmacokinetic and tolerability data. Fluconazole has been successfully reported to reduce calciuria in patients with CYP24A1 or SLC34A3 mutations, with no safety warnings. Thus, based on these case reports, we hypothesize that fluconazole is effective to decrease and normalize calciuria in patients with hypercalciuria and increased 1,25(OH)(2)D levels. METHODS: The FLUCOLITH trial is a prospective, interventional, randomized in parallel groups (1:1), placebo-controlled, double-blind trial. A total of 60 patients (10-60 years) with nephrolithiasis and/or nephrocalcinosis history, hypercalciuria (\textgreater 0.1 mmol/kg/day), increased 1,25(OH)(2)D levels (\textgreater 150 pmol/L), and 25-OH-D levels \textgreater20 nmol/L will be included. Inclusions will be performed only from mid-September to the beginning of February to avoid bias due to sunlight-induced vitamin D synthesis. The primary endpoint will be the proportion of patients with normalization of 24-h calciuria between baseline and 16 weeks, or with a relative decrease of at least 30% of 24-h calciuria in patients who still display at W16 a 24-h hypercalciuria. DISCUSSION: The current challenge is to propose an efficient treatment to patients with hypercalciuria and increased 1,25(OH)(2)D levels in order to prevent later complications and notably CKD that can ultimately lead to end-stage renal disease. Based on improvement of knowledge in phosphate/calcium metabolism, pathophysiology and genetics, the "off-label" use of fluconazole was recently reported to be useful in hypercalciuric patients with increased 1,25(OH)(2)D levels. Thus, the FLUCOLITH study is a unique opportunity to develop a new indication of a well-known and not expensive drug in orphan renal diseases, the ultimate objective being the secondary prevention of CKD worsening in these patients. TRIAL REGISTRATION: ClinicalTrials.gov NCT04495608 . Registered on July 23, 2020

Root cone angle is enlarged in docs1 LRR-RLK mutants in rice

Abstract Background The DEFECTIVE IN OUTER CELL LAYER SPECIFICATION 1 (DOCS1) gene belongs to the Leucine-Rich Repeat Receptor-Like Kinase (LRR-RLK) subfamily. It has been discovered few years ago in Oryza sativa (rice) in a screen to isolate mutants with defects in sensitivity to aluminum. The c68 (docs1–1) mutant possessed a nonsense mutation in the C-terminal part of the DOCS1 kinase domain. Findings We have generated a new loss-of-function mutation in the DOCS1 gene (docs1–2) using the CRISPR-Cas9 technology. This new loss-of-function mutant and docs1–1 present similar phenotypes suggesting the original docs1–1 was a null allele. Besides the aluminum sensitivity phenotype, both docs1 mutants shared also several root phenotypes described previously: less root hairs and mixed identities of the outer cell layers. Moreover, our new results suggest that DOCS1 could also play a role in root cap development. We hypothesized these docs1 root phenotypes may affect gravity responses. As expected, in seedlings, the early gravitropic response was delayed. Furthermore, at adult stage, the root gravitropic set angle of docs1 mutants was also affected since docs1 mutant plants displayed larger root cone angles. Conclusions All these observations add new insights into the DOCS1 gene function in gravitropic responses at several stages of plant development