Plant RNases T2, but not Dicer-like proteins, are major players of tRNA-derived fragments biogenesis

RNA fragments deriving from tRNAs (tRFs) exist in all branches of life and the repertoire of their biological functions regularly increases. Paradoxically, their biogenesis remains unclear. The human RNase A, Angiogenin, and the yeast RNase T2, Rny1p, generate long tRFs after cleavage in the anticodon region. The production of short tRFs after cleavage in the D or T regions is still enigmatic. Here, we show that the Arabidopsis Dicer-like proteins, DCL1-4, do not play a major role in the production of tRFs. Rather, we demonstrate that the Arabidopsis RNases T2, called RNS, are key players of both long and short tRFs biogenesis. Arabidopsis RNS show specific expression profiles. In particular, RNS1 and RNS3 are mainly found in the outer tissues of senescing seeds where they are the main endoribonucleases responsible of tRNA cleavage activity for tRFs production. In plants grown under phosphate starvation conditions, the induction of RNS1 is correlated with the accumulation of specific tRFs. Beyond plants, we also provide evidence that short tRFs can be produced by the yeast Rny1p and that, in vitro, human RNase T2 is also able to generate long and short tRFs. Our data suggest an evolutionary conserved feature of these enzymes in eukaryotes

Digital Image Analysis of Picrosirius Red Staining: A Robust Method for Multi-Organ Fibrosis Quantification and Characterization

Current understanding of fibrosis remains incomplete despite the increasing burden of related diseases. Preclinical models are used to dissect the pathogenesis and dynamics of fibrosis, and to evaluate anti-fibrotic therapies. These studies require objective and accurate measurements of fibrosis. Existing histological quantification methods are operator-dependent, organ-specific, and/or need advanced equipment. Therefore, we developed a robust, minimally operator-dependent, and tissue-transposable digital method for fibrosis quantification. The proposed method involves a novel algorithm for more specific and more sensitive detection of collagen fibers stained by picrosirius red (PSR), a computer-assisted segmentation of histological structures, and a new automated morphological classification of fibers according to their compactness. The new algorithm proved more accurate than classical filtering using principal color component (red-green-blue; RGB) for PSR detection. We applied this new method on established mouse models of liver, lung, and kidney fibrosis and demonstrated its validity by evidencing topological collagen accumulation in relevant histological compartments. Our data also showed an overall accumulation of compact fibers concomitant with worsening fibrosis and evidenced topological changes in fiber compactness proper to each model. In conclusion, we describe here a robust digital method for fibrosis analysis allowing accurate quantification, pattern recognition, and multi-organ comparisons useful to understand fibrosis dynamics

Innovations 2022 en néphrologie

Nous discutons les résultats négatifs d’un essai randomisé contrôlé de l’arrêt des inhibiteurs de l’enzyme de conversion ou des sartans dans la maladie rénale chronique au stade G4 ou G5. Nous discutons ensuite les modalités d’initiation du traitement par dapagliflozine et finerenone dans la maladie rénale chronique. Enfin, nous revoyons les progrès récents dans le traitement de la néphropathie à IgA

mTORC Pathway Activation and Effect of Sirolimus on Native Kidney Antiphospholipid Syndrome Nephropathy: A Case Report.

Despite optimal anticoagulation and blood pressure control, patients with antiphospholipid syndrome (APS) nephropathy frequently progress to kidney failure, and recurrence after transplantation is common. The mTORC (mechanistic target of rapamycin complex) pathway was recently identified as a potential intermediate and a therapeutic target in vascular lesions associated with APS nephropathy. However, these results were derived from the retrospective analysis of a small cohort of patients receiving sirolimus after kidney transplantation. Therefore, they warranted external validation and the demonstration of the potential benefit of sirolimus in native kidney APS nephropathy. We report a patient with active APS nephropathy lesions occurring on native kidneys, in which endothelial mTORC activation was substantiated at the molecular level. Treatment with sirolimus was shown on a repeat kidney biopsy to successfully inhibit the AKT/mTORC pathway and was associated with significant improvement in kidney function and lesions of vasculopathy. Drug tolerance was excellent during the entire follow-up. This case validates and extends previous observations in kidney transplant recipients and demonstrates that endothelial activation of the AKT/mTORC pathway occurs in the damaged renal vasculature of native kidneys in APS nephropathy. These findings further support the potential of precision medicine and the use of mTORC activation as a biomarker of disease activity and as therapeutic target in patients with APS nephropathy

Allogeneic bone marrow transplantation in craniometaphyseal dysplasia

International audienc

κ-Carrageenan Associated with Fructose/Glycerol/Water LTTM: Toward Natural Thermosensitive Physical Gels

International audienceκ-Carrageenan was combined to a natural lowtransitiontemperature mixture composed of fructose, glycerol, andwater in a 1:1:5 molar ratio (FGW) to generate fully biobasedphysical gels through a simple method. The resulting gels can beeasily prepared in various shapes. As for their hydrogel analogues,the rheological characterization of FGW-based samples evidencedthermosensitive gelation, attributed to the formation of aggregatedH-bonded helices composed of κ-carrageenan chains. FGW-basedgels exhibit a gel−sol transition temperature (Tg/s) higher than theone of hydrogels with recoverable and reversible viscoelasticproperties upon successive heating/cooling cycles. SAXS analysisrevealed a more extended conformation of chains in FGW thatleads to more physical cross-linking junction zones within thematerials. Such peculiar spatial internal organization provides a mechanical reinforcement demonstrated by compression tests. Inconclusion, the use of the FGW solvent allows for designing κ-carrageenan physical gels with enhanced thermal and mechanicalproperties

Digital Image Analysis of Picrosirius Red Staining: A Robust Method for Multi-Organ Fibrosis Quantification and Characterization.

Current understanding of fibrosis remains incomplete despite the increasing burden of related diseases. Preclinical models are used to dissect the pathogenesis and dynamics of fibrosis, and to evaluate anti-fibrotic therapies. These studies require objective and accurate measurements of fibrosis. Existing histological quantification methods are operator-dependent, organ-specific, and/or need advanced equipment. Therefore, we developed a robust, minimally operator-dependent, and tissue-transposable digital method for fibrosis quantification. The proposed method involves a novel algorithm for more specific and more sensitive detection of collagen fibers stained by picrosirius red (PSR), a computer-assisted segmentation of histological structures, and a new automated morphological classification of fibers according to their compactness. The new algorithm proved more accurate than classical filtering using principal color component (red-green-blue; RGB) for PSR detection. We applied this new method on established mouse models of liver, lung, and kidney fibrosis and demonstrated its validity by evidencing topological collagen accumulation in relevant histological compartments. Our data also showed an overall accumulation of compact fibers concomitant with worsening fibrosis and evidenced topological changes in fiber compactness proper to each model. In conclusion, we describe here a robust digital method for fibrosis analysis allowing accurate quantification, pattern recognition, and multi-organ comparisons useful to understand fibrosis dynamics

Rheumatoid arthritis, as a clinical disease, but not rheumatoid arthritis-associated autoimmunity, is linked to cardiovascular events

International audienceBackground: Rheumatoid arthritis (RA) is characterized by increased cardiovascular (CV) mortality. CV events are particularly high in patients with RA-specific autoimmunity, including rheumatoid factor (RF) and anti-citrullinated protein antibodies (ACPA), raising the question whether RA-specific autoimmunity itself is associated with CV events. Methods: New CV events (myocardial infarction, stroke or death by CV cause) were recorded in 20,625 subjects of the Electricité de France – Gaz de France (GAZEL) cohort. Self-reported RA cases in the GAZEL cohort were validated by phone interview on the basis of a specific questionnaire. In 1618 subjects, in whom plasma was available, RF and ACPA were measured. A piecewise exponential Poisson regression was used to analyze the association of CV events with presence of RA as well as RA-specific autoimmunity (without RA). Results: CV events in GAZEL were associated with age, male sex, smoking, hypertension, hyperlipidemia, and diabetes mellitus (HR from 1.06 to 1.87, p < 0.05). Forty-two confirmed RA cases were identified. Confirmed RA was significantly associated with CV risk increase (HR of 3.03; 95% CI: 1.13–8.11, p = 0.03) independently of conventional CV risk factors. One hundred seventy-eight subjects showed RF or ACPA positivity without presence of RA. CV events were not associated with ACPA positivity (HR: 1.52, 95% CI: 0.47–4.84, p = 0.48) or RF positivity (HR: 1.15, 95% CI: 0.55–2.40, p = 0.70) in the absence of RA. Conclusions: RA, as a clinical chronic inflammatory disease, but not mere positivity for RF or ACPA in the absence of clinical disease is associated with increased CV risk

Chronic and recurrent non-infectious paediatric-onset uveitis: a French cohort

International audienc

Impact of Sediment Bioturbation on Microphytobenthic Primary Producers: Importance of Macrobenthic Functional Traits

Microphytobenthos (MPB) is one of the most important primary producers in coastal and estuarine ecosystems, where it plays a substantial role in many ecological functions. Although the influence of several environmental factors on MPB biomass and productivity is well documented, the effects of macrofaunal bioturbation remain poorly assessed. The purpose of this study was to experimentally quantify the influence of sediment bioturbation processes (that is, sediment reworking and bioirrigation) on biogeochemical fluxes across the sediment–water interface and MPB biomass and photosynthetic capacities. Two infaunal deposit feeders (the polychaete Hediste diversicolor and the bivalve Scrobicularia plana) exhibiting contrasting bioturbation modes and rates were studied as model organisms. They differently affected MPB biomass and photosynthetic performance. Hence, through an intense bioirrigation activity and the stimulation of nutrient fluxes (NH4+ , NOx, PO42− and dSi) at the sediment surface, H. diversicolor enhanced MPB growth, which seemed to compensate for its direct consumption. Conversely, high sediment reworking rates generated by S. plana, associated with an extensive grazing pressure, drastically limited the development of MPB at the sediment surface. The negative impact of bivalves on MPB biomass increased with increasing density, whereas there was no significant relationship with polychaete density, possibly due to trophic competition. This study demonstrates that macrofaunal bioturbation is a key factor regulating MPB dynamics, with complex interactions that can result in a net either positive or negative effect depending on dominant species functional traits and abundances. This may, in particular, explain the strong spatial and temporal variability of the microbenthic primary productivity in intertidal mudflats