70 research outputs found
Dossier "Les enjeux de la planification - écritures professionnelles" : regroupant artificiellement l'article des coordinateurs du dossier "Planifier l'enseignement, cela s'apprend.", ainsi que des articles d'étudiants
No full textThèmes : Les enjeux de la planification - écritures professionnelles. Capitanescu Benetti, A. , Brauchli, B. et Vincent, V. ont coordonné la rédaction de plusieurs articles d'étudiants dans le cadre d'un module d'enseignement en CCEP – UNIGE « Du programme au situations d'apprentissage : planifier et conduire l'enseignement » (printemps 2017). Ces articles sont les suivants : - Capitanescu Benetti, A. , Brauchli, B. et Vincent, V. (2017) « Planifier l'enseignement, ça s'apprend »,Educateur, 7, 26. - Madeira, E. et Menoud, B. (2017). La planification : entre attentes institutionnelles et évaluations,Educateur, 8, 28. - Guccione, M.-L. et Walter, N. (2017). Planification : de l'intérêt des élèves…Educateur, 9, 30. - Lécureux, S. et Peccoux, C. (2017). La planification : quoi, quels détails et pour qui ? Educateur, 10, 28
Transfer RNA fragments induced during obesity hold regulatory functions in islet macrophage activation and beta cell homeostasis
No full textRole of tRNA fragments in islet macrophage activation and in the crosstalk with β-cells during obesity
No full textIslet-resident macrophages (Mφs) play a key role in pancreatic islet homeostasis but their activation in obesity results in β-cell dysfunction. This activation is likely to be elicited by modulatory molecules highly sensitive to environmental changes. The pool of transfer RNAs (tRNAs) is strictly regulated by nutrient availability and under stress conditions tRNAs can be cleaved, generating fragments (tRFs) with regulatory functions. Moreover, tRFs play a crucial role in extracellular vesicles (EVs)-mediated cell-to-cell crosstalk. The aim of the present work was to determine the impact of obesity on the tRF profile of islet Mφs and to investigate the role of these RNAs in Mφ activation and in the crosstalk with β-cells.
Islet Mφs and β-cells were isolated from obese db/db and lean wild type mice. Small RNA sequencing identified 15 modulated tRFs (≥1.5-fold change, p≤0.05, n=4) in db/db islet Mφs. To assess their role in Mφ activation, we compared the tRF profile of db/db islet Mφs to that of bone marrow derived Mφs (BMDMs), polarized into M1 pro- and M2 anti-inflammatory Mφs. Interestingly, 7 of the tRFs upregulated in db/db islet Mφs were enriched in M2 BMDMs (≥1.5-fold change, p≤0.05, n=3). Inhibition of one of these fragments, 5’tRFGlu(CTC), led to profound transcriptomic changes in both M1 and M2 BMDMs (n=3), with a preferential impact on genes involved in T-cell stimulation and in acute immune responses. Among the tRFs upregulated in obese islet Mφs, 5’tRFGlu(CTC), 5’tRFGly(GCC) and 5’tRFAsp(GTC) were also increased in β-cells of db/db mice and were abundant in EVs released by M2 BMDMs, suggesting a possible role in the crosstalk between islet cells.
Our data suggest that tRFs may act as key modulators of Mφs activation and that obesity induces an upregulation of anti-inflammatory tRFs in islet Mφs. RNA labelling and EVs transfer techniques are currently being used to investigate the contribution of tRFs in Mφ-β-cell crosstalk
Clinical cure of endometritis in cattle – Comparison of an antibiotic versus an herbal product
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Horizontal transfer of exosomal microRNAs transduce apoptotic signals between pancreatic beta-cells
No full textBackground: Diabetes mellitus is a common metabolic disorder characterized by dysfunction of insulin-secreting pancreatic beta-cells. MicroRNAs are important regulators of beta-cell activities. These non-coding RNAs have recently been discovered to exert their effects not only inside the cell producing them but, upon exosome-mediated transfer, also in other recipient cells. This novel communication mode remains unexplored in pancreatic beta-cells. In the present study, the microRNA content of exosomes released by beta-cells in physiological and physiopathological conditions was analyzed and the biological impact of their transfer to recipient cells investigated. Results: Exosomes were isolated from the culture media of MIN6B1 and INS-1 derived 832/13 beta-cell lines and from mice, rat or human islets. Global profiling revealed that the microRNAs released in MIN6B1 exosomes do not simply reflect the content of the cells of origin. Indeed, while a subset of microRNAs was preferentially released in exosomes others were selectively retained in the cells. Moreover, exposure of MIN6B1 cells to inflammatory cytokines changed the release of several microRNAs. The dynamics of microRNA secretion and their potential transfer to recipient cells were next investigated. As a proof-of-concept, we demonstrate that if cel-miR-238, a C. Elegans microRNA not present in mammalian cells, is expressed in MIN6B1 cells a fraction of it is released in exosomes and is transferred to recipient beta-cells. Furthermore, incubation of untreated MIN6B1 or mice islet cells in the presence of microRNA-containing exosomes isolated from the culture media of cytokine-treated MIN6B1 cells triggers apoptosis of recipient cells. In contrast, exosomes originating from cells not exposed to cytokines have no impact on cell survival. Apoptosis induced by exosomes produced by cytokine-treated cells was prevented by down-regulation of the microRNA-mediating silencing protein Ago2 in recipient cells, suggesting that the effect is mediated by the non-coding RNAs. Conclusions: Taken together, our results suggest that beta-cells secrete microRNAs that can be transferred to neighboring beta-cells. Exposure of donor cells to pathophysiological conditions commonly associated with diabetes modifies the release of microRNAs and affects survival of recipient beta-cells. Our results support the concept that exosomal microRNAs transfer constitutes a novel cell-to-cell communication mechanism regulating the activity of pancreatic beta-cells
Clinical cure of endometritis in cattle - comparison of an antibiotic versus an herbal product
No full textClinical endometritis in cattle has a strong detrimental effect on fertility. Routine therapy is based on the parenteral administration of prostaglandins or on intrauterine administration of antibiotics
A circular RNA generated from an intron of the insulin gene controls insulin secretion
No full textFine-tuning of insulin release from pancreatic β-cells is essential to maintain blood glucose homeostasis. Here, we report that insulin secretion is regulated by a circular RNA containing the lariat sequence of the second intron of the insulin gene. Silencing of this intronic circular RNA in pancreatic islets leads to a decrease in the expression of key components of the secretory machinery of β-cells, resulting in impaired glucose- or KCl-induced insulin release and calcium signaling. The effect of the circular RNA is exerted at the transcriptional level and involves an interaction with the RNA-binding protein TAR DNA-binding protein 43 kDa (TDP-43). The level of this circularized intron is reduced in the islets of rodent diabetes models and of type 2 diabetic patients, possibly explaining their impaired secretory capacity. The study of this and other circular RNAs helps understanding β-cell dysfunction under diabetes conditions, and the etiology of this common metabolic disorder
MicroRNA-9 controls the expression of Granuphilin/Slp4 and the secretory response of insulin-producing cells
No full textInsulin release from pancreatic beta-cells plays an essential role in blood glucose homeostasis. Several proteins controlling insulin exocytosis have been identified, but the factors determining the expression of the components of the secretory machinery of beta-cells remain largely unknown. MicroRNAs are newly discovered small non-coding RNAs acting as repressors of gene expression. We found that overexpression of mir-9 in insulin-secreting cells causes a reduction in exocytosis elicited by glucose or potassium. We show that mir-9 acts by diminishing the expression of the transcription factor Onecut-2 and, in turn, by increasing the level of Granuphilin/Slp4, a Rab GTPase effector associated with beta-cell secretory granules that exerts a negative control on insulin release. Indeed, electrophoretic mobility shift assays, chromatin immunoprecipitation, and transfection experiments demonstrated that Onecut-2 is able to bind to the granuphilin promoter and to repress its transcriptional activity. Moreover, we show that silencing of Onecut-2 by RNA interference increases Granuphilin expression and mimics the effect of mir-9 on stimulus-induced exocytosis. Our data provide evidence that in insulin-producing cells adequate levels of mir-9 are mandatory for maintaining appropriate Granuphilin levels and optimal secretory capacity
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