"Importance didactique des conceptions des enseignants tunisiens sur l’éducation à la sexualité dans une perspective citoyenne"- 8th international congress on research in science teaching

L’objectif de cette étude est d’analyser les conceptions d'enseignants et futurs enseignants tunisiens et d'identifier les valeurs qu'expriment ces conceptions. Les nombreuses conceptions exprimées sont étudiées en tant qu’interactions entre les connaissances scientifiques, les valeurs et les pratiques d’enseignement, au moyen d’une analyse en composante principale (ACP). L'échantillon est formé de 753 enseignants et futurs enseignants du primaire et du secondaire, qui ont répondu à un questionnaire, dans un contexte strictement contrôlé

Avian Neuropeptide Y : Beyond Feed Intake Regulation

Neuropeptide Y (NPY) is one of the most abundant and ubiquitously expressed neuropeptides in both the central and peripheral nervous systems, and its regulatory effects on feed intake and appetite- have been extensively studied in a wide variety of animals, including mammalian and non-mammalian species. Indeed, NPY has been shown to be involved in the regulation of feed intake and energy homeostasis by exerting stimulatory effects on appetite and feeding behavior in several species including chickens, rabbits, rats and mouse. More recent studies have shown that this neuropeptide and its receptors are expressed in various peripheral tissues, including the thyroid, heart, spleen, adrenal glands, white adipose tissue, muscle and bone. Although well researched centrally, studies investigating the distribution and function of peripherally expressed NPY in avian (non-mammalian vertebrates) species are very limited. Thus, peripherally expressed NPY merits more consideration and further in-depth exploration to fully elucidate its functions, especially in non-mammalian species. The aim of the current review is to provide an integrated synopsis of both centrally and peripherally expressed NPY, with a special focus on the distribution and function of the latter

The c- Jun N-terminal kinase JNK participates in cytokine- and isolation stress-induced rat pancreatic islet apoptosis

Aims/hypothesis: The protocols used for the preparation of human pancreatic islets immediately induce a sustained and massive activation of the c-Jun-N-terminal kinase (JNK). JNK, which participates in apoptosis of insulin-secreting cells, is activated by mechanical stresses, as well as by exposure to pro-inflammatory cytokines. Here, we investigated whether the delivery of a protease-resistant JNK inhibitory peptide (D-JNKI) through a protein transduction system during pancreatic digestion might impair JNK signalling throughout the transplantation procedure. Methods: Rat pancreases were treated with D-JNKI through the pancreatic duct and cells then isolated by enzymatic digestion. Protein extracts were prepared to determine JNK activity by kinase assays and total RNA was extracted to measure gene expressions by a Light-Cycler technique. Cell apoptosis rate was determined by terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) assay and by scoring cells displaying pycnotic nuclei. Results: Our data establish that the peptide transduction system used here efficiently transfects islets, allowing for stable in vivo (up to 2days) transfection of human islets transplanted under the kidney capsule. Further, D-JNKI decreases intracellular JNK signalling during isolation and following cytokine exposure in both human and rat islets, as measured by kinase assays and reduced c-fos expression; D-JNKI also confers protection against apoptosis induced during the rat islet preparation and subsequent to IL-1β exposure. Conclusions/interpretation: JNK signalling participates in islet isolation- and IL-1β-induced apoptosis in rat islets. Furthermore, the system we used might be more generally applicable for the persistent blockage (several days) of pro-apoptotic pathways in the transplanted islets; this days-long protection might potentially be an absolute prerequisite to help transplanted islets better survive the first wave of the non-specific inflammatory attac

Fibroblast Growth Factor-9 Enhances M2 Macrophage Differentiation and Attenuates Adverse Cardiac Remodeling in the Infarcted Diabetic Heart

Inflammation has been implicated as a perpetrator of diabetes and its associated complications. Monocytes, key mediators of inflammation, differentiate into pro-inflammatory M1 macrophages and anti-inflammatory M2 macrophages upon infiltration of damaged tissue. However, the inflammatory cell types, which propagate diabetes progression and consequential adverse disorders, remain unclear. The current study was undertaken to assess monocyte infiltration and the role of fibroblast growth factor-9 (FGF-9) on monocyte to macrophage differentiation and cardioprotection in the diabetic infarcted heart. Db/db diabetic mice were assigned to sham, myocardial infarction (MI), and MI+FGF-9 groups. MI was induced by permanent coronary artery ligation and animals were subjected to 2D transthoracic echocardiography two weeks post-surgery. Immunohistochemical and immunoassay results from heart samples collected suggest significantly increased infiltration of monocytes (Mean +/- SEM; MI: 2.02% +/- 0.23% vs. Sham 0.75% +/- 0.07%; p \u3c 0.05) and associated pro-inflammatory cytokines (TNF-alpha, MCP-1, and IL-6), adverse cardiac remodeling (Mean +/- SEM; MI: 33% +/- 3.04% vs. Sham 2.2% +/- 0.33%; p \u3c 0.05), and left ventricular dysfunction (Mean +/- SEM; MI: 35.4% +/- 1.25% vs. Sham 49.19% +/- 1.07%; p \u3c 0.05) in the MI group. Importantly, treatment of diabetic infarcted myocardium with FGF-9 resulted in significantly decreased monocyte infiltration (Mean +/- SEM; MI+FGF-9: 1.39% +/- 0.1% vs. MI: 2.02% +/- 0.23%; p \u3c 0.05), increased M2 macrophage differentiation (Mean +/- SEM; MI+FGF-9: 4.82% +/- 0.86% vs. MI: 0.85% +/- 0.3%; p \u3c 0.05) and associated anti-inflammatory cytokines (IL-10 and IL-1RA), reduced adverse remodeling (Mean +/- SEM; MI+FGF-9: 11.59% +/- 1.2% vs. MI: 33% +/- 3.04%; p \u3c 0.05), and improved cardiac function (Fractional shortening, Mean +/- SEM; MI+FGF-9: 41.51% +/- 1.68% vs. MI: 35.4% +/- 1.25%; p \u3c 0.05). In conclusion, our data suggest FGF-9 possesses novel therapeutic potential in its ability to mediate monocyte to M2 differentiation and confer cardiac protection in the post-MI diabetic heart

Effects of Cyclic Chronic Heat Stress on the Expression of Nutrient Transporters in the Jejunum of Modern Broilers and Their Ancestor Wild Jungle Fowl

snibaThe mechanisms associated between growth rate, gut integrity and heat stress (HS) responses are not known. The current study aimed to evaluate the effect of chronic HS on jejunal nutrient transport in slow- (ACRB from 1950), moderate- (95RAN from 1995), rapid-(modern broilers, MRB) growing birds, and their ancestor wild jungle fowl (JF). One-day male chicks (n=150/line) were placed by line in environmentally controlled chambers and kept under the same environmental conditions until d28. On d29, an 8-h daily cyclic HS (36ºC) was applied to half of the chambers, which lasts until d55, while keeping the rest under thermal neutral conditions (TN, 24°C). Jejunum tissues were collected for morphology assessment and molecular analysis of carbohydrate-, amino acid- and fatty acid- transporters. MRB exhibited the highest BW followed by 95RAN under both conditions. HS decreased FI in MRB and 95RAN, which results in lower BW compared to their TN counterparts, however no effect was observed in ACRB and JF. MRB showed greater villus height to crypt depth ratio under both environmental conditions. Molecular analyses showed that GLUT2, 5, 10, and 11 were upregulated in MRB compared to some of the other populations under TN conditions. HS down regulated GLUT2, 10, 11, and 12 in MRB while it increased the expression of GLUT1, 5, 10, and 11 in JF. GLUT2 protein expression was higher in JF compared to ACRB and MRB under TN conditions. It also showed an increase in ACRB but no effect on 95RAN and MRB under HS conditions. ACRB exhibited greater expression of EAAT3 gene as compared to the rest of populations maintained under TN conditions. HS exposure did not alter the gene expression of amino acid transporters in MRB. Gene expression of CD36 and FABP2 was up-regulated in HS JF birds. Protein expression of CD36 was down-regulated in HS JF while no effect was observed in ACRB, 95RAN and MRB. Taken together, these data are the first to show the effect of HS on jejunal expression of nutrient transporters in three broiler populations known to represent 70 years of genetic progress in the poultry industr

JNK3 is abundant in insulin-secreting cells and protects against cytokine-induced apoptosis

Aims/hypothesis: In insulin-secreting cells, activation of the c-Jun NH2-terminal kinase (JNK) pathway triggers apoptosis. Whereas JNK1 and JNK2 are ubiquitously produced, JNK3 has been described exclusively in neurons. This report aims to characterise the expression and role in apoptosis of the three JNK isoforms in insulin-secreting cells exposed to cytokines. Methods: Sections of human and mouse pancreases were used for immunohistochemistry studies with isoform-specific anti-JNK antibodies. Human, pig, mouse and rat pancreatic islets were isolated by enzymatic digestion and RNA or protein extracts were prepared. RNA and protein levels were determined by quantitative RT-PCR and western blotting respectively, using JNK-isoform-specific primers and isoform-specific antibodies; activities of the three JNK isoforms were determined by kinase assays following quantitative immunoprecipitation/depletion of JNK3. JNK silencing was performed with small interfering RNAs and apoptotic rates were determined in INS-1E cells by scoring cells displaying pycnotic nuclei. Results: JNK3 and JNK2 mRNAs are the predominant isoforms expressed in human pancreatic islets. JNK3 is nuclear while JNK2 is also cytoplasmic. In INS-1E cells, JNK3 knockdown increases c-Jun levels and caspase-3 cleavage and sensitises cells to cytokine-induced apoptosis; in contrast, JNK1 or JNK2 knockdown is protective. Conclusions/interpretation: In insulin-secreting cells, JNK3 plays an active role in preserving pancreatic beta cell mass from cytokine attacks. The specific localisation of JNK3 in the nucleus, its recruitment by cytokines, and its effects on key transcription factors such as c-Jun, indicate that JNK3 is certainly an important player in the transcriptional control of genes expressed in insulin-secreting cell

Regulation of the JNK3 signaling pathway during islet isolation: JNK3 and c-fos as new markers of islet quality for transplantation.

Stress conditions generated throughout pancreatic islet processing initiate the activation of pro-inflammatory pathways and beta-cell destruction. Our goal is to identify relevant and preferably beta-specific markers to assess the activation of beta-cell stress and apoptotic mechanisms, and therefore the general quality of the islet preparation prior to transplantation. Protein expression and activation were analyzed by Western blotting and kinase assays. ATP measurements were performed by a luminescence-based assay. Oxygen consumption rate (OCR) was measured based on standard protocols using fiber optic sensors. Total RNA was used for gene expression analyzes. Our results indicate that pancreas digestion initiates a potent stress response in the islets by activating two stress kinases, c-Jun N-terminal Kinase (JNK) and p38. JNK1 protein levels remained unchanged between different islet preparations and following culture. In contrast, levels of JNK3 increased after islet culture, but varied markedly, with a subset of preparations bearing low JNK3 expression. The observed changes in JNK3 protein content strongly correlated with OCR measurements as determined by the Spearman's rank correlation coefficient rho [Formula: see text] in the matching islet samples, while inversely correlating with c-fos mRNA expression [Formula: see text]. In conclusion, pancreas digestion recruits JNK and p38 kinases that are known to participate to beta-cell apoptosis. Concomitantly, the islet isolation alters JNK3 and c-fos expression, both strongly correlating with OCR. Thus, a comparative analysis of JNK3 and c-fos expression before and after culture may provide for novel markers to assess islet quality prior to transplantation. JNK3 has the advantage over all other proposed markers to be islet-specific, and thus to provide for a marker independent of non-beta cell contamination

Human high-density lipoprotein particles prevent activation of the JNK pathway induced by human oxidised low-density lipoprotein particles in pancreatic beta cells

Aims/hypothesis: We explored the potential adverse effects of pro-atherogenic oxidised LDL-cholesterol particles on beta cell function. Materials and methods: Isolated human and rat islets and different insulin-secreting cell lines were incubated with human oxidised LDL with or without HDL particles. The insulin level was monitored by ELISA, real-time PCR and a rat insulin promoter construct linked to luciferase gene reporter. Cell apoptosis was determined by scoring cells displaying pycnotic nuclei. Results: Prolonged incubation with human oxidised LDL particles led to a reduction in preproinsulin expression levels, whereas the insulin level was preserved in the presence of native LDL-cholesterol. The loss of insulin production occurred at the transcriptional levels and was associated with an increase in activator protein-1 transcriptional activity. The rise in activator protein-1 activity resulted from activation of c-Jun N-terminal kinases (JNK, now known as mitogen-activated protein kinase 8 [MAPK8]) due to a subsequent decrease in islet-brain 1 (IB1; now known as MAPK8 interacting protein 1) levels. Consistent with the pro-apoptotic role of the JNK pathway, oxidised LDL also induced a twofold increase in the rate of beta cell apoptosis. Treatment of the cells with JNK inhibitor peptides or HDL countered the effects mediated by oxidised LDL. Conclusions/interpretation: These data provide strong evidence that oxidised LDL particles exert deleterious effects in the progression of beta cell failure in diabetes and that these effects can be countered by HDL particle

JNK3 Is Required for the Cytoprotective Effect of Exendin 4.

Preservation of beta cell against apoptosis is one of the therapeutic benefits of the glucagon-like peptide-1 (GLP1) antidiabetic mimetics for preserving the functional beta cell mass exposed to diabetogenic condition including proinflammatory cytokines. The mitogen activated protein kinase 10 also called c-jun amino-terminal kinase 3 (JNK3) plays a protective role in insulin-secreting cells against death caused by cytokines. In this study, we investigated whether the JNK3 expression is associated with the protective effect elicited by the GLP1 mimetic exendin 4. We found an increase in the abundance of JNK3 in isolated human islets and INS-1E cells cultured with exendin 4. Induction of JNK3 by exendin 4 was associated with an increased survival of INS-1E cells. Silencing of JNK3 prevented the cytoprotective effect of exendin 4 against apoptosis elicited by culture condition and cytokines. These results emphasize the requirement of JNK3 in the antiapoptotic effects of exendin 4

The c-Jun N-terminal kinase JNK participates in cytokine- and isolation stress-induced rat pancreatic islet apoptosis

AIMS/HYPOTHESIS: The protocols used for the preparation of human pancreatic islets immediately induce a sustained and massive activation of the c-Jun-N-terminal kinase (JNK). JNK, which participates in apoptosis of insulin-secreting cells, is activated by mechanical stresses, as well as by exposure to pro-inflammatory cytokines. Here, we investigated whether the delivery of a protease-resistant JNK inhibitory peptide (D-JNKI) through a protein transduction system during pancreatic digestion might impair JNK signalling throughout the transplantation procedure. METHODS: Rat pancreases were treated with D-JNKI through the pancreatic duct and cells then isolated by enzymatic digestion. Protein extracts were prepared to determine JNK activity by kinase assays and total RNA was extracted to measure gene expressions by a Light-Cycler technique. Cell apoptosis rate was determined by terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) assay and by scoring cells displaying pycnotic nuclei. RESULTS: Our data establish that the peptide transduction system used here efficiently transfects islets, allowing for stable in vivo (up to 2 days) transfection of human islets transplanted under the kidney capsule. Further, D-JNKI decreases intracellular JNK signalling during isolation and following cytokine exposure in both human and rat islets, as measured by kinase assays and reduced c-fos expression; D-JNKI also confers protection against apoptosis induced during the rat islet preparation and subsequent to IL-1beta exposure. CONCLUSIONS/INTERPRETATION: JNK signalling participates in islet isolation- and IL-1beta-induced apoptosis in rat islets. Furthermore, the system we used might be more generally applicable for the persistent blockage (several days) of pro-apoptotic pathways in the transplanted islets; this days-long protection might potentially be an absolute prerequisite to help transplanted islets better survive the first wave of the non-specific inflammatory attack