Influence des barrières sur la propagation de la déformationle long des surfaces de décollement : étude expérimentale

International audienceA series of small-scale experiments has been done to study the influence of gap and thickness variations along a layer of potential decollement on the fault sequence in a thrust system. It is shown that a local thinning or discontinuity of the decollement layer can become a barrier which localises the deformation, initiates a ramp, and controls the order of fault development above the decollement layer.Une série d'expériences sur modèles réduits a été réalisée afin d'étudier l'influence des lacunes et des variations d'épaisseur d'un niveau de décollement potentiel sur la propagation d'un système chevauchant. Les résultats montrent qu'un amincissement ou une discontinuité de ce niveau crée une barrière qui peut bloquer au moins temporairement le décollement, localiser la déformation, servir de site d'initiation d'une rampe, et déterminer aissi l'ordre d'apparition des rampes suivantes

Transcriptional response of pancreatic beta cells to metabolic stimulation: large scale identification of immediate-early and secondary response genes

<p>Abstract</p> <p>Background</p> <p>Physiological long term adaptation of pancreatic beta cells is driven by stimuli such as glucose and incretin hormones acting via cAMP (e.g. GLP-1) and involves regulated gene expression. Several rapidly inducible immediate-early genes (IEGs) have been identified in beta cells. Many of these IEGs code for transcription factors and have the potential to control the transcription of downstream <it>target </it>genes likely involved in long term cellular adaptation. The identity of these <it>target </it>genes has not been determined, and the sequence of events occurring during beta cell adaptation is still unclear.</p> <p>Results</p> <p>We have developed a microarray-based strategy for the systematic search of <it>targets</it>. In Min6 insulin-secreting cells, we identified 592 <it>targets </it>and 1278 IEGs responding to a co-stimulation with glucose and cAMP. Both IEGs and <it>targets </it>were involved in a large panel of functions, including those important to beta cell physiology (metabolism, secretion). Nearly 200 IEGs were involved in signaling and transcriptional regulation. To find specific examples of the regulatory link between IEGs and <it>targets</it>, <it>target </it>promoter sequences were analyzed <it>in silico</it>. Statistically significant over-representation of AP-1 response elements notably suggested an important role for this transcription factor, which was experimentally verified. Indeed, cell stimulation altered expression of IEG-encoded components of the AP-1 complex, activating AP-1-dependent transcription. Loss and gain-of-function experiments furthermore allowed to validate a new AP-1 regulated gene (<it>sulfiredoxin</it>) among the <it>targets</it>. AP-1 and <it>sulfiredoxin </it>are sequentially induced also in primary cells from rat islets of Langerhans.</p> <p>Conclusion</p> <p>By identifying IEGs and their downstream <it>targets</it>, this study brings a comprehensive description of the transcriptional response occurring after beta cell stimulation, as well as new mechanistic insights concerning the AP-1 transcription factor.</p

Helioseismology and solar neutrinos: an update

We review recent advances concerning helioseismology, solar models and solar neutrinos. Particularly we address the following points: i) helioseismic tests of recent SSMs; ii) predictions of the Beryllium neutrino flux based on helioseismology; iii) helioseismic tests regarding the screening of nuclear reactions in the Sun.Comment: 7 pages with 6 eps figure included, LaTeX file with espcrc2.sty, to appear on the Proceedings of "EuroConference on Frontiers in Particle Astrophysics and Cosmology", San Feliu de Guixols, Spain, 30 September -5 October 200

Diabetogenic milieus induce specific changes in mitochondrial transcriptome and differentiation of human pancreatic islets

In pancreatic β-cells, mitochondria play a central role in coupling glucose metabolism to insulin secretion. Chronic exposure of β-cells to metabolic stresses impairs their function and potentially induces apoptosis. Little is known on mitochondrial adaptation to metabolic stresses, i.e. high glucose, fatty acids or oxidative stress; being all highlighted in the pathogenesis of type 2 diabetes. Here, human islets were exposed for 3 days to 25 mm glucose, 0.4 mm palmitate, 0.4 mm oleate and transiently to H2O2. Culture at physiological 5.6 mm glucose served as no-stress control. Expression of mitochondrion-associated genes was quantified, including the transcriptome of mitochondrial inner membrane carriers. Targets of interest were further evaluated at the protein level. Three days after acute oxidative stress, no significant alteration in β-cell function or apoptosis was detected in human islets. Palmitate specifically increased expression of the pyruvate carriers MPC1 and MPC2, whereas the glutamate carrier GC1 and the aspartate/glutamate carrier AGC1 were down-regulated by palmitate and oleate, respectively. High glucose decreased mRNA levels of key transcription factors (HNF4A, IPF1, PPARA and TFAM) and energy-sensor SIRT1. High glucose also reduced expression of 11 mtDNA-encoded respiratory chain subunits. Interestingly, transcript levels of the carriers for aspartate/glutamate AGC2, malate DIC and malate/oxaloacetate/aspartate UCP2 were increased by high glucose, a profile suggesting important mitochondrial anaplerotic/cataplerotic activities and NADPH-generating shuttles. Chronic exposure to high glucose impaired glucose-stimulated insulin secretion, decreased insulin content, promoted caspase-3 cleavage and cell death, revealing glucotoxicity. Overall, expression profile of mitochondrion-associated genes was selectively modified by glucose, delineating a glucotoxic-specific signatur

The diabetes-linked transcription factor PAX4 promotes β-cell proliferation and survival in rat and human islets

The mechanism by which the β-cell transcription factor Pax4 influences cell function/mass was studied in rat and human islets of Langerhans. Pax4 transcripts were detected in adult rat islets, and levels were induced by the mitogens activin A and betacellulin. Wortmannin suppressed betacellulin-induced Pax4 expression, implicating the phosphatidylinositol 3-kinase signaling pathway. Adenoviral overexpression of Pax4 caused a 3.5-fold increase in β-cell proliferation with a concomitant 1.9-, 4-, and 5-fold increase in Bcl-xL (antiapoptotic), c-myc, and Id2 mRNA levels, respectively. Accordingly, Pax4 transactivated the Bcl-xL and c-myc promoters, whereas its diabetes-linked mutant was less efficient. Bcl-xL activity resulted in altered mitochondrial calcium levels and ATP production, explaining impaired glucose-induced insulin secretion in transduced islets. Infection of human islets with an inducible adenoviral Pax4 construct caused proliferation and protection against cytokine-evoked apoptosis, whereas the mutant was less effective. We propose that Pax4 is implicated in β-cell plasticity through the activation of c-myc and potentially protected from apoptosis through Bcl-xL gene expression

Impact of anatase and rutile titanium dioxide nanoparticles on uptake carriers and efflux pumps in Caco-2 gut epithelial cells

International audienceTiO2 microparticles are widely used in food products, where they are added as a white food colouring agent. This food additive contains a significant amount of nanoscale particles; still the impact of TiO2 nanoparticles (TiO2-NPs) on gut cells is poorly documented. Our study aimed at evaluating the impact of rutile and anatase TiO2-NPs on the main functions of enterocytes, i.e. nutrient absorption driven by solute-liquid carriers (SLC transporters) and protection against other xenobiotics driven by efflux pumps from the ATP-binding cassette (ABC) family. We show that acute exposure of Caco-2 cells to both anatase (12 nm) and rutile (20 nm) TiO2-NPs induce early upregulation of a battery of efflux pumps and nutrient transporters. In addition they cause overproduction of reactive oxygen species and misbalance redox repair systems, without inducing cell mortality or DNA damage. Taken together, these data suggest that TiO2-NPs may increase the functionality of gut epithelial cells, particularly their property to form a protective barrier against exogenous toxicants and to absorb nutrients

The stop null mice model for schizophrenia displays [corrected] cognitive and social deficits partly alleviated by neuroleptics.

International audienceRecently evidence has accumulated that schizophrenia can arise from primary synaptic defects involving structural proteins particularly, microtubule associated proteins. Previous experiments have demonstrated that a STOP (stable tubule only peptide) gene deletion in mice leads to a phenotype mimicking some aspects of positive symptoms classically observed in schizophrenic patients. In the current study, we determined if STOP null mice demonstrate behavioral abnormalities related to the social and cognitive impairments of schizophrenia. Compared with wild-type mice, STOP null mice exhibited deficits in the non-aggressive component of social recognition, short term working memory and social and spatial learning. As described in humans, learning deficits in STOP null mice were poorly sensitive to long term treatment with typical neuroleptics. Since social and cognitive dysfunction have consistently been considered as central features of schizophrenia, we propose that STOP null mice may provide a useful model to understand the neurobiological correlates of social and cognitive defects in schizophrenia and to develop treatments that better target these symptoms

The diabetes-linked transcription factor Pax4 is expressed in human pancreatic islets and is activated by mitogens and GLP-1

We previously demonstrated that the transcription factor Pax4 is important for β-cell replication and survival in rat islets. Herein, we investigate Pax4 expression in islets of non-diabetic and diabetic donors, its regulation by mitogens, glucose and the incretin GLP-1 and evaluate its effect on human islet proliferation. Pax4 expression was increased in islets derived from Type 2 diabetic donors correlating with hyperglycaemia. In vitro studies on non diabetic islets demonstrated that glucose, betacellulin, activin A, GLP-1 and insulin increased Pax4 mRNA levels. Glucose-induced Pax4 expression was abolished by the inhibitors LY294002, PD98050 or H89. Surprisingly, increases in Pax4 expression did not prompt a surge in human islet cell replication. Furthermore, expression of the proliferation marker gene Id2 remained unaltered. Adenoviral-mediated expression of human Pax4 resulted in a small increase in Bcl-xL expression while Id2 transcript levels and cell replication were unchanged in human islets. In contrast, overexpression of mouse Pax4 induced human islet cell proliferation. Treatment of islets with 5-Aza-2′-deoxycytidine induced Pax4 without stimulating Bcl-xL and Id2 expression. Human Pax4 DNA binding activity was found to be lower than that of the mouse homologue. Thus, human pax4 gene expression is epigenetically regulated and induced by physiological stimuli through the concerted action of multiple signalling pathways. However, it is unable to initiate the transcriptional replication program likely due to post-translational modifications of the protein. The latter highlights fundamental differences between human and rodent islet physiology and emphasizes the importance of validating results obtained with animal models in human tissue

Baseline Assessment and Early Effects of a Network of Marine Protected Areas

Marine protected areas (MPAs) can be a useful tool to manage coastal ecosystems, delivering both social and ecological outcomes. However, in many instances, relevant data is missing to conduct proper impact assessments, which is key to identifying ecological and social synergies and potential trade-offs, and to adapting management according to local objectives. The ecological effects of an MPA established in Palawan, Philippines, in 2016, were assessed. The most common species targeted by fisheries were identified by local fishers. Species size and number were collected through underwater visual census with n = 288 belt transects assigned in different sites and locations to ensure to provide both protected and control (fished) sites for the MPA assessment, and baseline data for three new MPAs that were created in 2022. 91 coral-reef fish species belonging to 12 families were recorded. Mixed effect linear regression was used to compare target fish populations in protected and control sites. Compared to control locations, 5 years after its implementation, the MPA showed significantly higher species richness, abundance, mean size, and biomass while no significant difference was found on the average trophic level between MPA and control sites. Monitoring the early effects of an MPA and collecting baseline data prior the implementation of an MPA network is key for adaptive management. © 2024 The Authors. Conservation Science and Practice published by Wiley Periodicals LLC on behalf of Society for Conservation Biology

Coordinate Transcriptomic and Metabolomic Effects of the Insulin Sensitizer Rosiglitazone on Fundamental Metabolic Pathways in Liver, Soleus Muscle, and Adipose Tissue in Diabetic db/db Mice

Rosiglitazone (RSG), developed for the treatment of type 2 diabetes mellitus, is known to have potent effects on carbohydrate and lipid metabolism leading to the improvement of insulin sensitivity in target tissues. To further assess the capacity of RSG to normalize gene expression in insulin-sensitive tissues, we compared groups of 18-day-treated db/db mice with increasing oral doses of RSG (10, 30, and 100 mg/kg/d) with untreated non-diabetic littermates (db/+). For this aim, transcriptional changes were measured in liver, inguinal adipose tissue (IAT) and soleus muscle using microarrays and real-time PCR. In parallel, targeted metabolomic assessment of lipids (triglycerides (TGs) and free fatty acids (FFAs)) in plasma and tissues was performed by UPLC-MS methods. Multivariate analyses revealed a relationship between the differential gene expressions in liver and liver trioleate content and between blood glucose levels and a combination of differentially expressed genes measured in liver, IAT, and muscle. In summary, we have integrated gene expression and targeted metabolomic data to present a comprehensive overview of RSG-induced changes in a diabetes mouse model and improved the molecular understanding of how RSG ameliorates diabetes through its effect on the major insulin-sensitive tissues