Influence of phenological barriers and habitat differentiation on the population genetic structure of the balearic endemic Rhamnus ludovici-salvatoris Chodat and R. alaternus L

[EN] Rhamnus ludovici-salvatoris, endemic to the Gymnesian Islands, coexists with the related and widespread R. alaternus in Mallorca and Menorca. In both species, the population genetic structure using RAPD, and flowering during a 3-year period to check for possible phenological barriers, were analyzed. Rhamnus ludovici-salvatoris showed lower genetic diversity and stronger population structure than R. alaternus, the Cabrera population being less diverse and the most differentiated. Rhamnus ludovici-salvatoris flowered one month later, although flowering of both species coincided sporadically. These congeners seem to have diverged through isolation by time and differentiation in habitat. The population genetic structure of R. ludovici-salvatoris could mainly be due to the existence of small populations on the one hand, and a gene flow caused by rare hybridization events on the other, which may also explain the presence of morphologically intermediate individuals in Menorca. 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Validation of 3D neutronic-thermalhydraulic coupled codes RELAP5/PARCSv2.7 and TRACEv5.0P3/PARCSv3.0 against a PWR control rod drop transient

[EN] In nuclear safety field, neutronic and thermalhydraulic codes performance is an important issue. New capabilities implementation, as well as models and tools improvements are a significant part of the community effort in looking for better Nuclear Power Plants (NPP) designs. A procedure to analyze the PWR response to local deviations on neutronic or thermalhydraulic parameters is being developed. This procedure includes the simulation of Incore and Excore neutron flux detectors signals. A control rod drop real plant transient is used to validate the used codes and their new capabilities. Cross-section data are obtained by means of the SIMTAB methodology. Detailed thermalhydraulic models were developed: RELAP5 and TRACE models simulate three different azimuthal zones. Besides, TRACE model is performed with a fully 3D core, thus, the cross-flow can be obtained. A cartesian vessel represents the fuel assemblies and a cylindrical vessel the bypass and downcomer. Simulated detectors signals are obtained and compared with the real data collected during a control rod drop trial at a PWR NPP and also with data obtained with SIMULATE-3K code.The authors would like to acknowledge the economic support provided by Centrales Nucleares Almaraz-Trillo (CNAT) and IBERDROLA Ingeniería y Construcción (Iberinco) for the realization of this work, and express their great appreciation to Arturo López, Juan Antonio Bermejo and Alberto Ortego for their valuable collaboration and their willingness to develop this work. This work has also been supported by the Spanish Ministerio de Economía y Competitividad, through the projects NUC-MULTPHYS (ENE2012-34585) and VALIUN-3D (ENE2011-22823), and the Generalitat Valenciana (GVA), through the project PROMETEO II/2014/008.Garcia-Fenoll, M.; Mesado Melia, C.; Barrachina, T.; Miró Herrero, R.; Verdú Martín, GJ.; Bermejo, JA.; López, A.... (2017). Validation of 3D neutronic-thermalhydraulic coupled codes RELAP5/PARCSv2.7 and TRACEv5.0P3/PARCSv3.0 against a PWR control rod drop transient. Journal of Nuclear Science and Technology. 54(8):908-919. https://doi.org/10.1080/00223131.2017.1329035S90891954

Differences in MEF2 and NFAT Transcriptional Pathways According to Human Heart Failure Aetiology

BACKGROUND:Ca(2+) handling machinery modulates the activation of cardiac transcription pathways involved in heart failure (HF). The present study investigated the effect of HF aetiology on Ca(+2) handling proteins and NFAT1, MEF2C and GATA4 (transcription factors) in the same cardiac tissue. METHODOLOGY AND PRINCIPAL FINDINGS:A total of 83 hearts from ischemic (ICM, n = 43) and dilated (DCM, n = 31) patients undergoing heart transplantation and controls (CNT, n = 9) were analyzed by western blotting. Subcellular distribution was analyzed by fluorescence and electron microscopy. When we compared Ca(+2) handling proteins according to HF aetiology, ICM showed higher levels of calmodulin (24%, p<0.01), calcineurin (26%, p<0.01) and Ca(2+)/Calmodulin-dependent kinase II (CaMKIIδ(b) nuclear isoform 62%, p<0.001) than the CNT group. However, these proteins in DCM did not significantly increase. Furthermore, ICM showed a significant elevation in MEF2C (33%, p<0.01), and GATA4 (49%, p<0.05); also NFAT1 (66%, p<0.001) was increased, producing the resultant translocation of this transcriptional factor into the nuclei. These results were supported by fluorescence and electron microscopy analysis. Whereas, DCM only had a significant increase in GATA4 (52%, p<0.05). Correlations between NFAT1 and MEF2C in both groups (ICM r = 0.38 and DCM r = 0.59, p<0.05 and p<0.01, respectively) were found; only ICM showed a correlation between GATA4 and NFAT1 (r = 0.37, p<0.05). CONCLUSIONS/SIGNIFICANCE:This study shows an increase of Ca(2+) handling machinery synthesis and their cardiac transcription pathways in HF, being more markedly increased in ICM. Furthermore, there is a significant association between MEF2, NFAT1 and GATA4. These proteins could be therapeutic targets to improve myocardial function

Endolysosomal two‐pore channels regulate autophagy in cardiomyocytes

Key points Two‐pore channels (TPCs) were identified as a novel family of endolysosome‐targeted calcium release channels gated by nicotinic acid adenine dinucleotide phosphate, as also as intracellular Na+ channels able to control endolysosomal fusion, a key process in autophagic flux. Autophagy, an evolutionarily ancient response to cellular stress, has been implicated in the pathogenesis of a wide range of cardiovascular pathologies, including heart failure. We report direct evidence indicating that TPCs are involved in regulating autophagy in cardiomyocytes, and that TPC knockout mice show alterations in the cardiac lysosomal system. TPC downregulation implies a decrease in the viability of cardiomyocytes under starvation conditions. In cardiac tissues from both humans and rats, TPC transcripts and protein levels were higher in females than in males, and correlated negatively with markers of autophagy. We conclude that the endolysosomal channels TPC1 and TPC2 are essential for appropriate basal and induced autophagic flux in cardiomyocytes, and also that they are differentially expressed in male and female hearts. Abstract Autophagy participates in physiological and pathological remodelling of the heart. The endolysosomal two‐pore channels (TPCs), TPC1 and TPC2, have been implicated in the regulation of autophagy. The present study aimed to investigate the role of TPC1 and TPC2 in basal and induced cardiac autophagic activity. In cultured cardiomyocytes, starvation induced a significant increase in TPC1 and TPC2 transcripts and protein levels that paralleled the increase in autophagy identified by increased LC3‐II and decreased p62 levels. Small interfering RNA depletion of TPC2 alone or together with TPC1 increased both LC3II and p62 levels under basal conditions and in response to serum starvation, suggesting that, under conditions of severe energy depletion (serum plus glucose starvation), changes in the autophagic flux (as assessed by use of bafilomycin A1) occurred either when TPC1 or TPC2 were downregulated. The knockdown of TPCs diminished cardiomyocyte viability under starvation and simulated ischaemia. Electron micrographs of hearts from TPC1/2 double knockout mice showed that cardiomyocytes contained large numbers of immature lysosomes with diameters significantly smaller than those of wild‐type mice. In cardiac tissues from humans and rats, TPC1 and TPC2 transcripts and protein levels were higher in females than in males. Furthermore, transcript levels of TPCs correlated negatively with p62 levels in heart tissues. TPC1 and TPC2 are essential for appropriate basal and induced autophagic flux in cardiomyocytes (i.e. there is a negative effect on cell viability under stress conditions in their absence) and they are differentially expressed in male and female human and murine hearts, where they correlate with markers of autophagy. </p