Acute stress enhances heterodimerization and binding of corticosteroid receptors at glucocorticoid target genes in the hippocampus

A stressful event results in secretion of glucocorticoid hormones, which bind to mineralocorticoid receptors (MRs) and glucocorticoid receptors (GRs) in the hippocampus to regulate cognitive and affective responses to the challenge. MRs are already highly occupied by low glucocorticoid levels under baseline conditions, whereas GRs only become substantially occupied by stress- or circadian-driven glucocorticoid levels. Currently, however, the binding of MRs and GRs to glucocorticoid-responsive elements (GREs) within hippocampal glucocorticoid target genes under such physiological conditions in vivo is unknown. We found that forced swim (FS) stress evoked increased hippocampal RNA expression levels of the glucocorticoid-responsive genes FK506-binding protein 5 (Fkbp5), Period 1 (Per1), and serum- and glucocorticoid-inducible kinase 1 (Sgk1). Chromatin immunoprecipitation (ChIP) analysis showed that this stressor caused substantial gene-dependent increases in GR binding and surprisingly, also MR binding to GREs within these genes. Different acute challenges, including novelty, restraint, and FS stress, produced distinct glucocorticoid responses but resulted in largely similar MR and GR binding to GREs. Sequential and tandem ChIP analyses showed that, after FS stress, MRs and GRs bind concomitantly to the same GRE sites within Fkbp5 and Per1 but not Sgk1. Thus, after stress, MRs and GRs seem to bind to GREs as homo- and/or heterodimers in a gene-dependent manner. MR binding to GREs at baseline seems to be restricted, whereas after stress, GR binding may facilitate cobinding of MR. This study reveals that the interaction of MRs and GRs with GREs within the genome constitutes an additional level of complexity in hippocampal glucocorticoid action beyond expectancies based on ligand–receptor interactions

Distinct epigenetic and gene expression changes in rat hippocampal neurons after Morris water maze training

Gene transcription and translation in the hippocampus is of critical importance in hippocampus-dependent memory formation, including during Morris water maze (MWM) learning. Previous work using gene deletion models has shown that the immediate-early genes (IEGs) c-Fos, Egr-1 and Arc are crucial for such learning. Recently, we reported that induction of IEGs in sparse dentate gyrus neurons requires ERK MAPK signaling and downstream formation of a distinct epigenetic histone mark (i.e. phospho-acetylated histone H3). Until now, this signaling, epigenetic and gene transcriptional pathway has not been comprehensively studied in the MWM model. Therefore, we conducted a detailed study of the phosphorylation of ERK1/2 and serine10 in histone H3 (H3S10p) and induction of IEGs in the hippocampus of MWM trained rats and matched controls. MWM training evoked consecutive waves of ERK1/2 phosphorylation and H3S10 phosphorylation, as well as c-Fos, Egr-1 and Arc induction in sparse hippocampal neurons. The observed effects were most pronounced in the dentate gyrus. A positive correlation was found between the average latency to find the platform and the number of H3S10p-positive dentate gyrus neurons. Furthermore, chromatin immuno-precipitation (ChIP) revealed a significantly increased association of phospho-acetylated histone H3 (H3K9ac-S10p) with the gene promoters of c-Fos and Egr-1, but not Arc, after MWM exposure compared with controls. Surprisingly, however, we found very little difference between IEG responses (regarding both protein and mRNA) in MWM-trained rats compared with matched swim controls. We conclude that exposure to the water maze evokes ERK MAPK activation, distinct epigenetic changes and IEG induction predominantly in sparse dentate gyrus neurons. It appears, however, that a specific role for IEGs in the learning aspect of MWM training may become apparent in downstream AP-1- and Egr-1-regulated (second wave) genes and Arc-dependent effector mechanisms

The Care of Elderly People in Vietnam

The population ageing as an unprecedented phenomenon in the history of the humanity was considered. It is slow, but persistent and, according to the opinion of the experts, it is irreversible, at least for the next hundred years. Population ageing has a profound impact on economic growth, investment and labor market, the welfare of every citizen of any country. Changes in the structure of the population in terms of aging concerns every person, society, country and the international community. The increase in the number of elderly people determines the necessity of working out new strategies for the stable development of each country in the world. Vietnam is no exception in this case. Population ageing is a contemporary challenge for the worldwide society. It requires the development of the effective strategic and tactic decisions and new systems of care for elder people, aimed at transformation of the population ageing challenges into opportunities, which provide people’s welfare. The main aim of the study is to determine the ways of perfection of the care system of the Vietnamese older people. The methods: system analysis of statistic data about the demographic structure of the Vietnamese population and the morbidity structure of the Vietnamese seniors; situation analyses. The results: specific features and conditions of the system of care of elderly people in Vietnam are studied. The analysis of the main factors that affect the system of care of the older people is conducted. The conclusions and proposals to enhance the system of care of the older people are drawn

Piccole capitali creative

Nel secolo urbano che abbiamo di fronte, la citt\ue0 sar\ue0 lo scenario della competizione delle energie, delle risorse umane, delle intelligenze collettive e della creativit\ue0 per la costruzione di un\u2019evoluzione pi\uf9 compatibile con le identit\ue0 e le vocazioni e pi\uf9 sostenibile rispetto alle risorse ed alle sensibilit\ue0 del territorio. I segnali delle sue forme, delle sue relazioni e delle sue identit\ue0 sono gi\ue0 evidenti in alcune citt\ue0 del presente ed ad essi sono dedicate numerose ricerche urbanistiche, sociologiche ed economiche. Ma i segnali sono evidenti e trasmettono ispirazioni e stimoli anche a chi osserva la citt\ue0 per mestiere di progettista, di pianificatore, di stratega dello sviluppo. Il XXI secolo sar\ue0 l\u2019era indiscussa delle citt\ue0 e su di esse si misurer\ue0 lo sviluppo delle nazioni. Per la prima volta, pi\uf9 della met\ue0 della popolazione mondiale vivr\ue0 nelle citt\ue0, in Europa oggi la cifra \ue8 gi\ue0 di oltre il 75%, e nei paesi in via di sviluppo raggiunger\ue0 velocemente il 50%. Il mondo si svilupper\ue0 sia attorno a grandi megalopoli da decine di milioni di abitanti, ma anche attorno a citt\ue0 metropolitane, a conurbazioni diffuse e ad armature di micropoli: all\u2019armatura urbana delle citt\ue0 globali si annoder\ue0, soprattutto in Europa, l\u2019armatura delle citt\ue0 di secondo livello, produttrici di visioni alternative rispetto all\u2019esplosione delle megalopoli. L\u2019armatura urbana europea di secondo livello \u2013 le piccole capitali, sempre pi\uf9 citt\ue0-porta \u2013 si delinea come annodata attorno a \u201ccitt\ue0 della cultura\u201d, nel senso di citt\ue0 non solo detentrici di risorse culturali profonde lasciate dal palinsesto della storia, ma anche produttrici di nuova cultura: le culture-based competition cities saranno, infatti, quelle citt\ue0 in grado di competere nel panorama internazionale attraverso la valorizzazione e la promozione della propria identit\ue0 culturale, sia consolidata che in evoluzione

Salinity from Space Unlocks Satellite-Based Assessment of Ocean Acidification

Approximately a quarter of the carbon dioxide (CO2) that we emit into the atmosphere is absorbed by the ocean. This oceanic uptake of CO2 leads to a change in marine carbonate chemistry resulting in a decrease of seawater pH and carbonate ion concentration, a process commonly called “Ocean Acidification”. Salinity data are key for assessing the marine carbonate system, and new space-based salinity measurements will enable the development of novel space-based ocean acidification assess- ment. Recent studies have highlighted the need to develop new in situ technology for monitoring ocean acidification, but the potential capabilities of space-based measurements remain largely untapped. Routine measurements from space can provide quasi-synoptic, reproducible data for investigating processes on global scales; they may also be the most efficient way to monitor the ocean surface. As the carbon cycle is dominantly controlled by the balance between the biological and solubility carbon pumps, innovative methods to exploit existing satellite sea surface temperature and ocean color, and new satellite sea surface salinity measurements, are needed and will enable frequent assessment of ocean acidification parameters over large spatial scales

Fluid-structure interaction simulation of prosthetic aortic valves : comparison between immersed boundary and arbitrary Lagrangian-Eulerian techniques for the mesh representation

In recent years the role of FSI (fluid-structure interaction) simulations in the analysis of the fluid-mechanics of heart valves is becoming more and more important, being able to capture the interaction between the blood and both the surrounding biological tissues and the valve itself. When setting up an FSI simulation, several choices have to be made to select the most suitable approach for the case of interest: in particular, to simulate flexible leaflet cardiac valves, the type of discretization of the fluid domain is crucial, which can be described with an ALE (Arbitrary Lagrangian-Eulerian) or an Eulerian formulation. The majority of the reported 3D heart valve FSI simulations are performed with the Eulerian formulation, allowing for large deformations of the domains without compromising the quality of the fluid grid. Nevertheless, it is known that the ALE-FSI approach guarantees more accurate results at the interface between the solid and the fluid. The goal of this paper is to describe the same aortic valve model in the two cases, comparing the performances of an ALE-based FSI solution and an Eulerian-based FSI approach. After a first simplified 2D case, the aortic geometry was considered in a full 3D set-up. The model was kept as similar as possible in the two settings, to better compare the simulations' outcomes. Although for the 2D case the differences were unsubstantial, in our experience the performance of a full 3D ALE-FSI simulation was significantly limited by the technical problems and requirements inherent to the ALE formulation, mainly related to the mesh motion and deformation of the fluid domain. As a secondary outcome of this work, it is important to point out that the choice of the solver also influenced the reliability of the final results

Immersed boundary-finite element model of fluid-structure interaction in the aortic root

It has long been recognized that aortic root elasticity helps to ensure efficient aortic valve closure, but our understanding of the functional importance of the elasticity and geometry of the aortic root continues to evolve as increasingly detailed in vivo imaging data become available. Herein, we describe fluid-structure interaction models of the aortic root, including the aortic valve leaflets, the sinuses of Valsalva, the aortic annulus, and the sinotubular junction, that employ a version of Peskin's immersed boundary (IB) method with a finite element (FE) description of the structural elasticity. We develop both an idealized model of the root with three-fold symmetry of the aortic sinuses and valve leaflets, and a more realistic model that accounts for the differences in the sizes of the left, right, and noncoronary sinuses and corresponding valve cusps. As in earlier work, we use fiber-based models of the valve leaflets, but this study extends earlier IB models of the aortic root by employing incompressible hyperelastic models of the mechanics of the sinuses and ascending aorta using a constitutive law fit to experimental data from human aortic root tissue. In vivo pressure loading is accounted for by a backwards displacement method that determines the unloaded configurations of the root models. Our models yield realistic cardiac output at physiological pressures, with low transvalvular pressure differences during forward flow, minimal regurgitation during valve closure, and realistic pressure loads when the valve is closed during diastole. Further, results from high-resolution computations demonstrate that IB models of the aortic valve are able to produce essentially grid-converged dynamics at practical grid spacings for the high-Reynolds number flows of the aortic root

Direct targeting of hippocampal neurons for apoptosis by glucocorticoids is reversible by mineralocorticoid receptor activation

Prova tipográfica (In Press)An important question arising from previous observations in vivo is whether glucocorticoids can directly influence neuronal survival in the hippocampus. To this end, a primary postnatal hippocampal culture system containing mature neurons and expressing both glucocorticoid (GR) and mineralocorticoid (MR) receptors was developed. Results show that the GR agonist dexamethasone (DEX) targets neurons (microtubule-associated protein 2-positive cells) for death through apoptosis. GR-mediated cell death was counteracted by the MR agonist aldosterone (ALDO). Antagonism of MR with spironolactone ([7a-(acetylthio)-3-oxo-17a-pregn- 4-ene,21 carbolactone] (SPIRO)) causes a dose-dependent increase in neuronal apoptosis in the absence of DEX, indicating that nanomolar levels of corticosterone present in the culture medium, which are sufficient to activate MR, can mask the apoptotic response to DEX. Indeed, both SPIRO and another MR antagonist, oxprenoate potassium ((7a,17a)-17-Hydroxy-3-oxo-7- propylpregn-4-ene-21-carboxylic acid, potassium salt (RU28318)), accentuated DEX-induced apoptosis. These results demonstrate that GRs can act directly to induce hippocampal neuronal death and that demonstration of their full apoptotic potency depends on abolition of survival-promoting actions mediated by MR