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

Surface mesoscale pico–nanoplankton patterns at the main fronts of the Alboran Sea

© 2014 Elsevier B.V. The mesoscale (10-100. km, days-weeks) plays a key role in the Ocean's ecosystem structure and dynamics. This work compares the pico-nanoplankton patterns observed in the Alboran Sea (Western Mediterranean) during three oceanographic cruises. We analyse its response to different expressions of mesoscale circulation associated with the three major hydrodynamic features in the basin; namely the Northwestern Alboran Front (NWAF, surveyed in OMEGA-1 cruise), the Almeria-Oran Front (AOF, surveyed in OMEGA-2 cruise) and the Western Alboran Gyre (WAG, surveyed in BIOMEGA cruise). The first two surveys were carried out under the most typical quasi-stationary twin gyre conditions of the Alboran Sea, whereas the third cruise was performed after an eastward migration of the WAG. The analysis of pico and nanoplankton populations was carried out using flow cytometry. The patchiness observed in the three cruises indicates an association of phytoplankton peaks with the main frontal structures: abundances were higher in the NWAF/upwelling area in OMEGA-1, at the Mediterranean side of the AOF in OMEGA-2, and at a tongue of recent Atlantic Water west of the WAG in BIOMEGA. However, a more detailed analysis reveals that different factors explain the origin of the phytoplankton biomass in each front/cruise. Mixing processes at the Strait of Gibraltar and the subsequent advection of water properties into the Western Alboran Sea were the mechanisms responsible for the abundances observed in the NWAF. The highest concentrations observed in the AOF were related to the intrusion of Mediterranean Surface Waters to the north of the front. During the migrating WAG the phytoplankton distribution was influenced by the formation of a new gyre. The relation between phytoplankton and mesoscale dynamics is further explored in terms of vertical velocity diagnosis. In all cases, intense vertical motion is negatively correlated with the abundance of phytoplankton populations. This resulted from the intense geostrophic background flow associated with large vertical velocities, which drove low residence times of water mass properties and hence a weak biological response. Fast-repeated surveys made during the OMEGA-1 and OMEGA-2 cruises reveal that the surveyed hydrographic features are subjected to significant temporal variability. In this case, the impact on the biology is most evident at taxa level.This work was partially supported by the EU funded MAST project OMEGA (MAS3-CT95-0001) and by the BIOMEGA project, funded by the Spanish Marine Science and Technology Program (REN2002-04044-C02-02). P. Leon was financed by a FPI grant from the Spanish Ministry of Education and Science (BES-2003-1032)Peer Reviewe

Molecular and Epigenetic Mechanisms Underlying Cognitive and Adaptive Responses to Stress

Consolidation of contextual memories after a stressful encounter is essential for the survival of an organism and in allowing a more appropriate response to be elicited should the perceived threat reoccur. Recent evidence has explored the complex role that epigenetic mechanisms play in the formation of such memories, and the underlying signaling pathways are becoming more apparent. The glucocorticoid receptor (GR) has been shown to play a key role in these events having both genomic and non-genomic actions in the brain. GR has been shown to interact with the extracellular signal-regulated kinase mitogen-activated protein kinase (ERK MAPK) signaling pathway which, in concert, drives epigenetic modifications and chromatin remodeling, resulting in gene induction and memory consolidation. Evidence indicates that stressful events can have an effect on the offspring in utero, and that epigenetic marks altered early in life may persist into adulthood. A new and controversial area of research, however, suggests that epigenetic modifications could be inherited through the germline, a concept known as transgenerational epigenetics. This review explores the role that epigenetic processes play in the central nervous system, specifically in the consolidation of stress-induced memories, the concept of transgenerational epigenetic inheritance, and the potential role of epigenetics in revolutionizing the treatment of stress-related disorders through the emerging field of pharmacoepigenetics and personalized medical treatment

Compressibility of CeMIn5Ce M In_5 and Ce2MIn8Ce_2 M In_8 (M = Rh, Ir and Co) Compounds

The lattice parameters of the tetragonal compounds Ce$M$In$_{5}$ and Ce$_{2}M$In$_{8}$($M=$Rh, Ir and Co) have been studied as a function of pressure up to 15 GPa using a diamond anvil cell under both hydrostatic and quasihydrostatic conditions at room temperature. The addition of $M$In$_{2}$ layers to the parent CeIn$_{3}$ compound is found to stiffen the lattice as the 2-layer systems (average of bulk modulus values $B_{0}$ is 70.4 GPa) have a larger $B_{0}$ than CeIn$_{3}$ (67 GPa), while the 1-layer systems with the are even stiffer (average of $B_{0}$ is 81.4 GPa). Estimating the hybridization using parameters from tight binding calculations shows that the dominant hybridization is $fp$ in nature between the Ce and In atoms. The values of $V_{pf}$ at the pressure where the superconducting transition temperature $T_{c}$ reaches a maximum is the same for all Ce$M$In$_{5}$ compounds. By plotting the maximum values of the superconducting transition temperature $T_{c}$ versus $c/a$ for the studied compounds and Pu-based superconductors, we find a universal $T_{c}$ versus $c/a$ behavior when these quantities are normalized appropriately. These results are consistent with magnetically mediated superconductivity.Comment: Updated version resubmitted to Phys. Rev.

Trauma mechanism and patient reported outcome in tibial plateau fractures with posterior involvement

Introduction: Posterior tibial plateau fractures (PTPF) have a high impact on functional outcome and the optimal treatment strategy is not well established. The goal of this study was to assess the relationship between trauma mechanism, fracture morphology and functional outcome in a large multicenter cohort and define possible strategies to improve the outcome. Methods: An international retrospective cohort study was conducted in five level-1 trauma centers. All consecutive operatively treated PTPF were evaluated. Preoperative imaging was reviewed to determine the trauma mechanism. Patient reported outcome was scored using the Knee injury and Osteoarthritis Outcome Score (KOOS). Results: A total of 145 tibial plateau fractures with posterior involvement were selected with a median follow-up of 32.2 months (IQR 24.1-43.2). Nine patients (6%) sustained an isolated posterior fracture. Seventy-two patients (49%) sustained a two-column fracture and three-column fractures were diagnosed in 64 (44%) patients. Varus trauma was associated with poorer outcome on the 'symptoms' (p = 0.004) and 'pain' subscales (p = 0.039). Delayed-staged surgery was associated with worse outcome scores for all subscales except 'pain'. In total, 27 patients (18%) were treated with posterior plate osteosynthesis without any significant difference in outcome. Conclusions: Fracture morphology, varus trauma mechanism and delayed-staged surgery (i.e. extensive soft-tissue injury) were identified as important prognostic factors on postoperative outcome in PTPF. In order to assess possible improvement of outcome, future studies with routine preoperative MRI to assess associated ligamentous injury in tibial plateau fractures (especially for varus trauma) are needed. (c) 2021 Elsevier B.V. All rights reserved

Моделирование наземных испытаний рефлекторов антенн космических аппаратов на стенде с активной системой обезвешивания

Объектом исследования является стенд для раскрытия рефлектора антенны с восемью спицами диаметром 8,6 метров. Цель работы – моделирование наземных испытаний рефлекторов антенн космического аппарата (КА) на стенде с активной системой обезвешивания. В процессе исследования проводился анализ существующих способов обезвешивания элементов конструкций КА, разрабатывался алгоритм обезвешивания спицы, определялись кинематические зависимости углов механизма раскрытия спиц от перемещения мачты при раскрытии рефлектора антенны КА, разрабатывалась модель системы раскрытия спицы.The object of this study is to stand for the opening of the reflector antenna with eight spokes with a diameter of 8.6 meters. Objective - ground test simulation of the spacecraft antenna reflectors (CA) on a stand with an active obezveshivaniya system. The study analyzed the existing methods obezveshivaniya elements of spacecraft structures, developed an algorithm obezveshivaniya spokes, were determined according to the disclosure of the kinematic mechanism of the angles of the spokes on the displacement of the mast during the opening of the reflector antenna spacecraft designed spokes model disclosure system

Exercise Improves Cognitive Responses to Psychological Stress through Enhancement of Epigenetic Mechanisms and Gene Expression in the Dentate Gyrus

Background We have shown previously that exercise benefits stress resistance and stress coping capabilities. Furthermore, we reported recently that epigenetic changes related to gene transcription are involved in memory formation of stressful events. In view of the enhanced coping capabilities in exercised subjects we investigated epigenetic, gene expression and behavioral changes in 4-weeks voluntarily exercised rats. Methodology/Principal Findings Exercised and control rats coped differently when exposed to a novel environment. Whereas the control rats explored the new cage for the complete 30-min period, exercised animals only did so during the first 15 min after which they returned to sleeping or resting behavior. Both groups of animals showed similar behavioral responses in the initial forced swim session. When re-tested 24 h later however the exercised rats showed significantly more immobility behavior and less struggling and swimming. If rats were killed at 2 h after novelty or the initial swim test, i.e. at the peak of histone H3 phospho-acetylation and c-Fos induction, then the exercised rats showed a significantly higher number of dentate granule neurons expressing the histone modifications and immediate-early gene induction. Conclusions/Significance Thus, irrespective of the behavioral response in the novel cage or initial forced swim session, the impact of the event at the dentate gyrus level was greater in exercised rats than in control animals. Furthermore, in view of our concept that the neuronal response in the dentate gyrus after forced swimming is involved in memory formation of the stressful event, the observations in exercised rats of enhanced neuronal responses as well as higher immobility responses in the re-test are consistent with the reportedly improved cognitive performance in these animals. Thus, improved stress coping in exercised subjects seems to involve enhanced cognitive capabilities possibly resulting from distinct epigenetic mechanisms in dentate gyrus neurons

Poor sporting abilities after tibial plateau fractures involving the posterior column: how can we do better?

Purpose: Tibial plateau fractures with the involvement of the posterior column are an important prognostic factor towards poor functional outcome. We aimed to assess the sporting abilities postoperatively with special emphasis on the type of sports and sport-specific movements, as well as time needed to resume sports, restricting factors in sports engagement, and patient satisfaction. We aimed to provide prognostic information on return to sports. Methods: Demographic, clinical and radiological variables were retrospectively collected from 82 multicentric patients between 2014 and 2016. Prospectively, sporting abilities before and after surgery were determined using questionnaires at a mean follow-up of 33 months postoperatively. Results: Involvement in sports significantly decreased, with only 68.4% of patients resuming sports (p < 0.001). The mean time needed to partially or fully resume sports was 6–9 and 9–12 months, respectively. The ability to resume at the pre-injury level of effort and performance was 22% and 12%, respectively. Restricting factors were pain (66%), fear of re-injury (37%), limited range of motion (26%), and instability (21%). The majority (59%) of patients were unsatisfied with their physical abilities. Significantly worse outcomes were observed in patients playing high-impact sports, experiencing knee pain during physical activity, suffering from extension/valgus or flexion/varus trauma. Conclusions: Tibial plateau fractures with the involvement of the posterior column significantly hamper the patients’ sporting abilities, leaving the majority of patients unsatisfied. Preoperative counseling about prognosis, setting realistic expectations, optimizing rehabilitation and pain management postoperatively, and advising low-impact sports might improve engagement in physical activities and emotional impact on patients. Level of evidence: 3

The calcium-Activated potassium channel KCa3.1 is an important modulator of hepatic injury

The calcium-Activated potassium channel KCa3.1 controls different cellular processes such as proliferation and volume homeostasis. We investigated the role of KCa3.1 in experimental and human liver fibrosis. KCa3.1 gene expression was investigated in healthy and injured human and rodent liver. Effect of genetic depletion and pharmacological inhibition of KCa3.1 was evaluated in mice during carbon tetrachloride induced hepatic fibrogenesis. Transcription, protein expression and localisation of KCa3.1 was analysed by reverse transcription polymerase chain reaction, Western blot and immunohistochemistry. Hemodynamic effects of KCa3.1 inhibition were investigated in bile duct-ligated and carbon tetrachloride intoxicated rats. In vitro experiments were performed in rat hepatic stellate cells and hepatocytes. KCa3.1 expression was increased in rodent and human liver fibrosis and was predominantly observed in the hepatocytes. Inhibition of KCa3.1 aggravated liver fibrosis during carbon tetrachloride challenge but did not change hemodynamic parameters in portal hypertensive rats. In vitro, KCa3.1 inhibition leads to increased hepatocyte apoptosis and DNA damage, whereas proliferation of hepatic stellate cells was stimulated by KCa3.1 inhibition. Our data identifies KCa3.1 channels as important modulators in hepatocellular homeostasis. In contrast to previous studies in vitro and other tissues this channel appears to be anti-fibrotic and protective during liver injury