Circadian and Ultradian Rhythms of Free Glucocorticoid Hormone Are Highly Synchronized between the Blood, the Subcutaneous Tissue, and the Brain

Total glucocorticoid hormone levels in plasma of various species, including humans, follow a circadian rhythm that is made up from an underlying series of hormone pulses. In blood most of the glucocorticoid is bound to corticosteroid-binding globulin and albumin, resulting in low levels of free hormone. Although only the free fraction is biologically active, surprisingly little is known about the rhythms of free glucocorticoid hormones. We used single-probe microdialysis to measure directly the free corticosterone levels in the blood of freely behaving rats. Free corticosterone in the blood shows a distinct circadian and ultradian rhythm with a pulse frequency of approximately one pulse per hour together with an increase in hormone levels and pulse height toward the active phase of the light/dark cycle. Similar rhythms were also evident in the subcutaneous tissue, demonstrating that free corticosterone rhythms are transferred from the blood into peripheral target tissues. Furthermore, in a dual-probe microdialysis study, we demonstrated that the circadian and ultradian rhythms of free corticosterone in the blood and the subcutaneous tissue were highly synchronized. Moreover, free corticosterone rhythms were also synchronous between the blood and the hippocampus. These data demonstrate for the first time an ultradian rhythm of free corticosterone in the blood that translates into synchronized rhythms of free glucocorticoid hormone in peripheral and central tissues. The maintenance of ultradian rhythms across tissue barriers in both the periphery and the brain has important implications for research into aberrant biological rhythms in disease and for the development of improved protocols for glucocorticoid therapy

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

A functional role for both GABA transporter-1 and GABA transporter-3 in the modulation of extracellular GABA and GABAergic tonic conductances in the rat hippocampus

Tonic γ-aminobutyric acid (GABA)(A) receptor-mediated signalling controls neuronal network excitability in the hippocampus. Although the extracellular concentration of GABA (e[GABA]) is critical in determining tonic conductances, knowledge on how e[GABA] is regulated by different GABA transporters (GATs) in vivo is limited. Therefore, we studied the role of GATs in the regulation of hippocampal e[GABA] using in vivo microdialysis in freely moving rats. Here we show that GAT-1, which is predominantly presynaptically located, is the major GABA transporter under baseline, quiescent conditions. Furthermore, a significant contribution of GAT-3 in regulating e[GABA] was revealed by administration of the GAT-3 inhibitor SNAP-5114 during simultaneous blockade of GAT-1 by NNC-711. Thus, the GABA transporting activity of GAT-3 (the expression of which is confined to astrocytes) is apparent under conditions in which GAT-1 is blocked. However, sustained neuronal activation by K(+)-induced depolarization caused a profound spillover of GABA into the extrasynaptic space and this increase in e[GABA] was significantly potentiated by sole blockade of GAT-3 (i.e. even when uptake of GAT-1 is intact). Furthermore, experiments using tetrodotoxin to block action potentials revealed that GAT-3 regulates extrasynaptic GABA levels from action potential-independent sources when GAT-1 is blocked. Importantly, changes in e[GABA] resulting from both GAT-1 and GAT-3 inhibition directly precipitate changes in tonic conductances in dentate granule cells as measured by whole-cell patch-clamp recording. Thus, astrocytic GAT-3 contributes to the regulation of e[GABA] in the hippocampus in vivo and may play an important role in controlling the excitability of hippocampal cells when network activity is increased

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

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.

Оценка эффективности использования основных фондов нефтегазового предприятия (на примере ОАО «Стройтрансгаз Сибирь»)

Целью дипломной работы является анализ основных фондов и оценка эффективности их использования, а также разработка эффективных путей и инструментов управления основными средствами на предприятии. Объектом исследования послужило открытое акционерное общество «Стройтрансгаз Сибирь», осуществляющее свою деятельность на территории Томской области. Период исследования составил три года (2013-2015 гг.). В финансово-хозяйственной деятельности организации основные средства занимают одно из центральных мест. Эффективное их использование способствует оптимальному и экономному потреблению других видов ресурсов (например, сырья, материалов и т.д.). Таким образом, от состояния и эффективного использования основных средств зависят и качественные показатели деятельности хозяйствующего субъекта. Основными показателями, характеризующими эффективность использования основных средств, являются: фондоотдача, фондоемкость и фондорентабельность. Немаловажное значение имеют и коэффициенты технического состояния основных средств (коэффициенты годности, износа). В качестве конкретного мероприятия по повышению эффективности использования основных средств ОАО «Стройтрансгаз Сибирь» было предложено использовать специальный корректировочный коэффициент с целью сближения фактического физического состояния основных фондов и их бухгалтерского отражения.The aim of the thesis is the analysis of the fixed assets and estimation of efficiency of their use and the development of effective ways and tools of asset management at the enterprise. The object of the study served as an open joint stock company "Stroytransgaz Siberia" carries out its activity on the territory of Tomsk region. The study period was three years (2013-2015). In the financial-economic activity of the organization major means is one of the Central places. Their effective use promotes optimal and economical consumption of other types of resources (e.g., raw materials, etc.). Thus, the condition and effective use of fixed assets depend on the quality of the activities of the entity. The main indicators characterizing the efficiency of use of fixed assets are capital productivity, capital intensity and fondamentalisti. Also important, the coefficients of technical condition of fixed assets (coefficients of shelf life wear). As specific measures to improve the efficiency of use of fixed assets of OJSC "Stroytransgaz Siberia" it was proposed to use a special deemphasize the gaps between the actual physical condition of fixed assets and their accounting treatment

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

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