Rapid and Nongenomic Glucocorticoid Signaling in Rainbow Trout

Corticosteroids are key regulatory hormones involved in many aspects of physiology and have long been known to exert rapid and delayed effects. The delayed corticosteroid effects are mediated by transcriptional events downstream of glucocorticoid receptor activation. Conversely, the rapid effects are mediated independently of transcriptional regulation and are thought to involve non-classical steroid receptors and signaling pathways. Lately, research has begun to focus on delineating the rapid and nongenomic actions of glucocorticoids but most of these studies have been on mammalian models. Cortisol, the primary corticosteroid in teleosts, is an established genomic regulator of the physiological response to stress, but very little is known about either the rapid effects or their mechanisms of action in non-mammalian vertebrates. Additionally, nongenomic glucocorticoid action in the liver is poorly characterized in all animal species despite the importance of this organ in regulating glucocorticoid-mediated physiological adjustments during stress adaptation. The primary objective of this thesis is to investigate the rapid glucocorticoid effects, and their mode of action, associated with stressor-induced corticosteroid elevation in fish liver. The overriding hypothesis is that rapid effects of cortisol on acute stress adaptation involve changes to liver membrane order and rapid modulation of stress signaling pathways in rainbow trout (Oncorhynchus mykiss), a well studied teleost model. This hypothesis was tested by examining rapid plasma membrane and intracellular responses following stressor-induced cortisol elevations in vivo, as well as to cortisol treatment in vitro using liver plasma membrane, tissue slices, hepatocytes in suspension, or primary culture of hepatocytes. Steroid hormones are lipophilic molecules and freely incorporate into the plasma membrane. Through noncovalent interactions (hydrogen bonds and Van der Waal forces), glucocorticoids can potentially alter physical properties of the plasma membrane, thus leading to intracellular responses. The effect of stressor-induced cortisol elevations on physical changes to the hepatic plasma membrane was investigated by measuring the microviscosity of the plasma membrane. Plasma membrane fluidity (inverse of microviscosity) is an important determinant of transmembrane protein function, and changes to lipid order can transmit extracellular signals by activating membrane-associated signaling pathways. Fluidity of purified liver plasma membranes was monitored using steady-state fluorescence polarization of 1,6-diphenyl-1,3,5 hexatriene, a well characterized membrane probe. In addition to measuring lipid dynamics, the effect of cortisol on plasma membrane structure and surface properties were also investigated using atomic force microscopy. The effect of cortisol on the activation of key stress signaling pathways, including protein kinase (PKA), protein kinase (PKC), Akt, and mitogen-activated protein kinase (MAPK), was tested in fish liver. Also, as acute stress adaptation is regulated by an integrative hormonal response involving catecholamines (primarily epinephrine), the rapid effect of cortisol action on adrenergic signaling in the liver was evaluated in vitro. Finally, an attempt was made to identify cortisol-binding plasma membrane protein, as glucocorticoids are also thought to mediate rapid effects through a novel membrane glucocorticoid receptor. The results demonstrate for the first time that stressor exposure significantly increases liver plasma membrane fluidity (decreased microviscosity). A role for cortisol in mediating stressor-induced fluidization was confirmed in vitro, as physiological stress levels of this steroid (≥100 ng/ml) significantly increased liver plasma membrane fluidity. In addition to increasing lipid fluidity, acute stress and cortisol treatment altered membrane topography, including changes to membrane microdomains. The stressor-induced cortisol elevation also rapidly modulated major signaling cascades in rainbow trout liver, including PKA, PKC, and ERK1/2 MAPKs. A role for cortisol in the activation of these kinase pathways was confirmed in vitro. Specifically, cortisol rapidly and transiently increases cyclic AMP (cAMP) accumulation and induces the phosphorylation of PKA substrate proteins, including cAMP response element-binding (CREB) protein. In addition to activating PKA signaling, cortisol rapidly induced phosphorylation of PKC and Akt substrate proteins, while stimulating p38 MAPK dephosphorylation in vitro. Moreover, rapid cortisol signaling may stimulate metabolite oxidation in order to maintain the energy balance within liver tissue as cortisol acutely depleted key liver metabolites (including liver glucose), suggesting enhanced turnover without impacting the steady-state adenylate energy charge ratio (measure of the energy status of the cell). Also, rapid effects of cortisol alter the hormonal responsiveness of hepatocytes to adrenergic stimulation, including suppression of epinephrine-stimulated cAMP-CREB activation and glucose production. Preliminary results point to a plasma membrane protein that specifically binds cortisol in trout liver, but this remains to be characterized. Also, in addition the membrane-mediated response, mifepristone, a glucocorticoid receptor (GR)-antagonist, blocked some rapid cortisol effects suggesting the possible involvement of GR signaling pathway. Until now, cortisol has been primarily thought to play a role in the long-term recovery process to acute stress by enhancing plasma glucose levels through the upregulation of liver gluconeogenic capacity. The results presented in this thesis provide evidence for a novel role for rapid cortisol action on the acute metabolic adjustments that support liver function immediately following acute stressor exposure. Particularly, the results lead to the proposal that acute cortisol action stabilizes the energy status of the cell by maintaining ATP levels through increased metabolite turnover, suggesting enhanced metabolic activity of the liver immediately following acute stressor exposure. While the mechanism is unclear, plasma membrane alterations in response to cortisol intercalation may facilitate rapid steroid signaling either through mechanotransduction or by altering activity of plasma membrane proteins. The structural changes to the plasma membrane in response to acute stressor exposure and/or cortisol treatment highlight a novel membrane-mediated mechanism of rapid stress adaptation in hepatic tissue

Madzhab Kualitas Ashahhul Asanid Prespektif Imam al-Dhahabi

AbstractThis article is specifically for knowing hadith narrators in their capacity as narrators, so their study is included in the field of Rijal al-Hadith science. In further discussion, from this branch of knowledge emerged the science of al-Jarh wa al-Ta'dil and the science of Tarikh al-Ruwah. namely the sciences that discuss the credibility, personal integrity and intellectual capacity of the narrators as well as living history (biography). In collecting data, the library research method was used (library). And this research is included in descriptive qualitative research with a literature review approach. This study attempts to discuss more deeply the thoughts of Imam al-Dhahabi> on hadith critics.Keywords: Asanid Hadith; Hadith criticism; Imam al-Dhahabi.AbstrakArtikel ini khusus untuk memperoleh kajian ashahhul ashanid hadis yang membahas perawi hadis dalam kepasitasnya sebagai perawi, maka kajiannya termasuk dalam bidang ilmu Rijal al-Hadis. Dari cabang ilmu ini muncul al-Jarh wa al-Ta’dil dan ilmu Tarikh al-Ruwah yakni ilmu-ilmu yang membahas tentang kreadibilitasnya, integritas pribadi dan kapasitas intelektual para perawi serta sejarah hidup (biografi). Sehingga tujuan dari peneliti untuk menemukan kualitas ashahhul ashanid menurut prespektif imam al-Dhahabi>. Penelitian ini masuk ke dalam metode penelitian kualitatif diskriptif dengan pendekatan kajian pustaka. Dalam pengumpulan data digunakan metode library reseach (kepustakaan). Penelitian ini lebih memfokuskan mengenai pemikiran imam al-Dhahabi> pada kualitas tingkatan kesahihan perawi hadis.Kata Kunci: Asanid Hadis; Imam al-Dhahabi>; Kritik Hadi

Disclosure and relationship satisfaction in families

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Understanding the Role of Relationship Maintenance in Enduring Couple Partnerships in Later Adulthood

Intimate relationships in later adulthood are understudied despite their positive association with health and well-being. This cross-sectional mixed methods study sought to redress this gap by investigating relationship maintenance in later adulthood. Our international sub-sample comprised 1,565 participants aged 55 + and in an ongoing relationship. Results from hierarchical multiple regression indicated that overall happiness with the relationship had the largest effect size on relationship maintenance, with 53% of the variance explained. Content analyses of open-ended questions identified companionship and laughter as some of the “best liked” aspects of the relationship. Housework/cooking and saying “I love you” were among the behaviors that made participants feel appreciated. Results illustrated the types of maintenance behaviors adults in later adulthood who are in enduring partnerships employ

Relating at work : facets, dialectics and face

This article examines ‘relating at work’. Recent theorising in pragmatics has drawn attention to the importance of analysing relations, and yet the pragmatic study of relations is now intertwined so closely with the concept of face (e.g. Arundale, 2010a; Holmes et al., 2011; Locher and Watts 2005, 2008) that it might seem the two are synonymous. In this paper, I review this research from a multidisciplinary perspective, and then report a study on ‘relating at work’ in which leaders and interns were interviewed about their experiences of starting work in a culturally unfamiliar setting. I focus on one dialectic, connectedness–separateness, and report the challenges they described in ‘making contact’. In the discussion section and on the basis of my findings, I argue the following points: (a) relating at work entails a complex web of interrelated facets and ‘smooth relations’ is just one of employees’ relational concerns; (b) Relational Dialectic Theory offers much potential for interpersonal pragmatics; (c) dialectic tensions can occur at the individual as well as the interpersonal/relational levels and an interactional achievement analytic perspective needs to be complemented by an individual perspective; (d) Relational Dialect Theory and Face Theory are complementary to each other and should not be conflated

Contribution of Non-canonical Cortisol Actions in the Early Modulation of Glucose Metabolism of Gilthead Sea Bream (Sparus aurata)

Teleost fish are exposed to diverse stressors in farming and wildlife conditions during their lifespan. Cortisol is the main glucocorticoid hormone involved in the regulation of their metabolic acclimation under physiological stressful conditions. In this context, increased plasma cortisol is associated with energy substrate mobilization from metabolic tissues, such as liver and skeletal muscle, to rapidly obtain energy and cope with stress. The metabolic actions of cortisol have primarily been attributed to its genomic/classic action mechanism involving the interaction with intracellular receptors, and regulation of stress-responsive genes. However, cortisol can also interact with membrane components to activate rapid signaling pathways. In this work, using the teleost fish gilthead sea bream (Sparus aurata) as a model, we evaluated the effects of membrane-initiated cortisol actions on the early modulation of glucose metabolism. For this purpose, S. aurata juveniles were intraperitoneally administrated with cortisol and with its membrane impermeable analog, cortisol-BSA. After 1 and 6 h of each treatment, plasma cortisol levels were measured, together with glucose, glycogen and lactate in plasma, liver and skeletal muscle. Transcript levels of corticosteroids receptors (gr1, gr2, and mr) and key gluconeogenesis (g6pc and pepck)- and glycolysis (pgam1 and aldo) related genes in the liver were also measured. Cortisol and cortisol-BSA administration increased plasma cortisol levels in S. aurata 1 h after administration. Plasma glucose levels enhanced 6 h after each treatment. Hepatic glycogen content decreased in the liver at 1 h of both cortisol and cortisol-BSA administration, while increased at 6 h due to cortisol but not in response to cortisol-BSA. Expression of gr1, g6pc, pgam1, and aldo were preferentially increased by cortisol-BSA in the liver. Taking all these results in consideration, we suggest that non-canonical cortisol mechanisms contribute to the regulation of the early glucose metabolism responses to stress in S. aurata

Psychological climates in action learning sets: A manager’s perspective

Action Learning (AL) is often viewed as a process that facilitates professional learning through the creation of a positive psychological climate (Marquart, 2000; Schein, 1979). An psychological climate that fosters an environment in which learning set members feel psychologically safe enough to reflect upon both the successes, and failures in their professional life without any form of repercussion. However, there has been little attention given to the ways that that psychological climate develops, and the differing facets that create that climate. In response to such deficit, this paper reports the outcomes of interviews with eleven managers, all of whom are former AL set members on their experiences of action learning set membership. Drawing upon an interpretivist philosophy, the paper explores the key themes that emerged from the analysis of those interviews. The analysis serves to illustrate the differing facets that collectively contribute creation of a positive psychological climate that is conducive for learning. Analysis points to the relative importance of such facets as: trust, honesty, vulnerability, reciprocity, confidentiality and personal disclosure, all of which have the capacity to lead to a positive psychological climate in action learning sets. This paper is useful for developing an understanding of the differing facets in AL sets that create a psychological climate conducive for learning. As such, it has utility for action learning facilitators, set members, academics and educational consultants

“Hit me up and we can get down” U.S. youths’ risk behaviors and sexual self-disclosure in MySpace profiles

Young people’s sexual self-disclosures in social media profiles can be problematic for those who produce them and for those who consume them. This study merged a content analysis with survey data to identify the characteristics of youth who engaged in online sexual self-disclosure. MySpace profiles belonging to 560 National Study of Youth and Religion respondents in the United States (18 to 23 years old) were analyzed (56,462 content units). A third of the profiles contained at least one sexual self-disclosure; their average incidence was less than one per profile. Online sexual self-disclosure was associated with offline sexual risk behaviors (e.g., sex with casual partners), and with increased frequency of alcohol consumption. Among sexually active females, it was associated with early sexual debut. In light of problem behavior theory, these findings suggest that online sexual self-disclosure may be considered a sexual risk behavior