A non-transcriptional role for the glucocorticoid receptor in mediating the cell stress response

This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.The glucocorticoid receptor (GR) is essential for the stress response in mammals. We investigated potential non-transcriptional roles of GR in cellular stress response using fission yeast as a model.We surprisingly discovered marked heat stress resistance in yeast ectopically expressing human GR, which required expression of both the N-terminal transactivation domain, and the C-terminal ligand binding domain, but not the DNA-binding domain of the GR. This effect was not affected by GR ligand exposure, and occurred without significant GR nuclear accumulation. Mechanistically, the GR survival effect required Hsp104, and, indeed, GR expression increased Hsp104 expression. Proteomic analysis revealed GR binding to translasome components, including eIF3, a known partner for Sty1, a pattern of protein interaction which we confirmed using yeast two-hybrid studies.Taken together, we find evidence for a novel pathway conferring stress resistance in yeast that can be activated by the human GR, acting by protein-protein mechanisms in the cytoplasm. This suggests that in organisms where GR is natively expressed, GR likely contributes to stress responses through non-transcriptional mechanisms in addition to its well-established transcriptional responses

"I could cry, the amount of shoes I can't get into": A qualitative exploration of the factors that influence retail footwear selection in women with rheumatoid arthritis

<p>Abstract</p> <p>Background</p> <p>Studies have reported that women with rheumatoid arthritis (RA) are not wearing NHS supplied therapeutic footwear; therefore it is likely they are wearing footwear sourced through retailers. Previous research gives limited information (largely associated with cosmesis) on people's perceptions on the relationships that exist between retail footwear, well-being and quality of life. This study aimed to explore the perceptions of women with RA regarding their choice of retail footwear and identify the factors influencing retail footwear selection.</p> <p>Methods</p> <p>Eleven women with RA wearing normal retail footwear were recruited from an out-patient podiatry clinic in the south east of England. Semi-structured interviews were carried out and an interpretative phenomenological approach was adopted for data collection and transcript analysis.</p> <p>Results</p> <p>Six key themes were revealed from the analysis: (1) the nature of foot complaints and deformities, (2) aesthetic appearance and design of footwear, (3) body image, (4) psychosocial aspects, (5) Perceptions of footwear and (6) the therapeutic value of retail shoes. These contributed to an overarching concept of loss of choice associated with retail footwear. In particular, the areas discussed most frequently throughout were themes (2), (3) and (4), which were notably more 'emotional' in nature.</p> <p>Conclusions</p> <p>Limitations in retail footwear for these women have impacted on their individuality, linking significantly with their body image. The loss of choice in footwear as a consequence of the disease impacts negatively on emotions, wellbeing and was identified in reduced self-perceived quality of life.</p

REVERBa couples the circadian clock to hepatic glucocorticoid action.

The glucocorticoid receptor (GR) is a major drug target in inflammatory disease. However, chronic glucocorticoid (GC) treatment leads to disordered energy metabolism, including increased weight gain, adiposity, and hepatosteatosis - all programs modulated by the circadian clock. We demonstrated that while antiinflammatory GC actions were maintained irrespective of dosing time, the liver was significantly more GC sensitive during the day. Temporal segregation of GC action was underpinned by a physical interaction of GR with the circadian transcription factor REVERBa and co-binding with liver-specific hepatocyte nuclear transcription factors (HNFs) on chromatin. REVERBa promoted efficient GR recruitment to chromatin during the day, acting in part by maintaining histone acetylation, with REVERBa-dependent GC responses providing segregation of carbohydrate and lipid metabolism. Importantly, deletion of Reverba inverted circadian liver GC sensitivity and protected mice from hepatosteatosis induced by chronic GC administration. Our results reveal a mechanism by which the circadian clock acts through REVERBa in liver on elements bound by HNF4A/HNF6 to direct GR action on energy metabolism

Primary eye health services for older adults as a component of universal health coverage: A scoping review of evidence from high income countries

UNLABELLED: In pursuit of Universal Health Coverage (UHC) for eye health, countries must strengthen services for older adults, who experience the highest prevalence of eye conditions. This scoping review narratively summarised (i) primary eye health services for older adults in eleven high-income countries/territories (from government websites), and (ii) the evidence that eye health services reduced vision impairment and/or provided UHC (access, quality, equity, or financial protection) (from a systematic literature search). We identified 76 services, commonly comprehensive eye examinations ± refractive error correction. Of 102 included publications reporting UHC outcomes, there was no evidence to support vision screening in the absence of follow-up care. Included studies tended to report the UHC dimensions of access (n=70), equity (n=47), and/or quality (n=39), and rarely reported financial protection (n=5). Insufficient access for population subgroups was common; several examples of horizontal and vertical integration of eye health services within the health system were described. FUNDING: This work was funded by Blind Low Vision New Zealand for Eye Health Aotearoa

Spatially coordinated dynamic gene transcription in living pituitary tissue

Transcription at individual genes in single cells is often pulsatile and stochastic. A key question emerges regarding how this behaviour contributes to tissue phenotype, but it has been a challenge to quantitatively analyse this in living cells over time, as opposed to studying snap-shots of gene expression state. We have used imaging of reporter gene expression to track transcription in living pituitary tissue. We integrated live-cell imaging data with statistical modelling for quantitative real-time estimation of the timing of switching between transcriptional states across a whole tissue. Multiple levels of transcription rate were identified, indicating that gene expression is not a simple binary ‘on-off’ process. Immature tissue displayed shorter durations of high-expressing states than the adult. In adult pituitary tissue, direct cell contacts involving gap junctions allowed local spatial coordination of prolactin gene expression. Our findings identify how heterogeneous transcriptional dynamics of single cells may contribute to overall tissue behaviour. DOI: http://dx.doi.org/10.7554/eLife.08494.00

Adult Pituitary Data1

GFP fluorescence measured from single cells in adult pituitary tissue and subsequent modelling of transcription activity using a stochastic switch model

E18_5 Pituitary Data1

GFP fluorescence measured from single cells in embryonic day18.5 pituitary tissue and subsequent modelling of transcription activity using a stochastic switch model

Contemporary Mongolian folklore.

in english The aim of this work is to acquaint the reader with research on contemporary legends in Mongolia. This topic has not been explored among folklorists enought yet. I focused first on the general characteristics of contemporary legends, its dissemination, typology and history of research. I further elaborated, using literature and my own field research, the actual situation in Mongolia. Collected contemporary legends are accompanied by folkloric commentary. Attention is also paid to the city of Ulan Bator as a place where most of the tales were collected