Histone acetyltransferases (HATs) are important enzymes that transfer acetyl groups onto histones and thereby regulate both gene expression and chromosomal structures. Previous work has shown that the activation of sirtuins, which are histone deacetylases, can extend lifespan. This suggests that inhibiting HATs may have a similar beneficial effect. In the present study, we utilized a range of HAT inhibitors or heterozygous Gcn5 and Ngg1 mutants to demonstrate marked yeast life extension. In human cell lines, HAT inhibitors and selective RNAi-mediated Gcn5 or Ngg1 knockdown reduced the levels of aging markers and promoted proliferation in senescent cells. Furthermore, this observed lifespan extension was associated with the acetylation of histone H3 rather than that of H4. Specifically, it was dependent upon H3K9Ac and H3K18Ac modifications. We also found that the ability of caloric restriction to prolong lifespan is Gcn5-, Ngg1-, H3K9-, and H3K18-dependent. Transcriptome analysis revealed that these changes were similar to those associated with heat shock and were inversely correlated with the gene expression profiles of aged yeast and aged worms. Through a bioinformatic analysis, we also found that HAT inhibition activated subtelomeric genes in human cell lines. Together, our results suggest that inhibiting the HAT Gcn5 may be an effective means of increasing longevity. © 2020 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.Strategies to increase personal wellness and resilience are being increasingly promoted by organisations as a response to occupational burnout. Thought leaders in burnout research believe that this approach is unlikely to be effective as it does not address the underlying causes of burnout which is poor workplace design. © 2020 Australasian College for Emergency Medicine.BACKGROUND Realizing patient partnership in research requires a shift from patient participation in ancillary roles to engagement as contributing members of research teams. While engaging patient partners is often discussed, impact is rarely measured. OBJECTIVE Our primary aim was to conduct a scoping review of the impact of patient partnership on research outcomes. The secondary aim was to describe barriers and facilitators to realizing effective partnerships. SEARCH STRATEGY A comprehensive bibliographic search was undertaken in EBSCO CINAHL, and Embase, MEDLINE and PsycINFO via Ovid. Reference lists of included articles were hand-searched. INCLUSION CRITERIA Included studies were (a) related to health care; (b) involved patients or proxies in the research process; and (c) reported results related to impact/evaluation of patient partnership on research outcomes. DATA EXTRACTION AND SYNTHESIS Data were extracted from 14 studies meeting inclusion criteria using a narrative synthesis approach. MAIN RESULTS Patient partners were involved in a range of research activities. see more Results highlight critical barriers and facilitators for researchers seeking to undertake patient partnerships to be aware of, such as power imbalances between patient partners and researchers, as well as valuing of patient partner roles. DISCUSSION Addressing power dynamics in patient partner-researcher relationships and mitigating risks to patient partners through inclusive recruitment and training strategies may contribute towards effective engagement. Further guidance is needed to address evaluation strategies for patient partnerships across the continuum of patient partner involvement in research. CONCLUSIONS Research teams can employ preparation strategies outlined in this review to support patient partnerships in their work. © 2020 The Authors Health Expectations published by John Wiley & Sons Ltd.Recent evidence has linked the lysosomal cholesterol accumulation in Niemann-Pick type C1 with anomalies associated with primary ciliogenesis. Here, we report that perturbed intracellular cholesterol distribution imposed by lysosomal cholesterol accumulation during TMEM135 depletion is closely associated with impaired ciliogenesis. TMEM135 depletion does not affect the formation of the basal body and the ciliary transition zone. TMEM135 depletion severely blunts Rab8 trafficking to the centrioles without affecting the centriolar localization of Rab11 and Rabin8, the upstream regulators of Rab8 activation. Although TMEM135 depletion prevents enhanced IFT20 localization at the centrioles, ciliary vesicle formation is not affected. Furthermore, enhanced IFT20 localization at the centrioles is dependent on Rab8 activation. Supplementation of cholesterol in complex with cyclodextrin rescues Rab8 trafficking to the centrioles and Rab8 activation, thereby recovering primary ciliogenesis in TMEM135-depleted cells. Taken together, our data suggest that TMEM135 depletion prevents ciliary vesicle elongation, a characteristic of impaired Rab8 function. Our study thus reveals a previously uncharacterized effect of erroneous intracellular cholesterol distribution on impairing Rab8 function and primary ciliogenesis. © 2020 The Authors. Published under the terms of the CC BY 4.0 license.As a synthetic model for intra-protein interactions that reinforce binding affinities between proteins and ligands, the energetic interplay of binding and folding was investigated using foldamer-based receptors capable of adopting helical structures. The receptors were designed to have identical hydrogen-bonding sites for anion binding but different aryl appendages that simply provide additional π-stacking within the helical backbones without direct interactions with the bound anions. In particular, the presence of electron-deficient aryl appendages led to dramatic enhancements in the association constant between the receptor and chloride or nitrate ion, by up to three orders of magnitude. Extended stacking within the receptor contributes to the stabilization of the entire folding structure of complexes, thereby enhancing binding affinities. © 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.Glycogen in tissues functions not only as carbohydrate reserves, but also as molecular sensors capable of activating signaling pathways in response to physical activity. While glycogen in the skeletal muscles is mainly a local energy substrate, glycogen in the liver serves as a glucose reserve to maintain normal blood glucose levels in the body, even during the sleep state. The aim of this study is to compare the diurnal variation of glycogen in the muscle and liver of human subjects under normal conditions. The glycogen content was measured in the muscle and liver of 10 young, healthy, male volunteers using 13 C MRS, a non-invasive technique. The subjects remained sedentary, and glycogen concentration was measured six times daily. Experimental meals were provided to achieve individual energy balance, estimated according to the energy requirement guideline for patients from Japan. The largest variation in muscle glycogen compared with 1 h after supper (2000 on Day 1) was 3.1 ± 8.2 mmol/L (1600 on Day 2). In the liver, however, the glycogen content decreased by 80.