Adaptive Capacity to Bacterial Diet Modulates Aging in C. elegans

SummaryDiet has a substantial impact on cellular metabolism and physiology. Animals must sense different food sources and utilize distinct strategies to adapt to diverse diets. Here we show that Caenorhabditis elegans lifespan is regulated by their adaptive capacity to different diets, which is controlled by alh-6, a conserved proline metabolism gene. alh-6 mutants age prematurely when fed an Escherichia coli OP50 but not HT115 diet. Remarkably, this diet-dependent aging phenotype is determined by exposure to food during development. Mechanistically, the alh-6 mutation triggers diet-induced mitochondrial defects and increased generation of ROS, likely due to accumulation of its substrate 1-pyrroline-5-carboxylate. We also identify that neuromedin U receptor signaling is essential for diet-induced mitochondrial changes and premature aging. Moreover, dietary restriction requires alh-6 to induce longevity. Collectively, our data reveal a homeostatic mechanism that animals employ to cope with potential dietary insults and uncover an example of lifespan regulation by dietary adaptation

Lifespan Regulation by Evolutionarily Conserved Genes Essential for Viability

Evolutionarily conserved mechanisms that control aging are predicted to have prereproductive functions in order to be subject to natural selection. Genes that are essential for growth and development are highly conserved in evolution, but their role in longevity has not previously been assessed. We screened 2,700 genes essential for Caenorhabditis elegans development and identified 64 genes that extend lifespan when inactivated postdevelopmentally. These candidate lifespan regulators are highly conserved from yeast to humans. Classification of the candidate lifespan regulators into functional groups identified the expected insulin and metabolic pathways but also revealed enrichment for translation, RNA, and chromatin factors. Many of these essential gene inactivations extend lifespan as much as the strongest known regulators of aging. Early gene inactivations of these essential genes caused growth arrest at larval stages, and some of these arrested animals live much longer than wild-type adults. daf-16 is required for the enhanced survival of arrested larvae, suggesting that the increased longevity is a physiological response to the essential gene inactivation. These results suggest that insulin-signaling pathways play a role in regulation of aging at any stage in life

Queer activism begins at home: situating LGBTQ voices in National Trust historic houses

Despite a growing body of literature and practical examples of lesbian, gay, bisexual, trans and queer (LGBTQ) interventions in museums, there is a dearth of research in equivalent initiatives in historic houses, specifically in those owned and managed by the National Trust. My research aims to address that gap, by using a creative intervention in the form of an exhibition for LGBT History Month. This queered action research involved curating an intervention, using a crowd-sourced exhibition, at the National Trust’s Sutton House in Hackney, London. The exhibition and the process of curation is the primary case study in my thesis. The exhibition 126, saw 126 LGBTQ identified volunteers submitting smartphone recordings of Shakespeare’s Fair Youth Sonnets and short video portraits of themselves as contributors. These were edited into a film, and exhibited at the first ever ‘Queer Season’ at Sutton House in February and March 2015. While feedback from visitors and contributors was analysed, the video portraits formed the primary data in the thesis. The videos are presented as a means through which LGBTQ people have chosen to represent their queer identities in a National Trust property. The results are noteworthy for the diversity of ways that LGBTQ people choose to visually signify their queer identities when given autonomy to do so. Evident in the videos were performed gender identities as well as rejections of gender, parallels with ‘coming out’ video blog tropes, direct responses to the themes of invisibility and representation, and a suggestion of the radical potential of vanity, and of ‘selfies’, in historic buildings. My research concludes that queer identities, having been systematically repressed in historic houses, manifest themselves most authentically when the communities themselves are given the autonomy to represent their own queerness. The participants become stakeholders in facing the challenge of presenting LGBTQ identities to audiences unfamiliar with them, and take on a variety of roles, as cocurators, content creators and queer heritage activists

Lifespan Regulation by Evolutionarily Conserved Genes Essential for Viability

Evolutionarily conserved mechanisms that control aging are predicted to have prereproductive functions in order to be subject to natural selection. Genes that are essential for growth and development are highly conserved in evolution, but their role in longevity has not previously been assessed. We screened 2,700 genes essential for Caenorhabditis elegans development and identified 64 genes that extend lifespan when inactivated postdevelopmentally. These candidate lifespan regulators are highly conserved from yeast to humans. Classification of the candidate lifespan regulators into functional groups identified the expected insulin and metabolic pathways but also revealed enrichment for translation, RNA, and chromatin factors. Many of these essential gene inactivations extend lifespan as much as the strongest known regulators of aging. Early gene inactivations of these essential genes caused growth arrest at larval stages, and some of these arrested animals live much longer than wild-type adults. daf-16 is required for the enhanced survival of arrested larvae, suggesting that the increased longevity is a physiological response to the essential gene inactivation. These results suggest that insulin-signaling pathways play a role in regulation of aging at any stage in life

Negotiation, bargaining, and discounts:generating WoM and local tourism development at the Tabriz bazaar, Iran

This paper examines the effects of negotiation intention, bargaining propensity, and discount satisfaction on word-of-mouth (WoM) behaviours for tourists visiting Tabriz bazaar, Iran. Data from 615-survey respondents highlight that tourists are motivated to conduct WoM behaviour when they are experientially satisfied with the opportunity to negotiate and bargain, and when they are satisfied with the discount they receive. This paper makes theoretical contributions to social exchange theory and presents managerial implications for policy-makers to generate tourism development

The role of the Tim8p–Tim13p complex in a conserved import pathway for mitochondrial polytopic inner membrane proteins

Tim23p is imported via the TIM (translocase of inner membrane)22 pathway for mitochondrial inner membrane proteins. In contrast to precursors with an NH2-terminal targeting presequence that are imported in a linear NH2-terminal manner, we show that Tim23p crosses the outer membrane as a loop before inserting into the inner membrane. The Tim8p–Tim13p complex facilitates translocation across the intermembrane space by binding to the membrane spanning domains as shown by Tim23p peptide scans with the purified Tim8p–Tim13p complex and crosslinking studies with Tim23p fusion constructs. The interaction between Tim23p and the Tim8p–Tim13p complex is not dependent on zinc, and the purified Tim8p–Tim13p complex does not coordinate zinc in the conserved twin CX3C motif. Instead, the cysteine residues seemingly form intramolecular disulfide linkages. Given that proteins of the mitochondrial carrier family also pass through the TOM (translocase of outer membrane) complex as a loop, our study suggests that this translocation mechanism may be conserved. Thus, polytopic inner membrane proteins, which lack an NH2-terminal targeting sequence, pass through the TOM complex as a loop followed by binding of the small Tim proteins to the hydrophobic membrane spanning domains

Time cost associated with sports participation for athletes with high support needs : A time-motion analysis of tasks required for para swimming

Objectives People with cerebral palsy and high support needs (CP&HSN) are profoundly inactive but also under-represented in studies evaluating physical activity interventions. Reasons for their exclusion have not been evaluated. We hypothesised that CP&HSN would be associated with high time costs of preparatory activities (eg, getting dressed/undressed), possibly contributing to low participation and under-representation. Accordingly, this pilot study aimed to: (1) evaluate whether the time required for preparatory activities was extremely different (≥3 SD) between swimmers with and without CP&HSN; and (2) provide a qualitative indication of the preparatory tasks undertaken by swimmers with CP&HSN. Methods Each of three experienced (5 years) para swimmers with CP&HSN and 20 non-disabled swimmers were timed entering and then exiting the pool on three occasions. Mean entry and exit time for each para swimmer was compared with the group mean for non-disabled swimmers, and differences of greater than 3.0 SD were considered extreme. A qualitative description of the tasks completed by the para swimmers was recorded. Results The differences in time costs between para and non-disabled swimmers met the criterion of extreme. Pool entry times for para swimmers were 8–13 times greater (Effect size = 4.1–8.7). Pool exit times were 6–10 times greater (ES=7.0–9.5). 90% of tasks completed by para swimmers required personal assistance or wheeled mobility. Conclusions This pilot study suggests that, compared with non-disabled swimmers, time costs for preparation to commence or depart training are extremely high for swimmers with CP&HSN. Further research is required to evaluate the veracity of these findings

Prediction of C. elegans Longevity Genes by Human and Worm Longevity Networks

Intricate and interconnected pathways modulate longevity, but screens to identify the components of these pathways have not been saturating. Because biological processes are often executed by protein complexes and fine-tuned by regulatory factors, the first-order protein-protein interactors of known longevity genes are likely to participate in the regulation of longevity. Data-rich maps of protein interactions have been established for many cardinal organisms such as yeast, worms, and humans. We propose that these interaction maps could be mined for the identification of new putative regulators of longevity. For this purpose, we have constructed longevity networks in both humans and worms. We reasoned that the essential first-order interactors of known longevity-associated genes in these networks are more likely to have longevity phenotypes than randomly chosen genes. We have used C. elegans to determine whether post-developmental inactivation of these essential genes modulates lifespan. Our results suggest that the worm and human longevity networks are functionally relevant and possess a high predictive power for identifying new longevity regulators

A Glass Polyalkenoate Cement Carrier for Bone Morphogenetic Proteins

This work considers a glass polyalkenoate cement (GPC)-based carrier for the effective delivery of bone morphogenetic proteins (BMPs) at an implantation site. A 0.12 CaO–0.04 SrO–0.36 ZnO–0.48 SiO2 based glass and poly(acrylic acid) (PAA, Mw 213,000) were employed for the fabrication of the GPC. The media used for the water source in the GPC reaction was altered to produce a series of GPCs. The GPC liquid media was either 100 % distilled water with additions of albumin at 0, 2, 5 and 8 wt% of the glass content, 100 % formulation buffer (IFB), and 100 % BMP (150 µg rhBMP-2/ml IFB). Rheological properties, compressive strength, ion release profiles and BMP release were evaluated. Working times (Tw) of the formulated GPCs significantly increased with the addition of 2 % albumin and remained constant with further increases in albumin content or IFB solutions. Setting time (Ts) experienced an increase with 2 and 5 % albumin content, but a decrease with 8 % albumin. Changing the liquid source to IFB containing 5 % albumin had no significant effect on Ts compared to the 8 % albumin-containing BT101. Replacing the albumin with IFB/BMP-2 did not significantly affect Tw. However, Ts increased for the BT101_BMP-2 containing GPCs, compared to all other samples. The compressive strength evaluated 1 day post cement mixing was not affected significantly by the incorporation of BMPs, but the ion release did increase from the cements, particularly for Zn and Sr. The GPCs released BMP after the first day, which decreased in content during the following 6 days. This study has proven that BMPs can be immobilized into GPCs and may result in novel materials for clinical applications

Travelling for Umrah:destination attributes, destination image, and post-travel intentions

This paper examines the links between cosmopolitanism, self-identity, and a desire for social interaction perceived destination image and behavioural intentions. A model tested using a sample of 538 Iranian visitors to Mecca for the purpose of Umrah. The result from the structural model suggests that destination attributes influence perceived destination image. Further, such tourists are likely to revisit or recommend Islamic destinations if their experience matches their perceived image of the destination. This implies that, while the religious characteristics of the destination remain important, destination managers cannot disregard the tangential, non-religious attributes of a destination which are crucial in order to satisfy more conventional tourist desires. As such, this study suggests that those managing religious travel destinations should endeavour to foster a welcoming image, where experience, interaction and tolerance are at the forefront of the destination’s offering