Cyclin-Dependent Kinase Activity Controls the Onset of the HCMV Lytic Cycle

The onset of human cytomegalovirus (HCMV) lytic infection is strictly synchronized with the host cell cycle. Infected G0/G1 cells support viral immediate early (IE) gene expression and proceed to the G1/S boundary where they finally arrest. In contrast, S/G2 cells can be infected but effectively block IE gene expression and this inhibition is not relieved until host cells have divided and reentered G1. During latent infection IE gene expression is also inhibited, and for reactivation to occur this block to IE gene expression must be overcome. It is only poorly understood which viral and/or cellular activities maintain the block to cell cycle or latency-associated viral IE gene repression and whether the two mechanisms may be linked. Here, we show that the block to IE gene expression during S and G2 phase can be overcome by both genotoxic stress and chemical inhibitors of cellular DNA replication, pointing to the involvement of checkpoint-dependent signaling pathways in controlling IE gene repression. Checkpoint-dependent rescue of IE expression strictly requires p53 and in the absence of checkpoint activation is mimicked by proteasomal inhibition in a p53 dependent manner. Requirement for the cyclin dependent kinase (CDK) inhibitor p21 downstream of p53 suggests a pivotal role for CDKs in controlling IE gene repression in S/G2 and treatment of S/G2 cells with the CDK inhibitor roscovitine alleviates IE repression independently of p53. Importantly, CDK inhibiton also overcomes the block to IE expression during quiescent infection of NTera2 (NT2) cells. Thus, a timely block to CDK activity not only secures phase specificity of the cell cycle dependent HCMV IE gene expression program, but in addition plays a hitherto unrecognized role in preventing the establishment of a latent-like state

Happiness around the world: A combined etic-emic approach across 63 countries

What does it mean to be happy? The vast majority of cross-cultural studies on happiness have employed a Western-origin, or "WEIRD" measure of happiness that conceptualizes it as a self-centered (or "independent"), high-arousal emotion. However, research from Eastern cultures, particularly Japan, conceptualizes happiness as including an interpersonal aspect emphasizing harmony and connectedness to others. Following a combined emicetic approach (Cheung, van de Vijver & Leong, 2011), we assessed the cross-cultural applicability of a measure of independent happiness developed in the US (Subjective Happiness Scale; Lyubomirsky & Lepper, 1999) and a measure of interdependent happiness developed in Japan (Interdependent Happiness Scale; Hitokoto & Uchida, 2015), with data from 63 countries representing 7 sociocultural regions. Results indicate that the schema of independent happiness was more coherent in more WEIRD countries. In contrast, the coherence of interdependent happiness was unrelated to a country's "WEIRD-ness." Reliabilities of both happiness measures were lowest in African and Middle Eastern countries, suggesting these two conceptualizations of happiness may not be globally comprehensive. Overall, while the two measures had many similar correlates and properties, the self-focused concept of independent happiness is "WEIRD-er" than interdependent happiness, suggesting cross-cultural researchers should attend to both conceptualizations

Happiness around the world: A combined etic-emic approach across 63 countries.

What does it mean to be happy? The vast majority of cross-cultural studies on happiness have employed a Western-origin, or "WEIRD" measure of happiness that conceptualizes it as a self-centered (or "independent"), high-arousal emotion. However, research from Eastern cultures, particularly Japan, conceptualizes happiness as including an interpersonal aspect emphasizing harmony and connectedness to others. Following a combined emic-etic approach (Cheung, van de Vijver & Leong, 2011), we assessed the cross-cultural applicability of a measure of independent happiness developed in the US (Subjective Happiness Scale; Lyubomirsky & Lepper, 1999) and a measure of interdependent happiness developed in Japan (Interdependent Happiness Scale; Hitokoto & Uchida, 2015), with data from 63 countries representing 7 sociocultural regions. Results indicate that the schema of independent happiness was more coherent in more WEIRD countries. In contrast, the coherence of interdependent happiness was unrelated to a country's "WEIRD-ness." Reliabilities of both happiness measures were lowest in African and Middle Eastern countries, suggesting these two conceptualizations of happiness may not be globally comprehensive. Overall, while the two measures had many similar correlates and properties, the self-focused concept of independent happiness is "WEIRD-er" than interdependent happiness, suggesting cross-cultural researchers should attend to both conceptualizations

The economic well-being of nations is associated with positive daily situational experiences

People in economically advantaged nations tend to evaluate their life as more positive overall and report greater well-being than people in less advantaged nations. But how does positivity manifest in the daily life experiences of individuals around the world? The present study asked 15,244 college students from 62 nations, in 42 languages, to describe a situation they experienced the previous day using the Riverside Situational Q-sort (RSQ). Using expert ratings, the overall positivity of each situation was calculated for both nations and individuals. The positivity of the average situation in each nation was strongly related to the economic development of the nation as measured by the Human Development Index (HDI). For individuals’ daily experiences, the economic status of their nation also predicted the positivity of their experience, even more than their family socioeconomic status. Further analyses revealed the specific characteristics of the average situations for higher HDI nations that make their experiences more positive. Higher HDI was associated with situational experiences involving humor, socializing with others, and the potential to express emotions and fantasies. Lower HDI was associated with an increase in the presence of threats, blame, and hostility, as well as situational experiences consisting of family, religion, and money. Despite the increase in a few negative situational characteristics in lower HDI countries, the overall average experience still ranged from neutral to slightly positive, rather than negative, suggesting that greater HDI may not necessarily increase positive experiences but rather decrease negative experiences. The results illustrate how national economic status influences the lives of individuals even within a single instance of daily life, with large and powerful consequences when accumulated across individuals within each nation

Moving university campuses tobacco-free: collective responsibility and collaboration the key to a healthier Victoria

Full article Smoking is Victoria\u27s leading preventable cause of death and continues to kill 4,000 Victorians every year.1 In a demonstration of public health leadership, all Victorian universities have recently joined forces in the implementation of the Victorian Universities Tobacco-Free Initiative to contribute to reducing the burden from tobacco-related disease in Victoria. The reach of Victorian universities to implement public health initiatives is significant and growing, with nearly 300,000 students and more than 40,000 academic and professional staff, as is the potential for universities to influence the heath behaviours of young people in a period where life-long behaviours are formed. This is particularly important, given that Victorians of university age (aged 18–29 years) are more likely to smoke than people aged 30–49 years and 50+ years.2 The Initiative educates and engages students and staff on the benefits of reducing smoking, supports smokers to quit and creates smoke-free campuses. This approach is more than just asking students and staff to leave the campus to have a cigarette; it provides a comprehensive suite of supports to help smokers quit that is likely to have a real impact on reducing harm from tobacco. The Tobacco-Free Initiative approach is collaborative across all universities and has been designed and implemented in association with university communities. An advantage of adopting a settings-based health promotion approach is that real changes can be implemented at local level without the need for government intervention or new legislation. Health promotion approaches driven by the community are efficient, timely and allow flexibility. Like the approach used in the Initiative, they create an environment that encourages healthy choices, and supports changes in communities that will have a positive impact on individuals, and also households, families, friends and broader networks. Therefore, this approach is not about helping one individual – it is about supporting a community to be healthier. The prevalence of chronic disease is increasing in Victoria.3 Cardiovascular disease, diabetes and chronic kidney disease share many common lifestyle-related risk factors and contribute a large proportion of the disease burden.4 Lifestyle factors such as tobacco smoking, excessive alcohol use, unhealthy diet and lack of physical activity contribute to the chronic disease burden.5 The direct health costs and lost productivity from smoking add up to $2.4 billion annually in Victoria alone.1 These costs are incurred across businesses, governments and by individuals. Given the recent concern about the sustainability of the health system in Australia, the costs attributable to smoking need to be addressed immediately. Victorian universities are doing their bit to help. The Victorian Universities Tobacco-Free Initiative provides an effective framework for universities to continue to work together and demonstrate public health leadership in developing settings-based health promotion approaches to address the increasing incidence of chronic disease and lifestyle-related risk factors. The unprecedented degree of collaboration between Australian universities over this initiative also allows them to share resources and wisdom and to jointly evaluate the programs in place. This not only expedites the development and roll out of tobacco-free programs, but builds a very sound evidence-base for the most effective strategies in these settings. The framework provides guidance for other industries in Victoria to work together to support the implementation of collaborative health promotion initiatives. The gravity of the future health, social and economic burden of chronic disease requires a timely and continued investment by government, but also by the private sector. The universities of Victoria encourage other major employers to join them and take an active role in developing environments that promote health for all Victorians. References 1 Collins DJ, Lapsley HM. The Social Costs of Smoking in Victoria in 2008/09 and the Social Benefits of Public Policy Measures to Reduce Smoking Prevalence. Melbourne (AUST): Quit Victoria and the VicHealth Centre for Tobacco Control; 2011. 2 Emily Bain SD, Wakefield M. Smoking Prevalence and Consumption in Victoria: Key Findings from the 1998–2012 Population Surveys. Melbourne (AUST): Victorian Department of Health; 2013. 3 Department of Health. Victorian Population Health Survey 2010. Melbourne (AUST): State Government of Victoria; 2012. 4 Australian Institute of Health and Welfare. Chronic Diseases and Associated Risk Factors in Australia, 2001. Canberra (AUST): AIHW; 2012. 5 Begg S, Vos T, Barker B, Stevenson C, Stanley L, Lopez AD, The Burden of Disease and Injury in Australia 2003. Canberra (AUST): Australian Institute of Health and Welfare; 2007

Sex Modulates Response to Renal-Tubule-Targeted Insulin Receptor Deletion in Mice

Insulin facilitates renal sodium reabsorption and attenuates gluconeogenesis. Sex differences in this regulation have not been well characterized. Using tetracycline-inducible Cre-lox recombination, we knocked out (KO) the insulin receptor (InsR) from the renal tubule in adult male (M) and female (F) mice (C57Bl6 background) with a paired box 8 (PAX8) promoter. Body weights were not affected by the KO, but mean kidney weights were reduced in the KO mice (13 and 3%, in M and F, respectively, relative to wild-type (WT) mice). A microscopic analysis revealed 25 and 19% reductions in the proximal tubule (PT) and cortical collecting duct cell heights, respectively, in KOMs relative to WTMs. The reductions were 5 and 11% for KOFs. Western blotting of renal cortex homogenates showed decreased protein levels for the β and γ subunits of the epithelial sodium channel (ENaC) and the sodium-potassium-2-chloride cotransporter type 2 (NKCC2) in both sexes of KO mice; however, α-ENaC was upregulated in KOMs and downregulated in KOFs. Both sexes of KO mice cleared exogenously administered glucose faster than the WT mice and had lower semi-fasted, anesthetized blood glucose levels. However, KOMs (but not KOFs) demonstrated evidence of enhanced renal gluconeogenesis, including higher levels of renal glucose-6-phosphatase, the PT’s production of glucose, post-prandial blood glucose, and plasma insulin, whereas KOFs exhibited downregulation of renal high-capacity sodium glucose cotransporter (SGLT2) and upregulation of SGLT1; these changes appeared to be absent in the KOM. Overall, these findings suggest a sex-differential reliance on intact renal tubular InsR signaling which may be translationally important in type 2 diabetes, obesity, or insulin resistance when renal insulin signaling is reduced

Technology support to a telehealth in the home service: Qualitative observations

Introduction: The Flinders University Telehealth in the Home (FTH) trial was an action research initiative that introduced and evaluated the impact of telehealth services on palliative care patients living in the community, home-based rehabilitation services for the elderly, and services to the elderly in residential aged care. The aim of this study was to understand the issues encountered during the provision of technology services that supported this trial. Methods: A mixed methods approach was undertaken to analyse the roles of information and communication technology (ICT) and clinical staff in design, technology management and training. The data sources were staff observations and documents including job logs, meetings, emails and technology descriptions. Results: Use of consumer technology for telehealth required customisation of applications and services. Clinicians played a key role in definition of applications and the embedding of workflow into applications. Usability of applications was key to their subsequent use. Management of design creep and technology services, coupled with support and training for clinicians were important to maintenance of a telehealth service. Discussion: In the setting described, an iterative approach to the development of telehealth services to the home using consumer technologies was needed. The efficient management of consumer devices in multiple settings will become critical as telehealth services grow in scale. Effective collaboration between clinical and technical stakeholders and further workforce education in telehealth can be key enablers for the transition of face-to-face care to a telehealth mode of delivery.Alan Taylor, Victoria Wade, Greg Morris, Joanne Pech, Stuart Rechter, Michael Kidd and Colin Carat