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

Is Autosomal Dominant Polycystic Kidney Disease a pediatric disorder? From AdultDPKD to ADPediatricKD

In this PhD project, on the eve of broadening the AdultDPKD horizon with ADPediatricKD, we explored the childhood ADPKD phenotype and the challenges concerning its management, in order to urge the need for a standardized and multidisciplinary approach, as many ambiguities still exist. First, we confirmed the existence of the latter, by showing that the clinicians' attitudes and current clinical practice are lacking an agreement regarding testing in asymptomatic offspring and family planning. Indeed, this results in conflicting information given to the families followed up with ADPKD. More specifically, asymptomatic offspring might be undiagnosed until irreversible complications develop. As demonstrated in our survey, health caregivers share a responsibility to inform offspring on their risk, together with the parents. Second, we collected evidence for the care of ADPKD offspring. We demonstrated that children display both cardiovascular and phosphate and bone mineral metabolism alterations in the early disease stages of ADPKD. Concerning the latter, we encountered a significant prevalence of hypertension in ADPKD children and generated evidence that a 24h ABPM should be the preferred modality to monitor blood pressure in this population. Only by this means, the non-dipping, white-coat and masked hypertension phenotypes can be identified. As it has been shown in several reports that blood pressure control has an essential role in long-term cardiovascular outcome, it is important to screen for it in the at risk population. Finally, we generated novel tools to be used in the future to facilitate the establishment of childhood ADPKD management guidelines. We succeeded to initiate a global registry on childhood ADPKD, called 'ADPedKD' (www.ADPedKD.org) as a promising tool, together with a longitudinal biobank of well characterized and genotyped ADPKD children. We also described a new modality for TKV measurement in ADPKD children by demonstrating that the novel developed 3DUS technique is a valuable method to MRI to measure the renal volume. We have laid the foundations to meet the following challenges in the near future: identification of rapid progressors at childhood and defining childhood outcome parameters, which are fundamental milestones in the future pediatric research. After all, the best chance for preserving long-term renal function may be given by an early therapeutic start.status: publishe

Piscivorous cyprinid fish modulates suction feeding kinematics to capture elusive prey

Previous studies have shown that evasive prey generally elicit a different kinematical pattern of prey capture from suction feeding fish compared to non-evasive types of prey. However, no evidence exists that predatory fish can modulate their prey capture kinematics in response to whether or not an elusive prey performs an escape response. Here, we analyse prey capture kinematics of a specialist piscivore (asp, Aspius aspius) during feeding on untethered, live goldfish, which regularly displayed escape attempts when attacked by the asp. Significant modulation occurred in function of the escape attempts of prey: mouth opening was prolonged and increased in magnitude, and one individual also showed an increased hyoid depression when feeding on prey trying to escape. As the orientation of the prey with respect to the predator prior to the start of mouth opening was related to the probability of observing an escape attempt, asp could theoretically perform this type of modulation by a priori choosing a pre-programmed motor pattern. However, since contact between the prey and the asp's mouth appeared to be a factor improving the timing of mouth closing, this fine-tuning of prey capture kinematics is more likely to be caused by reflexive neural feedback control

PML contributes to a cellular mechanism of repression of herpes simplex virus type 1 infection that is inactivated by ICP0

Promyelocytic leukemia (PML) nuclear bodies (also known as ND10) are nuclear substructures that contain several proteins, including PML itself, Sp100, and hDaxx. PML has been implicated in many cellular processes, and ND10 are frequently associated with the replicating genomes of DNA viruses. During herpes simplex virus type 1 (HSV-1) infection, the viral regulatory protein ICP0 localizes to ND10 and induces the degradation of PML, thereby disrupting ND10 and dispersing their constituent proteins. ICP0-null mutant viruses are defective in PML degradation and ND10 disruption, and concomitantly they initiate productive infection very inefficiently. Although these data are consistent with a repressive role for PML and/or ND10 during HSV-1 infection, evidence in support of this hypothesis has been inconclusive. By use of short interfering RNA technology, we demonstrate that depletion of PML increases both gene expression and plaque formation by an ICP0-negative HSV-1 mutant, while having no effect on wild-type HSV-1. We conclude that PML contributes to a cellular antiviral repression mechanism that is countered by the activity of ICP0

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