Regulation of G protein-coupled receptors by palmitoylation and cholesterol

Due to their membrane location, G protein-coupled receptors (GPCRs) are subject to regulation by soluble and integral membrane proteins as well as membrane components, including lipids and sterols. GPCRs also undergo a variety of post-translational modifications, including palmitoylation. A recent article by Zheng et al. in BMC Cell Biology demonstrates cooperative roles for receptor palmitoylation and cholesterol binding in GPCR dimerization and G protein coupling, underlining the complex regulation of these receptors

Nucleation and Growth of the Superconducting Phase in the Presence of a Current

We study the localized stationary solutions of the one-dimensional time-dependent Ginzburg-Landau equations in the presence of a current. These threshold perturbations separate undercritical perturbations which return to the normal phase from overcritical perturbations which lead to the superconducting phase. Careful numerical work in the small-current limit shows that the amplitude of these solutions is exponentially small in the current; we provide an approximate analysis which captures this behavior. As the current is increased toward the stall current J*, the width of these solutions diverges resulting in widely separated normal-superconducting interfaces. We map out numerically the dependence of J* on u (a parameter characterizing the material) and use asymptotic analysis to derive the behaviors for large u (J* ~ u^-1/4) and small u (J -> J_c, the critical deparing current), which agree with the numerical work in these regimes. For currents other than J* the interface moves, and in this case we study the interface velocity as a function of u and J. We find that the velocities are bounded both as J -> 0 and as J -> J_c, contrary to previous claims.Comment: 13 pages, 10 figures, Revte

Intrauterine Candida albicans infection causes systemic fetal candidiasis with progressive cardiac dysfunction in a sheep model of early pregnancy

Introduction: Several recent studies have identified a potential role for intrauterine Candida albicans in adverse pregnancy outcomes, including preterm birth. There is, however, a limited understanding of the impact of intrauterine candida infection on fetal well-being in early pregnancy. Using a sheep model of early pregnancy, the aims of this study were to determine (1) the ability of experimentally induced intrauterine C albicans to infect the fetus and (2) whether C albicans exposure in early pregnancy is associated with alterations in fetal cardiac function, as measured by spectral tissue Doppler imaging analysis of fetal cardiac function. Methods: Merino ewes carrying singleton pregnancies at 89 days’ gestation (term is ∼150 days) received C albicans (n = 8) via ultrasound-guided intra-amniotic injection. Saline-exposed fetuses served as controls (n = 6). Spectral tissue Doppler imaging echocardiography and amniotic fluid collection were performed at baseline and 24 and 72 hours after intrauterine C albicans injection. Fetal tissues were collected at postmortem for analysis of infection and inflammation. Results: Relative to saline control, intrauterine C albicans infection resulted in pronounced increases in amniotic fluid tumor necrosis factor α (TNF-α; P < .05) and cytokine/chemokine messenger RNA (interleukin [IL] 1β, IL-6, TNF-α, and monocyte chemoattractant protein 1; P < .05) in the fetal myocardium, lung, skin, and liver at 72 and 96 hours postinfection. Spectral tissue Doppler imaging showed diastolic dysfunction at 24 hours and severe biventricular diastolic dysfunction 72 hours postinfection. Conclusion: Intrauterine C albicans infection in a sheep model of early pregnancy causes systemic fetal candidiasis, which is associated with a robust systemic inflammatory response and progressive cardiac dysfunction detectable by spectral tissue Doppler imaging

From endurance to power athletes: The changing shape of successful male professional tennis players.

The aim of the present study was to identify whether the relative shape and size characteristics of elite male tennis players have changed over time, and in addition whether any anthropometric parameters characterise the more successful players in Grand Slam tournaments. The height and body mass of the players qualifying for the first round in all four Grand Slam tennis tournaments during the period 1982-2011 was obtained, and successful players defined arbitrarily as those reaching round 3 or beyond. Body mass index (BMI) and the reciprocal ponderal index (RPI) were used as our measures of body shape. Multilevel modelling was used to explore the trend over time using non-linear polynomials. The results suggest that the body shape of elite tennis players has changed over time, with a non-linear (cubic polynomial regression model) increase in BMI and a similar non-linear decline in the RPI. BMI, reflecting greater muscle mass rather than greater adiposity, has emerged as an important factor associated with success, identified by a significantly positive (steeper) "successful player"-by-"year" interaction term. The evidence that the RPI of elite tennis players has also decreased over time, together with a significantly negative "successful player"-by-"year" interaction term, suggests that a more linear (ectomorphic) body shape is a less important factor in terms of success. These results suggest that elite male tennis players are becoming more power trained athletes as opposed to endurance athletes, with greater muscle mass being an important factor associated with success in all Grand Slam tournaments

Meaningful health outcomes for paediatric neurodisability: stakeholder prioritisation and appropriateness of patient reported outcome measures

BACKGROUND: Health services are increasingly focused on measuring and monitoring outcomes, particularly those that reflect patients' priorities. To be meaningful, outcomes measured should be valued by patients and carers, be consistent with what health professionals seek to achieve, and be robust in terms of measurement properties. The aim of this study was (i) to seek a shared vision between families and clinicians regarding key aspects of health as outcomes, beyond mortality and morbidity, for children with neurodisability, and (ii) to appraise which multidimensional patient reported outcome measures (PROMs) could be used to assess salient health domains. METHODS: Relevant outcomes were identified from (i) qualitative research with children and young people with neurodisability and parent carers, (ii) Delphi survey with health professionals, and (iii) systematic review of PROMs. The International Classification of Functioning Disability and Health provided a common language to code aspects of health. A subset of stakeholders participated in a prioritisation meeting incorporating a Q-sorting task to discuss and rank aspects of health. RESULTS: A total of 33 pertinent aspects of health were identified. Fifteen stakeholders from the qualitative and Delphi studies participated in the prioritisation meeting: 3 young people, 5 parent carers, and 7 health professionals. Aspects of health that emerged as more important for families and targets for health professionals were: communication, emotional wellbeing, pain, sleep, mobility, self-care, independence, mental health, community and social life, behaviour, toileting and safety. Whilst available PROMs measure many aspects of health in the ICF, no single PROM captures all the key domains prioritised as for children and young people with neurodisability. The paucity of scales for assessing communication was notable. CONCLUSIONS: We propose a core suite of key outcome domains for children with neurodisability that could be used in evaluative research, audit and as health service performance indicators. Future work could appraise domain-specific PROMs for these aspects of health; a single measure assessing the key aspects of health that could be applied across paediatric neurodisability remains to be developed

What Do Men Want from a Health Screening Mobile App? A Qualitative Study.

There is a lack of mobile app which aims to improve health screening uptake developed for men. As part of the study to develop an effective mobile app to increase health screening uptake in men, we conducted a needs assessment to find out what do men want from a health screening mobile app. In-depth interviews and focus group discussions were conducted with 31 men from a banking institution in Kuala Lumpur. The participants were purposely sampled according to their job position, age, ethnicity and screening status. The recruitment was stopped once data saturation was achieved. The audio-recorded interviews were transcribed verbatim and analyzed using thematic approach. Three themes emerged from the analysis and they were: content, feature and dissemination. In terms of the content, men wanted the app to provide information regarding health screening and functions that can assess their health; which must be personalized to them and are trustable. The app must have user-friendly features in terms of information delivery, ease of use, attention allocation and social connectivity. For dissemination, men proposed that advertisements, recommendations by health professionals, providing incentive and integrating the app as into existing systems may help to increase the dissemination of the app. This study identified important factors that need to be considered when developing a mobile app to improve health screening uptake. Future studies on mobile app development should elicit users' preference and need in terms of its content, features and dissemination strategies to improve the acceptability and the chance of successful implementation

Care planning for consumers on community treatment orders: an integrative literature review

Background Case management is the established model for care provision in mental health and is delivered within current care philosophies of person-centred and recovery-oriented care. The fact that people with a mental illness may be forced to receive care and treatment in the community poses challenges for clinicians aiming to engage in approaches that promote shared decision-making and self-determination. This review sought to gain an in-depth understanding of stakeholders’ perspectives and experiences of care planning for consumers’ on CTOs. Methods An integrative review method allowed for inclusion of a broad range of studies from diverse empirical sources. Systematic searches were conducted across six databases. Following appraisal, findings from included papers were coded into groups and presented against a framework of case management. Results Forty-eight papers were included in the review. Empirical studies came from seven countries, with the majority reporting on qualitative methods. Many similarities were reported across studies. Positive gains from CTOs were usually associated with the nature of support received, highlighting the importance of the therapeutic relationship in care planning. Key gaps in care planning included a lack of connection between CTO, treatment and consumer goals and lack of implementation of focussed interventions. Conclusions Current case management processes could be better utilised for consumers on CTOs, with exploration of how this could be achieved warranted. Workers need to be sensitive to the ‘control and care’ dynamic in the care planning relationship, with person-centred approaches requiring core and advanced practitioner and communication skills, including empathy and trust

Connectivity within and among a Network of Temperate Marine Reserves

Networks of marine reserves are increasingly being promoted as a means of conserving marine biodiversity. One consideration in designing systems of marine reserves is the maintenance of connectivity to ensure the long-term persistence and resilience of populations. Knowledge of connectivity, however, is frequently lacking during marine reserve design and establishment. We characterise patterns of genetic connectivity of 3 key species of habitat-forming macroalgae across an established network of temperate marine reserves on the east coast of Australia and the implications for adaptive management and marine reserve design. Connectivity varied greatly among species. Connectivity was high for the subtidal macroalgae Ecklonia radiata and Phyllospora comosa and neither species showed any clear patterns of genetic structuring with geographic distance within or among marine parks. In contrast, connectivity was low for the intertidal, Hormosira banksii, and there was a strong pattern of isolation by distance. Coastal topography and latitude influenced small scale patterns of genetic structure. These results suggest that some species are well served by the current system of marine reserves in place along this temperate coast but it may be warranted to revisit protection of intertidal habitats to ensure the long-term persistence of important habitat-forming macroalgae. Adaptively managing marine reserve design to maintain connectivity may ensure the long-term persistence and resilience of marine habitats and the biodiversity they support

Staged Models for Interdisciplinary Research

Modellers of complex biological or social systems are often faced with an invidious choice: to use simple models with few mechanisms that can be fully analysed, or to construct complicated models that include all the features which are thought relevant. The former ensures rigour, the latter relevance. We discuss a method that combines these two approaches, beginning with a complex model and then modelling the complicated model with simpler models. The resulting "chain" of models ensures some rigour and relevance. We illustrate this process on a complex model of voting intentions, constructing a reduced model which agrees well with the predictions of the full model. Experiments with variations of the simpler model yield additional insights which are hidden by the complexity of the full model. This approach facilitated collaboration between social scientists and physicists- The complex model was specified based on the social science literature, and the simpler model constrained to agree (in core aspects) with the complicated model

Uncovering Intrinsic Modular Organization of Spontaneous Brain Activity in Humans

The characterization of topological architecture of complex brain networks is one of the most challenging issues in neuroscience. Slow (<0.1 Hz), spontaneous fluctuations of the blood oxygen level dependent (BOLD) signal in functional magnetic resonance imaging are thought to be potentially important for the reflection of spontaneous neuronal activity. Many studies have shown that these fluctuations are highly coherent within anatomically or functionally linked areas of the brain. However, the underlying topological mechanisms responsible for these coherent intrinsic or spontaneous fluctuations are still poorly understood. Here, we apply modern network analysis techniques to investigate how spontaneous neuronal activities in the human brain derived from the resting-state BOLD signals are topologically organized at both the temporal and spatial scales. We first show that the spontaneous brain functional networks have an intrinsically cohesive modular structure in which the connections between regions are much denser within modules than between them. These identified modules are found to be closely associated with several well known functionally interconnected subsystems such as the somatosensory/motor, auditory, attention, visual, subcortical, and the “default” system. Specifically, we demonstrate that the module-specific topological features can not be captured by means of computing the corresponding global network parameters, suggesting a unique organization within each module. Finally, we identify several pivotal network connectors and paths (predominantly associated with the association and limbic/paralimbic cortex regions) that are vital for the global coordination of information flow over the whole network, and we find that their lesions (deletions) critically affect the stability and robustness of the brain functional system. Together, our results demonstrate the highly organized modular architecture and associated topological properties in the temporal and spatial brain functional networks of the human brain that underlie spontaneous neuronal dynamics, which provides important implications for our understanding of how intrinsically coherent spontaneous brain activity has evolved into an optimal neuronal architecture to support global computation and information integration in the absence of specific stimuli or behaviors