Cyclic AMP Control Measured in Two Compartments in HEK293 Cells: Phosphodiesterase KM Is More Important than Phosphodiesterase Localization

The intracellular second messenger cyclic AMP (cAMP) is degraded by phosphodiesterases (PDE). The knowledge of individual families and subtypes of PDEs is considerable, but how the different PDEs collaborate in the cell to control a cAMP signal is still not fully understood. In order to investigate compartmentalized cAMP signaling, we have generated a membrane-targeted variant of the cAMP Bioluminiscence Resonance Energy Transfer (BRET) sensor CAMYEL and have compared intracellular cAMP measurements with it to measurements with the cytosolic BRET sensor CAMYEL in HEK293 cells. With these sensors we observed a slightly higher cAMP response to adenylyl cyclase activation at the plasma membrane compared to the cytosol, which is in accordance with earlier results from Fluorescence Resonance Energy Transfer (FRET) sensors. We have analyzed PDE activity in fractionated lysates from HEK293 cells using selective PDE inhibitors and have identified PDE3 and PDE10A as the major membrane-bound PDEs and PDE4 as the major cytosolic PDE. Inhibition of membrane-bound or cytosolic PDEs can potentiate the cAMP response to adenylyl cyclase activation, but we see no significant difference between the potentiation of the cAMP response at the plasma membrane and in cytosol when membrane-bound and cytosolic PDEs are inhibited. When different levels of stimulation were tested, we found that PDEs 3 and 10 are mainly responsible for cAMP degradation at low intracellular cAMP concentrations, whereas PDE4 is more important for control of cAMP at higher concentrations

Positive Youth Development, Life Satisfaction and Problem Behaviour Among Chinese Adolescents in Hong Kong: A Replication

The purpose of this replication study was to examine the relationships among life satisfaction, positive youth development and problem behaviour. The respondents were 7,151 Chinese Secondary 2 (Grade 8) students (3,707 boys and 3,014 girls) recruited from 44 schools in Hong Kong. Validated assessment tools measuring positive youth development, life satisfaction and problem behaviour were used. As predicted, positive youth development was positively correlated with life satisfaction, and positive youth development and life satisfaction were negatively correlated with adolescent problem behaviour. Based on a series of structural equation models, the present findings replicated the previous findings that adolescents with a higher level of positive youth development were more satisfied with life and had lesser problem behaviour, with higher level of life satisfaction and lower level of problem behaviour mutually influencing each other. These replicated findings provide a further advance in the literature on positive youth development, particularly in the Chinese context. Implications for future research and intervention were discussed

Spatial variation of trace metals within intertidal beds of native mussels (Mytilus edulis) and non-native Pacific oysters (Crassostrea gigas): implications for the food web?

Abstract Pollution is of increasing concern within coastal regions and the prevalence of invasive species is also rising. Yet the impact of invasive species on the distribution and potential trophic transfer of metals has rarely been examined. Within European intertidal areas, the non-native Pacific oyster (Crassostrea gigas) is becoming established, forming reefs and displacing beds of the native blue mussel (Mytilus edulis). The main hypothesis tested is that the spatial pattern of metal accumulation within intertidal habitats will change should the abundance and distribution of C. gigas continue to increase. A comparative analysis of trace metal content (cadmium, lead, copper and zinc) in both species was carried out at four shores in south-east England. Metal concentrations in bivalve and sediment samples were determined after acid digestion by inductively coupled plasma-optical emission spectrometry. Although results showed variation in the quantities of zinc, copper and lead (mg m-2) in the two bivalve species, differences in shell thickness are also likely to influence the feeding behaviour of predators and intake of metals. The availability and potential for trophic transfer of metals within the coastal food web, should Pacific oysters transform intertidal habitats, is discussed

Lithium side effects and toxicity: prevalence and management strategies

Despite its virtually universal acceptance as the gold standard in treating bipolar disorder, prescription rates for lithium have been decreasing recently. Although this observation is multifactorial, one obvious potential contributor is the side effect and toxicity burden associated with lithium. Additionally, side effect concerns assuredly play some role in lithium nonadherence. This paper summarizes the knowledge base on side effects and toxicity and suggests optimal management of these problems. Thirst and excessive urination, nausea and diarrhea and tremor are rather common side effects that are typically no more than annoying even though they are rather prevalent. A simple set of management strategies that involve the timing of the lithium dose, minimizing lithium levels within the therapeutic range and, in some situations, the prescription of side effect antidotes will minimize the side effect burden for patients. In contrast, weight gain and cognitive impairment from lithium tend to be more distressing to patients, more difficult to manage and more likely to be associated with lithium nonadherence. Lithium has adverse effects on the kidneys, thyroid gland and parathyroid glands, necessitating monitoring of these organ functions through periodic blood tests. In most cases, lithium-associated renal effects are relatively mild. A small but measurable percentage of lithium-treated patients will show progressive renal impairment. Infrequently, lithium will need to be discontinued because of the progressive renal insufficiency. Lithium-induced hypothyroidism is relatively common but easily diagnosed and treated. Hyperparathyroidism from lithium is a relatively more recently recognized phenomenon

The personal and contextual contributors to school belongingness among primary school students

School belongingness has gained currency among educators and school health professionals as an important determinant of adolescent health. The current cross-sectional study presents the 15 most significant personal and contextual factors that collectively explain 66.4% (two-thirds) of the variability in 12-year old students' perceptions of belongingness in primary school. The study is part of a larger longitudinal study investigating the factors associated with student adjustment in the transition from primary to secondary school. The study found that girls and students with disabilities had higher school belongingness scores than boys, and their typically developing counterparts respectively; and explained 2.5% of the variability in school belongingness. The majority (47.1% out of 66.4%) of the variability in school belongingness was explained by student personal factors, such as social acceptance, physical appearance competence, coping skills, and social affiliation motivation; followed by parental expectations (3% out of 66.4%), and school-based factors (13.9% out of 66.4%) such as, classroom involvement, task-goal structure, autonomy provision, cultural pluralism, and absence of bullying. Each of the identified contributors of primary school belongingness can be shaped through interventions, system changes, or policy reforms