The Atlantic Ocean at the last glacial maximum: 1. Objective mapping of the GLAMAP sea-surface conditions

Recent efforts of the German paleoceanographic community have resulted in a unique data set of reconstructed sea-surface temperature for the Atlantic Ocean during the Last Glacial Maximum, plus estimates for the extents of glacial sea ice. Unlike prior attempts, the contributing research groups based their data on a common definition of the Last Glacial Maximum chronozone and used the same modern reference data for calibrating the different transfer techniques. Furthermore, the number of processed sediment cores was vastly increased. Thus the new data is a significant advance not only with respect to quality, but also to quantity. We integrate these new data and provide monthly data sets of global sea-surface temperature and ice cover, objectively interpolated onto a regular 1°x1° grid, suitable for forcing or validating numerical ocean and atmosphere models. This set is compared to an existing subjective interpolation of the same base data, in part by employing an ocean circulation model. For the latter purpose, we reconstruct sea surface salinity from the new temperature data and the available oxygen isotope measurements

Verbal, Facial and Autonomic Responses to Empathy-Eliciting Film Clips by Disruptive Male Adolescents with High Versus Low Callous-Unemotional Traits

This study examined empathy-related responding in male adolescents with disruptive behavior disorder (DBD), high or low on callous-unemotional (CU) traits. Facial electromyographic (EMG) and heart rate (HR) responses were monitored during exposure to empathy-inducing film clips portraying sadness, anger or happiness. Self-reports were assessed afterward. In agreement with expectations, DBD adolescents with high CU traits showed significantly lower levels of empathic sadness than healthy controls across all response systems. Between DBD subgroups significant differences emerged at the level of autonomic (not verbal or facial) reactions to sadness, with high CU respondents showing less HR change from baseline than low CU respondents. The study also examined basal patterns of autonomic function. Resting HR was not different between groups, but resting respiratory sinus arrhythmia (RSA) was significantly lower in DBD adolescents with high CU traits compared to controls. Results support the notion that CU traits designate a distinct subgroup of DBD individuals

Emotional Dynamics in the Development of Early Adolescent Psychopathology: A One-Year Longitudinal Study

This study examined the role of the level and variability of happiness, anger, anxiety, and sadness in the development of adolescent-reported anxiety disorder symptoms, depressive symptoms, and aggressive behavior in 452 adolescents (250 male) followed from age 13 to 14. Level and between-day variability of emotions were assessed through adolescent report at 3-month intervals across a 1 year period. Level and variability of the four emotions contributed to changes in anxiety disorder and depressive symptoms more consistently than to changes in aggressive behavior. All four emotions were predictive of changes in internalizing problems, while anger played the most prominent role in the development of aggressive behavior. Variability of emotions contributed to changes in anxiety disorder symptoms, while heightened levels of negative emotions and diminished happiness contributed to changes in depression. Results suggested somewhat stronger effects of negative affect on aggressive behavior for females than for males. Results underscore the role of emotion dysregulation in the development of psychopathology

Age-related transcriptional changes in gene expression in different organs of mice support the metabolic stability theory of aging

Individual differences in the rate of aging are determined by the efficiency with which an organism transforms resources into metabolic energy thus maintaining the homeostatic condition of its cells and tissues. This observation has been integrated with analytical studies of the metabolic process to derive the following principle: The metabolic stability of regulatory networks, that is the ability of cells to maintain stable concentrations of reactive oxygen species (ROS) and other critical metabolites is the prime determinant of life span. The metabolic stability of a regulatory network is determined by the diversity of the metabolic pathways or the degree of connectivity of genes in the network. These properties can be empirically evaluated in terms of transcriptional changes in gene expression. We use microarrays to investigate the age-dependence of transcriptional changes of genes in the insulin signaling, oxidative phosphorylation and glutathione metabolism pathways in mice. Our studies delineate age and tissue specific patterns of transcriptional changes which are consistent with the metabolic stability–longevity principle. This study, in addition, rejects the free radical hypothesis which postulates that the production rate of ROS, and not its stability, determines life span

Molecular Characterisation of Small Molecule Agonists Effect on the Human Glucagon Like Peptide-1 Receptor Internalisation

The glucagon-like peptide receptor (GLP-1R), which is a G-protein coupled receptor (GPCR), signals through both Gαs and Gαq coupled pathways and ERK phosphorylation to stimulate insulin secretion. The aim of this study was to determine molecular details of the effect of small molecule agonists, compounds 2 and B, on GLP-1R mediated cAMP production, intracellular Ca2+ accumulation, ERK phosphorylation and its internalisation. In human GLP-1R (hGLP-1R) expressing cells, compounds 2 and B induced cAMP production but caused no intracellular Ca2+ accumulation, ERK phosphorylation or hGLP-1R internalisation. GLP-1 antagonists Ex(9-39) and JANT-4 and the orthosteric binding site mutation (V36A) in hGLP-1R failed to inhibit compounds 2 and B induced cAMP production, confirming that their binding site distinct from the GLP-1 binding site on GLP-1R. However, K334A mutation of hGLP-1R, which affects Gαs coupling, inhibited GLP-1 as well as compounds 2 and B induced cAMP production, indicating that GLP-1, compounds 2 and B binding induce similar conformational changes in the GLP-1R for Gαs coupling. Additionally, compound 2 or B binding to the hGLP-1R had significantly reduced GLP-1 induced intracellular Ca2+ accumulation, ERK phosphorylation and hGLP-1R internalisation. This study illustrates pharmacology of differential activation of GLP-1R by GLP-1 and compounds 2 and B

Intergenerational Transmission of Multiple Problem Behaviors: Prospective Relationships between Mothers and Daughters

Much of the research examining intergenerational continuity of problems from mother to offspring has focused on homotypic continuity (e.g., depression), despite the fact that different types of mental health problems tend to cluster in both adults and children. It remains unclear whether mothers with multiple mental health problems compared to mothers with fewer or no problems are more likely to have daughters with multiple mental health problems during middle childhood (ages 7 to 11). Six waves of maternal and child data from the Pittsburgh Girls Study (n = 2,451) were used to examine the specificity of effects of maternal psychopathology on child adjustment. Child multiple mental health problems comprised disruptive behavior, ADHD symptoms, depressed mood, anxiety symptoms and somatic complaints, while maternal multiple mental health problems consisted of depression, prior conduct problems and somatic complaints. Generalized Estimating Equations (GEE) was used to examine the prospective relationships between mother’s single and multiple mental health problems and their daughter’s single and multiple mental health problems across the elementary school-aged period (ages 7–11 years). The results show that multiple mental health problems in the mothers predicted multiple mental health problems in the daughters even when earlier mental health problem of the daughters, demographic factors, and childrearing practices were controlled. Maternal low parental warmth and harsh punishment independently contributed to the prediction of multiple mental health problems in their daughter, but mediation analyses showed that the contribution of parenting behaviors to the explanation of girls’ mental health problems was small

Deconvolution of complex G protein–coupled receptor signaling in live cells using dynamic mass redistribution measurements

Label-free biosensor technology based on dynamic mass redistribution (DMR) of cellular constituents promises to translate GPCR signaling into complex optical 'fingerprints' in real time in living cells. Here we present a strategy to map cellular mechanisms that define label-free responses, and we compare DMR technology with traditional second-messenger assays that are currently the state of the art in GPCR drug discovery. The holistic nature of DMR measurements enabled us to (i) probe GPCR functionality along all four G-protein signaling pathways, something presently beyond reach of most other assay platforms; (ii) dissect complex GPCR signaling patterns even in primary human cells with unprecedented accuracy; (iii) define heterotrimeric G proteins as triggers for the complex optical fingerprints; and (iv) disclose previously undetected features of GPCR behavior. Our results suggest that DMR technology will have a substantial impact on systems biology and systems pharmacology as well as for the discovery of drugs with novel mechanisms