The Association of AMPK with ULK1 Regulates Autophagy

Autophagy is a highly orchestrated intracellular bulk degradation process that is activated by various environmental stresses. The serine/threonine kinase ULK1, like its yeast homologue Atg1, is a key initiator of autophagy that is negatively regulated by the mTOR kinase. However, the molecular mechanism that controls the inhibitory effect of mTOR on ULK1-mediated autophagy is not fully understood. Here we identified AMPK, a central energy sensor, as a new ULK1-binding partner. We found that AMPK binds to the PS domain of ULK1 and this interaction is required for ULK1-mediated autophagy. Interestingly, activation of AMPK by AICAR induces 14-3-3 binding to the AMPK-ULK1-mTORC1 complex, which coincides with raptor Ser792 phosphorylation and mTOR inactivation. Consistently, AICAR induces autophagy in TSC2-deficient cells expressing wild-type raptor but not the mutant raptor that lacks the AMPK phosphorylation sites (Ser722 and Ser792). Taken together, these results suggest that AMPK association with ULK1 plays an important role in autophagy induction, at least in part, by phosphorylation of raptor to lift the inhibitory effect of mTOR on the ULK1 autophagic complex

Cells of the adult human heart

Abstract: Cardiovascular disease is the leading cause of death worldwide. Advanced insights into disease mechanisms and therapeutic strategies require a deeper understanding of the molecular processes involved in the healthy heart. Knowledge of the full repertoire of cardiac cells and their gene expression profiles is a fundamental first step in this endeavour. Here, using state-of-the-art analyses of large-scale single-cell and single-nucleus transcriptomes, we characterize six anatomical adult heart regions. Our results highlight the cellular heterogeneity of cardiomyocytes, pericytes and fibroblasts, and reveal distinct atrial and ventricular subsets of cells with diverse developmental origins and specialized properties. We define the complexity of the cardiac vasculature and its changes along the arterio-venous axis. In the immune compartment, we identify cardiac-resident macrophages with inflammatory and protective transcriptional signatures. Furthermore, analyses of cell-to-cell interactions highlight different networks of macrophages, fibroblasts and cardiomyocytes between atria and ventricles that are distinct from those of skeletal muscle. Our human cardiac cell atlas improves our understanding of the human heart and provides a valuable reference for future studies

Cells of the adult human heart

Abstract: Cardiovascular disease is the leading cause of death worldwide. Advanced insights into disease mechanisms and therapeutic strategies require a deeper understanding of the molecular processes involved in the healthy heart. Knowledge of the full repertoire of cardiac cells and their gene expression profiles is a fundamental first step in this endeavour. Here, using state-of-the-art analyses of large-scale single-cell and single-nucleus transcriptomes, we characterize six anatomical adult heart regions. Our results highlight the cellular heterogeneity of cardiomyocytes, pericytes and fibroblasts, and reveal distinct atrial and ventricular subsets of cells with diverse developmental origins and specialized properties. We define the complexity of the cardiac vasculature and its changes along the arterio-venous axis. In the immune compartment, we identify cardiac-resident macrophages with inflammatory and protective transcriptional signatures. Furthermore, analyses of cell-to-cell interactions highlight different networks of macrophages, fibroblasts and cardiomyocytes between atria and ventricles that are distinct from those of skeletal muscle. Our human cardiac cell atlas improves our understanding of the human heart and provides a valuable reference for future studies

The Effect of Knowledge and Applying Educational Technology by Teachers in Improving Quality of Students Learning Process

This paper aims to study of knowledge and applying educational technology teachers in learning process of students with problem solving and systematic approaches in experimental science has been in primary education. In this study, two methods: descriptive study (survey) and semi-experimental that design with two groups pre-test and post-test has been used. Samples were teachers and students in grade of 4th primary education in Ardabil province. The results showed that teachers knowledge and use of educational technology low and medium level were evaluated also there is significant relationship between teachers knowledge of educational technology and applying and so applying it improved students learning

Social Determinants of Health, Violent Radicalization, and Terrorism: A Public Health Perspective

Background: Terrorism-related deaths are at an all-time high as there were 32,685 and 29,376 terrorism-related deaths in 2014 and 2015, respectively. Terrorism is defined as the use of violence and intimidation in the pursuit of political aims. Terrorism is detrimental for mental health, premature mortality, and economic losses and undermines the central tenets of public health to improve the health and well-being of populations. Despite the impact terrorism has on avoidable morbidity and mortality, population health research largely overlooks social determinants of terrorism and risk factors that contribute to terrorist activities. Methods: Drawing from what is known about commonly studied social determinants of health topics, including the relationships between structural and interpersonal discrimination, social cohesion, and gang violence and health, we present a public health framework, rooted in the social determinants of health, for identifying potential factors influencing terrorism and violent radicalization. Results: Social determinants of health provide unique insight into how interpersonal and structural factors can influence risk for violent radicalization and terrorist activity. Each of the topics we review provides an entry point for existing public health and behavioral science knowledge to be used in preventing and understanding violent radicalization and terrorism. For example, anti-Muslim sentiment has promoted discrimination against Muslims, while also serving to marginalize and stigmatize Muslim communities. These conditions limit the social resources, like social cohesion, that Muslims have access to and make political violence more appealing to some. Conclusions: Public health can contribute much to the ongoing debate around terrorism. The field must take a more prevention-focused approach to the problem of terrorism. Failure to do so only perpetuates approaches that have not been successful

Psychiatry as a career choice among medical students: A cross-sectional study examining school-related and non-school factors

10.1136/bmjopen-2018-022201BMJ Open88e02220

Social Media-Driven Routes to Positive Mental Health Among Youth: Qualitative Enquiry and Concept Mapping Study

10.2196/32758JMIR Pediatrics and Parenting51e32758

Okadaic acid-induced, naringin-sensitive phosphorylation of glycine N-methyltransferase in isolated rat hepatocytes.

Glycine N-methyltransferase (GNMT) is an abundant cytosolic enzyme that catalyses the methylation of glycine into sarcosine, coupled with conversion of the methyl donor, S -adenosylmethionine (AdoMet), into S -adenosylhomocysteine (AdoHcy). GNMT is believed to play a role in monitoring the AdoMet/AdoHcy ratio, and hence the cellular methylation capacity, but regulation of the enzyme itself is not well understood. In the present study, treatment of isolated rat hepatocytes with the protein phosphatase inhibitor okadaic acid, was found to induce an overphosphorylation of GNMT, as shown by proteomic analysis. The analysis comprised two-dimensional gel electrophoretic separation of (32)P-labelled phosphoproteins and identification of individual protein spots by matrix-assisted laser-desorption ionization-time-of-flight mass spectrometry. The identity of GNMT was verified by N-terminal Edman sequencing of tryptic peptides. Chromatographic separation of proteolytic peptides and (32)P-labelled amino acids suggested that GNMT was phosphorylated within a limited region, and only at serine residues. GNMT phosphorylation could be suppressed by naringin, an okadaic acid-antagonistic flavonoid. To assess the possible functional role of GNMT phosphorylation, the effect of okadaic acid on hepatocytic AdoMet and AdoHcy levels was examined, using HPLC separation for metabolite analysis. Surprisingly, okadaic acid was found to have no effect on the basal levels of AdoMet or AdoHcy. An accelerated AdoMet-AdoHcy flux, induced by the addition of methionine (1 mM), was likewise unaffected by okadaic acid. 5-Aminoimidazole-4-carboxamide riboside, an activator of the hepatocytic AMP-activated protein kinase, similarly induced GNMT phosphorylation without affecting AdoMet and AdoHcy levels. Activation of cAMP-dependent protein kinase by dibutyryl-cAMP, reported to cause GNMT phosphorylation under cell-free conditions, also had little effect on hepatocytic AdoMet and AdoHcy levels. Phosphorylation of GNMT would thus seem to play no role in regulation of the intracellular AdoMet/AdoHcy ratio, but could be involved in other GNMT functions, such as the binding of folates or aromatic hydrocarbons

Attitudes towards psychiatry amongst medical and nursing students in Singapore

10.1186/s12909-019-1518-xBMC Medical Education1919