Requirement for distinct vesicle-associated membrane proteins in insulin- and AMP-activated protein kinase (AMPK)-induced translocation of GLUT4 and CD36 in cultured cardiomyocytes

Upon stimulation of insulin signalling or contraction-induced AMP-activated protein kinase (AMPK) activation, the glucose transporter GLUT4 and the long-chain fatty acid (LCFA) transporter CD36 similarly translocate from intracellular compartments to the plasma membrane of cardiomyocytes to increase uptake of glucose and LCFA, respectively. This similarity in regulation of GLUT4 traffic and CD36 traffic suggests that the same families of trafficking proteins, including vesicle-associated membrane proteins (VAMPs), are involved in both processes. While several VAMPs have been implicated in GLUT4 traffic, nothing is known about the putative function of VAMPs in CD36 traffic. Therefore, we compared the involvement of the myocardially produced VAMP isoforms in insulin- or contraction-induced GLUT4 and CD36 translocation. Five VAMP isoforms were silenced in HL-1 cardiomyocytes. The cells were treated with insulin or the contraction-like AMPK activator oligomycin or were electrically stimulated to contract. Subsequently, GLUT4 and CD36 translocation as well as substrate uptake were measured. Three VAMPs were demonstrated to be necessary for both GLUT4 and CD36 translocation, either specifically in insulin-treated cells (VAMP2, VAMP5) or in oligomycin/contraction-treated cells (VAMP3). In addition, there are VAMPs specifically involved in either GLUT4 traffic (VAMP7 mediates basal GLUT4 retention) or CD36 traffic (VAMP4 mediates insulin- and oligomycin/contraction-induced CD36 translocation). The involvement of distinct VAMP isoforms in both GLUT4 and CD36 translocation indicates that CD36 translocation, just like GLUT4 translocation, is a vesicle-mediated process dependent on soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complex formation. The ability of other VAMPs to discriminate between GLUT4 and CD36 translocation allows the notion that myocardial substrate preference can be modulated by these VAMPs

The chemokine RANTES is secreted by human melanoma cells and is associated with enhanced tumour formation in nude mice

Modulation of tumour cell growth by tumour-infiltrating leucocytes is of high importance for the biological behaviour of malignant neoplasms. In melanoma, tumour-associated macrophages (TAM) and tumour-infiltrating lymphocytes (TIL) are of particular interest as inhibitors or enhancers of cell growth. Recruitment of leucocytes from the peripheral blood into the tumour site is mediated predominantly by chemotaxins, particularly by the group of chemokines

Assessment of burnout in veterinary medical students using the Maslach Burnout Inventory-Educational Survey: a survey during two semesters

BACKGROUND: Burnout among veterinary students can result from known stressors in the absence of a support system. The objectives of this study were to evaluate use of the Maslach Burnout Inventory-Educator Survey (MBI-ES) to assess burnout in veterinary students and evaluate the factors that predict the MBI-ES scores. METHODS: The MBI-ES was administered to first (Class of 2016) and second year (Class of 2015) veterinary medical students during the 2012-2013 academic year in the fall and spring semesters. Factor analysis and test reliability for the survey were determined. Mean scores for the subscales determining burnout namely emotional exhaustion (EE), depersonalization (DP) and lack of personal accomplishment (PA) were calculated for both classes in the 2 semesters. Multiple regression analysis was performed to evaluate other factors that predict the MBI-ES scores. RESULTS: A non-probability sampling method was implemented consisting of a voluntary sample of 170 and 123 students in the fall and spring semesters, respectively. Scores for EE, DP and PA were not different between the 2 classes within the same semester. Mean ± SD scores for EE, DP and PA for the fall semester were 22.9 ± 9.6, 5.0 ± 4.8 and 32.3 ± 6.7, respectively. Mean ± SD scores for EE, DP and PA the spring semester were 27.8 ± 10.7, 6.5 ± 6.1and 31.7 ± 6.8, respectively. The EE score was higher in spring compared to fall while DP and PA scores were not different between the 2 semesters. Living arrangements specifically as to whether or not a student lived with another veterinary medical students was the only variable significantly associated with the MBI-ES scores. Students in this study had moderate levels of burnout based on the MBI-ES scores. CONCLUSIONS: The MBI-ES was an acceptable instrument for assessing burnout in veterinary medical students. The EE scores were higher in the spring semester as compared to the fall semester. Thus students in the first and second years of veterinary school under the current curriculum experience the greatest levels of emotional exhaustion during the spring semester. This has administrative implications for the school, when considering the allocation and use of resources for student support systems during each semester

Physics of Neutron Star Crusts

The physics of neutron star crusts is vast, involving many different research fields, from nuclear and condensed matter physics to general relativity. This review summarizes the progress, which has been achieved over the last few years, in modeling neutron star crusts, both at the microscopic and macroscopic levels. The confrontation of these theoretical models with observations is also briefly discussed.Comment: 182 pages, published version available at <http://www.livingreviews.org/lrr-2008-10

An experimental study exploring the impact of vignette gender on the quality of university students’ mental health first aid for peers with symptoms of depression

Background University students have high rates of depression, and friends are often the most commonly-used source of support for emotional distress in this population. This study aimed to explore students’ ability to provide effective support for their peers with depressive symptoms and the factors influencing the quality of their mental health first aid (MHFA) skills, including students’ gender, course of study, and gender of student experiencing depression. Methods Via an online survey, students at two British universities (N = 483) were quasi-randomly allocated to view a video vignette of either a male or female student depicting symptoms of depression. An open-ended question probed MHFA actions they would take to help the vignette character, which were rated using a standardised scoring scheme based on MHFA guidelines. Results Students reported low MHFA scores (mean 2.89, out of possible 12). The most commonly reported action was provision of support and information, but only eight (1.6 %) students stated an intention to assess risk of harm. Those studying clinically non-relevant degrees with limited mental health content reported poorer MHFA (p = <0.001) and were less confident about their ability to support a friend with depression (p = 0.04). There was no main effect of vignette gender, but within the group of students on non-relevant courses the male vignette received significantly poorer MHFA than the female vignette (p = 0.02). A significant three-way interaction found that male participants studying non-relevant degrees who viewed a male vignette had poorer MHFA compared to females studying non-relevant degrees who viewed the female vignette (p = 0.005). Conclusions Most students lack the necessary MHFA skills to support friends suffering from symptoms of depression, or to help them get appropriate support and prevent risk of harm. Students on courses which do not include mental health related content are particularly ill-equipped to support male students, with male students receiving the poorest quality MHFA from fellow male students on these courses. MHFA training has the potential to improve outcomes for students with depression, and could have a valuable role in reducing the excess risk of harm seen in male students

The Biochemistry, Ultrastructure, and Subunit Assembly Mechanism of AMPA Receptors

The AMPA-type ionotropic glutamate receptors (AMPA-Rs) are tetrameric ligand-gated ion channels that play crucial roles in synaptic transmission and plasticity. Our knowledge about the ultrastructure and subunit assembly mechanisms of intact AMPA-Rs was very limited. However, the new studies using single particle EM and X-ray crystallography are revealing important insights. For example, the tetrameric crystal structure of the GluA2cryst construct provided the atomic view of the intact receptor. In addition, the single particle EM structures of the subunit assembly intermediates revealed the conformational requirement for the dimer-to-tetramer transition during the maturation of AMPA-Rs. These new data in the field provide new models and interpretations. In the brain, the native AMPA-R complexes contain auxiliary subunits that influence subunit assembly, gating, and trafficking of the AMPA-Rs. Understanding the mechanisms of the auxiliary subunits will become increasingly important to precisely describe the function of AMPA-Rs in the brain. The AMPA-R proteomics studies continuously reveal a previously unexpected degree of molecular heterogeneity of the complex. Because the AMPA-Rs are important drug targets for treating various neurological and psychiatric diseases, it is likely that these new native complexes will require detailed mechanistic analysis in the future. The current ultrastructural data on the receptors and the receptor-expressing stable cell lines that were developed during the course of these studies are useful resources for high throughput drug screening and further drug designing. Moreover, we are getting closer to understanding the precise mechanisms of AMPA-R-mediated synaptic plasticity

QCD and strongly coupled gauge theories : challenges and perspectives

We highlight the progress, current status, and open challenges of QCD-driven physics, in theory and in experiment. We discuss how the strong interaction is intimately connected to a broad sweep of physical problems, in settings ranging from astrophysics and cosmology to strongly coupled, complex systems in particle and condensed-matter physics, as well as to searches for physics beyond the Standard Model. We also discuss how success in describing the strong interaction impacts other fields, and, in turn, how such subjects can impact studies of the strong interaction. In the course of the work we offer a perspective on the many research streams which flow into and out of QCD, as well as a vision for future developments.Peer reviewe