Insulin secretion profiles are modified by overexpression of glutamate dehydrogenase in pancreatic islets

Aims/hypothesis: Glutamate dehydrogenase (GDH) is a mitochondrial enzyme playing a key role in the control of insulin secretion. However, it is not known whether GDH expression levels in beta cells are rate-limiting for the secretory response to glucose. GDH also controls glutamine and glutamate oxidative metabolism, which is only weak in islets if GDH is not allosterically activated by L-leucine or (+/−)-2-aminobicyclo-[2,2,1]heptane-2-carboxylic acid (BCH). Methods: We constructed an adenovirus encoding for GDH to overexpress the enzyme in the beta-cell line INS-1E, as well as in isolated rat and mouse pancreatic islets. The secretory responses to glucose and glutamine were studied in static and perifusion experiments. Amino acid concentrations and metabolic parameters were measured in parallel. Results: GDH overexpression in rat islets did not change insulin release at basal or intermediate glucose (2.8 and 8.3mmol/l respectively), but potentiated the secretory response at high glucose concentrations (16.7mmol/l) compared to controls (+35%). Control islets exposed to 5mmol/l glutamine at basal glucose did not increase insulin release, unless BCH was added with a resulting 2.5-fold response. In islets overexpressing GDH glutamine alone stimulated insulin secretion (2.7-fold), which was potentiated 2.2-fold by adding BCH. The secretory responses evoked by glutamine under these conditions correlated with enhanced cellular metabolism. Conclusions/interpretation: GDH could be rate-limiting in glucose-induced insulin secretion, as GDH overexpression enhanced secretory responses. Moreover, GDH overexpression made islets responsive to glutamine, indicating that under physiological conditions this enzyme acts as a gatekeeper to prevent amino acids from being inappropriate efficient secretagogue

The Relationship between Squat Jump Performance and Sprint Profile in Collegiate Track and Field Athletes

The squat jump (SJ) necessitates the inter-play of various biomechanical components for better jump performance. Good sprint performance requires the inter-play of many of the same biomechanical components. Researchers have previously examined how the speed, force, velocity, and power interact during sprinting, but have yet to examine how these measures are associated with SJ performance measures. PURPOSE: Examine the relationship between squat jump performance measures and the sprint profile measurements of collegiate track and field athletes. METHODS: Twenty-five athletes (18 males and 7 females) completed two squat jump trials with a linear encoder attached to a 45 lbs. bar placed on the athlete’s upper back. Measures of interest during the concentric phase of the SJ included jump height, maximum force, maximum velocity, maximum power, and rate of force development. Athletes then completed two 30-meter acceleration sprints. The MySprint mobile application was used to acquire the athlete’s sprint profile and to assess maximal theoretical horizontal force, maximal theoretical velocity, optimal velocity, maximal theoretical power, maximal speed, maximal ratio of force, force-velocity slope, and decrease in ratio of force. The best trial was used for statistical analysis. Pearson’s or Spearman’s correlation coefficients were conducted between SJ measures and sprint profile measures. RESULTS: There was a positive correlation between SJ height and maximal speed (r = 0.402; p = 0.042). Maximal power during the SJ was positively correlated with maximal speed (r = 0.476; p = 0.014); optimal velocity (r = 0.469; p = 0.018); maximal theoretical power (r = 0.462; p = 0.018); maximal theoretical velocity (r = 0.452; p = 0.021); theoretical horizontal force (r = 0.431; p = 0.028); and maximal ratio force (r = 0.428; p = 0.029). Maximal velocity during the SJ was correlated with maximal speed (r = 0.519; p = 0.007); maximal theoretical velocity (r = 0.499; p = 0.010); optimal velocity (r = 0.486; p = 0.014); and maximal theoretical power (r = 0.484; p = 0.012). No other correlations were significant. CONCLUSION: Maximal velocity and power during the concentric phase of the SJ are moderately to strongly correlated with maximal sprinting speed, velocity, and power. SJ height is positively correlated with maximum sprint speed. There is a lack of significant correlations between other measures of the SJ and sprint profile measures. SJ power and velocity are correlated with sprint performance, therefore power and velocity improved through plyometric SJ training may be transferable to achieve better sprint performance

Localization criteria for Anderson models on locally finite graphs

We prove spectral and dynamical localization for Anderson models on locally finite graphs using the fractional moment method. Our theorems extend earlier results on localization for the Anderson model on \ZZ^d. We establish geometric assumptions for the underlying graph such that localization can be proven in the case of sufficiently large disorder

Predicted gamma-ray line emission from the Cygnus complex

The Cygnus region harbours a huge complex of massive stars at a distance of 1.0-2.0kpc from us. About 170 O stars are distributed over several OB associations, among which the Cyg OB2 cluster is by far the most important with about 100-120 O stars. These massive stars inject large quantities of radioactive nuclei into the interstellar medium, such as 26Al and 60Fe, and their gamma-ray line decay signals can provide insight into the physics of massive stars and core-collapse supernovae. Past studies of the nucleosynthesis activity of Cygnus have concluded that the level of 26Al decay emission as deduced from CGRO/COMPTEL observations was a factor 2-3 above the predictions based on the theoretical yields available at that time and on the observed stellar content of the Cygnus region. We reevaluate the situation from new measurements of the gamma-ray decay fluxes with INTEGRAL/SPI and new predictions based on recently improved stellar models including some of the effects of stellar rotation for the higher mass stars and a coherent estimate of the contribution from SNIb/c. We developed a population synthesis code to predict the nucleosynthesis activity and corresponding decay fluxes of a given stellar population of massive stars. The observed decay fluxes from the Cygnus complex are found to be consistent with the values predicted by population synthesis at solar metallicity. The observed extent of the 1809keV emission from Cygnus is found to be consistent with the result of a numerical simulation of the diffusion of 26Al inside the superbubble blown by Cyg OB2. Our work indicates that the past dilemma regarding the gamma-ray line emission from Cygnus resulted from an overestimate of the 1809keV flux of the Cygnus complex, combined with an underestimate of the nucleosynthesis yields.Comment: 13 pages, 9 figures, accepted for publication in A&

Potential common radiation problems for components and diagnostics in future magnetic and inertial confinement fusion devices

This work aims at identifying common potential problems that future fusion devices will encounter for both magnetic (MC) and inertial (IC) confinement approaches in order to promote joint efforts and to avoid duplication of research

Recent Advancements in the LC- and GC-Based Analysis of Malondialdehyde (MDA): A Brief Overview

Malondialdehyde (MDA) is an end-product of lipid peroxidation and a side product of thromboxane A2 synthesis. Moreover, it is not only a frequently measured biomarker of oxidative stress, but its high reactivity and toxicity underline the fact that this molecule is more than “just” a biomarker. Additionally, MDA was proven to be a mutagenic substance. Having said this, it is evident that there is a major interest in the highly selective and sensitive analysis of this molecule in various matrices. In this review, we will provide a brief overview of the most recent developments and techniques for the liquid chromatography (LC) and gas chromatography (GC)-based analysis of MDA in different matrices. While the 2-thiobarbituric acid assay still is the most prominent methodology for determining MDA, several advanced techniques have evolved, including GC–MS(MS), LC–MS(MS) as well as several derivatization-based strategies

Preventive and curative effect of melatonin on mammary carcinogenesis induced by dimethylbenz[a]anthracene in the female Sprague–Dawley rat

INTRODUCTION: It has been well documented that the pineal hormone, melatonin, which plays a major role in the control of reproduction in mammals, also plays a role in the incidence and growth of breast and mammary cancer. The curative effect of melatonin on the growth of dimethylbenz [a]anthracene-induced (DMBA-induced) mammary adenocarcinoma (ADK) has been previously well documented in the female Sprague–Dawley rat. However, the preventive effect of melatonin in limiting the frequency of cancer initiation has not been well documented. METHODS: The aim of this study was to compare the potency of melatonin to limit the frequency of mammary cancer initiation with its potency to inhibit tumor progression once initiation, at 55 days of age, was achieved. The present study compared the effect of preventive treatment with melatonin (10 mg/kg daily) administered for only 15 days before the administration of DMBA with the effect of long-term (6-month) curative treatment with the same dose of melatonin starting the day after DMBA administration. The rats were followed up for a year after the administration of the DMBA. RESULTS: The results clearly showed almost identical preventive and curative effects of melatonin on the growth of DMBA-induced mammary ADK. Many hypotheses have been proposed to explain the inhibitory effects of melatonin. However, the mechanisms responsible for its strong preventive effect are still a matter of debate. At least, it can be envisaged that the artificial amplification of the intensity of the circadian rhythm of melatonin could markedly reduce the DNA damage provoked by DMBA and therefore the frequency of cancer initiation. CONCLUSION: In view of the present results, obtained in the female Sprague–Dawley rat, it can be envisaged that the long-term inhibition of mammary ADK promotion by a brief, preventive treatment with melatonin could also reduce the risk of breast cancer induced in women by unidentified environmental factors

Female Genital Mutilation: perceptions of healthcare professionals and the perspective of the migrant families

<p>Abstract</p> <p>Background</p> <p>Female Genital Mutilation (FGM) is a traditional practice which is harmful to health and is profoundly rooted in many Sub-Saharan African countries. It is estimated that between 100 and 140 million women around the world have been victims of some form of FGM and that each year 3 million girls are at risk of being submitted to these practices. As a consequence of the migratory phenomena, the problems associated with FGM have extended to the Western countries receiving the immigrants. The practice of FGM has repercussions on the physical, psychic, sexual and reproductive health of women, severely deteriorating their current and future quality of life. Primary healthcare professionals are in a privileged position to detect and prevent these situations of risk which will be increasingly more present in Spain.</p> <p>Methods/Design</p> <p>The objective of the study is to describe the knowledge, attitudes and practices of the primary healthcare professionals, working in 25 health care centres in Barcelona and Girona regions, regarding FGM, as well as to investigate the perception of this subject among the migrant communities from countries with strong roots in these practices. A transversal descriptive study will be performed with a questionnaire to primary healthcare professionals and migrant healthcare users.</p> <p>Using a questionnaire specifically designed for this study, we will evaluate the knowledge, attitudes and skills of the healthcare professionals to approach this problem. In a sub-study, performed with a similar methodology but with the participation of cultural mediators, the perceptions of the migrant families in relation to their position and expectancies in view of the result of preventive interventions will be determined.</p> <p>Variables related to the socio-demographic aspects, knowledge of FGM (types, cultural origin, geographic distribution and ethnicity), evaluation of attitudes and beliefs towards FGM and previous contact or experience with cases or risk situations will be obtained.</p> <p>Discussion</p> <p>Knowledge of these harmful practices and a preventive approach from a transcultural perspective may represent a positive intervention model for integrative care of immigrants, respecting their values and culture while also being effective in eliminating the physical and psychic consequences of FGM.</p

A Protective Role for ELR+ Chemokines during Acute Viral Encephalomyelitis

The functional role of ELR-positive CXC chemokines in host defense during acute viral-induced encephalomyelitis was determined. Inoculation of the neurotropic JHM strain of mouse hepatitis virus (JHMV) into the central nervous system (CNS) of mice resulted in the rapid mobilization of PMNs expressing the chemokine receptor CXCR2 into the blood. Migration of PMNs to the CNS coincided with increased expression of transcripts specific for the CXCR2 ELR-positive chemokine ligands CXCL1, CXCL2, and CXCL5 within the brain. Treatment of JHMV-infected mice with anti-CXCR2 blocking antibody reduced PMN trafficking into the CNS by >95%, dampened MMP-9 activity, and abrogated blood-brain-barrier (BBB) breakdown. Correspondingly, CXCR2 neutralization resulted in diminished infiltration of virus-specific T cells, an inability to control viral replication within the brain, and 100% mortality. Blocking CXCR2 signaling did not impair the generation of virus-specific T cells, indicating that CXCR2 is not required to tailor anti-JHMV T cell responses. Evaluation of mice in which CXCR2 is genetically silenced (CXCR2−/− mice) confirmed that PMNs neither expressed CXCR2 nor migrated in response to ligands CXCL1, CXCL2, or CXCL5 in an in vitro chemotaxis assay. Moreover, JHMV infection of CXCR2−/− mice resulted in an approximate 60% reduction of PMN migration into the CNS, yet these mice survived infection and controlled viral replication within the brain. Treatment of JHMV-infected CXCR2−/− mice with anti-CXCR2 antibody did not modulate PMN migration nor alter viral clearance or mortality, indicating the existence of compensatory mechanisms that facilitate sufficient migration of PMNs into the CNS in the absence of CXCR2. Collectively, these findings highlight a previously unappreciated role for ELR-positive chemokines in enhancing host defense during acute viral infections of the CNS

Respiratory Dendritic Cell Subsets Differ in Their Capacity to Support the Induction of Virus-Specific Cytotoxic CD8+ T Cell Responses

Dendritic cells located at the body surfaces, e.g. skin, respiratory and gastrointestinal tract, play an essential role in the induction of adaptive immune responses to pathogens and inert antigens present at these surfaces. In the respiratory tract, multiple subsets of dendritic cells (RDC) have been identified in both the normal and inflamed lungs. While the importance of RDC in antigen transport from the inflamed or infected respiratory tract to the lymph nodes draining this site is well recognized, the contribution of individual RDC subsets to this process and the precise role of migrant RDC within the lymph nodes in antigen presentation to T cells is not clear. In this report, we demonstrate that two distinct subsets of migrant RDC - exhibiting the CD103+ and CD11bhi phenotype, respectively - are the primary DC presenting antigen to naïve CD4+ and CD8+ T lymphocytes in the draining nodes in response to respiratory influenza virus infection. Furthermore, the migrant CD103+ RDC subset preferentially drives efficient proliferation and differentiation of naive CD8+ T cells responding to infection into effector cells, and only the CD103+ RDC subset can present to naïve CD8+ T cells non-infectious viral vaccine introduced into the respiratory tract. These results identify CD103+ and CD11bhi RDC as critical regulators of the adaptive immune response to respiratory tract infection and potential targets in the design of mucosal vaccines