Changes in plasma levels of N-arachidonoyl ethanolamine and N-palmitoylethanolamine following bariatric surgery in morbidly obese females with impaired glucose homeostasis

Aim: We examined endocannabinoids (ECs) in relation to bariatric surgery and the association between plasma ECs and markers of insulin resistance. Methods: A study of 20 participants undergoing bariatric surgery. Fasting and 2-hour plasma glucose, lipids, insulin, and C-peptide were recorded preoperatively and 6 months postoperatively with plasma ECs (AEA, 2-AG) and endocannabinoid-related lipids (PEA, OEA). Results: Gender-specific analysis showed differences in AEA, OEA, and PEA preoperatively with reductions in AEA and PEA in females postoperatively. Preoperatively, AEA was correlated with 2-hour glucose (r = 0.55, P = 0.01), HOMA-IR (r = 0.61, P = 0.009), and HOMA %S (r = -0.71, P = 0.002). OEA was correlated with weight (r = 0.49, P = 0.03), waist circumference (r = 0.52, P = 0.02), fasting insulin (r = 0.49, P = 0.04), and HOMA-IR (r = 0.48, P = 0.05). PEA was correlated with fasting insulin (r = 0.49, P = 0.04). 2-AG had a negative correlation with fasting glucose (r = -0.59, P = 0.04). Conclusion: Gender differences exist in circulating ECs in obese subjects. Females show changes in AEA and PEA after bariatric surgery. Specific correlations exist between different ECs and markers of obesity and insulin and glucose homeostasis

Reductions in plasma endocannabinoids following bariatric surgery in morbidly obese females with impaired glucose homeostasis: a non-randomized prospective study

Reductions in plasma endocannabinoids following bariatric surgery in morbidly obese females with impaired glucose homeostasis: A non-randomized prospective study • Endocannabinoids (ECs) are bioactive lipid mediators − N-arachidonyl ethanolamine (AEA) − N-palmitoyl ethanolamine (PEA) − N-oleoyl ethanolamine (OEA) − related N-acylethanolamine (NAE) derivatives − 2-arachidonyl glycerol (2-AG) • Endocannabinoid system (ECS) plays a critical role in regulation of body weight and may have a role in aetiopathogenesis of Type 2 Diabetes (T2DM) • Elevated circulating levels of AEA and 2-AG in obese people compared to non-obese controls of both genders • Little information available on the effects of extreme weight loss associated with bariatric surgery in relation to the ECS

Regioisomeric family of novel fluorescent substrates for SHIP2

ABSTRACT: SHIP2 (SH2-domain containing inositol 5-phosphatase type 2) is a canonical 5-phosphatase which, through its catalytic action on PtdInsP3, regulates the PI3K/Akt pathway and metabolic action of insulin. It is a drug target but there is limited evidence of inhibition of SHIP2 by small molecules in the literature. With the goal to investigate inhibition, we report a homologous family of synthetic, chromophoric benzene phosphate substrates of SHIP2 that display the headgroup regiochemical hallmarks of the physiological inositide substrates that have proved difficult to crystallize with 5-phosphatases. Using time-dependent density functional theory (TD-DFT), we explore the intrinsic fluorescence of these novel substrates and show how fluorescence can be used to assay enzyme activity. The TD-DFT approach promises to inform rational design of enhanced active site probes for the broadest family of inositide-binding / metabolizing proteins, whilst maintaining the regiochemical properties of bona fide inositide substrates

Adipose segmentation in small animals at 7T: a preliminary study

<p>Abstract</p> <p>Background</p> <p>Small animal MRI at 7 Tesla (T) provides a useful tool for adiposity research. For adiposity researchers, separation of fat from surrounding tissues and its subsequent quantitative or semi- quantitative analysis is a key task. This is a relatively new field and a priori it cannot be known which specific biological questions related to fat deposition will be relevant in a specific study. Thus it is impossible to predict what accuracy and what spatial resolution will be required in all cases and even difficult what accuracy and resolution will be useful in most cases. However the pragmatic time constraints and the practical resolution ranges are known for small animal imaging at 7T. Thus we have used known practical constraints to develop a method for fat volume analysis based on an optimized image acquisition and image post processing pair.</p> <p>Methods</p> <p>We designed a fat segmentation method based on optimizing a variety of factors relevant to small animal imaging at 7T. In contrast to most previously described MRI methods based on signal intensity of T1 weighted image alone, we chose to use parametric images based on Multi-spin multi-echo (MSME) Bruker pulse sequence which has proven to be particularly robust in our laboratory over the last several years. The sequence was optimized on a T1 basis to emphasize the signal. T2 relaxation times can be calculated from the multi echo data and we have done so on a pixel by pixel basis for the initial step in the post processing methodology. The post processing consists of parallel paths. On one hand, the weighted image is precisely divided into different regions with optimized smoothing and segmentation methods; and on the other hand, a confidence image is deduced from the parametric image according to the distribution of relaxation time relationship of typical adipose. With the assistance of the confidence image, a useful software feature was implemented to which enhances the data and in the end results in a more reliable and flexible method for adipose evaluation.</p> <p>Results</p> <p>In this paper, we describe how we arrived at our recommended procedures and key aspects of the post-processing steps. The feasibility of the proposed method is tested on both simulated and real data in this preliminary research. A research tool was created to help researchers segment out fat even when the anatomical information is of low quality making it difficult to distinguish between fat and non-fat. In addition, tool is designed to allow the operator to make adjustments to many of the key steps for comparison purposes and to quantitatively assess the difference these changes make. Ultimately our flexible software lets the researcher define key aspects of the fat segmentation and quantification.</p> <p>Conclusions</p> <p>Combining the full T2 parametric information with the optimized first echo image information, the research tool enhances the reliability of the results while providing more flexible operations than previous methods. The innovation in the method is to pair an optimized and very specific image acquisition technique to a flexible but tuned image post processing method. The separation of the fat is aided by the confidence distribution of regions produced on a scale relevant to and dictated by practical aspects of MRI at 7T.</p

The nutrition transition and its health implications in lower-income countries

OBJECTIVE: This article reviews information on the rapid changes in diet, activity and body composition that lower- and middle-income countries are undergoing and then examines some of the potential health implications of this transition. DESIGN AND SETTING: Data came from numerous countries and also from national food balance (FAOSTAT) and World Bank sources. Nationally representative and nationwide surveys are used. The nationally representative Russian Longitudinal Monitoring Surveys from 1992-96 and the nationwide China Health and Nutrition Survey from 1989-93 are examined in detail. RESULTS: Rapid changes in the structure of diet, in particular associated with urbanization, are documented. In addition, large changes in occupation types are documented. These are linked with rapid increases in adult obesity in Latin America and Asia. Some of the potential implications for adult health are noted. CONCLUSIONS: The rapid changes in diet, activity and obesity that are facing billions of residents of lower- and middle-income countries are cause for great concern. Linked with these changes will be a rapid increase in chronic diseases. Little to date has been done at the national level to address these problems

Acetylcholine turnover in an autoactive molluscan neuron

1. We have studied acetylcholine (ACh) turnover at the cholinergic synapse between an identified motoneuron, the salivary burster (SB), and the muscle cells of the salivary duct (SD) in the terrestrial mollusk Limax maximus.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/44284/1/10571_2004_Article_BF00710939.pd

Ras Conformational Switching: Simulating Nucleotide-Dependent Conformational Transitions with Accelerated Molecular Dynamics

Ras mediates signaling pathways controlling cell proliferation and development by cycling between GTP- and GDP-bound active and inactive conformational states. Understanding the complete reaction path of this conformational change and its intermediary structures is critical to understanding Ras signaling. We characterize nucleotide-dependent conformational transition using multiple-barrier-crossing accelerated molecular dynamics (aMD) simulations. These transitions, achieved for the first time for wild-type Ras, are impossible to observe with classical molecular dynamics (cMD) simulations due to the large energetic barrier between end states. Mapping the reaction path onto a conformer plot describing the distribution of the crystallographic structures enabled identification of highly populated intermediate structures. These structures have unique switch orientations (residues 25–40 and 57–75) intermediate between GTP and GDP states, or distinct loop3 (46–49), loop7 (105–110), and α5 C-terminus (159–166) conformations distal from the nucleotide-binding site. In addition, these barrier-crossing trajectories predict novel nucleotide-dependent correlated motions, including correlations of α2 (residues 66–74) with α3-loop7 (93–110), loop2 (26–37) with loop10 (145–151), and loop3 (46–49) with α5 (152–167). The interconversion between newly identified Ras conformations revealed by this study advances our mechanistic understanding of Ras function. In addition, the pattern of correlated motions provides new evidence for a dynamic linkage between the nucleotide-binding site and the membrane interacting C-terminus critical for the signaling function of Ras. Furthermore, normal mode analysis indicates that the dominant collective motion that occurs during nucleotide-dependent conformational exchange, and captured in aMD (but absent in cMD) simulations, is a low-frequency motion intrinsic to the structure

Journeys from quantum optics to quantum technology

Sir Peter Knight is a pioneer in quantum optics which has now grown to an important branch of modern physics to study the foundations and applications of quantum physics. He is leading an effort to develop new technologies from quantum mechanics. In this collection of essays, we recall the time we were working with him as a postdoc or a PhD student and look at how the time with him has influenced our research

New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms

Impact of COVID-19 on cardiovascular testing in the United States versus the rest of the world

Objectives: This study sought to quantify and compare the decline in volumes of cardiovascular procedures between the United States and non-US institutions during the early phase of the coronavirus disease-2019 (COVID-19) pandemic. Background: The COVID-19 pandemic has disrupted the care of many non-COVID-19 illnesses. Reductions in diagnostic cardiovascular testing around the world have led to concerns over the implications of reduced testing for cardiovascular disease (CVD) morbidity and mortality. Methods: Data were submitted to the INCAPS-COVID (International Atomic Energy Agency Non-Invasive Cardiology Protocols Study of COVID-19), a multinational registry comprising 909 institutions in 108 countries (including 155 facilities in 40 U.S. states), assessing the impact of the COVID-19 pandemic on volumes of diagnostic cardiovascular procedures. Data were obtained for April 2020 and compared with volumes of baseline procedures from March 2019. We compared laboratory characteristics, practices, and procedure volumes between U.S. and non-U.S. facilities and between U.S. geographic regions and identified factors associated with volume reduction in the United States. Results: Reductions in the volumes of procedures in the United States were similar to those in non-U.S. facilities (68% vs. 63%, respectively; p = 0.237), although U.S. facilities reported greater reductions in invasive coronary angiography (69% vs. 53%, respectively; p < 0.001). Significantly more U.S. facilities reported increased use of telehealth and patient screening measures than non-U.S. facilities, such as temperature checks, symptom screenings, and COVID-19 testing. Reductions in volumes of procedures differed between U.S. regions, with larger declines observed in the Northeast (76%) and Midwest (74%) than in the South (62%) and West (44%). Prevalence of COVID-19, staff redeployments, outpatient centers, and urban centers were associated with greater reductions in volume in U.S. facilities in a multivariable analysis. Conclusions: We observed marked reductions in U.S. cardiovascular testing in the early phase of the pandemic and significant variability between U.S. regions. The association between reductions of volumes and COVID-19 prevalence in the United States highlighted the need for proactive efforts to maintain access to cardiovascular testing in areas most affected by outbreaks of COVID-19 infection