Macropinocytosis is decreased in diabetic mouse macrophages and is regulated by AMPK

<p>Abstract</p> <p>Background</p> <p>Macrophages (MΦs) utilize macropinocytosis to integrate immune and metabolic signals in order to initiate an effective immune response. Diabetes is characterized by metabolic abnormalities and altered immune function. Here we examine the influence of diabetes on macropinocytosis in primary mouse macrophages and in an <it>in vitro </it>diabetes model.</p> <p>Results</p> <p>The data demonstrate that peritoneal MΦs from diabetic (<it>db/db</it>) mice had reduced macropinocytosis when compared to MΦs from non-diabetic (<it>db/+</it>) mice. Additionally, MΦs cultured in hyperglycemic conditions were less adept at macropinocytosis than those cultured in low glucose. Notably, AMP-activated protein kinase (AMPK) activity was decreased in MΦs cultured in hyperglycemic conditions. Activation of AMPK with leptin or 5-aminoimidazole-4-carboxamide-1-β-riboside (AICAR) increased macropinocytosis and inhibition of AMPK with compound C decreased macropinocytosis.</p> <p>Conclusion</p> <p>Taken together, these findings indicate that MΦs from diabetic mice have decreased macropinocytosis. This decrease appears dependent on reduced AMPK activity. These results demonstrate a previously unrealized role for AMPK in MΦs and suggest that increasing AMPK activity in diabetic MΦs could improve innate immunity and decrease susceptibility to infection.</p

The Science of Marine Protected Areas (3rd edition, Mediterranean)

The main purpose of the booklet is to present the latest scientific information about the effects of MPAs in the Mediterranean in order to inform current management dialogues. This is particularly relevant given the increasing legislative frameworks and political initiatives to implement networks of MPAs in countries across the Mediterranean Sea. Importantly, this Edition does much more than simply tailor the earlier content for the Mediterranean region. The edition update the basic content of the booklet, drawing on the wealth of new published scientific literature, highlighting case studies from the Mediterranean Sea

Phagocytosis of Cholesteryl Ester Is Amplified in Diabetic Mouse Macrophages and Is Largely Mediated by CD36 and SR-A

Type 2 diabetes (T2D) is associated with accelerated atherosclerosis, which accounts for approximately 75% of all diabetes-related deaths. Here we investigate the link between diabetes and macrophage cholesteryl ester accumulation. When diabetic (db/db) mice are given cholesteryl ester intraperitoneally (IP), peritoneal macrophages (PerMΦs) recovered from these animals showed a 58% increase in intracellular cholesteryl ester accumulation over PerMΦs from heterozygote control (db/+) mice. Notably, PerMΦ fluid-phase endocytosis and large particle phagocytosis was equivalent in db/+and db/db mice. However, IP administration of CD36 and SR-A blocking antibodies led to 37% and 25% reductions in cholesteryl ester accumulation in PerMΦ. Finally, in order to determine if these scavenger receptors (SRs) were part of the mechanism responsible for the increased accumulation of cholesteryl esters observed in the diabetic mouse macrophages, receptor expression was quantified by flow cytometry. Importantly, db/db PerMΦs showed a 43% increase in CD36 expression and an 80% increase in SR-A expression. Taken together, these data indicate that direct cholesteryl ester accumulation in mouse macrophages is mediated by CD36 and SR-A, and the magnitude of accumulation is increased in db/db macrophages due to increased scavenger receptor expression

Understanding the nature and mechanism of foot pain

Approximately one-quarter of the population are affected by foot pain at any given time. It is often disabling and can impair mood, behaviour, self-care ability and overall quality of life. Currently, the nature and mechanism underlying many types of foot pain is not clearly understood. Here we comprehensively review the literature on foot pain, with specific reference to its definition, prevalence, aetiology and predictors, classification, measurement and impact. We also discuss the complexities of foot pain as a sensory, emotional and psychosocial experience in the context of clinical practice, therapeutic trials and the placebo effect. A deeper understanding of foot pain is needed to identify causal pathways, classify diagnoses, quantify severity, evaluate long term implications and better target clinical intervention

Effect of age, sex and gender on pain sensitivity: A narrative review

© 2017 Eltumi And Tashani. Introduction: An increasing body of literature on sex and gender differences in pain sensitivity has been accumulated in recent years. There is also evidence from epidemiological research that painful conditions are more prevalent in older people. The aim of this narrative review is to critically appraise the relevant literature investigating the presence of age and sex differences in clinical and experimental pain conditions. Methods: A scoping search of the literature identifying relevant peer reviewed articles was conducted on May 2016. Information and evidence from the key articles were narratively described and data was quantitatively synthesised to identify gaps of knowledge in the research literature concerning age and sex differences in pain responses. Results: This critical appraisal of the literature suggests that the results of the experimental and clinical studies regarding age and sex differences in pain contain some contradictions as far as age differences in pain are concerned. While data from the clinical studies are more consistent and seem to point towards the fact that chronic pain prevalence increases in the elderly findings from the experimental studies on the other hand were inconsistent, with pain threshold increasing with age in some studies and decreasing with age in others. Conclusion: There is a need for further research using the latest advanced quantitative sensory testing protocols to measure the function of small nerve fibres that are involved in nociception and pain sensitivity across the human life span. Implications: Findings from these studies should feed into and inform evidence emerging from other types of studies (e.g. brain imaging technique and psychometrics) suggesting that pain in the older humans may have unique characteristics that affect how old patients respond to intervention

Maltose Binding Protein Is Partially Structured in Its Molten Globule State

Seven double cysteine mutants of maltose binding protein (MBP) were generated with one each in the active cleft at position 298 and the second cysteine distributed over both domains of the protein. These cysteines were spin labeled and distances between the labels in biradical pairs determined by pulsed double electron-electron resonance (DEER) measurements. The values were compared with theoretical predictions of distances between the labels in biradicals constructed by molecular modeling from the crystal structure of MBP without maltose and were found to be in excellent agreement. MBP is in a molten globule state at pH 3.3 and is known to still bind its substrate maltose. The nitroxide spin label was sufficiently stable under these conditions. In preliminary experiments, DEER measurements were carried out with one of the mutants yielding a broad distance distribution as was to be expected if there is no explicit tertiary structure and the individual helices pointing into all possible directions