The role of macrophages in obesity-associated islet inflammation and β-cell abnormalities.

Chronic, unresolved tissue inflammation is a well-described feature of obesity, type 2 diabetes mellitus (T2DM) and other insulin-resistant states. In this context, adipose tissue and liver inflammation have been particularly well studied; however, abundant evidence demonstrates that inflammatory processes are also activated in pancreatic islets from obese animals and humans with obesity and/or T2DM. In this Review, we focus on the characteristics of immune cell-mediated inflammation in islets and the consequences of this with respect to β-cell function. In contrast to type 1 diabetes mellitus, the dominant immune cell type causing inflammation in obese and T2DM islets is the macrophage. The increased macrophage accumulation in T2DM islets primarily arises through local proliferation of resident macrophages, which then provide signals (such as platelet-derived growth factor) that drive β-cell hyperplasia (a classic feature of obesity). In addition, islet macrophages also impair the insulin secretory capacity of β-cells. Through these mechanisms, islet-resident macrophages underlie the inflammatory response in obesity and mechanistically participate in the β-cell hyperplasia and dysfunction that characterizes this insulin-resistant state. These findings point to the possibility of therapeutics that target islet inflammation to elicit beneficial effects on β-cell function and glycaemia

Music of France - Doug Lindsey

KSU School of Music presents Music of France, Douglas Lindsey, trumpet and Kristine Olefsky, piano.https://digitalcommons.kennesaw.edu/musicprograms/2232/thumbnail.jp

Neuronal SIRT1 Regulates Metabolic and Reproductive Function and the Response to Caloric Restriction.

Sirt1 is an NAD-dependent, class III deacetylase that functions as a cellular energy sensor. In addition to its well-characterized effects in peripheral tissues, emerging evidence suggests that neuronal Sirt1 activity plays a role in the central regulation of energy balance and glucose metabolism. In this study, we generated mice expressing an enzymatically inactive form (N-MUT) or wild-type (WT) SIRT1 (N-OX) in mature neurons. N-OX male and female mice had impaired glucose tolerance, and N-MUT female, but not male, mice had improved glucose tolerance compared with that of WT littermates. Furthermore, glucose tolerance was improved in all mice with caloric restriction (CR) but was greater in the N-OX mice, who had better glucose tolerance than their littermates. At the reproductive level, N-OX females had impaired estrous cycles, with increased cycle length and more time in estrus. LH and progesterone surges were absent on the evening of proestrus in the N-OX mice, suggesting a defect in spontaneous ovulation, which was confirmed by the ovarian histology revealing fewer corpora lutea. Despite this defect, the mice were still fertile when mated to WT mice on the day of proestrus, indicating that the mice could respond to normal pheromonal or environmental cues. When subjected to CR, the N-OX mice went into diestrus arrest earlier than their littermates. Together, these results suggested that the overexpression of SIRT1 rendered the mice more sensitive to the metabolic improvements and suppression of reproductive cycles by CR, which was independent of circadian rhythms

High fat diet causes depletion of intestinal eosinophils associated with intestinal permeability.

The development of intestinal permeability and the penetration of microbial products are key factors associated with the onset of metabolic disease. However, the mechanisms underlying this remain unclear. Here we show that, unlike liver or adipose tissue, high fat diet (HFD)/obesity in mice does not cause monocyte/macrophage infiltration into the intestine or pro-inflammatory changes in gene expression. Rather HFD causes depletion of intestinal eosinophils associated with the onset of intestinal permeability. Intestinal eosinophil numbers were restored by returning HFD fed mice to normal chow and were unchanged in leptin-deficient (Ob/Ob) mice, indicating that eosinophil depletion is caused specifically by a high fat diet and not obesity per se. Analysis of different aspects of intestinal permeability in HFD fed and Ob/Ob mice shows an association between eosinophil depletion and ileal paracelullar permeability, as well as leakage of albumin into the feces, but not overall permeability to FITC dextran. These findings provide the first evidence that a high fat diet causes intestinal eosinophil depletion, rather than inflammation, which may contribute to defective barrier integrity and the onset of metabolic disease

VAMPIRE microarray suite: a web-based platform for the interpretation of gene expression data

Microarrays are invaluable high-throughput tools used to snapshot the gene expression profiles of cells and tissues. Among the most basic and fundamental questions asked of microarray data is whether individual genes are significantly activated or repressed by a particular stimulus. We have previously presented two Bayesian statistical methods for this level of analysis, collectively known as variance-modeled posterior inference with regional exponentials (VAMPIRE). These methods each require a sophisticated modeling step followed by integration of a posterior probability density. We present here a publicly available, web-based platform that allows users to easily load data, associate related samples and identify differentially expressed features using the VAMPIRE statistical framework. In addition, this suite of tools seamlessly integrates a novel gene annotation tool, known as GOby, which identifies statistically overrepresented gene groups. Unlike other tools in this genre, GOby can localize enrichment while respecting the hierarchical structure of annotation systems like Gene Ontology (GO). By identifying statistically significant enrichment of GO terms, Kyoto Encyclopedia of Genes and Genomes pathways, and TRANSFAC transcription factor binding sites, users can gain substantial insight into the physiological significance of sets of differentially expressed genes. The VAMPIRE microarray suite can be accessed at

Bridging the gender gap in computing: An integrative approach to content design for girls

Although some observed differences in males\u27 and females\u27 attitudes toward and uses of computers appear to be narrowing, the gender gap remains widest in relation to programming and software design, which are still male preserves. In response, software and Web site designers have applied feminist theories to develop three distinct approaches to creating content for girls that might increase their interest in computers. These approaches involve appealing to girls\u27 traditional “feminine” interests, nontraditional “masculine” interests, and gender-neutral interests. This study proposes that to bridge today\u27s gender gap, prior approaches need to integrate appeals to girls\u27 traditional and nontraditional interests, and focus content more clearly on learning about computer design itself. An experimental test of this integrative strategy, used to develop a prototype World Wide Web site tested on girls in their homes (n = 125), obtained significant increases in the treatment group\u27s interest in, sense of relevancy of, and motivation to use computers, compared to a control group

Concert recording 2013-03-10

[Track 01]. Cello suite no. 5 in C minor, BWV 101. Prelude / Johann Sebastian Bach ; translated by Ralph Sauer -- [Track 02]. Du bist die ruh, op. 59, no. 3, D776 / Franz Schubert ; translated by Andrew Jones -- [Track 03]. Capriccio for solo tuba / Krzysztof Penderecki -- [Track 04]. Etre ou ne pa etre: Monologue d\u27Hamlet / Henri Tomasi -- [Track 05]. Concerto for bass tuba and orchestra in F minor / Ralph Vaughn William

Concert recording 2022-04-07

[Track 1]. Moose the mooche / Charlie Parker -- Red clay / Freddie Hubbard -- Mr. Tinfoil / Max Morrow -- Sonata for alto saxophone and piano. I. Andante moderato ; II. Adagio, dolce exspressivo ; II. Allegro con brio / John C. Worley -- Tsu / Max Morrow