Tribbles 3 Mediates Endoplasmic Reticulum Stress-Induced Insulin Resistance in Skeletal Muscle

Endoplasmic Reticulum (ER) stress has been linked to insulin resistance in multiple tissues but the role of ER stress in skeletal muscle has not been explored. ER stress has also been reported to increase tribbles 3 (TRB3) expression in multiple cell lines. Here, we report that high fat feeding in mice, and obesity and type 2 diabetes in humans significantly increases TRB3 and ER stress markers in skeletal muscle. Overexpression of TRB3 in C2C12 myotubes and mouse tibialis anterior muscles significantly impairs insulin signaling. Incubation of C2C12 cells and mouse skeletal muscle with ER stressors thapsigargin and tunicamycin increases TRB3 and impairs insulin signaling and glucose uptake, effects reversed in cells overexpressing RNAi for TRB3 and in muscles from TRB3 knockout mice. Furthermore, TRB3 knockout mice are protected from high fat diet-induced insulin resistance in skeletal muscle. These data demonstrate that TRB3 mediates ER stress-induced insulin resistance in skeletal muscle

Prostate Health Index (Phi) and Prostate Cancer Antigen 3 (PCA3) Significantly Improve Prostate Cancer Detection at Initial Biopsy in a Total PSA Range of 2-10 ng/ml

Many efforts to reduce prostate specific antigen (PSA) overdiagnosis and overtreatment have been made. To this aim, Prostate Health Index (Phi) and Prostate Cancer Antigen 3 (PCA3) have been proposed as new more specific biomarkers. We evaluated the ability of phi and PCA3 to identify prostate cancer (PCa) at initial prostate biopsy in men with total PSA range of 2-10 ng/ml. The performance of phi and PCA3 were evaluated in 300 patients undergoing first prostate biopsy. ROC curve analyses tested the accuracy (AUC) of phi and PCA3 in predicting PCa. Decision curve analyses (DCA) were used to compare the clinical benefit of the two biomarkers. We found that the AUC value of phi (0.77) was comparable to those of %p2PSA (0.76) and PCA3 (0.73) with no significant differences in pairwise comparison (%p2PSA vs phi p = 0.673, %p2PSA vs. PCA3 p = 0.417 and phi vs. PCA3 p = 0.247). These three biomarkers significantly outperformed fPSA (AUC = 0.60), %fPSA (AUC = 0.62) and p2PSA (AUC = 0.63). At DCA, phi and PCA3 exhibited a very close net benefit profile until the threshold probability of 25%, then phi index showed higher net benefit than PCA3. Multivariable analysis showed that the addition of phi and PCA3 to the base multivariable model (age, PSA, %fPSA, DRE, prostate volume) increased predictive accuracy, whereas no model improved single biomarker performance. Finally we showed that subjects with active surveillance (AS) compatible cancer had significantly lower phi and PCA3 values (p < 0.001 and p = 0.01, respectively). In conclusion, both phi and PCA3 comparably increase the accuracy in predicting the presence of PCa in total PSA range 2-10 ng/ml at initial biopsy, outperforming currently used %fPSA

The Influence of Animation Videos on Expressive Language Skills in Preschool Kobar Anugerah, Batujala Village, Bontoramba District, Jeneponto Regency

This research aims to: 1) find out what the effect is after being given an animated video at the Kobar Anugrah Early Childhood Education in Batujala Village. 2) To find out what the influence was before being given an animated video at the Kobar Anugrah Early Childhood Education in Batujal Village. 3) To find out whether there is an influence of learning videos in Kobar Anugrah Early Childhood Education in Batujala Village. This research is a quantitative descriptive research by describing variables that support the data in the form of numbers generated from the actual situation. This research uses primary data which collects data using questionnaires and interviews. The researcher uses quantitative analysis, multiple linear regression analysis and analysis of the coefficient of determination. with the help of SPSS17. The population in this study was 47 early childhood children at the Kobar Anugrah Early Childhood Education School, Batujala Village, carried out on May 15 2023 at Kobar early childhood education in Batujala Village, Bontoramba District, Jeneponto Regency, South Sulawesi Province. The results of the research obtained using the Animated videos have the effect of helping young children be active in expressive language at early childhood education schools in Kobar, and teachers are also more active in the early childhood education learning process using animated digital media learning methods. And master digital media materials with animated video materials

Evaluating IMATU and SAMWU policy responses to Igoli 2002

Abstract The restructuring of the Greater Johannesburg Metropolitan Council (GJMC) under the plan iGoli 2002 was part of the broader restructuring initiatives of the economy and social institutions in South Africa after the advent of democracy. Johannesburg is particularly important for any study that examines local government, not only due to its socioeconomic and cultural prominence but also because the plan represented a test case for the restructuring of the local government fraternity. The report examines the restructuring plan in the context of South Africa’s development trajectory since the country was ushered into a democracy. The report examines not only what the iGoli 2002 plan represents in development terms, but organised labour’s policy responses to the changes that were imminent in Johannesburg

Metformin Attenuates Palmitate-Induced Endoplasmic Reticulum Stress, Serine Phosphorylation of IRS-1 and Apoptosis in Rat Insulinoma Cells

Lipotoxicity refers to cellular dysfunctions caused by elevated free fatty acid levels playing a central role in the development and progression of obesity related diseases. Saturated fatty acids cause insulin resistance and reduce insulin production in the pancreatic islets, thereby generating a vicious cycle, which potentially culminates in type 2 diabetes. The underlying endoplasmic reticulum (ER) stress response can lead to even β-cell death (lipoapoptosis). Since improvement of β-cell viability is a promising anti-diabetic strategy, the protective effect of metformin, a known insulin sensitizer was studied in rat insulinoma cells. Assessment of palmitate-induced lipoapoptosis by fluorescent microscopy and by detection of caspase-3 showed a significant decrease in metformin treated cells. Attenuation of β-cell lipotoxicity was also revealed by lower induction/activation of various ER stress markers, e.g. phosphorylation of eukaryotic initiation factor 2α (eIF2α), c-Jun N-terminal kinase (JNK), insulin receptor substrate-1 (IRS-1) and induction of CCAAT/enhancer binding protein homologous protein (CHOP). Our results indicate that the β-cell protective activity of metformin in lipotoxicity can be at least partly attributed to suppression of ER stress

Synergistic precipitation reactions in a novel high-temperature Ti-alloy

There is a pressing need for the development of new Ti-alloys tailored to wire-based directed energy deposition (waDED), to enable the wider uptake of this additive manufacturing process by the aerospace and energy industries. Here we present a novel high-temperature Ti-alloy for waDED. Our alloy design aims to exploit phase transformations and precipitation to achieve fine and homogeneous microstructures during processing and to provide improved high-temperature mechanical properties. Our new alloy design features combined additions of Si, Cu, Nb, and Y. We study its microstructural evolution during a simulated waDED solidification route and after various heat-treatments replicating the waDED thermal history in a deposited layer. Our alloy shows significant potential for the formation of fine and equiaxed β grains during waDED. Atom probe and transmission electron microscopy reveal the formation of nm-sized Ti2Cu, (Ti, Zr)6Si3 and sandwich-like Y-Cu dispersoids that are known to improve high-temperature properties in Ti-alloys

Short-term HIIT impacts HDL function differently in lean, obese, and diabetic subjects

Introduction: High density lipoproteins (HDL) exert cardiovascular protection in part through their antioxidant capacity and cholesterol efflux function. Effects of exercise training on HDL function are yet to be well established, while impact on triacylglycerol (TG)-lowering has been often reported. We previously showed that a short-term high-intensity interval training (HIIT) program improves insulin sensitivity but does not inhibit inflammatory pathways in immune cells in insulin-resistant subjects. The purpose of this study is to evaluate HDL function along with changes of lipoproteins after the short-term HIIT program in lean, obese nondiabetic, and obese type 2 diabetic (T2DM) subjects. Methods: All individuals underwent a supervised 15-day program of alternative HIIT for 40 minutes per day. VO2peak was determined before and after this training program. A pre-training fasting blood sample was collected, and the post-training fasting blood sample collection was performed 36 hours after the last exercise session. Results: Blood lipid profile and HDL function were analyzed before and after the HIIT program. Along with improved blood lipid profiles in obese and T2DM subjects, the HIIT program affected circulating apolipoprotein amounts differently. The HIIT program increased HDL-cholesterol levels and improved the cholesterol efflux capacity only in lean subjects. Furthermore, the HIIT program improved the antioxidant capacity of HDL in all subjects. Data from multiple logistic regression analysis showed that changes in HDL antioxidant capacity were inversely associated with changes in atherogenic lipids and changes in HDL-TG content. Discussion: We show that a short-term HIIT program improves aspects of HDL function depending on metabolic contexts, which correlates with improvements in blood lipid profile. Our results demonstrate that TG content in HDL particles may play a negative role in the anti-atherogenic function of HDL