The oral lipid sensor GPR120 is not indispensable for the orosensory detectionof dietary lipids in the mouse

International audienceImplication of the long-chain fatty acid (LCFA) receptor GPR120, also termed free fatty acid receptor 4 (FFAR4), in the taste-guided preference for lipids is a matter of debate. To further unravel the role of GPR120 in the "taste of fat", the present study was conducted on GPR120-null mice and their wild-type littermates. Using a combination of morphological (i.e. immunohistochemical staining of circumvallate papillae - CVP), behavioral (i.e. two-bottle preference tests, licking tests and conditioned taste aversion) and functional studies (i.e. calcium imaging in freshly isolated taste bud cells - TBC), we show that absence of GPR120 in oral cavity was not associated with changes in i) the gross anatomy of CVP, ii) the LCFA-mediated increases in [Ca2+]i, iii) the preference for oily and LCFA solutions and iv) the conditioned avoidance of LCFA solutions. In contrast, the rise in [Ca2+]i triggered by grifolic acid (GA), a specific GPR120 agonist, was dramatically curtailed when GPR120 gene was lacking. Taken together these data demonstrate that activation of lingual GPR120 and preference for fat are disconnected, suggesting that GPR120 expressed in TBC is not absolutely required for the oral fat detection in the mouse

Stochastic Numerical Simulation for the Evaluation of Mechanical Properties of Filled Polymer Composites

Reinforced polymeric composites are profoundly used in variety of applications due to its high strength to weight ratio and ease of fabrication. The wide spread application of reinforced polymeric materials in the electronic industries have created a great demand in fabricating a kind of reinforced polymeric system, which is light but has better mechanical strength and good thermal properties. Especially glass microsphere filled epoxy resin composites is used as a potting compound in electronic and aviation industries. Therefore, knowledge of the fundamental thermal and mechanical properties of these systems is highly essential in the formulation of advanced electronic potting compounds. In this work, the effective mechanical properties of glass microsphere filled epoxy system is investigated numerically by stochastic simulation. Numerical simulation software ANSYS is used to characterise the microstructure of the filled epoxy system. MATLAB code has been developed to model the randomness of the particle. The geometric model generated from the MATLAB code is given as an input to ANSYS. Random particle Representative Volume Element (RVE) model is used to evaluate the mechanical properties at various loading fractions. The effect of particle size on mechanical properties of glass microsphere filled epoxy composite is studied. Further the random RVE modeling scheme is compared with single RVE modeling scheme and its significance is reported. The numerically predicted values of effective modulus is then compared with the analytical models and with the literature experimental data. Also the significance of the analytical model on the determination of properties is reported. Then, the effect of interface on the mechanical characterisation by stochastic model is analysed and the debonding of the particle is also simulated

Synthesis of Pyrazine Substituted 1,3,4-Thiadiazole Derivatives and Their Anticonvulsant Activity

Wide-angle X-ray diffraction studies of physically and chemically treated silk fibers like bivoltine mulberry silk and tassar silk were carried out to evaluate their crystal size, lattice distortion, and minimum enthalpy, as these determine the properties of silk fibers. The results are also compared with tenacity measurement. (C) 1996 John Wiley & Sons, Inc

Unraveling the role of medicinal plants and Gut microbiota in colon cancer: Towards microbiota- based strategies for prevention and treatment

Colon cancer remains one of the leading causes of morbidity and mortality worldwide. Given its widespread prevalence, the identification of new anticancer drugs is crucial. Medicinal plants have provided many natural products that have proven to be successful anticancer drugs in clinical use and have shown significant efficacy. Over the last decade, researchers have gathered significant information regarding the contribution of gut microbiota to the development and progression of colon cancer. Manipulating the gut microbiota to reverse microbial dysbiosis is an innovative strategy for addressing human diseases and intestinal disorders. Recent scientific findings have shown that this approach has a significant positive impact on the prevention and treatment of colon cancer. This review aims to provide a comprehensive understanding of the fundamental concepts related to intestinal microbiota and dysbiosis, as well as the interactions between microbiota and phytochemicals that can affect the bioavailability and bioactivity of these compounds. The primary components of the gut, including carbohydrates, enzymes, lipids, vitamins, and secondary metabolites such as alkaloids, flavonoids, polyphenols, and terpenoids, can activate gut dysbiosis. While these strategies show promising outcomes by rectifying microbiota proportion, modifying innate immune systems, emphasizing gut barrier operation, inhibiting pathogen colonization, and exhibiting selective cytotoxicity against colon cancer cells, further research is necessary to fully understand their mechanisms of action. This review also highlights the relationship between medicinal plants, gut microbiota, and colon cancer, which may lead to the development and clinical translation of potential microbiota-based strategies for cancer prevention

ERK1 and ERK2 activation modulates diet-induced obesity in mice.

IF 3.112International audienceObesity is a worldwide problem, and dietary lipids play an important role in its pathogenesis. Recently, Erk1 knock-out (ERK1(-/-)) mice have been shown to exhibit low preference for dietary fatty acids. Hence, we maintained Erk1(-/-) mice on a high-fat diet (HFD) to assess the implication of this mitogen-activated protein (MAP) kinase in obesity. The Erk1(-/-) mice, fed the HFD, were more obese than wild-type (WT) animals, fed the same diet. Erk1(-/-) obese mice gained more fat and liver mass than WT obese animals. No difference was observed in daily food and energy intake in HFD-fed both group of animals. However, feed efficiency was higher in Erk1(-/-) than WT animals. Blood cholesterol, triglyceride and insulin concentrations were higher in Erk1(-/-) obese mice compared to WT obese animals. Accordingly, homeostatic model assessment of insulin resistance (HOMA-IR) value was higher in Erk1(-/-) obese mice compared to WT obese animals. Interestingly, only Erk1(-/-) obese mice, but not WT-obese animals, exhibited high degree of phosphorylation of liver MEK, the upstream regulator of ERK1/2. This phenomenon was associated with high liver ERK2 phosphorylation in Erk1(-/-) obese mice which also had high liver acetyl-CoA carboxylase 1 (ACC1) and fatty acid synthase (FAS) mRNA expression, suggesting high lipogenesis in these animals. The Erk1(-/-) obese mice also had low PPAR-α and CPT1β mRNA, indicating low fatty acid oxidation. Our observations suggest that ERK1 and ERK2 might play key roles in the regulation of obesity

Brake fault diagnosis using histogram features and artificial immune recognition system (AIRS)

Brakes are one of the most important components in automobiles because they allow the vehicle to stop or slow down. It requires extra caution in terms of safety and dependability. As a result, it is critical to monitor the brake system’s condition in order to assure safety. Vibration signals play an important function in detecting brake system faults. A machine learning approach was employed in this work to identify brake defects under various scenarios. A piezoelectric type transducer and data collecting system were used to collect vibration signals. The vibration signals were used to obtain the relevant histogram features. The feature selection and feature classification were done using the vibration signals obtained from the transducer. An artificial immune recognition system was used to classify the extracted features (AIRS). The classification accuracy as well as the classifier’s performance level have been reported

Enhanced isolation of lymphoid cells from human skin.

Studying skin immune cells under various pathophysiological conditions is vital for understanding the nature of cutaneous inflammatory responses. Available methods of isolating cells from the skin have relatively low yield or require in vitro culture. To increase effective isolation of skin immune cells we used collagenase P treatment. The number of T cells obtained ex vivo using this technique was dramatically greater than conventional methods without the need for long term culture. The phenotype and function of isolated cells were comparable to the cells isolated by EDTA treatment. Collagenase P-based methodology will enhance the ability to investigate lymphoid cell function in healthy and diseased skin

Grape seed and skin extract reduces pancreas lipotoxicity, oxidative stress and inflammation in high fat diet fed rats.

IF 2.326International audienceObesity is related to an elevated risk of diabetes and the mechanisms whereby fat adversely affects the pancreas are poorly understood. We studied the effect of a high fat diet (HFD) on pancreas steatosis, oxidative stress and inflammation as well as the putative protection afforded by grape seed and skin extract (GSSE). HFD induced body weight gain, without affecting insulinemia, nor glycemia and dropped adiponectemia. HFD also provoked the ectopic deposition of cholesterol and triglyceride, and an oxidative stress characterized by increased lipoperoxidation and carbonylation, inhibition of antioxidant enzyme activities such as CAT, GPx and SOD, depletion of zinc and a concomitant increase in calcium and H2O2. HFD induced pro-inflammatory chemokines mRNA as RANTES and MCP1 as well as cytokines expression as TNFα, IL6 and IL1β. Importantly GSSE counteracted all the deleterious effects of HFD on pancreas in vivo i-e lipotoxicity, oxidative stress and inflammation. In conclusion, GSSE could find potential applications in fat-induced pancreas lipotoxicity and dysfunction

Epigenetic regulation of the nuclear genome associated with mitochondrial dysfunction in Leber’s hereditary optic neuropathy (LHON)

Abstract Leber’s hereditary optic neuropathy (LHON) is a mitochondrial hereditary disease in which visual loss affects complex 1 activity of the electron transport chain of mitochondria. It first manifests as painless dulling or blurry in one or even both eyes, and as it develops, sharpness and color perception are lost. In addition to primary mitochondrial DNA (mtDNA) mutations, there are also other environmental and epigenetic factors involved in the pathogenesis of LHON. One of the most common locations for deadly pathogenic mutations in humans is the human complex I accessory NDUFS4 subunit gene. The iron-sulfur clusters of the electron input domain were distorted in the absence of NDUFS4, which reduced complex I function and elevated the production of reactive oxygen species. Therefore, here, we studied the epigenetic alterations of NDUFS4 by focusing on histone activation and repressive markers. We isolated peripheral blood mononuclear cells (PBMCs) from LHON patients and healthy individuals and examined epigenetic modifications in ND4 mutant cells and control cells. Chromatin immunoprecipitation-qRT PCR (ChIP-qRT PCR) assays were performed to investigate the modifications of histones. In comparison to their controls, both LHON patients and ND4 mutant cells exhibited a significant enrichment in activation and repressive markers. This finding indicates that these modifications might mitigate the impact of LHON mutations on complex 1 and aid in elucidating the mechanism underlying the progression of LHON disease