Gastric Mammalian Target of Rapamycin Signaling Contributes to Inhibition of Ghrelin Expression Induced by Roux-En-Y Gastric Bypass

Background/Aims: Roux-en-Y Gastric Bypass, RYGB, is the most effective strategy to control body weight in morbid obesity. RYGB leads to rapid improvement of glycemic status and weight loss, which are largely attributed to the alteration of gastrointestinal hormones including ghrelin. The current study examined potential mechanisms of altered ghrelin synthesis after RYGB. Methods: Gastric mammalian target of rapamycin (mTOR) signaling, ghrelin synthesis and secretion were determined in lean or obese male mice with or without RYGB operation, as well as in obese patients pre- and post-RYGB surgery. Ghrelin expression and mTOR signaling were investigated by western blotting and immunohistochemistry. Ghrelin mRNA levels were detected by real-time PCR. Plasma ghrelin was measured by enzyme immunoassay. Results: mTOR activity in the gastric fundus was significantly lower than in the forestomachs. Both of them were decreased after 24h fasting. A significant negative correlation was found between gastric levels of phospho-S6 (phospho-S6 ribosomal protein) and proghrelin during changes of energy status. mTOR activity was activated, whereas ghrelin expression was inhibited by Roux-en-Y Gastric Bypass in both rodents and human beings. Increment of ghrelin synthesis and decline of mTOR signaling induced by rapamycin were significantly reversed by RYGB in both lean and obese mice. Administration of Ad-S6K1 (adenovirus-mediated p70 ribosomal protein subunit 6 kinase 1) from tail vein suppressed the expression of ghrelin in RYGB-operated mice relative to control animals. Conclusion: mTOR is therefore a gastric fuel sensor whose activity is linked to the regulation of ghrelin after Roux-en-Y Gastric Bypass

Centrifuge application of fibre Bragg gratings: pile axial loads and wall bending moments

One challenge for geotechnical centrifuge testing of soil-structure interaction problems is the reliable measurement of induced structural strains/forces. This paper presents a novel application of fibre Bragg grating (FBG) sensors for strain measurement within geotechnical centrifuge tests. FBG sensors have several advantages for centrifuge testing, in particular their small size and minimal self-weight. This paper gives an overview of recently developed installation and calibration procedures for FBG sensors within buried centrifuge model structures. The effect of thermal expansion/contraction of the materials (including both the fibre and structures) is considered and assessed. The precision and reliability of the FBG sensors are demonstrated using verification tests. The application of the FBG sensors is considered for two geotechnical problems, namely, pile jacking and a 'retaining wall' adjacent to a tunnel (acting as a protective wall to prevent an adjacent structure from tunnelling induced ground movement). Results demonstrate that the FBG sensors can provide reliable measurements of pile axial strains/forces and protective wall bending moments. The paper provides evidence to support the routine adoption of FBG sensors for strain/force measurement of structures in geotechnical centrifuge modelling

Ghrelin and cell differentiation

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/71538/1/j.1745-7270.2008.00465.x.pd

Numerical study on the effect of protective wall depth in reducing structure deformations caused by tunnelling

To reduce tunnelling induced damage of buildings, a 'protective wall' is sometimes constructed between the location of the new tunnel and existing foundations. One of the key design questions relates to the optimal wall depth, where further increase has a limited benefit in reducing structural distortions. This paper presents the results from finite element analyses used to study how protective walls reduce tunnelling induced damage to adjacent structures. A scenario where the protective is located very close to a tunnel is studied, which is considered to be of practical interest and a critical case concerning potential for building damage. The analyses consider a tunnel with a row of 4 piles (in sand) supporting a 5-storey steel frame running transverse to the tunnel direction, with a wall located between the tunnel and the first pile. Results show that the protective wall's depth affects soil and pile settlements, the redistribution of loads applied to the piles (due to structure stiness), and ultimately structural deformations and building damage. For the case considered, the optimal depth of the wall is approximately 1.25 times the tunnel axis depth; marginal reductions in pile settlements and building damage are obtained as wall depth is increased further

Collision-Free Formation-Containment Tracking of Multi-USV Systems with Constrained Velocity and Driving Force

This paper studied the collision avoidance issue in the formation-containment tracking control of multi-USVs (unmanned surface vehicles) with constrained velocity and driving force. Specifically, based on a dual-layer control framework, it designed a multi-USV formation-containment tracking control strategy that accounts for constrained motion velocity and input driving force and validated the stability of this strategy using the Lyapunov method. Then, by utilizing zeroing control barrier function certificates, it considered collision avoidance among USVs with various roles as well as between each USV and static obstacles. A collision-free multi-USV formation-containment tracking control strategy considering constrained motion velocity and driving force was thus established, and its effectiveness was validated through the proposed simulation

Effects of embedded walls on tunnelling-induced sandy ground displacements: a numerical investigation

Urban tunnelling projects pose significant risks to the integrity of nearby structures due to ground movements induced by the excavation process. Embedded walls are commonly employed as a protective measure to mitigate these adverse effects. This paper presents a comprehensive numerical investigation into the effects of embedded walls on tunnelling-induced ground displacements, aiming to provide insights and recommendations for optimal embedded wall design. The study assesses the impact of varying embedded wall length and horizontal distance from the tunnel on soil settlement and horizontal displacements. Results demonstrate the complex interplay between embedded wall length, horizontal distance, and ground movement patterns, and the highly non-linear influence of key parameters on embedded wall efficiency (i.e. its ability to reduce settlements). A preliminary design chart is proposed to guide engineers in determining the appropriate horizontal location and depth of embedded walls to effectively reduce tunnelling- induced ground displacements. The findings contribute to a better understanding of embedded wall performance in the context of tunnelling and provide valuable guidance for the practical design and implementation of protective measures in urban areas

mTOR-dependent Modulation of Gastric Nesfatin-1/NUCB2

Background: Nesfatin-1, an 82 amino acid peptide derived from the prohormone nucleobindin-2 (NUCB2), is a novel satiety hormone acting through a leptin-independent mechanism in the hypothalamus. The mechanisms by which production of nesfatin-1/NUCB2 is regulated remain unknown. Methods: Nesfatin-1/NUCB2 mRNA and immunoreactivity were examined in gastric tissue and Min-6 cells by RT-PCR and immunofluorescent staining or Western blotting. Results: Nesfatin-1/NUCB2 is co-localized with pS6K1, the downstream target of mammalian target of rapamycin (mTOR), in gastric X/A like cells. A parallel relationship between gastric mTOR signaling and nesfatin-1/NUCB2 was observed during changes in energy status. Both mTOR activity and gastric nesfatin-1/NUCB2 were down-regulated by fasting, and returned to basal levels with re-feeding. In high fat diet induced obese mice, gastric mTOR signaling and nesfatin-1/NUCB2 were increased. Inhibition of the gastric mTOR signaling by rapamycin attenuated the expression of gastric nesfatin-1/NUCB2 mRNA and protein in both lean and obese mice. Attenuation of mTOR activity by rapamycin or over-expression of TSC1 or TSC2 reduced the expression of nesfatin-1/NUCB2 in Min-6 cells, suggesting a direct effect of mTOR signaling. Conclusion: Gastric mTOR is a gastric energy sensor whose activity is linked to the regulation of gastric nesfatin-1/NUCB2. Copyright (C) 2012 S. Karger AG, Baselhttp://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000302752600018&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=8e1609b174ce4e31116a60747a720701Cell BiologyPhysiologySCI(E)PubMed19ARTICLE3-4493-5002

Activation of PPARα Ameliorates Cardiac Fibrosis in Dsg2-Deficient Arrhythmogenic Cardiomyopathy

Background: Arrhythmogenic cardiomyopathy (ACM) is a genetic heart muscle disease characterized by progressive fibro-fatty replacement of cardiac myocytes. Up to now, the existing therapeutic modalities for ACM are mostly palliative. About 50% of ACM is caused by mutations in genes encoding desmosomal proteins including Desmoglein-2 (Dsg2). In the current study, the cardiac fibrosis of ACM and its underlying mechanism were investigated by using a cardiac-specific knockout of Dsg2 mouse model. Methods: Cardiac-specific Dsg2 knockout (CS-Dsg2−/−) mice and wild-type (WT) mice were respectively used as the animal model of ACM and controls. The myocardial collagen volume fraction was determined by histological analysis. The expression levels of fibrotic markers such as α-SMA and Collagen I as well as signal transducers such as STAT3, SMAD3, and PPARα were measured by Western blot and quantitative real-time PCR. Results: Increased cardiac fibrosis was observed in CS-Dsg2−/− mice according to Masson staining. PPARα deficiency and hyperactivation of STAT3 and SMAD3 were observed in the myocardium of CS-Dsg2−/− mice. The biomarkers of fibrosis such as α-SMA and Collagen I were upregulated after gene silencing of Dsg2 in HL-1 cells. Furthermore, STAT3 gene silencing by Stat3 siRNA inhibited the expression of fibrotic markers. The activation of PPARα by fenofibrate or AAV9-Pparα improved the cardiac fibrosis and decreased the phosphorylation of STAT3, SMAD3, and AKT in CS-Dsg2−/− mice. Conclusions: Activation of PPARα alleviates the cardiac fibrosis in ACM

The Role of Pancreatic Fatty Acid Synthesis in Islet Morphology and Function after Caloric Restriction or Roux-En-Y Gastric Bypass Surgery in Mice

Background: Both caloric restriction (CR) and Roux-en-Y gastric bypass (RYGB) are practical interventions for type 2 diabetes mellitus (T2DM), while the molecular mechanisms of CR and RYGB regarding glycemic control are still poorly understood. Here, we explore the effects and underlying mechanisms of CR and RYGB on β-cell area and function. Methods: Average islet size was measured by histological analysis. The pancreatic lipid content was detected by using a commercial lipid assay kit. The expression levels of lipogenic transcription factors and enzymes in mouse pancreas were determined by quantitative PCR, Western blot, and immunofluorescence. Results: CR decreased the mean size of islets and pancreatic insulin production in both regular diet-fed and high-fat diet-fed mice. Increased β-cell apoptosis was detected in the calorie-restricted mice. Interestingly, the lipogenic transcription factors and enzymes such as SREBP1c, PPARγ, FASN and ACC were upregulated in the pancreas after CR. In contrast to CR, RYGB decreased the apoptosis of β-cells and the expression of fatty acid synthase. Conclusions: Pancreatic fatty acid synthesis is critical to the β-cell function after CR and RYGB