Down-regulation of vascular GLP-1 receptor expression in human subjects with obesity

It has been thought that incretin signaling prevents arteriosclerosis, and very recently anti-arteriosclerotic effects through GLP-1 receptor were finally demonstrated in clinical human study. The purpose of this study was to investigate how vascular GLP-1 receptor expression is influenced in human subjects. First, we evaluated GLP-1 receptor expression in human arteries in immunostaining. Next, we separated the artery into the intima and media, and evaluated gene expression levels of various factors. We divided the subjects into obesity and non-obesity group and compared their expression levels between them. Finally, we evaluated which factors determine vascular GLP-1 receptor expression. GLP-1 receptor expression in intima and media was lower in obesity group compared to non-obesity group which was correlated with the alteration of TCF7L2 expression. Multiple regression analyses showed that BMI was an independent determining factor for GLP-1 receptor expression in the intima and media. Furthermore, using small interfering RNA method and TCF7L2-EGFP adenovirus, we showed that TCF7L2 was involved in GLP-1 receptor expression in human vascular cells. Taken together, vascular GLP-1 receptor and TCF7L2 expression was significantly down-regulated in human subjects with obesity. In addition, it is likely that TCF7L2 functions as a modulator of vascular GLP-1 receptor expression

An ErbB2/c-Src axis links bioenergetics with PRC2 translation to drive epigenetic 2 reprogramming and mammary tumourigenesis

Dysregulation of histone modifications promotes carcinogenesis by altering transcription. Breast cancers frequently overexpress the histone methyltransferase EZH2, the catalytic subunit of Polycomb Repressor Complex 2 (PRC2). However, the role of EZH2 in this setting is unclear due to the context-dependent functions of PRC2 and the heterogeneity of breast cancer. Moreover, the mechanisms underlying PRC2 overexpression in cancer are obscure. Here, using multiple models of breast cancer driven by the oncogene ErbB2, we show that the tyrosine kinase c-Src links energy sufficiency with PRC2 overexpression via control of mRNA translation. By stimulating mitochondrial ATP production, c-Src suppresses energy stress, permitting sustained activation of the mammalian/mechanistic target of rapamycin complex 1 (mTORC1), which increases the translation of mRNAs encoding the PRC2 subunits Ezh2 and Suz12. We show that Ezh2 overexpression and activity are pivotal in ErbB2-mediated mammary tumourigenesis. These results reveal the hitherto unknown c-Src/mTORC1/PRC2 axis, which is essential for ErbB2-driven carcinogenesis

A Lazy Algorithm for Planning Motions in Contact

Planning the motion of objects in contact is an important stage of the analysis of mechanical assembly tasks. This paper concerns with the case of a polyhedron moving within a polyhedral environment. It presents an algorithm to plan the motion of a convex polyhedron translating and rotating in contact with a neither necessarily convex nor connected polyhedral obstacle. This algorithm uses a new description of the obstacle in the configuration space -- the C-obstacle -- with the help of several contact predicates and of a topological adjacency graph. However, in the nonconvex case, the complete computation of the boundary of the C-obstacle is usually intractable. Our algorithm is lazy: it takes into account progressively and only if it is necessary the non-convexity of the polyhedra. Indeed, the main idea is to describe the Cobstacle as if it were convex, in order to perform as few computations as possible to find a motion and, in case of failure, to build a new description of the C-obs..

A Motion Planning Algorithm of Polyhedra in Contact for Mechanical Assembly

\Gamma A motion planning of objects in contact is one of most important technologies to realize autonomous mechanical assembly by robot manipulators. This paper studies a motion planning of polyhedra in contact. We show a complete algorithm in the case that a convex polyhedron translates and rotates in contact with another one. We also discuss what happens in the nonconvex cases. The principle idea is `astute geometric formulations make the algebraic problem easier to solve'. INTRODUCTION Mechanical assembly occupies one of the greatest parts in manufacturing processes which have not automated yet. Undoubtedly, it is significant to automate it, but many problems remain open to execute the task autonomously by robot manipulators. One of the problems is the motion planning of objects in contact, which plays an important role in the mechanical assembly. Avnaim and Boissonnat studied the problem in which a polygon translates and rotates among polygonal obstacles in 2-space [1], and devel..

Designing Telerobotic Systems as Distributed CORBA-based Applications

Virtual laboratories and on-line robots are examples of distributed telerobotic systems based on emerging Internet technologies