SNX3 controls Wingless/Wnt secretion through regulating retromer-dependent recycling of Wntless

Drosophila Wingless (Wg) acts as a morphogen during development. Wg secretion is controlled by a seven-pass transmembrane cargo Wntless (Wls). We have recently identified retromer as a key regulator involved in Wls trafficking. As sorting nexin (SNX) molecules are essential components of the retromer complex, we hypothesized that specific SNX(s) is required for retromer-mediated Wnt secretion. Here, we generated Drosophila mutants for all of the eight snx members, and identified Drosophila SNX3 (DSNX3) as an essential molecule required for Wg secretion. We show that Wg secretion and its signaling activity are defective in Dsnx3 mutant clones in wing discs. Wg levels in the culture medium of Dsnx3-depleted S2 cells are also markedly reduced. Importantly, Wls levels are strikingly reduced in Dsnx3 mutant cells, and overexpression of Wls can rescue the Wg secretion defect observed in Dsnx3 mutant cells. Moreover, DSNX3 can interact with the retromer component Vps35, and co-localize with Vps35 in early endosomes. These data indicate that DSNX3 regulates Wg secretion via retromer-dependent Wls recycling. In contrast, we found that Wg secretion is not defective in cells mutant for Drosophila snx1 and snx6, two components of the classical retromer complex. Ectopic expression of DSNX1 or DSNX6 fails to rescue the Wg secretion defect in Dsnx3 mutant wing discs and in Dsnx3 dsRNA-treated S2 cells. These data demonstrate the specificity of the DSNX3-retromer complex in Wls recycling. Together, our findings suggest that DSNX3 acts as a cargo-specific component of retromer, which is required for endocytic recycling of Wls and Wg/Wnt secretion

The disruption of proteostasis in neurodegenerative diseases

Cells count on surveillance systems to monitor and protect the cellular proteome which, besides being highly heterogeneous, is constantly being challenged by intrinsic and environmental factors. In this context, the proteostasis network (PN) is essential to achieve a stable and functional proteome. Disruption of the PN is associated with aging and can lead to and/or potentiate the occurrence of many neurodegenerative diseases (ND). This not only emphasizes the importance of the PN in health span and aging but also how its modulation can be a potential target for intervention and treatment of human diseases.info:eu-repo/semantics/publishedVersio

Association of mast cell-derived VEGF and proteases in dengue shock syndrome

Background: Recent in-vitro studies have suggested that mast cells are involved in Dengue virus infection. To clarify the role of mast cells in the development of clinical Dengue fever, we compared the plasma levels of several mast cell-derived mediators (vascular endothelial cell growth factor [VEGF], soluble VEGF receptors [sVEGFRs], tryptase, and chymase) and -related cytokines (IL-4, -9, and -17) between patients with differing severity of Dengue fever and healthy controls. Methodology/Principal Findings: The study was performed at Children\u27s Hospital No. 2, Ho Chi Minh City, and Vinh Long Province Hospital, Vietnam from 2002 to 2005. Study patients included 103 with Dengue fever (DF), Dengue hemorrhagic fever (DHF), and Dengue shock syndrome (DSS), as diagnosed by the World Health Organization criteria. There were 189 healthy subjects, and 19 febrile illness patients of the same Kinh ethnicity. The levels of mast cell-derived mediators and -related cytokines in plasma were measured by ELISA. VEGF and sVEGFR-1 levels were significantly increased in DHF and DSS compared with those of DF and controls, whereas sVEGFR-2 levels were significantly decreased in DHF and DSS. Significant increases in tryptase and chymase levels, which were accompanied by high IL-9 and -17 concentrations, were detected in DHF and DSS patients. By day 4 of admission, VEGF, sVEGFRs, and proteases levels had returned to similar levels as DF and controls. In-vitro VEGF production by mast cells was examined in KU812 and HMC-1 cells, and was found to be highest when the cells were inoculated with Dengue virus and human Dengue virus-immune serum in the presence of IL-9. Conclusions: As mast cells are an important source of VEGF, tryptase, and chymase, our findings suggest that mast cell activation and mast cell-derived mediators participate in the development of DHF. The two proteases, particularly chymase, might serve as good predictive markers of Dengue disease severity

Building information modeling for smart built environments

Building information modelling (BIM) provides architectural 3D visualization and a standardized way to share and exchange building information. Recently, there has been an increasing interest in using BIM, not only for design and construction, but also the post-construction management of the built facility. With the emergence of smart built environment (SBE) technology, which embeds most spaces with smart objects to enhance the building’s efficiency, security and comfort of its occupants, there is a need to understand and address the challenges BIM faces in the design, construction and management of future smart buildings. In this paper, we investigate how BIM can contribute to the development of SBE. Since BIM is designed to host information of the building throughout its life cycle, our investigation has covered phases from architecture design to facility management. Firstly, we extend BIM for the design phase to provide material/device profiling and the information exchange interface for various smart objects. Next, we propose a three-layer verification framework to assist BIM users in identifying possible defects in their SBE design. For the post-construction phase, we have designed a facility management tool to provide advanced energy management of smart grid-connected SBEs, where smart objects, as well as distributed energy resources (DERs) are deployed

Location estimation in wireless sensor networks using spring-relaxation technique.

Accurate and low-cost autonomous self-localization is a critical requirement of various applications of a large-scale distributed wireless sensor network (WSN). Due to its massive deployment of sensors, explicit measurements based on specialized localization hardware such as the Global Positioning System (GPS) is not practical. In this paper, we propose a low-cost WSN localization solution. Our design uses received signal strength indicators for ranging, light weight distributed algorithms based on the spring-relaxation technique for location computation, and the cooperative approach to achieve certain location estimation accuracy with a low number of nodes with known locations. We provide analysis to show the suitability of the spring-relaxation technique for WSN localization with cooperative approach, and perform simulation experiments to illustrate its accuracy in localization

Hybrid RF mapping and Kalman filtered spring relaxation for sensor network localization

An accurate and low-cost hybrid solution to the problem of autonomous self-localization in wireless sensor networks (WSN) is presented. The solution is designed to perform robustly under challenging radio propagation conditions in mind, while requiring low deployment efforts, and utilizing only low-cost hardware and light-weight distributed algorithms for location computation. Our solution harnesses the strengths of two approaches for environments with complex propagation characteristics: RF mapping to provide an initial estimate of each sensor's position based on a coarse-grain RF map acquired with minimal efforts; and a cooperative light-weight spring relaxation technique for each sensor to refine its estimate using Kalman filtered inter-node distance measurements. Using Kalman filtering to pre-process noisy distance measurements inherent in complex propagation environments, is found to have significant positive impacts on the subsequent accuracy and the convergence of our spring relaxation algorithm. Through extensive simulations using realistic settings and real data set, we show that our approach is a practical localization solution which can achieve sub-meter accuracy and fast convergence under harsh propagation conditions, with no specialized hardware or significant efforts required to deploy. © 2012 IEEE

Fuzzy logic-based resource allocation algorithm for V2X communications in 5G cellular networks

202208 bcchAuthor’s OriginalOthersPolyU (ZVQ5)Publishe