GOLPH3 Regulates EGFR in T98G Glioblastoma Cells by Modulating Its Glycosylation and Ubiquitylation

Protein trafficking is altered when normal cells acquire a tumor phenotype. A key subcellular compartment in regulating protein trafficking is the Golgi apparatus, but its role in carcinogenesis is still not well defined. Golgi phosphoprotein 3 (GOLPH3), a peripheral membrane protein mostly localized at the trans-Golgi network, is overexpressed in several tumor types including glioblastoma multiforme (GBM), the most lethal primary brain tumor. Moreover, GOLPH3 is currently considered an oncoprotein, however its precise function in GBM is not fully understood. Here, we analyzed in T98G cells of GBM, which express high levels of epidermal growth factor receptor (EGFR), the effect of stable RNAi-mediated knockdown of GOLPH3. We found that silencing GOLPH3 caused a significant reduction in the proliferation of T98G cells and an unexpected increase in total EGFR levels, even at the cell surface, which was however less prone to ligand-induced autophosphorylation. Furthermore, silencing GOLPH3 decreased EGFR sialylation and fucosylation, which correlated with delayed ligand-induced EGFR downregulation and its accumulation at endo-lysosomal compartments. Finally, we found that EGF failed at promoting EGFR ubiquitylation when the levels of GOLPH3 were reduced. Altogether, our results show that GOLPH3 in T98G cells regulates the endocytic trafficking and activation of EGFR likely by affecting its extent of glycosylation and ubiquitylation.     

New cardo silylated poly(azomethine)s containing 9,9′‐diphenylfluorene units as materials with Brønsted acid‐dependent fluorescence

Aromatic poly(azomethine)s have been studied due to their attractive properties such as high thermal stability, semiconducting behavior and the ability to coordinate species with their imine units (C?N). In this paper, the synthesis and characterization of two novel silylated poly(azomethine)s containing cardo units are reported. These materials were highly soluble in organic solvents such as chloroform and m‐cresol and were thermally stable, and PAzMC1 exhibited a high glass transition temperature value (287 °C), while that for PAzMC2 was not observed. UV–visible spectrophotometry revealed absorption bands related to the aromatic backbone of both PAzMCs, 300–285 nm in tetrahydrofuran and 310–301 nm in dimethylsulfoxide, and bands attributed to the conjugated imine unit at around 350 nm. In order to investigate the phenomenon of the emission of fluorescence promoted by dopant agents with regard to potential optoelectronic applications, the materials were doped with H₂SO₄ and their optical and electrochemical properties investigated. Thus, the absorption band of the imine group was suppressed due to the nitrogen atoms being protonated. Fluorescence spectroscopy analysis developed in dilute solutions of polymers showed no emission from the undoped polymers, whereas the acid‐doped species emitted fluorescence in the UV and violet regions (322 nm). Cyclic voltammetry measurements were carried out and HOMO–LUMO energies were estimated. This study provides a starting point for the development of new poly(azomethine)s with doping‐dependent emission. © 2019 Society of Chemical Industry     

Robust h-index

Scientometrics - The h-index is the most used measurement of impact for researchers. Sites such as Web of Science, Google Scholar, Microsoft Academic, and Scopus leverage it to show and compare the...     

Mortality due to lung, laryngeal and bladder cancer in towns lying in the vicinity of combustion installations

Background

Installations that burn fossil fuels to generate power may represent a health problem due to the toxic substances which they release into the environment.

Objectives

To investigate whether there might be excess mortality due to tumors of lung, larynx and bladder in the population residing near Spanish combustion installations included in the European Pollutant Emission Register.

Methods

Ecologic study designed to model sex-specific standardized mortality ratios for the above three tumors in Spanish towns, over the period 1994-2003. Population exposure to pollution was estimated on the basis of distance from town of residence to pollution source. Using mixed Poisson regression models, we analyzed: risk of dying from cancer in a 5-kilometer zone around installations that commenced operations before 1990; effect of type of fuel used; and risk gradient within a 50-kilometer radius of such installations.

Results

Excess mortality (relative risk, 95% confidence interval) was detected in the vicinity of pre-1990 installations for lung cancer (1.066, 1.041-1.091 in the overall population; 1.084, 1.057-1.111 in men), and laryngeal cancer among men (1.067, 0.992-1.148). Lung cancer displayed excess mortality for all types of fuel used, whereas in laryngeal and bladder cancer, the excess was associated with coal-fired industries. There was a risk gradient effect in the proximity of a number of installations.

Conclusions

Our results could support the hypothesis of an association between risk of lung, laryngeal and bladder cancer mortality and proximity to Spanish combustion installations.     

Challenges for integrated design (ID) in sustainable buildings

It is often argued that integrated design (ID) is a powerful way to enhance collaboration in construction projects. This collaboration is seen as a way of improving innovation to create more sustainable buildings. Contrary to the traditional silo-type and linear design process, ID is based on upfront stakeholder involvement and a holistic approach to project decision-making. Although ID’s premises are theoretically-founded, a close empirical look at its practices shows that numerous challenges compromise its results and efficiency. This study examines the ID process through an iterative process that includes the construction of a conceptual framework and its empirical validation. We examine three green construction projects in Canada. Based on the analysis of 26 interviews with key project stakeholders and more than 198 construction documents, the study assembles – and ultimately applies – a multi-lens framework based on four themes: the fragmented nature of construction; risk perception; stakeholders’ commitment; and efficiency in the design process. Results show that three tensions arise in ID practices: between collaboration and process efficiency, between short-term and long-term goals, and between integrated methods and traditional ones. The study sheds light on ID limits and reveals how stakeholders can improve their interactions to design more sustainable buildings.     

Nanostructured copper/porous silicon hybrid systems as efficient sound-emitting devices

In the present work, the photo-acoustic emission from nanostructured copper/porous silicon hybrid systems was studied. Copper nanoparticles were grown by photo-assisted electroless deposition on crystalline silicon and nanostructured porous silicon (nanoPS). Both the optical and photo-acoustic responses from these systems were determined. The experimental results show a remarkable increase in the photo-acoustic intensity when copper nanoparticles are incorporated to the porous structure. The results thus suggest that the Cu/nanoPS hybrid systems are suitable candidates for several applications in the field of thermoplasmonics, including the development of sound-emitting devices of great efficiency.     

A differential inclusion approach for modeling and analysis of dynamical systems under uncertainty

In this paper we deal with the application of differential inclusions to modeling nonlinear dynamical systems under uncertainty in parameters. In this case, differential inclusions seem to be better suited to modeling practical situations under uncertainty and imprecision than formulations by means of fuzzy differential equations. We develop a practical algorithm to approximate the reachable sets of a class of nonlinear differential inclusion, which eludes the computational problems of a previous set-valued version of the Heun’s method. Our algorithm is based on a complete discretization (time and state space) of the differential inclusion and it suits hardware features, handling the memory used by the method in a controlled fashion during all iterations. As a case of study, we formulate a differential inclusion to model an epidemic outbreak of dengue fever under Cuban conditions. The model takes into account interaction of human and mosquito populations as well as vertical transmission in the mosquito population. It is studied from the theoretical point of view to apply the Practical Algorithm. Also, we estimate the temporal evolution of the different human and mosquito populations given by the model in the Dengue 3 epidemic in Havana 2001, through the computation of the reachable sets using the Practical Algorithm.