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.     

Autosensitized Photooxidation of the Rose Hip (Wild Rose) Oil - Mechanism and Quantum Yield for Singlet Molecular Oxygen O2 (1 Δg) Generation

The autosensitized photooxidation of the fatty acid components of rose hip (Wild Rose) oil was studied. Two important facts arise from the present investigation: a) Fatty acids of rose hip oil decompose upon visible light irradiation in the absence of external sensitizers by a mechanism that involves O₂(¹Δ_g). The pigments present in rose hip oil themselves efficiently sensitize the generation of O₂(¹Δ_g) with a quantum yield of 0.038 (upper limit). b) Visible irradiation also produces the degradation of the anthocyanines, native pigments which could behave as O₂(¹Δ_g) sensitizers in the oil. In this case a mechanism involving the production of superoxide ions by the pigment and further attack of the radicals on the phenol groups of the anthocyanine could account for the observed experimental evidences. These results should be carefully considered in a practical sense when rose hip oil is stored or employed under daylight conditions. Exposure to visible radiation may cause irreversible transformations in rose hip oil.     

Identifying a putative common binding site shared by substance P receptor and an anti-substance P monoclonal antibody

Substance P G-protein coupled receptor and the antigen recognitionsite of a monoclonal antibody raised against substance P sharea stretch of five contiguous identical amino acids. This observationprompted us to build an atomic model of both the receptor andthe antibody and to analyse their common features. In particular,we report here that a pocket of similar size and compositionis present in both proteins, strongly suggesting a similarityin the mode of binding of both macromolecules to substance P.From the analysis of our models, the available data on the modeof binding of the antibody to substance P and recent data onsubstance P receptor mutants, we concluded that the pocket isvery likely to be involved in binding of the C-terminal 'messagesequence' of the tachykinin. This allowed us to suggest specificsite-directed mutants of the receptor which should shed somelight on the mechanism of peptide recognition by G-protein coupledreceptors.     

Cell-protection mechanism through autophagy in HGFs/<Emphasis Type="Italic">S. mitis</Emphasis> co-culture treated with Chitlac-nAg

Silver-based products have been proven to be effective in retarding and preventing bacterial growth since ancient times. In the field of restorative dentistry, the use of silver ions/nanoparticles has been explored to counteract bacterial infections, as silver can destroy bacterial cell walls by reacting with membrane proteins. However, it is also cytotoxic towards eukaryotic cells, which are capable of internalizing nanoparticles. In this work, we investigated the biological effects of Chitlac-nAg, a colloidal system based on a modified chitosan (Chitlac), administered for 24–48?h to a co-culture of primary human gingival fibroblasts and Streptococcus mitis in the presence of saliva, developed to mimic the microenvironment of the oral cavity. We sought to determine its efficiency to combat oral hygiene-related diseases without affecting eukaryotic cells. Cytotoxicity, reactive oxygen species production, apoptosis induction, nanoparticles uptake, and lysosome and autophagosome metabolism were evaluated. In vitro results show that Chitlac-nAg does not exert cytotoxic effects on human gingival fibroblasts, which seem to survive through a homoeostasis mechanism involving autophagy. That suggests that the novel biomaterial Chitlac-nAg could be a promising tool in the field of dentistry.     

Reactive flash sintering of powders of four constituents into a single phase of a complex oxide in a few seconds below 700°C

Recent work on reactive flash sintering of powders of two oxides, bismuth and of iron oxide, into pure single phase bismuth ferrite, which was accomplished in a few seconds at low furnace temperatures, is expanded to four constituents, alumina, lithia, zirconia, and lanthana, to produce reasonably dense polycrystals of a predominantly single phase, cubic LLZO(Al). Transformation and sintering occur concurrently at a furnace temperature near 700°C, in ambient atmosphere, in just a few seconds. The process may simplify the preparation of complex ceramics with new chemistries and dopants, which are predicted from ab intio calculations to have special attributes, not only because the powders sinter quickly at low temperatures, but also because the need for stoichiometric powders as starting materials is obviated.     

Deforming Time in a Nonadditive Discount Function

The aim of this paper is to present a methodology to generate a partially subadditive (respectively superadditive) discount function starting from an entirely subadditive (respectively superadditive) discount model. To do this, we are going to use the concept of deformation of time in a discount function, focusing on Stevens' power law. A deformation of time is a function that mathematically represents the perception from an individual or a group of individuals about how the calendar time evolves. This approach will be important when describing the treatment of addictions and other diseases in patients who show a certain degree of impulsivity in their intertemporal choice.